tag:blogger.com,1999:blog-334960692024-03-26T10:04:15.867-07:00TZPSS - The Scientist's MindWith curiosity on overdrive, I'm David Wong, a pharmaceutical scientist obsessed in nature and technology. This blog is my platform for sharing ideas and mind-blown moments.Unknownnoreply@blogger.comBlogger137125tag:blogger.com,1999:blog-33496069.post-46223983471784118942024-02-15T11:09:00.000-08:002024-02-15T11:09:35.581-08:005 Health Supplements good for Liver Inflammation<div><span style="font-size: x-large;">W</span>hen it comes to liver health and inflammation, there are several supplements that may offer potential benefits. Remember to consult with a healthcare professional before starting any new supplements, especially if you have existing health conditions. Here are some options:</div><div><br /></div><div><b>Milk Thistle (Silymarin): </b><i>Silybum marianum</i> L. (milk thistle) is a popular herbal remedy known for its potential anti-inflammatory properties. <b>Milk Thistle</b> has
been used for treating different complications such as jaundice,
hepatitis, and cancers. It has also been shown that silymarin, a
flavonolignan extract of the plant, demonstrates chemo-preventive effects
against cancers. (1)</div><div><br /></div><div><b>Turmeric (Curcumin):</b> Turmeric contains curcumin, which has both anti-inflammatory and antioxidant qualities. It may help reduce liver inflammation and support overall liver health. Pathological progression often develops from non-alcoholic fatty liver disease (NAFLD) to liver fibrosis (LF) then finally to hepatocellular carcinoma (HCC). In 52 studies of animals, curcumin demonstrates a significant improvement
in key indicators across the stages of NAFLD, liver fibrosis, and HCC.
Researchers then conducted a detailed analysis of common inflammatory markers IL-1β,
IL-6, and TNF-α, which traverse the entire disease process. (2) </div><div><br /></div><div><b>Zinc: </b>Zinc (Zn) is an essential mineral that plays a role in various bodily functions, including liver health. Some studies suggest that zinc supplementation may help prevent liver damage from infections and toxins. A study shows the serum Zn and Se levels were significantly associated with serum
albumin levels, and inversely associated with the stages of hepatic
fibrosis. Furthermore, serum Zn levels were inversely correlated with the grades of
hepatic steatosis in patients with hepatitis C virus-related CLD, (3)</div><div><br /></div><div><b>Licorice Root Extract:</b> Licorice root has been studied for its potential anti-inflammatory effects. It may help protect the liver and reduce inflammation. In an animal study, isoliquiritigenin and liquorice roots aqueous extract reduced high-fat diet-induced hyperglycaemia, (4) </div><div><br /></div><div><b>Omega-3 Fatty Acids: </b>Consuming fatty fish or fish oil supplements rich in omega-3 fatty acids may help reduce inflammation associated with liver conditions like nonalcoholic fatty liver disease (NAFLD). Omega-3s are also beneficial for overall health.</div><div><br /></div><div>Remember that individual responses to supplements can vary, and it’s essential to maintain a balanced diet, stay hydrated, and avoid excessive alcohol consumption. Always consult with a healthcare provider to determine the best approach for your specific situation.</div><div><br /></div><div><b>REFERENCE</b></div><div><br /></div><div>1. Seyyed Amir Emadi et al, A review of therapeutic potentials of milk thistle (Silybum marianum L.) and its main constituent, silymarin, on cancer, and their related patents, Iran J Basic Med Sci. 2022 Oct;25(10):1166-1176.</div><div>2. Yubing Li et al, Protective role of curcumin in disease progression from non-alcoholic fatty liver disease to hepatocellular carcinoma: a meta-analysis, Front Pharmacol. 2024 Jan 19:15:1343193. </div><div>3. Takashi Himoto et al, Involvement of essential trace elements in the pathogenesis of hepatitis C virus‑related chronic liver disease and nonalcoholic steatohepatitis, Exp Ther Med. 2023 Nov 17;27(1):19.</div><div>4. Mohammed Abdo Yahya et al, Liquorice root extract and isoliquiritigenin attenuate high-fat diet-induced hepatic steatosis and damage in rats by regulating AMPK, Arch Physiol Biochem. 2022 Sep 19:1-16.</div><div>5. Hao Liu et al, Protectin D1 inhibits TLR4 signaling pathway to alleviate non-alcoholic steatohepatitis via upregulating IRAK-M, Free Radic Biol Med. 2024 Jan:210: 42-53.</div><div><br /></div><div><br /></div><div><br /></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-19462683372277820212024-02-13T11:41:00.000-08:002024-02-13T11:41:50.391-08:00Five Health Supplements for Hair Growth<p><span style="font-family: helvetica; font-size: medium;"><b> Here are supplements with some supporting evidence:</b></span></p>
<ul data-sourcepos="5:1-10:0">
<li data-sourcepos="5:1-5:207"><span style="font-family: helvetica; font-size: medium;"><strong>Biotin (Vitamin B7):</strong> Plays a role in keratin production, a key component of hair. However, deficiency is less common, and benefits of supplementation appear limited unless the users have a diagnosed deficiency.</span></li>
<li data-sourcepos="6:1-6:151"><span style="font-family: helvetica; font-size: medium;"><strong>Zinc:</strong> Deficiency can lead to hair loss. Ensuring adequate dietary intake through foods like meat, seafood, and pumpkin seeds is often sufficient.</span></li>
<li data-sourcepos="7:1-7:116"><span style="font-family: helvetica; font-size: medium;"><strong>Iron:</strong> Deficiency can also trigger hair loss. One may consider dietary sources like lentils, spinach, and beans.</span></li>
<li data-sourcepos="8:1-8:184"><span style="font-family: helvetica; font-size: medium;"><strong>Vitamin D:</strong> Plays a role in cell growth and cycling, impacting hair follicles. Deficiency is common, and supplementation may benefit hair growth, although more study is needed.</span></li>
<li data-sourcepos="9:1-10:0"><span style="font-family: helvetica; font-size: medium;"><strong>Vitamin C:</strong> An antioxidant essential for collagen production, crucial for hair structure. One may focus on dietary sources like citrus fruits and peppers.</span></li></ul><div><b><span style="font-family: helvetica; font-size: medium;">Reference</span></b></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;">1. Shaher Duchi et al, The formulation and in vitro evaluation of WS Biotin, a novel encapsulated form of D-Biotin with improved water solubility for hair and skin treatment applications, Int J Cosmet Sci. 2024 Feb;46(1):119-129.</span></div><div><span style="font-family: helvetica; font-size: medium;">2. Jovan Lalosevic et al, Serum Zinc Concentration in Patients with Alopecia Areata, Acta Derm Venereol. 2023 Oct 3:103:adv13358. </span></div><div><span style="font-family: helvetica; font-size: medium;">3. Chia-Shuen Lin et al, Diagnosis and treatment of female alopecia: Focusing on the iron deficiency-related alopecia, Tzu Chi Med J. 2023 Aug 22;35(4):322-328. </span></div><div><span style="font-family: helvetica; font-size: medium;">4. Kriteeka Saini et al, Role of vitamin D in hair loss: A short review, J Cosmet Dermatol. 2021 Nov;20(11):3407-3414. </span></div><div><span style="font-family: helvetica; font-size: medium;">5. Hind M Almohanna et al, The Role of Vitamins and Minerals in Hair Loss: A Review , Dermatol Ther (Heidelb). 2019 Mar;9(1):51-70. </span></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-42032816978747328902024-02-12T13:35:00.000-08:002024-02-12T15:10:41.219-08:00Health Supplements for Spider (Varicose) Veins<p>There's no known way to truly <strong>reverse</strong> spider (varicose) veins once they have formed. These damaged veins won't magically heal themselves back to normal. However, there are effective <strong>treatments</strong> available to reduce their appearance and improve the affected area's overall health. Here are the treatments options: </p><message-content _ngcontent-ng-c2170765079="" _nghost-ng-c2770215737="" class="model-response-text ng-tns-c2170765079-16 ng-star-inserted" id="message-content-id-r_61d071eae33cb6bf" style="height: auto;"><div _ngcontent-ng-c2770215737="" class="markdown markdown-main-panel ui-v2-enabled" dir="ltr" style="--animation-duration: 600ms; --fade-animation-function: cubic-bezier(0.05, 0.7, 0.91, 1);"><ul data-sourcepos="7:1-16:0">
<li data-sourcepos="7:1-10:93"><strong>Professional treatments:</strong> These are performed by dermatologists or vein specialists and generally offer the most effective results. Options include:
<ul data-sourcepos="8:5-10:93">
<li data-sourcepos="8:5-8:96"><strong>Sclerotherapy:</strong> Injections of a solution that closes the vein, causing it to fade away.</li>
<li data-sourcepos="9:5-9:68"><strong>Laser therapy:</strong> Uses lasers to target and destroy the vein.</li>
<li data-sourcepos="10:5-10:93"><strong>Microphlebectomy:</strong> Tiny incisions are made to remove small clusters of spider veins.</li>
</ul>
</li>
<li data-sourcepos="11:1-16:0"><strong>Lifestyle changes:</strong> While not a direct reversal, these modifications can help prevent further development and improve circulation:
<ul data-sourcepos="12:5-16:0">
<li data-sourcepos="12:5-12:84"><strong>Avoidance of prolonged standing and straining, elevation</strong> of the affected leg.</li><li data-sourcepos="12:5-12:84"><strong>Weight management:</strong> Maintaining a healthy weight reduces pressure on veins.</li>
<li data-sourcepos="13:5-13:82"><strong>Exercise:</strong> Regular physical activity improves blood flow and vein health.</li>
<li data-sourcepos="14:5-14:105"><strong>Compression stockings:</strong> Applying graduated pressure can enhance circulation and reduce swelling.</li>
<li data-sourcepos="15:5-16:0"><strong>Sun protection:</strong> Avoid excessive sun exposure to protect skin and prevent vein damage.</li>
</ul>
</li>
</ul><p data-sourcepos="17:1-17:23"><strong>Health supplements:</strong></p><p data-sourcepos="19:1-19:444">Various supplements are marketed for spider veins, but there is <b>only </b><strong>limited/no scientific evidence to support their effectiveness</strong> in treating or reversing them. </p><p data-sourcepos="3:1-3:13">Here are some <strong>popular supplements</strong> associated with varicose veins, but remember, strong scientific evidence to support their use is currently absent:</p><ul data-sourcepos="13:1-17:0">
<li data-sourcepos="5:1-5:127"><strong>Horse Chestnut: </strong>This plant might offer mild benefits for circulation.</li><li data-sourcepos="5:1-5:127"><strong>Butcher's broom:</strong> This plant extract is thought to improve circulation and vein tone, but studies haven't been conclusive.</li>
<li data-sourcepos="6:1-6:106"><strong>Grape seed extract:</strong> Rich in antioxidants, it might benefit circulation, scientific direct support is needed.</li>
<li data-sourcepos="7:1-7:143"><strong>Diosmin and hesperidin:</strong> These citrus flavonoids are sometimes combined and might offer mild improvements, but again, evidence is limited.</li>
<li data-sourcepos="8:1-8:63"><strong>Turmeric and ginger:</strong> These anti-inflammatory spices might indirectly help with circulation, but their direct effect on varicose veins is unclear. No scientific research articles (experiment results) were found, as of 2/12/2024.</li>
<li data-sourcepos="9:1-10:0"><strong>Vitamins C, E, and K:</strong> These essential nutrients contribute to overall vein health, but supplementation likely won't reverse existing varicose veins</li>
</ul><p data-sourcepos="25:1-25:30">
</p><p data-sourcepos="18:1-18:194">Remember, self-treating varicose veins can potentially worsen the issue. Consulting a healthcare professional is crucial for getting the right guidance and exploring effective treatment options.</p><p data-sourcepos="18:1-18:194"><br /></p><p data-sourcepos="18:1-18:194"><b>Reference</b></p><p data-sourcepos="18:1-18:194">Faris Fayyaz et al, Advancements in Varicose Vein Treatment: Anatomy, Pathophysiology, Minimally Invasive Techniques, Sclerotherapy, Patient Satisfaction, and Future Directions, Cureus. 2024 Jan 10;16(1):e51990.</p><p data-sourcepos="18:1-18:194">Hongcheng Ren et al, Combination of Minimally Invasive Methods for the Treatment of Varicose Veins, Vasc Endovascular Surg. 2023 Oct 6:15385744231199548. </p><p data-sourcepos="18:1-18:194">Wenhong Jiang et al, Endovenous Radiofrequency Ablation Versus Laser Ablation in Patients with Lower Extremity Varicose Veins: A Meta-analysis J Vasc Surg Venous Lymphat Disord. 2024.</p><p data-sourcepos="18:1-18:194">Richard H Jones et al, Management of varicose veins, Am Fam Physician. 2008 Dec 1;78(11):1289-94.</p><p data-sourcepos="18:1-18:194">Beniamino Palmieri et al, A nutraceutical formulation combined with sclerofoam-assisted laser treatment ameliorates chronic venous insufficiency , Lasers Med Sci. 2022 Sep;37(7):2831-2835.</p><p data-sourcepos="18:1-18:194">Brandon P Kitchens et a, lA Literature Review of Pharmacological Agents to Improve Venous Leg Ulcer Healing, Wounds. 2020 Jul;32(7):195-207. </p><p data-sourcepos="18:1-18:194">Lukasz Gwozdzinski et al, The Effect of Diosmin, Escin, and Bromelain on Human Endothelial Cells Derived from the Umbilical Vein and the Varicose Vein-A Preliminary Study Biomedicines. 2023 Jun 13;11(6):1702.</p><p data-sourcepos="18:1-18:194">Laura Gheucă Solovăstru et al, Randomized, controlled study of innovative spray formulation containing ozonated oil and α-bisabolol in the topical treatment of chronic venous leg ulcers, Adv Skin Wound Care . 2015 Sep;28(9):406-9.</p><p data-sourcepos="18:1-18:194"><br /></p><p data-sourcepos="18:1-18:194"><br /></p><p data-sourcepos="18:1-18:194"><br /></p><p data-sourcepos="18:1-18:194"><br /></p><p data-sourcepos="18:1-18:194"><br /></p><p data-sourcepos="18:1-18:194"><br /></p></div></message-content>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-75945247270368606762024-02-11T13:13:00.000-08:002024-02-11T13:13:20.918-08:005 Popular Health Supplements for Anti-aging<p data-sourcepos="1:1-1:405">It is important to understand that there is no magic bullet or one-size-fits-all approach to anti-aging. While certain supplements may offer some benefits, they are most effective when combined with a healthy lifestyle that includes a balanced diet, regular exercise, and adequate sleep. Additionally, the "best" supplements for we will depend on our individual health needs and potential risk factors. Thus, the "best" supplements could be different among individuals. Anyway, here are some popular supplements that have been associated with potential anti-aging benefits, along with their pros and cons:</p><p data-sourcepos="5:1-5:17"><strong>1. Vitamin D:</strong></p><ul data-sourcepos="7:1-10:0">
<li data-sourcepos="7:1-7:246"><strong>Benefits:</strong> Vitamin D is essential for bone health and may also play a role in immune function, cell growth, and reducing inflammation. Some studies suggest it may be linked to a reduced risk of certain chronic diseases associated with aging. Here is the argument: Vitamin D3 helps our immune system fight
infections and diseases. It does this by controlling many genes in
immune cells, especially those involved in learning and remembering
threats. This control comes from a special protein
called VDR (vitamin D receptor) that works with other proteins to program immune cells.
These cells, like soldiers, become better at recognizing and fighting
off dangers. Since a strong immune system is crucial for
healthy aging, keeping your vitamin D levels up can help you stay
strong and fight off problems as you get older. (1) On the other hand, scientists found that 1,25(OH)<sub>2</sub>D<sub>3</sub> restored impaired cell proliferation,
migration, and tube formation induced by high-glucose, and up-regulated
expression of angiogenesis-related factors. These protective effects
might be mediated through PI3K/AKT/HIF-1α pathway. These findings
suggested that 1,25(OH)<sub>2</sub>D<sub>3</sub> accelerated diabetic
wound healing by modulating inflammation, restoring vascular endothelial
dysfunction, and promoting angiogenesis. (2) </li>
<li data-sourcepos="8:1-8:127"><strong>Side effects:</strong> At high doses, vitamin D can lead to toxicity, causing symptoms like nausea, vomiting, and kidney problems. The maximum recommended amount for long-term supplementation is 2,000
units per day. Vitamin D3 toxicity can present in various
scenarios, ranging from asymptomatic to gastrointestinal, and in severe
cases with neuropsychiatric and life-threatening symptoms. (3)</li>
<li data-sourcepos="9:1-10:0"><strong>Considerations:</strong> Most people get enough vitamin D from sunlight exposure and their diet. </li></ul><p data-sourcepos="13:1-13:4"><strong>2. Omega-3 fatty acids:</strong></p><ul data-sourcepos="15:1-18:0">
<li data-sourcepos="15:1-15:242"><strong>Benefits:</strong> Omega-3s are essential fats that have been shown to support heart health, brain function, and reduce inflammation. Some studies suggest they may also help protect against cognitive decline and age-related macular degeneration. Epidemiological studies suggested an association between omega-3 fatty acids and cognitive function. Studies linked omega-3 fatty acids to better brain function, but it wasn't clear if certain genes involved in making these fatty acids directly impacted thinking. Scientists analyzed genetic data from large groups and found that changes in genes called FADS, important for omega-3 production, indeed affect cognitive function. Looking deeper, specific brain regions and cell types showed connections between FADS genes and thinking ability. Even analyzing blood cells supported this link, strengthening the evidence. This suggests targeting FADS genes could be a potential strategy for maintaining healthy brain function. (4) Inflammation is a conserved process that involves the activation of
immune and non-immune cells aimed at protecting the host from bacteria,
viruses, toxins and injury. Several studies have demonstrated that different dietary
components may influence modifiable risk factors for diverse chronic
human pathologies. Marine n-3 polyunsaturated fatty acids (n-3 PUFAs),
mainly eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), are
well-recognized anti-inflammatory and immunomodulatory agents that are
able to influence many aspects of the inflammatory. (5) process.</li>
<li data-sourcepos="16:1-16:231"><strong>Side effects:</strong> Omega-3s can cause side effects like belching, heartburn, and loose stools, especially at high doses. (6)</li>
<li data-sourcepos="17:1-18:0"><strong>Considerations:</strong> Omega-3s are found in fatty fish like salmon, tuna, and mackerel. If you don't eat much fish, a supplement may be a good option.</li></ul><p data-sourcepos="21:1-21:16"><strong>3. Curcumin:</strong></p><ul data-sourcepos="23:1-24:141">
<li data-sourcepos="23:1-23:229"><strong>Benefits:</strong> Curcumin is the active ingredient in turmeric and has anti-inflammatory and antioxidant properties. Studies suggest it may be beneficial for joint health, brain function, and reducing the risk of chronic diseases. A study suggests that highly bioavailable curcumin formulation has a beneficial effect on the traumatic brain in mice. (7) Osteoarthritis (OA) is a chronic degenerative joint disorder primarily
affecting the elderly, characterized by a prominent inflammatory
component. A study results reveal that both Vitamin D and
curcumin attenuate the expression of PAR-2, leading to a reduction in
the downstream proinflammatory cytokines, such as Tumor Necrosis
Factor-alpha (TNF-α), Interleukin 6 (IL-6), and Interleukin 8 (IL-8),
implicated in the OA pathogenesis. (8)</li>
<li data-sourcepos="24:1-24:141"><strong>Side effects:</strong> Curcumin is generally well-tolerated, but some people may experience stomach upset or diarrhea. It can also interact with certain medications, so talk to a doctor before taking it.</li></ul><p data-sourcepos="29:1-29:28"><strong>4. Coenzyme Q10 (CoQ10):</strong></p><ul data-sourcepos="31:1-33:203">
<li data-sourcepos="31:1-31:265"><strong>Benefits:</strong> CoQ10 is an antioxidant that is naturally produced in the body and plays a role in energy production. Levels of CoQ10 decline with age, and some studies suggest that supplementing may improve heart health, reduce fatigue, and slow cognitive decline.</li>
<li data-sourcepos="32:1-32:134"><strong>Side effects:</strong> CoQ10 is generally safe, but some people may experience mild side effects like nausea, headache, or stomach upset.</li></ul><p data-sourcepos="37:1-37:19"><strong>5. Resveratrol:</strong></p><ul data-sourcepos="39:1-42:0">
<li data-sourcepos="39:1-39:262"><strong>Benefits:</strong> Resveratrol is a compound found in red wine, grapes, and berries that has antioxidant and anti-inflammatory properties. Some studies suggest it may be beneficial for heart health, brain function, and longevity, but the evidence is not conclusive.</li>
<li data-sourcepos="40:1-40:196"><strong>Side effects:</strong> Resveratrol is generally safe, but some people may experience stomach upset or diarrhea. It can also interact with certain medications, so talk to a doctor before taking it.</li></ul><p>
</p><p data-sourcepos="45:1-45:269">The content of this article is based on multiple research/review articles. For accuracy and details, please check with the listed reference below. Remember, it is always best to talk to the doctor before starting any new supplements<span class="animating">.</span></p><p data-sourcepos="45:1-45:269"><span class="animating"><b>REFERENCE</b></span></p><p data-sourcepos="45:1-45:269"><span class="animating">1. Carsten Carlberg et al, Vitamin D and Aging: Central Role of Immunocompetence, Nutrients. 2024 Jan 30;16(3):398. </span></p><p data-sourcepos="45:1-45:269"><span class="animating">2. Yiming Ma et al, 1,25(OH)2D3 improves diabetic wound healing by modulating inflammation and promoting angiogenesis, J Steroid Biochem Mol Biol. 2024 Feb 8:106477. </span></p><p data-sourcepos="45:1-45:269"><span class="animating">3. Zahra Nekoukar et al, Accidental vitamin D3 overdose in a young man, Int J Vitam Nutr Res. 2023 Nov 17. </span></p><p data-sourcepos="45:1-45:269"><span class="animating">4. Xueyan Wu et al, Brain tissue- and cell type-specific eQTL Mendelian randomization reveals efficacy of FADS1 and FADS2 on cognitive function Transl Psychiatry . 2024 Feb 5;14(1):77. </span></p><p data-sourcepos="45:1-45:269"><span class="animating">5. Cinzia Parolini The Role of Marine n-3 Polyunsaturated Fatty Acids in Inflammatory-Based Disease: The Case of Rheumatoid Arthritis Mar Drugs. 2023 Dec 27;22(1):17</span></p><p data-sourcepos="45:1-45:269"><span class="animating">6. Marlene P Freeman et al, Tolerability of omega-3 fatty acid supplements in perinatal women, Prostaglandins Leukot Essent Fatty Acids. 2007 Oct-Nov;77(3-4):203-8.</span></p><p data-sourcepos="45:1-45:269"><span class="animating">7. Ayse Arzu Sakul et al, A highly bioavailable curcumin formulation ameliorates inflammation cytokines and neurotrophic factors in mice with traumatic brain injury , Chem Biol Drug Des. 2024 Jan;103(1):e14439.</span></p><p data-sourcepos="45:1-45:269"><span class="animating">8. Rajashree Patnaik et al, Evaluating the potential of Vitamin D and curcumin to alleviate inflammation and mitigate the progression of osteoarthritis through their effects on human chondrocytes: A proof-of-concept investigation ,PLoS One. 2023 Dec 29;18(12):e0290739.</span></p><p data-sourcepos="45:1-45:269"><span class="animating"><br /></span></p><p data-sourcepos="45:1-45:269"><span class="animating"><br /></span></p><div _ngcontent-ng-c4150723369="" class="avatar-gutter ng-tns-c4150723369-17 ng-star-inserted"><recitations-gutter _ngcontent-ng-c4150723369="" _nghost-ng-c3233054947="" class="ng-tns-c4150723369-17 ng-trigger ng-trigger-hideElement ng-star-inserted" style="opacity: 1;"><div _ngcontent-ng-c3233054947="" class="resize-observable"></div></recitations-gutter></div><recitation-tooltip _ngcontent-ng-c4150723369="" _nghost-ng-c3652922878="" class="ng-tns-c4150723369-17 ng-star-inserted"><div aria-hidden="true" class="cdk-visually-hidden cdk-focus-trap-anchor"></div><div _ngcontent-ng-c3123385773="" aria-atomic="true" aria-live="polite" class="container" role="dialog"><div _ngcontent-ng-c3652922878="" aria-atomic="true" aria-live="polite" class="recitation-tooltip"><a _ngcontent-ng-c3652922878="" class="recitation-link" href="https://healthans.com/5-htp-and-exercise/" jslog="180390;track:generic_click,impression;BardVeMetadataKey:[["r_47145938b47caa97","c_04315eb598dd63e7",null,"rc_e4d31561ecf60c18","https://healthans.com/5-htp-and-exercise/",null,"en",null,1,null,null,1,0]]" rel="noopener noreferrer" target="_blank"><div _ngcontent-ng-c3652922878="" class="text-container"><span _ngcontent-ng-c3652922878="" class="label ellipsis"></span></div><span _ngcontent-ng-c3652922878="" aria-label="Opens in a new window"></span></a></div></div><div aria-hidden="true" class="cdk-visually-hidden cdk-focus-trap-anchor"></div></recitation-tooltip>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-22709880995801542392024-02-07T08:42:00.000-08:002024-02-07T08:50:56.048-08:00Outline of CMC for vaccines<p><span style="font-family: helvetica; font-size: medium;">Here's a breakdown of CMC specifically for vaccines:</span></p>
<p data-sourcepos="3:1-3:14"><strong><span style="font-family: helvetica; font-size: medium;">Chemistry:</span></strong></p>
<ul data-sourcepos="5:1-18:0">
<li data-sourcepos="5:1-10:51"><span style="font-family: helvetica; font-size: medium;"><strong>Drug substance -</strong> the antigen component itself, which can be:
</span><ul data-sourcepos="6:5-10:51">
<li data-sourcepos="6:5-6:51"><span style="font-family: helvetica; font-size: medium;">Inactivated or attenuated viruses or bacteria</span></li>
<li data-sourcepos="7:5-7:63"><span style="font-family: helvetica; font-size: medium;">Purified proteins or carbohydrates derived from pathogens.</span></li>
<li data-sourcepos="8:5-8:53"><span style="font-family: helvetica; font-size: medium;">Recombinant proteins expressed in cell cultures.</span></li>
<li data-sourcepos="9:5-9:50"><span style="font-family: helvetica; font-size: medium;">Nucleic acids (DNA or RNA) encoding antigens.</span></li>
<li data-sourcepos="10:5-10:51"><span style="font-family: helvetica; font-size: medium;">Conjugates of antigens with carrier molecules.</span></li>
</ul>
</li>
<li data-sourcepos="11:1-15:40"><span style="font-family: helvetica; font-size: medium;"><strong>Drug product -</strong> the final, injectable form of the vaccine, containing the drug substance formulated with:
</span><ul data-sourcepos="12:5-15:40">
<li data-sourcepos="12:5-12:40"><span style="font-family: helvetica; font-size: medium;">Adjuvants: Enhance immune response</span>.</li>
<li data-sourcepos="13:5-13:39"><span style="font-family: helvetica; font-size: medium;">Preservatives: Maintain sterility</span>.</li>
<li data-sourcepos="14:5-14:38"><span style="font-family: helvetica; font-size: medium;">Stabilizers: Prevent degradation</span>.</li>
<li data-sourcepos="15:5-15:40"><span style="font-family: helvetica; font-size: medium;">Excipients: Fillers, buffers, etc.</span></li>
</ul>
</li>
<li data-sourcepos="16:1-16:128"><span style="font-family: helvetica; font-size: medium;"><strong>Analytical methods - </strong>specific methods are established to characterize and quantify the antigen, impurities, and excipients.</span></li>
<li data-sourcepos="17:1-18:0"><span style="font-family: helvetica; font-size: medium;"><strong>Raw materials and excipients - </strong>selection and qualification to ensure purity, consistency, and suitability for vaccine production.</span></li>
</ul>
<p data-sourcepos="19:1-19:18"><strong><span style="font-family: helvetica; font-size: medium;">Manufacturing:</span></strong></p>
<ul data-sourcepos="21:1-21:110">
<li data-sourcepos="21:1-21:110"><span style="font-family: helvetica; font-size: medium;"><strong>Process development:</strong> Designing a scalable and reproducible process for antigen production, purification, formulation, and filling.</span></li>
<li data-sourcepos="22:1-22:123"><span style="font-family: helvetica; font-size: medium;"><strong>Process validation:</strong> Demonstrating the consistency and control of the manufacturing process through extensive testing.</span></li>
<li data-sourcepos="23:1-24:0"><span style="font-family: helvetica; font-size: medium;"><strong>Quality control:</strong> Implementing measures throughout the process to ensure product quality and adherence to specifications.</span></li>
</ul>
<p data-sourcepos="25:1-25:13"><strong><span style="font-family: helvetica; font-size: medium;">Controls:</span></strong></p>
<ul data-sourcepos="27:1-30:0">
<li data-sourcepos="27:1-27:94"><span style="font-family: helvetica; font-size: medium;"><strong>Stability studies:</strong> Evaluating the vaccine's shelf life under various storage conditions.</span></li>
<li data-sourcepos="28:1-28:116"><span style="font-family: helvetica; font-size: medium;"><strong>Packaging and storage:</strong> Defining appropriate packaging and storage protocols to maintain potency and sterility.</span></li>
<li data-sourcepos="29:1-30:0"><span style="font-family: helvetica; font-size: medium;"><strong>Batch release testing:</strong> Each batch undergoes rigorous testing to ensure it meets all quality standards before release.</span></li>
</ul>
<p data-sourcepos="31:1-31:46"><strong><span style="font-family: helvetica; font-size: medium;">Additional considerations for vaccine CMC:</span></strong></p>
<ul data-sourcepos="33:1-36:0">
<li data-sourcepos="33:1-33:136"><span style="font-family: helvetica; font-size: medium;"><strong>Highly sensitive materials:</strong> Many vaccine components require careful handling and processing to avoid degradation or contamination.</span></li>
<li data-sourcepos="34:1-34:112"><span style="font-family: helvetica; font-size: medium;"><strong>Aseptic processing:</strong> Ensuring sterility throughout the manufacturing process is crucial for vaccine safety.</span></li>
<li data-sourcepos="35:1-36:0"><span style="font-family: helvetica; font-size: medium;"><strong>Regulatory requirements:</strong> Stringent regulations govern vaccine development, manufacturing, and testing, demanding detailed documentation and compliance.</span></li>
</ul><div><span style="font-family: helvetica; font-size: medium;">For details, please review FDA guidance listed in the section of resources.</span></div>
<p data-sourcepos="37:1-37:14"><strong><span style="font-family: helvetica; font-size: medium;">Resources:</span></strong></p>
<ul data-sourcepos="39:1-39:52">
<li data-sourcepos="39:1-39:52"><span style="font-family: helvetica; font-size: medium;"><a href="https://www.fda.gov/media/73614/download" target="_blank">FDA Guidance</a>: Content & Format CMC for Vaccine & Related Product. Accessed on Feb 07, 2024.</span></li>
<li data-sourcepos="40:1-41:0"><span style="font-family: helvetica; font-size: medium;">Maria Monica Castellanos, CMC Strategies and Advanced Technologies for Vaccine Development to Boost Acceleration and Pandemic Preparedness, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10386492/">Vaccines</a> (Basel). 2023 Jul; 11(7): 1153</span></li></ul><div><br /></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-72904108798616849382024-02-07T08:30:00.000-08:002024-02-07T08:30:44.289-08:00Outline of CMC for Biologics<p><span style="font-family: helvetica; font-size: medium;"> <strong>CMC (Chemistry, Manufacturing, and Controls)</strong> is a critical aspect of bringing biologics, such as vaccines, blood products, and gene therapies, to market. It ensures that the biologics are safe, pure, potent, and consistent between batches.</span></p>
<p data-sourcepos="5:1-5:53"><span style="font-family: helvetica; font-size: medium;">Here are the key steps involved in CMC for biologics:</span></p>
<ol data-sourcepos="7:1-20:13">
<li data-sourcepos="7:1-11:0">
<p data-sourcepos="7:4-7:17"><strong><span style="font-family: helvetica; font-size: medium;">Chemistry:</span></strong></p>
<ul data-sourcepos="8:5-11:0">
<li data-sourcepos="8:5-8:119"><span style="font-family: helvetica; font-size: medium;">Characterization of the biologic drug substance and drug product, including its structure, purity, and stability.</span></li>
<li data-sourcepos="9:5-9:68"><span style="font-family: helvetica; font-size: medium;">Development of analytical methods to measure these attributes.</span></li>
<li data-sourcepos="10:5-11:0"><span style="font-family: helvetica; font-size: medium;">Selection and qualification of raw materials and excipients.</span></li>
</ul>
</li>
<li data-sourcepos="12:1-16:0">
<p data-sourcepos="12:4-12:21"><strong><span style="font-family: helvetica; font-size: medium;">Manufacturing:</span></strong></p>
<ul data-sourcepos="13:5-16:0">
<li data-sourcepos="13:5-13:115"><span style="font-family: helvetica; font-size: medium;">Development of a robust and scalable manufacturing process that consistently produces a high-quality product.</span></li>
<li data-sourcepos="14:5-14:93"><span style="font-family: helvetica; font-size: medium;">Validation of the manufacturing process to ensure it meets all regulatory requirements.</span></li>
<li data-sourcepos="15:5-16:0"><span style="font-family: helvetica; font-size: medium;">Implementation of quality control measures throughout the manufacturing process.</span></li>
</ul>
</li>
<li data-sourcepos="17:1-20:13">
<p data-sourcepos="17:4-17:16"><strong><span style="font-family: helvetica; font-size: medium;">Controls:</span></strong></p>
<ul data-sourcepos="18:5-20:13">
<li data-sourcepos="18:5-18:83"><span style="font-family: helvetica; font-size: medium;">Development of stability studies to determine the shelf life of the biologic.</span></li>
<li data-sourcepos="19:5-19:99"><span style="font-family: helvetica; font-size: medium;">Development of packaging and storage specifications to protect the biologic from degradation.</span></li>
<li data-sourcepos="20:5-20:13"><span style="font-family: helvetica; font-size: medium;">Ongoing monitoring of the manufacturing process and product quality.</span></li>
</ul>
</li>
</ol>
<p data-sourcepos="22:1-22:22"><strong><span style="font-family: helvetica; font-size: medium;">CMC documentation:</span></strong></p>
<p data-sourcepos="24:1-24:234"><span style="font-family: helvetica; font-size: medium;">All of the CMC activities are documented in a comprehensive set of reports that are submitted to regulatory agencies, such as the FDA, for approval. This documentation is essential for ensuring the safety and efficacy of the biologic.</span></p>
<p data-sourcepos="26:1-26:37"><strong><span style="font-family: helvetica; font-size: medium;">CMC considerations for biologics:</span></strong></p>
<ul data-sourcepos="28:1-31:0">
<li data-sourcepos="28:1-28:88"><span style="font-family: helvetica; font-size: medium;">Biologics are complex molecules that can be difficult to characterize and manufacture.</span></li>
<li data-sourcepos="29:1-29:140"><span style="font-family: helvetica; font-size: medium;">The manufacturing process for biologics can be very sensitive to changes, so it is important to have a robust and well-controlled process.</span></li>
<li data-sourcepos="30:1-31:0"><span style="font-family: helvetica; font-size: medium;">Biologics can be very potent, so it is important to ensure that they are sterile and free of impurities.</span></li></ul>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-40048644984901513902024-02-07T05:42:00.000-08:002024-02-08T09:06:30.367-08:00In vitro vs. In vivo Performance of Gastric Retentive Dosage Forms: Bridging the Gap<p></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; mso-outline-level: 2;"><span style="font-family: helvetica;"><span style="font-size: x-large;">G</span></span><span style="font-family: helvetica; font-size: medium;">astric retentive dosage forms (GRDFs) have seen
significant progress in recent years, driven by their potential to improve drug
delivery and patient compliance. Some key recent developments include multi-mechanistic
approaches, and magnetic systems. In multi-mechanistic
approaches, a combination of different mechanisms like floating, swelling, and
bio-adhesion is used to achieve more robust and consistent gastric retention,
even in the fasted state. And, in magnetic systems, magnetic nanoparticles are used within
the dosage form allows for external control of its movement and positioning
within the stomach. This allows a more precise drug delivery.</span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: helvetica; font-size: x-large;">I</span><span style="font-family: helvetica; font-size: medium;">n the last few years, advanced materials and
complicated manufacturing technology have also been applied in the GRDFs. New
polymers with tailored properties are being developed to offer improved biocompatibility,
controlled release profiles, and enhanced gastric retention capabilities. <b>3D
printing</b> technology allows for the creation of complex and customized GRDFs
with precise drug distribution and release characteristics.<o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: helvetica; font-size: x-large;">I</span><span style="font-family: helvetica; font-size: medium;">n clinical translation, more products are reached the
market and patient compliance is improved. Several GRDFs have been approved by
regulatory agencies in recent years, demonstrating the potential of this
technology for clinical use. In improved patient compliance, GRDFs can reduce
dosing frequency, which can improve patient adherence to treatment regimens.<o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: helvetica; font-size: medium;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;"><b>Challenge: </b></span><strong>In vitro vs. in vivo performance<o:p></o:p></strong></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: helvetica;"><span style="font-size: x-large;">A</span><span style="font-size: medium;">ccurately predicting the in vivo performance of GRDFs
based on in vitro experiments remains a significant challenge. While in vitro
tests offer valuable insights into the formulation's basic properties, the
complex and dynamic environment of the human stomach introduces several factors
not easily replicated in the lab. Here's a deeper look at the discrepancies and
ongoing efforts to bridge the gap:</span><b style="font-size: large;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><o:p></o:p></span></b></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: helvetica; font-size: medium;"><b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;">Key Discrepancies:</span></b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;"><o:p></o:p></span></span></p>
<ul type="disc">
<li class="MsoNormal" style="line-height: normal; mso-list: l1 level1 lfo1; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list .5in;"><span style="font-family: helvetica; font-size: medium;"><b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;">Dynamic vs. Static Conditions:</span></b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;"> In vitro tests typically use
static media with fixed pH and agitation, while the stomach exhibits a
dynamic environment with changing pH, viscosity, and gastric emptying
rate. This can significantly impact the performance of GRDFs, like
floating systems, whose buoyancy depends on gastric fluids.<o:p></o:p></span></span></li>
<li class="MsoNormal" style="line-height: normal; mso-list: l1 level1 lfo1; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list .5in;"><span style="font-family: helvetica; font-size: medium;"><b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;">Fed vs. Fasted State:</span></b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;"> Most in vitro tests are
conducted in simulated fasted state conditions, but food intake
significantly alters gastric motility and fluid composition, affecting
GRDF behavior. Developing biorelevant fed-state dissolution methods is
crucial for improved prediction.<o:p></o:p></span></span></li>
<li class="MsoNormal" style="line-height: normal; mso-list: l1 level1 lfo1; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list .5in;"><span style="font-family: helvetica; font-size: medium;"><b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;">Interindividual Variability:</span></b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;"> Stomach anatomy, physiology, and
emptying rate vary considerably between individuals, impacting GRDF
performance. In vitro models often lack this variability, potentially
leading to misleading results.<o:p></o:p></span></span></li>
</ul>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: helvetica; font-size: medium;"><b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;">Bridging the Gap:</span></b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;"><o:p></o:p></span></span></p>
<ul type="disc">
<li class="MsoNormal" style="line-height: normal; mso-list: l0 level1 lfo2; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list .5in;"><span style="font-family: helvetica; font-size: medium;"><b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;">Advanced In vitro Models:</span></b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;"> Researchers are developing more
sophisticated in vitro models incorporating aspects of gastric physiology,
like peristaltic movements and fed-state conditions. These models provide
a more realistic environment for evaluating GRDFs.<o:p></o:p></span></span></li>
<li class="MsoNormal" style="line-height: normal; mso-list: l0 level1 lfo2; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list .5in;"><span style="font-family: helvetica; font-size: medium;"><b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;">Multi-method Approach:</span></b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;"> Utilizing a combination of in
vitro tests with different dissolution media, agitation conditions, and
biorelevant fed-state models can offer a more comprehensive understanding
of GRDF behavior.<o:p></o:p></span></span></li>
<li class="MsoNormal" style="line-height: normal; mso-list: l0 level1 lfo2; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list .5in;"><span style="font-family: helvetica; font-size: medium;"><b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;">In silico Modeling:</span></b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;"> Computational simulations based
on physiological data can predict the in vivo behavior of GRDFs,
complementing in vitro experiments and informing formulation design.<o:p></o:p></span></span></li>
</ul>
<p class="MsoNormal" style="line-height: normal; margin-left: 0.25in; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: helvetica; font-size: x-large;">D</span><span style="font-family: helvetica; font-size: medium;">espite the challenges, researchers
are continuously advancing in vitro models and methodologies to bridge the gap
with in vivo performance. Combining these efforts within silico modeling holds
great promise for optimizing GRDF design and ultimately achieving more
predictable and effective drug delivery in the complex environment of the human
stomach.<o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;"><o:p><span style="font-family: helvetica; font-size: medium;"> </span></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;"><span style="font-family: helvetica; font-size: medium;">References:<o:p></o:p></span></span></b></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;"><span style="font-family: helvetica; font-size: medium;">Felix Schneider, et al, In Vitro and In Vivo Test
Methods for the Evaluation of Gastroretentive Dosage Forms, Pharmaceutics. 2019
Aug; 11(8): 416.<o:p></o:p></span></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;"><span style="font-family: helvetica; font-size: medium;">Liza Józsa et al, Recent Options and Techniques to
Assess Improved Bioavailability: In Vitro and Ex Vivo Methods, Pharmaceutics.
2023 Apr; 15(4): 1146.<o:p></o:p></span></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-font-kerning: 0pt; mso-ligatures: none;"><span style="font-family: helvetica; font-size: medium;">Dhaivat C Parikh et al, In vitro and in vivo techniques
to assess the performance of gastro-retentive drug delivery systems: a review,
Expert Opin Drug Deliv . 2008 Sep;5(9):951-65.</span><o:p></o:p></span></p><br /><p></p>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-48133245243356079402024-02-06T10:27:00.000-08:002024-02-06T10:27:23.013-08:00EYLEA- aflibercept injection, solution, related lawsuits<div><p data-sourcepos="1:1-1:170"><span style="font-family: helvetica; font-size: medium;"><b>EYLEA</b> is a brand name for a medication called <strong>aflibercept</strong>. It is primarily used as an injection to treat various eye conditions. </span></p><p class="First"><span style="font-family: helvetica; font-size: medium;">Vascular endothelial growth factor-A (VEGF-A) and
placental growth factor (PlGF) are members of the VEGF family of
angiogenic factors that can act as mitogenic, chemotactic, and vascular
permeability factors for endothelial cells. VEGF acts via two receptor
tyrosine kinases, VEGFR-1 and VEGFR-2, present on the surface of
endothelial cells. PlGF binds only to VEGFR-1, which is also present on
the surface of leucocytes. Activation of these receptors by VEGF-A can
result in neovascularization and vascular permeability.</span></p><p data-sourcepos="1:1-1:170">
</p><p><span style="font-family: helvetica; font-size: medium;">Aflibercept acts as a soluble decoy receptor that binds VEGF-A and
PlGF, and thereby can inhibit the binding and activation of these
cognate VEGF receptors.</span></p>
<p data-sourcepos="3:1-3:15"><strong><span style="font-family: helvetica; font-size: medium;">Indication:</span></strong></p>
<ul data-sourcepos="5:1-10:0">
<li data-sourcepos="5:1-5:176"><span style="font-family: helvetica; font-size: medium;"><strong>Wet age-related macular degeneration (AMD):</strong> This is the most common use of EYLEA. It helps slow vision loss caused by abnormal blood vessel growth and leakage in the eye.</span></li>
<li data-sourcepos="6:1-6:138"><span style="font-family: helvetica; font-size: medium;"><strong>Diabetic macular edema (DME):</strong> This is swelling of the macula due to diabetes, and EYLEA can help improve vision and reduce swelling.</span></li>
<li data-sourcepos="7:1-7:153"><span style="font-family: helvetica; font-size: medium;"><strong>Retinal vein occlusion (RVO):</strong> Blockage of blood vessels in the retina can cause vision loss, and EYLEA can help restore vision and reduce swelling.</span></li>
<li data-sourcepos="8:1-8:143"><span style="font-family: helvetica; font-size: medium;"><strong>Diabetic retinopathy (DR):</strong> EYLEA may be used in some cases of advanced DR to reduce abnormal blood vessel growth and prevent vision loss.</span></li>
<li data-sourcepos="9:1-10:0"><span style="font-family: helvetica; font-size: medium;"><strong>Retinopathy of prematurity (ROP):</strong> In premature babies, EYLEA can help abnormal blood vessels in the eye develop normally, reducing the risk of vision problems.</span></li>
</ul>
<p data-sourcepos="11:1-11:16"><strong><span style="font-family: helvetica; font-size: medium;">Dosage form and Composition:</span></strong></p>
<ul data-sourcepos="13:1-14:0">
<li data-sourcepos="13:1-14:0"><span style="font-family: helvetica; font-size: medium;">EYLEA is available as a sterile solution for injection into the eye (intravitreal injection).</span></li><li data-sourcepos="13:1-14:0"><span style="font-family: helvetica; font-size: medium;">EYLEA is a sterile, clear, and colorless to pale
yellow solution. EYLEA does not contain anti-microbial preservative and
is supplied as a sterile, aqueous solution for intravitreal injection
in a single-dose pre-filled glass syringe or a single-dose glass vial
designed to deliver 0.05 mL (50 microliters) of solution containing 2 mg
of aflibercept in polysorbate 20 (0.015 mg), sodium chloride (0.117
mg), sodium phosphate monobasic monohydrate (0.055 mg), sodium phosphate
dibasic heptahydrate (0.027 mg), sucrose (2.5 mg) and water for
injection with a pH of 6.2.</span></li><li data-sourcepos="13:1-14:0"><span style="font-family: helvetica; font-size: medium;"><p class="First">EYLEA is a clear, colorless to pale yellow solution available as:</p>
<ul class="Disc">
<li>Injection: 2 mg (0.05 mL of a 40 mg/mL solution) in a single-dose pre-filled glass syringe</li>
<li>Injection: 2 mg (0.05 mL of a 40 mg/mL solution) in a single-dose glass vial.</li></ul></span></li>
</ul>
<p data-sourcepos="15:1-15:9"><strong><span style="font-family: helvetica; font-size: medium;">Dose:</span></strong></p>
<ul data-sourcepos="17:1-20:0">
<li data-sourcepos="17:1-17:122"><span style="font-family: helvetica; font-size: medium;">The dose and dosing schedule vary depending on the specific condition being treated and the individual patient's needs.</span></li>
<li data-sourcepos="18:1-18:184"><span style="font-family: helvetica; font-size: medium;">Typically, for wet AMD and DME, the initial dose is <b>2mg every 4 weeks</b> for the first 5 injections, followed by <b>2mg every 8 weeks</b>. Adjustments may be made based on individual response.</span></li>
</ul>
<p data-sourcepos="21:1-21:28"><strong><span style="font-family: helvetica; font-size: medium;">Route of administration:</span></strong></p>
<ul data-sourcepos="23:1-24:0">
<li data-sourcepos="23:1-24:0"><span style="font-family: helvetica; font-size: medium;">EYLEA is administered as an intravitreal injection, directly into the vitreous humor (jelly-like substance) in the eye. This is done by an ophthalmologist in a clinical setting.</span></li>
</ul>
<p data-sourcepos="25:1-25:15"><strong><span style="font-family: helvetica; font-size: medium;">Effectiveness compared to its peer group:</span></strong></p>
<ul data-sourcepos="27:1-30:0">
<li data-sourcepos="27:1-27:144"><span style="font-family: helvetica; font-size: medium;">EYLEA is considered one of the most effective medications for wet AMD and DME, comparable to other anti-VEGF drugs like Lucentis and Avastin.</span></li>
<li data-sourcepos="28:1-28:95"><span style="font-family: helvetica; font-size: medium;">Studies have shown similar effectiveness in terms of improving vision and reducing swelling.</span></li>
<li data-sourcepos="29:1-30:0"><span style="font-family: helvetica; font-size: medium;">The choice of medication may depend on factors such as individual response, cost, and potential side effects.</span></li>
</ul>
<p data-sourcepos="31:1-31:19"><strong><span style="font-family: helvetica; font-size: medium;">Adverse events:</span></strong></p>
<ul data-sourcepos="33:1-42:0">
<li data-sourcepos="33:1-39:16"><span style="font-family: helvetica; font-size: medium;">Like any medication, EYLEA can have side effects. Some common side effects include:
</span><ul data-sourcepos="34:5-39:16">
<li data-sourcepos="34:5-34:38"><span style="font-family: helvetica; font-size: medium;">Eye pain, redness, or irritation</span></li>
<li data-sourcepos="35:5-35:24"><span style="font-family: helvetica; font-size: medium;">Increased floaters</span></li>
<li data-sourcepos="36:5-36:25"><span style="font-family: helvetica; font-size: medium;">Bleeding in the eye</span></li>
<li data-sourcepos="37:5-37:37"><span style="font-family: helvetica; font-size: medium;">Eye infection (endophthalmitis)</span></li>
<li data-sourcepos="38:5-38:30"><span style="font-family: helvetica; font-size: medium;">Increased blood pressure</span></li>
<li data-sourcepos="39:5-39:16"><span style="font-family: helvetica; font-size: medium;">Nosebleeds</span></li>
</ul>
</li>
<li data-sourcepos="40:1-40:104"><span style="font-family: helvetica; font-size: medium;">More serious side effects are rare but can occur, such as stroke, heart attack, or allergic reaction.</span></li></ul><ul data-sourcepos="33:1-42:0"><li data-sourcepos="41:1-42:0"><span style="font-family: helvetica; font-size: medium;"><b>It is important to discuss the potential risks and benefits of EYLEA with your doctor before starting treatment.</b></span></li></ul></div><div><span style="font-family: helvetica; font-size: large;"><br /></span></div><div><span style="font-family: helvetica; font-size: large;">Recent News - Lawsuits</span></div><div><span style="font-family: helvetica;"><span style="font-size: large;"><br /></span></span></div><div><span style="font-family: helvetica;"><span style="font-size: large;">O</span>n Nevember 29, 2023, Regeneron Pharmaceuticals, Inc. filed a Compliant against Formycon AG (“Formycon”) in the U.S. District Court for the Northern District of West Virginia, alleging infringement of 39 patents under the BPCIA based on Formycon’s submission of an aBLA for FYB203, a proposed biosimilar of EYLEA (aflibercept). According to the news, this was the fourth infringement suit under the BPCIA concerning a proposed biosimilar of EYLEA, after Regeneron sued Mylan (August 2, 2022), Celltrion (November 8, 2023), and Samsung Bioepis (November 22, 2023).</span></div><div><span style="font-family: helvetica;"><br /></span></div><div><span style="font-family: helvetica;"><span style="font-size: large;">R</span>egeneron states that the use of Formycon's FYB203 will infringe multiple related to the methods of adminstering aflibercept, stable formulations of aflibercept, and its manufacturing process, totally 3 groups. And here are the 3 groups of patents: </span></div><div><span style="font-family: helvetica;"><br /></span></div><div><span style="font-family: helvetica;"><b>8 method of treatment patents:</b> U.S. Patent Nos. 9,254,338; 10,130,681; 10,828,345; 10,888,601; 11,253,572; 11,559,564; 11,707,506; and 11,769,597.</span></div><div><span style="font-family: helvetica;"><br /></span></div><div><span style="font-family: helvetica;"><b>4 formulation patents:</b> U.S. Patent Nos. 10,464,992; 11,066,458; 11,084,865; and 11,732,024.</span></div><div><span style="font-family: helvetica;"><br /></span></div><div><span style="font-family: helvetica;"><b>27 manufacturing process patents: </b> U.S. Patent Nos. 7,070,959; 7,771,997; 9,222,106; 9,562,238; 9,816,110; 9,932,605; 10,415,055; 10,669,594; 10,927,342; 11,053,280; 11,104,715; 11,174,283; 11,268,109; 11,299,532; 11,306,135; 11,312,936; 11,332,771; 11,472,861; 11,485,770; 11,535,663; 11,542,317; 11,548,932; 11,549,154; 11,555,176; 11,680,930; 11,753,459 and 11,788,102.</span></div><div><span style="font-family: helvetica;"><br /></span></div><div><span style="font-family: helvetica;">Here is the list of Purple Book Patents for Eylea (aflibercept)</span></div><div><span style="font-family: helvetica;"><br /></span></div><div><span style="font-family: helvetica;"><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEheq1Q-xUZDZMKwTqTQ1o1NzGwYVs-fw2otmwIfLcKe4diyR5HbHPD6t8JH0EBHE1_HoqUZDEMuEtTBeZxxB2qN9a8PKJUFg5ErK56HEKQvh-ByrI3ttInMaoRvpcYX94Om01WrYLcth-fYg2UODtErhxiti8Uto7CZRZGoq8lbcWaqoYpA_d8M" style="margin-left: 1em; margin-right: 1em;"><img alt="" data-original-height="1630" data-original-width="498" height="1583" src="https://blogger.googleusercontent.com/img/a/AVvXsEheq1Q-xUZDZMKwTqTQ1o1NzGwYVs-fw2otmwIfLcKe4diyR5HbHPD6t8JH0EBHE1_HoqUZDEMuEtTBeZxxB2qN9a8PKJUFg5ErK56HEKQvh-ByrI3ttInMaoRvpcYX94Om01WrYLcth-fYg2UODtErhxiti8Uto7CZRZGoq8lbcWaqoYpA_d8M=w482-h1583" width="482" /></a></div><br /><br /></span></div><div><span style="font-family: helvetica;"><b>Reference: </b></span></div><div><span style="font-family: helvetica;"><br /></span></div><div><span style="font-family: helvetica;">Product Insert,</span></div><div><span style="font-family: helvetica;"><br /></span></div><div><span style="font-family: helvetica;">Kristin M. Beale, Regeneron sues Formycon AG for proposed biosimilar of EYLEA in West Virginia District Court, Bio Molecule Watch, December 11, 2023. Assessed on Feb 06, 2024.</span></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-88025973277245106782024-02-06T08:40:00.000-08:002024-02-06T08:40:46.450-08:00Herb - Drug Interaction<div><span style="font-family: helvetica; font-size: large;"><b>Herbal medicines</b> are often administered in combination with drugs for potential benefits of combining herbal medicines and drugs, even while acknowledging the interaction risks. </span></div><div><span style="font-family: helvetica; font-size: large;"><br /></span></div><div><span style="font-family: helvetica; font-size: large;"><b>Pharmacokinetic and Pharmacodynamic Mechanisms</b></span></div><div><span style="font-family: helvetica; font-size: large;"><br /></span></div><div><span style="font-family: helvetica;"><span style="font-size: x-large;">C</span></span><span style="font-family: helvetica; font-size: large;">ases have been published reporting enhanced anticoagulation and bleeding when patients on long-term warfarin therapy also took dan shen herb. [1] Interactions between herbal medicines and drugs can occur and may lead to serious clinical consequences. There are other theoretical interactions indicated by preclinical data. Both pharmacokinetic and/or pharmacodynamic mechanisms can also contribute to these interactions, dependent on the nature of the drug substance.</span></div><div><span style="font-family: helvetica; font-size: medium;"><br />
</span></div><div><span style="font-family: helvetica; font-size: medium;"><b>Duration of the Use of the Herbs</b></span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: x-large;">D</span><span style="font-family: helvetica; font-size: medium;">an Shen herb extract is widely used for the treatment and prevention of coronary heart disease and some other diseases. Dan Shen herb extract and theophylline are prescribed together to treat patients with asthma in some areas. In human, theophylline with low therapeutic index is mainly metabolized by CYP1A2. In vitro findings have shown that human CYP1A2 is inhibited by the ethyl acetate extract of Dan Shen Herb or Dan Shen pharmaceutical product. Thus, this suggests the possibility of drug interactions between Dan Shen extract and theophylline (CYP1A2 substrate). However, it was found that long-term oral intake of Dan Shen Herb extract does not change the basic pharmacokinetic parameters of theophylline in healthy subjects.<b> </b>Dose adjustment of theophylline thus may not be necessary in patients receiving concomitant therapy with Dan Shen extract. [2]</span></div><div><span style="font-family: helvetica; font-size: medium;"><br />
</span></div><div><span style="font-family: helvetica; font-size: medium;"><b>Components</b></span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: x-large;">D</span><span style="font-family: helvetica; font-size: medium;">an Shan Herb contains protocatechualdehyde, salvianolic acid B, tanshinone II(A), cryptotanshinone, etc. Some Dan Shen components in the hydrophilic extract depress the absorption of the protocatechualdehyde in rats, on the contrary, enhance the absorption of the salvianolic acid B and depress its elimination rate. The concomitant components in the lipophilic extract might enhance the absorption of cryptotanshinone and its distribution from the centre compartment to the peripheral compartment, and the metabolism to tanshinone II(A). [3]</span></div><div><span style="font-family: helvetica; font-size: medium;"><br />
</span></div><div><span style="font-family: helvetica; font-size: medium;">Thus, the other components present in the extract of Chinese material medica had significant effect on the pharmacokinetics of its 'active components'. These components can exhibit competitive, synergistic, or metabolic effects. Therefore, the traditional Chinese medicine was a complicated system, It should be taken a scientific and holistic view in the research and development processes. [3]</span></div><div><span style="font-family: helvetica; font-size: medium;"><br />
</span></div><div><span style="font-family: helvetica; font-size: x-large;">S</span><span style="font-family: helvetica; font-size: medium;">trong protein (albumin) binding of Dan Shen (50-70%) in serum was found. Salicylate, a chemical, is also strongly bound to albumin; it is also a widely used over-the-counter medicine in the U.S., we studied Danshen-salicylate interaction in vitro. No significant change in free Dan shen concentrations was observed when salicylate concentrations were subtherapeutic (< or = 100 microg/mL). </span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;">However, at therapeutic concentrations of salicylate (</span>≥<span style="font-family: helvetica; font-size: medium;"> = 150 microg/mL), free Dan Shen concentrations significantly decreased. On the other hand, Dan Shen potentially displaced salicylate from protein binding, thereby increasing the free salicylate concentration. </span></div><div><br /></div><div><p data-sourcepos="13:1-13:16"><span style="font-family: helvetica; font-size: medium;"><b>Always remember:</b></span></p>
<ul data-sourcepos="15:1-18:0">
<li data-sourcepos="15:1-15:104"><span style="font-family: helvetica; font-size: medium;">Consult a qualified healthcare professional before combining herbal medicines with conventional drugs.</span></li></ul></div><div><span style="font-family: helvetica; font-size: medium;"><br />
</span></div><div><span style="font-family: helvetica; font-size: medium;"><br />
</span></div><div><span style="font-family: helvetica; font-size: medium;"><b>REFERENCE</b></span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;">[1] Hu Z, et al, Herb-drug interactions: a literature review. Drugs. 2005;65(9):1239-82. </span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;">[2] Qiu F, Effect of danshen extract on pharmacokinetics of theophylline in healthy volunteers.Br J Clin Pharmacol. 2008 Feb;65(2):270-4. </span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;">[3] Song M, et al, Pharmacokinetic interactions between the main components in the extracts of Salvia miltiorrhiza Bge. in rat Yao Xue Xue Bao. 2007 Mar;42(3):301-7. </span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;">[4] Gupta D, et al, Drug-herb interactions: unexpected suppression of free Danshen concentrations by salicylate. J Clin Lab Anal. 2002;16(6):290-4.</span></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-78644003881567868992024-02-06T04:06:00.000-08:002024-02-06T04:06:09.224-08:00Chromium - Health Benefits and Side Effects<!--[if gte mso 9]><xml> <w:WordDocument> <w:View>Normal</w:View> <w:Zoom>0</w:Zoom> <w:Compatibility> <w:UseFELayout/> </w:Compatibility> <w:DoNotOptimizeForBrowser/> </w:WordDocument> </xml><![endif]--><div _ngcontent-ng-c3313135737="" class="avatar-gutter ng-tns-c3313135737-16 ng-star-inserted"><recitations-gutter _ngcontent-ng-c3313135737="" _nghost-ng-c3233054947="" class="ng-tns-c3313135737-16 ng-trigger ng-trigger-hideElement ng-star-inserted" style="opacity: 1;"><div _ngcontent-ng-c3233054947="" class="resize-observable"></div></recitations-gutter></div><div _ngcontent-ng-c3313135737="" class="response-container-content ng-tns-c3313135737-16" selection=""><div _ngcontent-ng-c2384518117="" class="response-content ng-trigger ng-trigger-responsePopulation ng-tns-c3313135737-16"><message-content _ngcontent-ng-c2384518117="" _nghost-ng-c2014343474="" class="model-response-text ng-tns-c2384518117-15 ng-star-inserted" id="message-content-id-r_5ad28ef8bc5f5ee7" style="height: auto;"><div _ngcontent-ng-c2014343474="" class="markdown markdown-main-panel" dir="ltr" style="--animation-duration: 600ms; --fade-animation-function: cubic-bezier(0.05, 0.7, 0.91, 1);"><span style="font-family: helvetica;"><p data-sourcepos="1:1-1:203"><span style="font-size: large;">C</span><span style="font-size: medium;">hromium supplements at certain daily doses can be safe for some people, but it's important to understand the potential benefits, side effects, and the current state of the research before taking them. Here's what I can share:</span></p><p data-sourcepos="3:1-3:23" style="font-size: large;"><strong>Potential benefits:</strong></p><ul data-sourcepos="5:1-8:0" style="font-size: large;">
<li data-sourcepos="5:1-5:230"><strong>Blood sugar control:</strong> In a recent study, the co-supplementation of chromium and Magnesium improves glycemic and lipid
levels and reduces the inflammatory response and oxidative stress
profiles of individuals with impaired glucose tolerance and insulin
resistance. (1) Another recent study suggests chromium might improve blood sugar control in
people with type 2 diabetes (2), However, the evidence
is mixed to a certain extent, depending on the experimental design, subject selection and the supplement use in the study. It may work best for those who are chromium deficient.</li>
<li data-sourcepos="6:1-6:132"><strong>PCOS:</strong> Chromium may offer some benefits for women with polycystic ovary syndrome (PCOS), which is linked to insulin resistance. (3)</li>
<li data-sourcepos="7:1-8:0"><strong>Weight loss:</strong> Some research suggests chromium may aid weight loss, Common ingredients of fat burning supplements such as green tea, caffeine,
chromium, carnitine, and conjugated linoleic acid could act synergistically with a healthy diet and physical
exercise for decreasing adipose tissue deposition in patients with
lipedema and resolve related health issues. However, the effects of fat burners
in human studies are sometimes contradictory, and further studies should
test their effectiveness in treating lipedema. (4) </li></ul><p data-sourcepos="9:1-9:17" style="font-size: large;"><strong>Side effects:</strong></p><ul data-sourcepos="11:1-14:0" style="font-size: large;">
<li data-sourcepos="11:1-11:79"><strong>Generally well-tolerated:</strong> At recommended doses, chromium is usually safe.</li>
<li data-sourcepos="12:1-12:111"><strong>Potential side effects:</strong> Stomach upset, headaches, and skin rashes are possible, especially at high doses.</li>
<li data-sourcepos="13:1-14:0"><strong>Interactions:</strong> Chromium can interact with certain medications, like insulin and blood pressure drugs.</li></ul><ul data-sourcepos="17:1-19:0" style="font-size: large;">
</ul><p data-sourcepos="20:1-20:21" style="font-size: large;"><strong>Important points:</strong></p><ul data-sourcepos="22:1-25:0" style="font-size: large;">
<li data-sourcepos="22:1-22:175"><strong>Consult your doctor:</strong>
Before taking any new supplement, including chromium, consult your
doctor to discuss potential risks and interactions with your current
medications.</li>
<li data-sourcepos="23:1-23:123"><strong>Don't exceed recommended doses:</strong> Stick to the recommended dosage on the supplement label or as advised by your doctor.</li>
<li data-sourcepos="24:1-25:0"><strong>Food sources first:</strong>
Getting chromium from food sources like meat, whole grains, and
vegetables is generally recommended before considering supplements.</li>
</ul><div><span style="font-size: medium;"><b>REFERENCE</b></span></div><div><span style="font-size: medium;"><br /></span></div><div><span style="font-size: medium;">1. Yang Zhao et al, Effects of co-supplementation of chromium and magnesium on metabolic profiles, inflammation, and oxidative stress in impaired glucose tolerance, Diab Vasc Dis Res. 2024 Jan-Feb;21(1):14791641241228156. </span></div><div><span style="font-size: medium;"><br /></span></div><div><span style="font-size: medium;">2. Fatima Alkhalidi, A comparative study to assess the use of chromium in type 2 diabetes mellitus, J Med Life. 2023 Aug;16(8):1178-1182. </span></div><div><span style="font-size: medium;"><br /></span></div><div><span style="font-size: medium;">3. Xinyin Hu et al, Comparison of nutritional supplements in improving glycolipid metabolism and endocrine function in polycystic ovary syndrome: a systematic review and network meta-analysis PeerJ. 2023 Nov 13:11:e16410</span></div><div><span style="font-size: medium;"><br /></span></div><div><span style="font-size: medium;">4. Gabriele Bonetti et al, Dietary supplements for lipedema, J Prev Med Hyg. 2022 Oct 17;63(2 Suppl 3):E169-E173. </span></div><div><span style="font-size: medium;"><br /></span></div><p data-sourcepos="31:1-31:220" style="font-size: large;">This information is intended for general knowledge purposes only and should not be interpreted as a substitute for professional medical advice.</p></span></div></message-content></div></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-56520098796624934452024-02-05T16:46:00.000-08:002024-02-05T16:46:52.252-08:00Rhodiola rosea -health benefits and side effects<div class="profile_part"> <h2 style="font-family: Arial, Helvetica, sans-serif;"><div _ngcontent-ng-c3313135737="" class="avatar-gutter ng-tns-c3313135737-28 ng-star-inserted"><recitations-gutter _ngcontent-ng-c3313135737="" _nghost-ng-c3233054947="" class="ng-tns-c3313135737-28 ng-trigger ng-trigger-hideElement ng-star-inserted" style="opacity: 1;"><span style="font-family: helvetica; font-size: medium; font-weight: normal;"><div _ngcontent-ng-c3233054947="" class="resize-observable"></div></span></recitations-gutter></div></h2><h2 data-sourcepos="1:1-1:75" style="font-family: Arial, Helvetica, sans-serif;"><div _ngcontent-ng-c3313135737="" class="avatar-gutter ng-tns-c3313135737-28 ng-star-inserted"><recitations-gutter _ngcontent-ng-c3313135737="" _nghost-ng-c3233054947="" class="ng-tns-c3313135737-28 ng-trigger ng-trigger-hideElement ng-star-inserted" style="opacity: 1;"><span style="font-family: helvetica; font-size: medium; font-weight: normal;"><div _ngcontent-ng-c3233054947="" class="resize-observable"></div></span></recitations-gutter></div></h2><h2 data-sourcepos="1:1-1:75" style="text-align: left;"><p data-sourcepos="3:1-3:318"><span style="font-family: helvetica; font-size: medium;">Rhodiola rosea</span><span style="font-family: helvetica; font-size: medium; font-weight: normal;">, also known as golden root or rose root, is a flowering plant that grows in cold regions of Europe and Asia. It has a long history of use in traditional medicine, particularly in Russia and Scandinavia, as an </span><span style="font-family: helvetica; font-size: medium;">adaptogen</span><span style="font-family: helvetica; font-size: medium; font-weight: normal;">. (1) Adaptogens are believed to help the body adapt to stress, both physical and mental.</span></p><p data-sourcepos="5:1-5:30"><span style="font-family: helvetica; font-size: medium;">Potential Health Benefits:</span></p><p data-sourcepos="7:1-7:193"><span style="font-family: helvetica; font-size: x-large; font-weight: normal;">R</span><span style="font-family: helvetica; font-size: medium; font-weight: normal;">esearch on Rhodiola rosea is ongoing, and while some studies suggest potential benefits, more high-quality research is needed to confirm these findings. Some of the potential benefits include:</span></p><p></p><ul data-sourcepos="9:1-14:0"><li data-sourcepos="9:1-9:197"><span style="font-family: helvetica; font-size: medium; font-weight: normal;">Reducing fatigue and improving energy levels:
Some studies suggest that Rhodiola may help improve energy levels and
combat fatigue, possibly also in people with chronic fatigue syndrome
(CFS). (2, 3)</span></li></ul><ul data-sourcepos="9:1-14:0"><li data-sourcepos="10:1-10:169"><span style="font-family: helvetica; font-size: medium; font-weight: normal;">Improving mood and reducing symptoms of depression: Some research indicates that Rhodiola may help improve mood and reduce symptoms of mild to moderate depression. (2)</span></li></ul><ul data-sourcepos="9:1-14:0"><li data-sourcepos="11:1-11:129"><span style="font-family: helvetica; font-size: medium; font-weight: normal;">Reducing stress and anxiety: Rhodiola may help manage stress and anxiety symptoms, although the evidence is not conclusive. (4)</span></li></ul><ul data-sourcepos="9:1-14:0"><li data-sourcepos="12:1-12:140"><span style="font-family: helvetica; font-size: medium;"><span style="font-weight: normal;">Enhancing cognitive function: Some studies suggest Rhodiola may improve memory, focus, and concentration. Salidroside is a phenylpropanoid mainly isolated from </span><i style="font-weight: normal;">Rhodiola</i><span style="font-weight: normal;"> species with various pharmacological effects. A total of 20 studies were included, and the results showed that the </span><span style="font-weight: 400;">Salidroside treatment</span><span style="font-weight: normal;"> significantly improved behavior abnormalities in Alzheimer's Disease animal
models. The authors reported that salidroside treatment could effectively increase superoxide dismutase, decrease malondialdehyde, and decrease interleukin
1β, interleukin 6, and tumor necrosis factor α. Salidroside treatment was
effective in reducing amyloid-β
levels and the number of apoptotic cells, as well. (5) But more research is needed.</span></span></li></ul><ul data-sourcepos="28:1-32:0"><li data-sourcepos="13:1-14:0"><span style="font-family: helvetica; font-size: medium; font-weight: normal;">Boosting physical performance: Some evidence suggests Rhodiola may improve exercise performance and reduce muscle fatigue. (4)</span></li></ul><p></p><p data-sourcepos="15:1-15:17"><span style="font-family: helvetica; font-size: medium;">Side Effects:</span></p><p><span style="font-family: helvetica; font-size: medium; font-weight: normal;">R</span><span style="font-family: helvetica; font-size: medium;"><span style="font-weight: normal;">hodiola is generally considered safe for most people when taken in recommended doses for short periods. However, based on information over the internet, some potential side effects may </span><span style="font-weight: 400;">include</span><span style="font-weight: normal;"> headache, dizziness, stomach upset, dry mouth, sleep disturbance and irritability. </span></span></p><p data-sourcepos="26:1-26:29"><span style="font-family: helvetica; font-size: medium;">Important Considerations include l</span><span style="font-family: helvetica; font-size: large; font-weight: normal;">imited evidence for the health claims and drug interactions. </span></p><p data-sourcepos="33:1-33:21"><span style="font-family: helvetica; font-size: medium;">Current Research:</span></p><p data-sourcepos="35:1-35:309"><span style="font-family: helvetica; font-size: x-large; font-weight: normal;">S</span><span style="font-family: helvetica; font-size: medium; font-weight: normal;">everal ongoing research studies are investigating the potential benefits of Rhodiola for various conditions. These studies are crucial for understanding its true efficacy and potential side effects. It is important to stay updated on the latest research findings before using Rhodiola for any health concern.</span></p><p data-sourcepos="37:1-37:13"><span style="font-family: helvetica; font-size: medium;">Remember:</span></p><p data-sourcepos="39:1-39:195"><span style="font-family: helvetica; font-size: x-large; font-weight: normal;">A</span><span style="font-family: helvetica; font-size: medium; font-weight: normal;">lways consult your doctor before taking any new supplement, including Rhodiola rosea. They can advise you on the potential benefits and risks based on your individual health and medical history.</span></p><p data-sourcepos="39:1-39:195"><span style="font-family: helvetica;"><span style="font-size: large;">REFERENCE</span><br /></span></p><span style="font-family: helvetica; font-size: medium;"><span style="font-weight: 400;">1. Anastasia Agapouda et al, Rhodiola Rosea Extract Counteracts Stress in an Adaptogenic Response Curve Manner via Elimination of ROS and Induction of Neurite Outgrowth, Oxid Med Cell Longev. 2022; 2022: 5647599.</span></span></h2><div><span style="font-family: helvetica; font-size: medium;"><span style="font-weight: 400;">2. </span>Jurga Bernatoniene et al, Phenolic Compounds of Rhodiola rosea L. as the Potential Alternative Therapy in the Treatment of Chronic Diseases Int J Mol Sci. 2023 Jul 31;24(15):12293.</span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;">3. Yevgeniya Lekomtseva et al, Rhodiola rosea in Subjects with Prolonged or Chronic Fatigue Symptoms: Results of an Open-Label Clinical Trial, Complement Med Res. 2017;24(1):46-52.</span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;">4. Grant M Tinsley et al, Rhodiola rosea as an adaptogen to enhance exercise performance: a review of the literature, Br J Nutr. 2024 Feb 14;131(3):461-473. </span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;">5. Nan Zhang et al, Neuroprotective Mechanisms of Salidroside in Alzheimer's Disease: A Systematic Review and Meta-analysis of Preclinical Studies J Agric Food Chem. 2023 Nov 22;71(46):17597-17614.</span></div></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-9023128352948944362024-02-05T15:45:00.000-08:002024-02-05T15:45:07.016-08:00Thunder God Vine - Health Benefits and Side Effects<div><span style="font-family: helvetica; font-size: large;">Thunder God Vine, also known as Tripterygium wilfordii,</span><span style="font-family: helvetica; font-size: large;"> is a climbing vine native to Southeast China.</span><span style="font-family: helvetica; font-size: large;"> Traditionally used in Chinese medicine,</span><span style="font-family: helvetica; font-size: large;"> its leaves and root have been studied for various potential health benefits but also carry </span><strong style="font-family: helvetica; font-size: large;">significant risks and side effects</strong><span style="font-family: helvetica; font-size: large;">.</span></div><div>
<p data-sourcepos="3:1-3:20"><strong><span style="font-family: helvetica; font-size: medium;">Health Benefits:</span></strong></p>
<ul data-sourcepos="5:1-7:0">
<li data-sourcepos="5:1-5:161"><span style="font-family: helvetica; font-size: medium;"><strong>Rheumatoid Arthritis:</strong> Some research suggests it may improve pain, swelling, and physical function in rheumatoid arthritis patients. Celastrol and triptolide isolated from thunder god vine are believed to be effective against rheumatoid arthritis. </span><span style="font-family: helvetica; font-size: medium;">Celastrol targets numerous signaling pathways involving NF‑κB,
endoplasmic reticulum Ca2+‑ATPase, myeloid differentiation factor 2,
toll‑like receptor 4, pro‑inflammatory chemokines, DNA damage, cell
cycle arrest and apoptosis. While triptolide, inhibits NF‑κB, the receptor
activator of NF‑κB (RANK)/RANK ligand/osteoprotegerin signaling pathway,
cyclooxygenase‑2, matrix metalloproteases and cytokines. (1) B</span><span style="font-family: helvetica; font-size: medium;">ut evidence is limited and inconclusive.</span></li>
<li data-sourcepos="6:1-7:0"><span style="font-family: helvetica; font-size: medium;"><strong>Other Conditions:</strong> Studies have explored its potential benefits for Crohn's disease, kidney problems, mouth sores, and eye issues in thyroid disease, but results are preliminary and require further investigation.</span></li>
</ul>
<p data-sourcepos="8:1-8:17"><strong><span style="font-family: helvetica; font-size: medium;">Side Effects:</span></strong></p>
<ul data-sourcepos="10:1-12:0">
<li data-sourcepos="10:1-10:342"><span style="font-family: helvetica; font-size: medium;"><strong>Serious Risks:</strong> Thunder God Vine can be <strong>extremely toxic</strong> if improperly prepared or used in high doses. Side effects include digestive problems, abnormal heart rates, high blood pressure, decreased blood cell production, kidney damage, bone mineral loss, infertility, menstrual cycle changes, rashes, diarrhea, headache, and hair loss. </span></li>
<li data-sourcepos="11:1-12:0"><span style="font-family: helvetica; font-size: medium;"><strong>Pregnancy and Breastfeeding:</strong> Completely avoid due to birth defect risks.</span></li>
</ul>
<p data-sourcepos="13:1-13:25"><strong><span style="font-family: helvetica; font-size: medium;">Popularity in the US:</span></strong></p>
<ul data-sourcepos="15:1-17:0">
<li data-sourcepos="15:1-15:166"><span style="font-family: helvetica; font-size: medium;"><strong>Not Popular:</strong> Due to its safety concerns and lack of conclusive evidence for most claimed benefits, Thunder God Vine is not widely used or recommended in the US.</span></li>
<li data-sourcepos="16:1-17:0"><span style="font-family: helvetica; font-size: medium;"><strong>Legal Status:</strong> The FDA hasn't approved it as a safe or effective medication.</span></li>
</ul>
<p data-sourcepos="18:1-18:19"><strong><span style="font-family: helvetica; font-size: medium;">Important Note:</span></strong></p>
<ul data-sourcepos="20:1-21:0">
<li data-sourcepos="20:1-21:0"><span style="font-family: helvetica; font-size: medium;"><strong>Consult a Doctor:</strong> Before considering any herbal supplement, including Thunder God Vine, consult a healthcare professional to discuss potential risks and interactions with other medications you might be taking.</span></li>
</ul>
<p data-sourcepos="22:1-22:100"><span style="font-family: helvetica; font-size: medium;">Remember, prioritizing safety and evidence-based medicine is crucial when managing health concerns.</span></p><p data-sourcepos="22:1-22:100"><span style="font-family: helvetica; font-size: medium;"><b>REFERENCE</b></span></p><p data-sourcepos="22:1-22:100"><span style="font-family: helvetica; font-size: medium;">1. Xingiang Song et al, Therapeutic targets of thunder god vine (Tripterygium wilfordii hook) in rheumatoid arthritis (Review), Mol Med Rep. 2022 Jun;21(6):2303-2310.</span></p><p data-sourcepos="22:1-22:100"><span style="font-family: helvetica; font-size: medium;">2. T Allard et al, Mechanisms of herb-induced nephrotoxicity, Curr Med Che. 2013;20(22):2812-9.</span></p><p data-sourcepos="22:1-22:100"><span style="font-family: helvetica; font-size: medium;">3. Heng Xu et al, Celastrol suppresses colorectal cancer via covalent targeting peroxiredoxin 1, Singnal Transduct Target Ther. 2023 Feb 3;8(1):51.</span></p><p data-sourcepos="22:1-22:100"><span style="font-family: helvetica; font-size: medium;">4. Haoran Zhang et al, Triptolide leads to hepatic intolerance to exogenous lipopolysaccharide and natural-killer-cell mediated hepatocellular damage by inhibiting MHC class I molecules. Phytomedicine, 2023 Jan:109:154621.</span></p><p data-sourcepos="22:1-22:100"><span style="font-family: helvetica; font-size: medium;">5. Kevin Liaw et al, Systemic dendrimer delivery of triptoide to tumor-associated macrophages improves anti-tumor efficacy and reduces systemic toxicity in glioblastomas, J Control Release, 2021 Jan 10:329:434-444.</span></p><p data-sourcepos="22:1-22:100"><span style="font-family: helvetica; font-size: medium;">6. Runping Liu et al, Toxicity of traditional Chinese medicine herbal and mineral products, Adv Pharmacol. 2020:87:301-346.</span></p><p data-sourcepos="22:1-22:100"><span style="font-family: helvetica; font-size: medium;"><br /></span></p><p data-sourcepos="22:1-22:100"><span style="font-family: helvetica; font-size: medium;"><br /></span></p></div><div><br /></div><div><br /></div><div><br /></div><div><br /></div><div><br /></div><div><br /></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-86112091600380948062024-02-05T11:11:00.000-08:002024-02-05T11:12:00.054-08:00Overview: Chronic fatigue syndrome or Myalgic encephalomyelitis<div style="font-family: Arial, Helvetica, sans-serif;"><span><p data-sourcepos="3:1-3:128"><span style="font-size: x-large;">C</span>hronic fatigue can be a confusing term, as it can refer to both a symptom and a specific medical condition. Here's a breakdown:</p><p data-sourcepos="5:1-5:213" style="font-size: medium;"><strong>Symptom:</strong> Chronic fatigue is a feeling of <strong>excessive tiredness</strong> that lasts for <strong>at least 6 months</strong> and <strong>doesn't improve with rest</strong>. This can be a symptom of various underlying medical conditions, such as:</p><ul data-sourcepos="7:1-12:0" style="font-size: medium;">
<li data-sourcepos="7:1-7:259"><b>Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)</b><strong>:</strong>
This is a complex, long-term illness characterized by severe fatigue,
post-exertional malaise (worsening symptoms after physical or mental
activity), and other cognitive and physical symptoms.</li>
<li data-sourcepos="8:1-8:153"><strong>Thyroid disorders:</strong>
Hypothyroidism (underactive thyroid) can cause fatigue, along with other
symptoms like weight gain and difficulty concentrating.</li>
<li data-sourcepos="9:1-9:144"><strong>Anemia:</strong> This condition
occurs when your blood doesn't have enough red blood cells, leading to
fatigue, shortness of breath, and pale skin.</li>
<li data-sourcepos="10:1-10:118"><strong>Sleep disorders:</strong> Sleep apnea, insomnia, and restless leg syndrome can disrupt sleep and lead to daytime fatigue.</li>
<li data-sourcepos="11:1-12:0"><strong>Mental health conditions:</strong> Depression and anxiety can also cause fatigue and decreased energy levels.</li>
</ul><p data-sourcepos="13:1-13:375" style="font-size: medium;"><strong>Medical Condition:</strong> In specific cases, chronic fatigue itself can be diagnosed as a medical condition called <strong>Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)</strong>. This condition is characterized by specific criteria, including severe fatigue, post-exertional malaise, and cognitive difficulties, that are not explained by any other underlying medical condition.</p><h2 data-sourcepos="15:1-15:34" style="font-size: medium;">Prevalence in the United States</h2><p data-sourcepos="17:1-17:259" style="font-size: medium;">Estimating the exact number of Americans with chronic fatigue is challenging because it can be a symptom of various conditions. However, some studies suggest that <strong>ME/CFS affects approximately 1-2.5 million Americans</strong>.</p><h2 data-sourcepos="19:1-19:28" style="font-size: medium;">Symptoms of Chronic Fatigue Syndrome</h2><p data-block-key="mqtpt" style="font-size: medium;"><b>Common symptoms of ME/CFS include:</b></p><ul style="font-size: medium;"><li data-block-key="8k8kq">feeling extremely tired all the time – you may find it very hard to do daily activities</li><li data-block-key="dumet">still feeling tired after resting or sleeping</li><li data-block-key="fdkt7">taking a long time to recover after physical activity</li><li data-block-key="6un4g">problems sleeping, such as waking up often during the night</li><li data-block-key="a1dmo">problems with thinking, memory and concentration</li></ul><p data-block-key="464p1" style="font-size: medium;"><b>Other symptoms include:</b></p><ul style="font-size: medium;"><li data-block-key="e7d02">muscle or joint pain</li><li data-block-key="3onia">headaches</li><li data-block-key="b0a2e">a sore throat</li><li data-block-key="73jkd">flu-like symptoms.</li><li data-block-key="cjc36">feeling dizzy or sick</li><li data-block-key="9n2c8">fast or irregular heartbeats</li></ul><h2 data-sourcepos="19:1-19:28" style="font-size: medium;">Causes of Chronic Fatigue</h2><p data-sourcepos="21:1-21:161" style="font-size: medium;">The exact causes of chronic fatigue are not fully understood, and it likely results from a <strong>complex interplay of factors</strong>. Some potential contributors include:</p><ul data-sourcepos="23:1-27:0" style="font-size: medium;">
<li data-sourcepos="23:1-23:137"><strong>Viral infections:</strong> Some theories suggest that viruses like Epstein-Barr virus (EBV) might trigger ME/CFS in susceptible individuals.</li>
<li data-sourcepos="24:1-24:96"><strong>Immune system dysfunction:</strong> Abnormalities in the immune system might play a role in ME/CFS.</li>
<li data-sourcepos="25:1-25:98"><strong>Genetic factors:</strong> Certain genes might make some people more susceptible to developing ME/CFS.</li>
<li data-sourcepos="26:1-27:0"><strong>Psychological factors:</strong> Stress, anxiety, and depression can worsen chronic fatigue symptoms.</li>
</ul><h2 data-sourcepos="28:1-28:29" style="font-size: medium;">Preventing Chronic Fatigue</h2><p data-sourcepos="30:1-30:219" style="font-size: medium;">Unfortunately, there is no guaranteed way to prevent chronic fatigue. However, focusing on healthy lifestyle habits can help reduce your risk of developing some underlying conditions that contribute to fatigue, such as:</p><ul data-sourcepos="32:1-38:0" style="font-size: medium;">
<li data-sourcepos="32:1-32:73"><strong>Getting enough sleep:</strong> Aim for 7-8 hours of quality sleep per night.</li>
<li data-sourcepos="33:1-33:112"><strong>Eating a healthy diet:</strong> Consume a balanced diet rich in fruits, vegetables, whole grains, and lean protein.</li>
<li data-sourcepos="34:1-34:88"><strong>Exercising regularly:</strong> Engage in moderate-intensity exercise most days of the week.</li>
<li data-sourcepos="35:1-35:78"><strong>Managing stress:</strong> Practice relaxation techniques like yoga or meditation.</li>
<li data-sourcepos="36:1-36:103"><strong>Maintaining healthy relationships:</strong> Strong social connections can boost your emotional well-being.</li>
<li data-sourcepos="37:1-38:0"><strong>Seeking regular medical checkups:</strong> Address any underlying medical conditions that might contribute to fatigue.</li>
</ul><div style="font-size: medium;"><section>
<h2 id="medical-treatments">Treating ME/CFS</h2>
<p data-block-key="83y27">Treatment for ME/CFS aims to relieve the symptoms, i.e. conditions. Treatments include:</p><ul><li data-block-key="8kkjt">cognitive behavioral therapy</li><li data-block-key="8u5e1">energy
management</li><li data-block-key="cmc2j">medicine to control symptoms such as pain and sleeping problems.</li></ul><p data-block-key="99cej">Some people with ME/CFS will improve over time, especially with treatment.</p><p data-block-key="kg4d">Many
people with ME/CFS will need to adapt their daily routine and pattern
of activities on a long-term basis. There may be periods when your
symptoms get better or worse.</p></section></div><h2 data-sourcepos="39:1-39:18" style="font-size: medium;">Important Note:</h2><p data-sourcepos="41:1-41:270" style="font-size: medium;">If you are experiencing chronic fatigue, it's important to <strong>consult a doctor</strong> to rule out any underlying medical conditions and discuss appropriate management strategies. They can help you determine the cause of your fatigue and recommend the best course of treatment.</p></span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;"><b><br /></b></span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;"><b>Reference</b></span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;">1. Overview: Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), <a href="https://www.nhs.uk/conditions/chronic-fatigue-syndrome-cfs/" target="_blank">NHS website</a>, accessed on February 05, 2024.</span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;">2. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), <a href="https://www.mayoclinic.org/diseases-conditions/chronic-fatigue-syndrome/symptoms-causes/syc-20360490" target="_blank">Mayo Clinic website</a>, accessed on February 05, 2024.</span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;">3. Joseph R. Yancey, Chronic fatigue syndrome: diagnosis and treatment, Am Fam Physician. 2012 Oct 15;86(8):741-6.</span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;">4. </span>Myalgic encephalomyelitis/chronic fatigue syndrome, <a href="https://www.cdc.gov/me-cfs/index.html" target="_blank">CDC</a>, accessed on February 05, 2024</div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;"><br /></span></div><div style="font-family: Arial, Helvetica, sans-serif;"><br /></div><div style="font-family: Arial, Helvetica, sans-serif;"><br />
</div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;">-----------------------------------------------------------------------------</span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;"><br />
</span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: large;"><b>Researchers' Note:</b></span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;"><b><br /></b></span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;"><p data-sourcepos="1:1-1:531"><b>Recent Findings</b></p><p data-sourcepos="1:1-1:531">A study investigated the clinical characteristics of young people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) following infectious mononucleosis (IM) caused by Epstein-Barr virus (EBV). They recruited 25 young people (12 adolescents and 13 young adults) who fulfilled the Canadian consensus criteria for ME/CFS following EBV-IM. The researchers assessed the frequency and severity of symptoms, physical functioning, and health-related quality of life (HRQoL) at the time of diagnosis and 6 and 12 months later.</p>
<p data-sourcepos="3:1-3:429">They found that young adults had more severe symptoms and poorer physical functioning and HRQoL than adolescents throughout the study. After one year, more than half of the adolescents no longer met the diagnostic criteria for ME/CFS, while none of the young adults did. Adolescents who recovered showed improvement in physical functioning, symptom frequency and severity, and HRQoL, while young adults showed little improvement.</p>
<p data-sourcepos="5:1-5:239">The researchers also found that EBV serology and EBV DNA load were not associated with distinct clinical features of ME/CFS, and there was no evidence of inflammation. The median time from symptom onset to ME/CFS diagnosis was 13.8 months.</p>
<p data-sourcepos="7:1-7:231">These findings suggest that ME/CFS following EBV-IM is a more severe and persistent illness in young adults than in adolescents. There is a need for better biomarkers and more effective treatments for ME/CFS, especially in adults.</p><p data-sourcepos="7:1-7:231"><b>Reference: </b></p><p data-sourcepos="7:1-7:231">Rafael Pricoco et al, Front Pediatr. 2024 Jan 18:11:1266738</p></span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;"><br /></span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;"><b>Older Stories</b></span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;"><br /></span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;">Researchers have identified a family of retroviruses in patients with chronic fatigue syndrome, opening up a potentially promising new avenue of treatment for a debilitating disease that afflicts as many as four million Americans and 17 million people world-wide. [1]</span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;"><br /></span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;">Based on other recent research linking the syndrome to a retrovirus called XMRV, some doctors are already prescribing drugs approved for HIV for fatigue patients. Unfortunately,the syndrome has no effective treatments yet. The group of viruses identified in fatigue patients, called murine leukemia virus-related viruses, or MLV, are known to cause cancer and neurological problems in mice, but whether they cause disease in humans isn't known. XMRV is among several different members of the MLV family. [1]</span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;"><br /></span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;">XMRV is a identified human retrovirus that is similar to a group of mouse retroviruses (called murine leukemia viruses, or MLVs) scientists have known about for years. XMRV refers to xenotropic murine leukemia virus-related virus. It was first identified in 2006 in tissue samples from men with prostate cancer. [2]</span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;"><br />
</span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;">As early as October 2009, scientists reported a potential association of XMRV with chronic fatigue syndrome (CFS). In this study, XMRV was detected in approximately two-thirds of patients diagnosed with CFS. They also identified DNA of XMRV in the blood cells of some healthy persons and suggested a potential for XMRV transmission by transfusion or transplantation. [2]</span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;"><br /></span></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;"><br /></span></div><div style="font-family: Arial, Helvetica, sans-serif;"><br /></div><div style="font-family: Arial, Helvetica, sans-serif;"><span style="font-size: small;">SOURCE [1] New Hope in Fatigue Fight wsj.com 2010 [2] CDC.gov</span></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-51479516953287341192024-02-05T07:52:00.000-08:002024-02-05T07:52:17.719-08:00Fish Oil Vs Cod Liver Oil<p> Cod liver oil Vs Fish oil - <span class="text"><b><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 14px; line-height: 17px;">Comparison & Contrast</span></span></b></span></p><span class="text"><b><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 14px; line-height: 17px;"><br /></span></span></b></span><br /><table border="2" cellpadding="0" cellspacing="2" style="height: 176px; width: 705px;"><tbody><tr><td height="17" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="422"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Manufacturing processes Comparison (Cod Liver Oil Vs. Fish Oil Capsules)</span></span></span></td><td height="17" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="269"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Similar</span></span></span></td></tr><tr><td height="17" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="422"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Raw materials (Cod Liver Oil Vs. Fish Oil Capsules)</span></span></span></td><td height="17" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="269"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Cod liver used for cod liver oil</span></span></span></td></tr><tr><td height="17" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="422"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Types of Omega-3 (Cod Liver Oil Vs. Fish Oil Capsules)</span></span></span></td><td height="17" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="269"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Same</span></span></span></td></tr><tr><td height="17" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="422"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Compositions (Cod Liver Oil Vs Fish Oil Capsules)</span></span></span></td><td height="17" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="269"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Cod Liver Oil has more vitamins A and D</span></span></span></td></tr><tr><td height="46" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="422"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Contaminants (Cod Liver Oil Vs Fish Oil Capsules)</span></span></span></td><td height="46" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="269"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">More contaminants may be present in cod liver<br />oil, however it is really dependent on the<br />manufacturing / purification process.</span></span></span></td></tr><tr><td height="32" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="422"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Side Effects Comparison (Cod Liver Oil Vs Fish Oil Capsules)</span></span></span></td><td height="32" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="269"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Excessive amount of vitamins A and D will offer<br />side effects</span></span></span></td></tr></tbody></table><br /><div style="text-align: center;"><span class="text"><b><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 14px; line-height: 17px;">Cod Liver Oil Vs Fish Oil<br />Composition Comparison</span></span></b></span></div><table border="2" cellpadding="0" cellspacing="2" style="height: 361px; width: 690px;"><tbody><tr><td align="center" height="121" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="256"></td><td align="center" height="121" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="141"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Nows Food<br />Salmon Oil<br /><br />1,000 mg salmon oil<br />concentrate per softgel<br /><br />Serving Size 2 Softgels<br />Amount Per Serving</span></span></span></td><td align="center" height="121" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="129"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Carlson Norwegian<br />Cod Liver Oil Lightly<br />Lemon<br /><br />Potency:<br />1000 mg<br /><br />Serving Size: 1 Softgel</span></span></span></td><td align="center" height="121" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="142"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Nordic Naturals Arctic<br />Cod Liver Oil 1000 mg<br /><br /><br /><br />Serving Size 3 Soft Gels</span></span></span></td></tr><tr><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="256"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Calories</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="141"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">20</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="129"><span class="text"><span style="font-size: 16px; line-height: 19px;">9</span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="142"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">27</span></span></span></td></tr><tr><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="256"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Calories from Fat</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="141"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">20</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="129"><span class="text"><span style="font-size: 16px; line-height: 19px;">9</span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="142"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">27</span></span></span></td></tr><tr><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="256"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Total Fat</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="141"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">2 g</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="129"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">1 g</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="142"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">3.0 g</span></span></span></td></tr><tr><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="256"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Saturated Fat</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="141"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">0.5 g</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="129"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Not listed</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="142"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">0.6 g</span></span></span></td></tr><tr><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="256"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Trans Fat</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="141"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">0 g</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="129"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Not listed</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="142"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">0 g</span></span></span></td></tr><tr><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="256"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Cholesterol</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="141"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">9 mg</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="129"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">4 mg</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="142"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">7.5 mg</span></span></span></td></tr><tr><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="256"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Total Omega-3 Fatty Acids</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="141"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">400 mg</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="129"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">230 mg</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="142"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">756 mg</span></span></span></td></tr><tr><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="256"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Eicosapentaenoic Acid (EPA)</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="141"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">240 mg</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="129"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">85 mg</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="142"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">246 mg</span></span></span></td></tr><tr><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="256"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Docosahexaenoic Acid (DHA)</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="141"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">160 mg</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="129"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">100 mg</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="142"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">375 mg</span></span></span></td></tr><tr><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="256"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Vitamin A / D / E</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="141"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">Not listed</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="129"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">150 /80/2 IU</span></span></span></td><td align="center" height="19" style="border: 1px inset rgb(220, 220, 220);" valign="top" width="142"><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 12px; line-height: 15px;">900–1650/1-12/40</span></span></span></td></tr></tbody></table><div style="text-align: center;"><br /></div><div style="text-align: center;"><br /></div><div><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 14px; line-height: 17px;">Some people said cod liver oil products contains more impurities than fish oil products. They explain that liver is the place for detoxification to occur, and so cod liver oil has more impurities. I can't wait to disagree with them, it really depends on the purification and manufacturing process. A high-quality cod-liver oil product should contain less impurities than a poor-quality fish oil product.</span></span></span></div><div><br /></div><div><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 14px; line-height: 17px;">On the other hand, cod liver oil products contain extra amounts of vitamin A, D and E. If you lack these vitamins, yeah, you may consider cod liver oil products, but if you have a good source of vitamins A, D and E, then fish oil is the choice. Please, consult with your doctor before taking any supplements.</span></span><b><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 14px; line-height: 17px;"><br /></span></span></b></span></div><div><span class="text"><span style="font-family: Arial; font-size: x-small;"><span style="font-size: 14px; line-height: 17px;"><br /></span></span></span></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-38071865762303906622024-02-04T20:17:00.000-08:002024-02-04T20:17:47.119-08:00REVIEW: JOENJA® (leniolisib) tablets**<p>JOENJA® (leniolisib) tablets, for oral use
Initial U.S. Approval: 2023</p><p><strong style="box-sizing: border-box; color: #222222; font-family: "Helvetica Neue", Helvetica, Arial, sans-serif; font-size: 15.84px;">Application Number:</strong><span style="background-color: white; color: #222222; font-family: "Helvetica Neue", Helvetica, Arial, sans-serif; font-size: 15.84px;"> N217759</span><br style="box-sizing: border-box; color: #222222; font-family: "Helvetica Neue", Helvetica, Arial, sans-serif; font-size: 15.84px;" /><strong style="box-sizing: border-box; color: #222222; font-family: "Helvetica Neue", Helvetica, Arial, sans-serif; font-size: 15.84px;">Approval Date:</strong><span style="background-color: white; color: #222222; font-family: "Helvetica Neue", Helvetica, Arial, sans-serif; font-size: 15.84px;"> Mar 24, 2023</span><br style="box-sizing: border-box; color: #222222; font-family: "Helvetica Neue", Helvetica, Arial, sans-serif; font-size: 15.84px;" /><strong style="box-sizing: border-box; color: #222222; font-family: "Helvetica Neue", Helvetica, Arial, sans-serif; font-size: 15.84px;">Applicant Holder Full Name:</strong><span style="background-color: white; color: #222222; font-family: "Helvetica Neue", Helvetica, Arial, sans-serif; font-size: 15.84px;"> PHARMING TECHNOLOGIES BV</span></p><p><b>MECHANISM</b></p><p>Leniolisib inhibits PI3K-delta by blocking the active binding site of PI3K-delta. In cell-free
isolated enzyme assays, leniolisib was selective for PI3K-delta over PI3K-alpha
(28-fold), PI3K-beta (43-fold), and PI3K-gamma (257-fold), as well as the broader
kinome. In cell-based assays, leniolisib reduced pAKT pathway activity and inhibited
proliferation and activation of B and T cell subsets. Gain-of-function variants in the gene
encoding the p110-delta catalytic subunit or loss of function variants in the gene
encoding the p85-alpha regulatory subunit each cause hyperactivity of PI3K-delta.
Leniolisib inhibits the signalling pathways that lead to increased production of PIP3,
hyperactivity of the downstream mTOR/AKT pathway, and to the dysregulation of B and
T cells. </p><p><b>INDICATION</b></p><p>JOENJA is a kinase inhibitor indicated for the treatment of activated
phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) in adult and
pediatric patients 12 years of age and older.</p><p><b>DOSAGE ADMINSTRATION</b></p><p>Recommended dosage: 70 mg administered orally twice daily
approximately 12 hours apart, with or without food, in adult and
pediatric patients 12 years of age and older and weighing ≥45kg. </p><p><b>DOSAGE FORM AND STRENGTH</b></p><p>Tablets: 70 mg leniolisib</p><p><b>API</b></p><p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEhzElSKZ3GAIpNPFlAJY5ywMtQFdDV9zZ-Z2K-oqnrWGsnugLQeYPuWlE0GyddT0DvTPXwbrKGehhdKStMrHYhnDNv2nSwLwEe8zwIZWZ4LgAe83KSj2gfnRDM8l0RFWDO7h9mYcshmmE81a6YVjpaQW_JR_IxPJGeZk1u843l7P0nWUYOu8ywE" style="margin-left: 1em; margin-right: 1em;"><img alt="" data-original-height="313" data-original-width="457" height="289" src="https://blogger.googleusercontent.com/img/a/AVvXsEhzElSKZ3GAIpNPFlAJY5ywMtQFdDV9zZ-Z2K-oqnrWGsnugLQeYPuWlE0GyddT0DvTPXwbrKGehhdKStMrHYhnDNv2nSwLwEe8zwIZWZ4LgAe83KSj2gfnRDM8l0RFWDO7h9mYcshmmE81a6YVjpaQW_JR_IxPJGeZk1u843l7P0nWUYOu8ywE=w423-h289" width="423" /></a></div><br /><br /><p></p><p>Leniolisib phosphate is a white to yellowish to yellowish-greenish powder. <b>The aqueous
solubility of leniolisib phosphate is pH dependent with decreasing solubility observed
with increasing pH.</b></p><p><b> COMPOSITION/EXCIPIENTS</b></p><p>JOENJA film-coated tablets are for oral administration. Each tablet contains 70 mg of
leniolisib (equivalent to 85 mg leniolisib phosphate) with the following inactive
ingredients: colloidal silicon dioxide, hydroxypropyl methylcellulose, lactose
monohydrate, magnesium stearate, microcrystalline cellulose, and sodium starch
glycolate. The tablet film-coating contains hydroxypropyl methylcellulose, iron oxide red,
iron oxide yellow, polyethylene glycol, talc, and titanium dioxide. </p><p>PK</p><p>The systemic drug exposure (AUC and Cmax) of leniolisib increased dose proportionally
within the studied range of doses (20 to 140 mg twice a day dosing and single doses of
10 to 400 mg). During twice daily dosing approximately 12 hours apart, leniolisib
accumulates approximately 1.4-fold (range of 1.0 to 2.2) in achieving steady-state,
consistent with an effective half-life (t1/2) of approximately 7 hours. Steady state drug
concentrations can be expected to be reached after approximately 2 to 3 days of
JOENJA treatment. </p><p>In a placebo controlled, single and multiple ascending dose study in healthy
participants, leniolisib median time to maximum plasma concentration (Tmax) occurred at
about 1 hour postdose. Tmax appeared independent of dose and was not altered after
multiple oral doses. Food is unlikely to have a clinically meaningful effect on the
systemic exposure of leniolisib during JOENJA treatment.</p><p>The mean recovery of total 14C-radioactivity following a single oral dose of 70 mg
14C-leniolisib was 92.5% (<b>67.0%</b> and 25.5% recovered via <b>feces</b> and urine,
respectively) 168 hours postdose. Unchanged leniolisib (6.32%) was the predominant
drug-related material recovered in urine.</p><p><b>Leniolisib was 60% metabolized by the liver</b>, with CYP3A4 being the most predominant
enzyme involved (94.5%) in the primary oxidative metabolism of leniolisib with minor
contribution from other enzymes (3.5% CYP3A5, 0.7% CYP1A2 and 0.4% CYP2D6).
Intestinal secretion by BCRP as well as extrahepatic CYP1A1 cannot be excluded as
excretion routes. </p><p><b>ADVERSE REACTIONS</b></p><p>Most common adverse reactions (incidence >10%) were headache,
sinusitis, and atopic dermatitis.</p><p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEh68rMhHme1HMztvcKuP0wViXTVpy1Ah3Tu_DL0_nBbs8g5tcF9yPj9HZdV1hlckhuYhTnZ5NAbraXR8c5o5YsT45fMb8pzknZbrr0Ri5pfNUUvugteoDIX5z4tmothdOzORPbai_Q5m3VCy0Tb84fzNq6zMqlvHKRlUnwMF_Jkp1ghWbRHeNSd" style="margin-left: 1em; margin-right: 1em;"><img alt="" data-original-height="780" data-original-width="1162" height="353" src="https://blogger.googleusercontent.com/img/a/AVvXsEh68rMhHme1HMztvcKuP0wViXTVpy1Ah3Tu_DL0_nBbs8g5tcF9yPj9HZdV1hlckhuYhTnZ5NAbraXR8c5o5YsT45fMb8pzknZbrr0Ri5pfNUUvugteoDIX5z4tmothdOzORPbai_Q5m3VCy0Tb84fzNq6zMqlvHKRlUnwMF_Jkp1ghWbRHeNSd=w524-h353" width="524" /></a></div><br /><br /><p></p><p><b>Orange Book</b></p><p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEinGTRglSW9V7BkH4t5BlfwGTz2HRi1jd2-GWKf-St3AVXFyLaYbtnsQctZ9fVH28_AMm2bl1bozfKPEo0N9RrzyjDLOCihA-gFyOzvzlyCO4Z75shmpMYKY1PtBHsLkKn5-jX_VK60WMbvVsO5MmdZUnqfDcmLFavalRvmr1sni7gccRz9BUK5" style="margin-left: 1em; margin-right: 1em;"><img alt="" data-original-height="225" data-original-width="1753" height="86" src="https://blogger.googleusercontent.com/img/a/AVvXsEinGTRglSW9V7BkH4t5BlfwGTz2HRi1jd2-GWKf-St3AVXFyLaYbtnsQctZ9fVH28_AMm2bl1bozfKPEo0N9RrzyjDLOCihA-gFyOzvzlyCO4Z75shmpMYKY1PtBHsLkKn5-jX_VK60WMbvVsO5MmdZUnqfDcmLFavalRvmr1sni7gccRz9BUK5=w675-h86" width="675" /></a></div><p><br /></p><p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEiAH1gepg6Qnaj7oPVkRuBfz2h7Qm2wJTLUkn1ZR-QOgDY8wo8sldjzkBSs0Y_2RlzuOHM3ccHabvaUkzOhAQMV8GfJeHiSWNB59UMyvd9XUR2ZcCIpakORhyzwN0LtDIATNQyXqb09bfDmUKMxJu2wIT6-5lxj34oiEKRGNponzQRxv4KBYbT5" style="margin-left: 1em; margin-right: 1em;"><img alt="" data-original-height="518" data-original-width="1633" height="208" src="https://blogger.googleusercontent.com/img/a/AVvXsEiAH1gepg6Qnaj7oPVkRuBfz2h7Qm2wJTLUkn1ZR-QOgDY8wo8sldjzkBSs0Y_2RlzuOHM3ccHabvaUkzOhAQMV8GfJeHiSWNB59UMyvd9XUR2ZcCIpakORhyzwN0LtDIATNQyXqb09bfDmUKMxJu2wIT6-5lxj34oiEKRGNponzQRxv4KBYbT5=w657-h208" width="657" /></a></div><br /><br /><p></p><span style="background-color: #f9f9f9; color: #222222; font-family: "Helvetica Neue", Helvetica, Arial, sans-serif; font-size: 13.86px;">8653092 - a chemical patent</span><br /><br /><p></p><p><br /></p>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-88817322493296183482024-02-04T10:21:00.000-08:002024-02-04T10:21:22.974-08:00Overview: Excipients used in mRNA vaccines - Moderna, Pfizer/BioNTech<div><span style="font-family: helvetica; font-size: medium;"><b>Excipients play a crucial role in mRNA vaccines:</b></span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;">Protect the fragile mRNA sequence from degradation.</span></div><div><span style="font-family: helvetica; font-size: medium;">Facilitate delivery of the mRNA into cells and release it from internal compartments.</span></div><div><span style="font-family: helvetica; font-size: medium;">Modulate immune response: Different lipids can trigger specific types of immune reactions.</span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: large;"><b>Examples of excipients in COVID-19 mRNA vaccines:</b></span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;"><b>Moderna: </b>messenger ribonucleic acid (mRNA), lipids (SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG], cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC]), tromethamine, tromethamine hydrochloride, acetic acid, sodium acetate, and sucrose</span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;"><b>Pfizer/BioNTech: </b>messenger ribonucleic acid (mRNA), lipids (((4-hydroxybutyl) azanediyl) bis(hexane-6,1-diyl), bis(2-hexyldecanoate), 2 [(polyethylene glycol)-2000] N, N-ditetradecylacetamide, 1,2-distearoyl-sn-glycero-3-phosphocholine, and cholesterol), potassium chloride, monobasic potassium phosphate, sodium chloride, dibasic sodium phosphate dihydrate, and sucrose.</span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;"><b>Functions of Excipients </b></span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;"><b>(Pfizer/BioNTech)</b></span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;"><b>Lipids: </b>Nanolipids, or tiny fat molecules, protect the mRNA and provide a “greasy” exterior that helps the mRNA slide inside cells. </span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;"><b>Nanolipid components in the Pfzer-BioNTech vaccine include: </b>((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 2 [(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 1,2-distearoyl-sn-glycero-3-phosphocholine, and cholesterol</span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;"><b>Salts: </b>Helping to balance the acidity in your body, the following salts are included in the Pfzer-BioNTech vaccine: potassium chloride, monobasic potassium phosphate, sodium chloride, and dibasic sodium phosphate dihydrate </span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;"><b>Sugar: </b>Basic table sugar, also known as sucrose, can also be found in the Pfzer-BioNTech vaccine. This ingredient helps the molecules maintain their shape during freezing.</span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;"><b>(Moderna)</b></span></div><div><span style="font-family: helvetica; font-size: medium;">- <b>Lipids: </b>Nanolipids help deliver the mRNA to the vaccine recipient’s cells. Nanolipid components of the Moderna vaccine include: (SM-102, 1,2-dimyristoyl-rac-glycero3-methoxypolyethylene glycol-2000 [PEG2000-DMG], cholesterol, and 1,2-distearoyl-snglycero-3-phosphocholine [DSPC])</span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;">- <b>The remaining excipients</b>, including acids (acetic acid), acid stabilizers (tromethamine and tromethamine hydrochloride), salt (sodium acetate), and sugar (sucrose) all work together to maintain the stability of the vaccine after it’s produced.</span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;">In 2023, Lizhou Zhang and colleagues reported that the ionizable lipid, SM-102, in Moderna’s vaccine performed better than
ALC-0315 in Pfizer-BioNTech’s vaccine for intramuscular delivery of mRNA
and antibody production in mice and long-term stability at 4 °C.
Moreover, Pfizer-BioNTech’s 5′ UTR and Moderna’s 3′ UTR outperform their
counterparts in their contribution to transgene expression in mice. They further found that varying N1-methylpseudouridine content at the wobble
position of mRNA has little effect on vaccine efficacy. (1)</span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: large;"><b>Benefits of using excipients in mRNA vaccines:</b></span></div><div><span style="font-family: helvetica; font-size: medium;"><b><br /></b></span></div><div><span style="font-family: helvetica; font-size: medium;"><b>Faster development and production: </b>Easier to adapt existing platforms for new vaccines. </span></div><div><span style="font-family: helvetica; font-size: medium;"><b>Reduced risk of pre-existing immunity: </b>Compared to viral vector-based vaccines.</span></div><div><b style="font-family: helvetica; font-size: large;">More targeted immune response: </b><span style="font-family: helvetica; font-size: large;">Can be tailored to specific needs. </span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: large;"><b>Challenges with excipients: </b></span></div><div><span style="font-family: helvetica; font-size: medium;">Long-term safety data is limited.</span></div><div><span style="font-family: helvetica; font-size: medium;">Finding the right combination for different applications.</span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;"><b>Overall, excipients are essential components of mRNA vaccines, offering numerous advantages but also requiring further research.</b></span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: large;"><b>Reference:</b></span></div><div><br /></div><div><span style="font-family: helvetica; font-size: medium;">Shireesh P. Apte, Excipients and mRNA Vaccines, J. Excipients and Food Chem. 11 (4) 2020.</span></div><div><span style="font-family: helvetica; font-size: medium;">What Ingredients are in the Covid-19 Vaccine? Connecticut Department of Public Health</span></div><div><span style="font-family: helvetica; font-size: medium;"><br /></span></div><div><span style="font-family: helvetica; font-size: medium;">(1) Lizhou Zhang et al, Effect of mRNA-LNP components of two globally-marketed COVID-19 vaccines on efficacy and stability, NPJ Vaccines. 2023; 8: 156. </span></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-2022111051695390792024-02-03T08:06:00.000-08:002024-02-03T08:06:13.960-08:00Overview: Excipients used in antibody products<span style="font-family: helvetica;">There are many different excipients used in antibody products, but some of the most common ones include: </span><div><span style="font-family: helvetica;"><br /></span></div><div><span style="font-family: helvetica;"><b>Buffers: </b>These help to maintain the correct pH of the antibody product, which is important for its stability and activity. Common buffers used in antibody products include sodium phosphate, histidine, citrate, and acetate. </span><div><span style="font-family: helvetica;"><br /></span></div><div><span style="font-family: helvetica;"><b>Sodium phosphate buffer
Surfactants: </b>These help to reduce surface tension and prevent the antibody from sticking to the container or other surfaces. Common surfactants used in antibody products include polysorbates (such as polysorbate 80 and polysorbate 20) and poloxamers. </span></div><div><b><span style="font-family: helvetica;"><br /></span></b></div><div><span style="font-family: helvetica;"><b>Polysorbate 80
Tonicity agents: </b>These help to adjust the osmotic pressure of the antibody product so that it is similar to the osmotic pressure of the body's fluids. This helps to prevent the product from causing irritation or pain when it is injected. Common tonicity agents used in antibody products include sodium chloride and mannitol. </span></div><div><span style="font-family: helvetica;"><br /></span></div><div><span style="font-family: helvetica;"><b>Sodium chloride
Sugars: </b>These can act as bulking agents in lyophilized (freeze-dried) antibody products, and they can also help to stabilize the antibody. Common sugars used in antibody products include sucrose and trehalose. </span></div><div><span style="font-family: helvetica;"><br /></span></div><div><span style="font-family: helvetica;"><b>Trehalose
Amino acids: </b>These can help to stabilize the antibody and prevent it from aggregating. Common amino acids used in antibody products include glycine and arginine. </span></div><div><span style="font-family: helvetica;"><br /></span></div><div><span style="font-family: helvetica;"><b>Antioxidants: </b>These help to protect the antibody from damage caused by free radicals. Common antioxidants used in antibody products include methionine and histidine. </span></div><div><span style="font-family: helvetica;"><br /></span></div><div><span style="font-family: helvetica;">The specific excipients used in a particular antibody product will depend on a number of factors, such as the properties of the antibody, the route of administration, the type of dosage forms (liquid, <span style="color: #222222;">lyophilized powder<span style="background-color: white;">) and</span></span> the desired shelf life.</span><p><span style="font-family: helvetica;"><b>Here is a list of a few antibody-products for reference:</b></span></p><p style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 0.8em; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><b>Avastin (bevacizumab) injection</b> is a sterile, preservative-free, clear to slightly opalescent, colorless to pale brown solution in a single-dose vial for intravenous use. Avastin contains bevacizumab at a concentration of 25 mg/mL in either a 100 mg/4 mL or 400 mg/16 mL single-dose vial.</p><p style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 0.8em; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;">Each mL of solution contains 25 mg bevacizumab, α,α-trehalose dihydrate (60 mg), polysorbate 20 (0.4 mg), sodium phosphate dibasic, anhydrous (1.2 mg), sodium phosphate monobasic, monohydrate (5.8 mg), and Water for Injection, USP. The <b>pH is 6.2</b>.</p><p style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 0.8em; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><b>Epogen (epoetin alfa) injection</b> for intravenous or <b>subcutaneous</b> administration is formulated as a sterile, clear, colorless liquid in vials in multiple formulations. Single-dose vials, formulated with an isotonic sodium chloride/sodium citrate-buffered solution, are supplied in multiple strengths. Each single-dose 1 mL vial contains 2,000, 3,000, 4,000, or 10,000 Units of epoetin alfa, Albumin (Human) (2.5 mg), citric acid (0.06 mg), sodium chloride (5.9 mg), and sodium citrate (5.8 mg) in Water for Injection, USP (pH 6.9 ± 0.3). Multiple-dose, 2 mL vials contain 10,000 Units epoetin alfa, albumin (human) (2.5 mg), benzyl alcohol (1%), sodium chloride (8.2 mg), citric acid (0.11 mg), and sodium citrate (1.3 mg) per 1 mL Water for Injection, USP (pH 6.1 ± 0.3). Multiple-dose 1 mL vials contain 20,000 Units epoetin alfa, albumin (human) (2.5 mg), benzyl alcohol (1%), sodium chloride (8.2 mg), citric acid (0.11 mg), and sodium citrate (1.3 mg), per 1 mL in Water for Injection, USP (<b>pH 6.1 ± 0.3</b>).</p><p style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 0.8em; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><b>Herceptin (trastuzumab)</b> for injection is a sterile, white to pale yellow, preservative-free <b>lyophilized powder</b> with a cake-like appearance, for <b>intravenous administration</b>.</p><p style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 0.8em; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;">Each single-dose vial of Herceptin delivers 150 mg trastuzumab, 136.2 mg α,α-trehalose dihydrate, 3.4 mg L-histidine HCl monohydrate, 2.2 mg L-histidine, and 0.6 mg polysorbate 20. Reconstitution with 7.4 mL of sterile water for injection (SWFI) yields a solution containing 21 mg/mL trastuzumab that delivers 7.15 mL (150 mg trastuzumab), at a <b>pH of approximately 6</b>.</p><p style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 0.8em; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><b>HERCEPTIN HYLECTA (trastuzumab and hyaluronidase) injection</b> is a sterile, preservative-free, colorless to yellowish, clear to opalescent solution supplied in single-dose vials for <b>subcutaneous</b> administration.</p><p style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 0.8em; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;">HERCEPTIN HYLECTA is supplied as 600 mg trastuzumab and 10,000 units hyaluronidase per 5 mL in single-dose vials. Each mL of solution contains trastuzumab (120 mg), hyaluronidase (2,000 units), L-histidine (0.39 mg), L-histidine hydrochloride monohydrate (3.67 mg), L-methionine (1.49 mg), polysorbate 20 (0.4 mg), α,α-trehalose dihydrate (79.45 mg), and Water for Injection.</p><p style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 0.8em; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><b>HUMIRA (adalimumab) injection</b> is supplied as a sterile, preservative-free solution for <b>subcutaneous</b> administration. The drug product is supplied as either a single-dose, prefilled pen (HUMIRA Pen), as a single-dose, 1 mL prefilled glass syringe, or as a single-dose institutional use vial. Enclosed within the pen is a single-dose, 1 mL prefilled glass syringe. The solution of HUMIRA is clear and colorless, with a <b>pH of about 5.2</b>.</p><p style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 0.8em; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;">Each 80 mg/0.8 mL prefilled syringe or prefilled pen delivers 0.8 mL (80 mg) of drug product. Each 0.8 mL of HUMIRA contains adalimumab (80 mg), mannitol (33.6 mg), polysorbate 80 (0.8 mg), and Water for Injection, USP.</p><p style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 0.8em; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;">Each 40 mg/0.4 mL prefilled syringe or prefilled pen delivers 0.4 mL (40 mg) of drug product. Each 0.4 mL of HUMIRA contains adalimumab (40 mg), mannitol (16.8 mg), polysorbate 80 (0.4 mg), and Water for Injection, USP.</p><p style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 0.8em; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;">Each 40 mg/0.8 mL prefilled syringe, prefilled pen, or single-dose institutional use vial delivers 0.8 mL (40 mg) of drug product. Each 0.8 mL of HUMIRA contains adalimumab (40 mg), citric acid monohydrate (1.04 mg), dibasic sodium phosphate dihydrate (1.22 mg), mannitol (9.6 mg), monobasic sodium phosphate dihydrate (0.69 mg), polysorbate 80 (0.8 mg), sodium chloride (4.93 mg), sodium citrate (0.24 mg) and Water for Injection, USP. Sodium hydroxide is added as necessary to adjust pH.</p><p style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 0.8em; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;">Each 20 mg/0.2 mL prefilled syringe delivers 0.2 mL (20 mg) of drug product. Each 0.2 mL of HUMIRA contains adalimumab (20 mg), mannitol (8.4 mg), polysorbate 80 (0.2 mg), and Water for Injection, USP.</p><p style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 0.8em; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;">Each 20 mg/0.4 mL prefilled syringe delivers 0.4 mL (20 mg) of drug product. Each 0.4 mL of HUMIRA contains adalimumab (20 mg), citric acid monohydrate (0.52 mg), dibasic sodium phosphate dihydrate (0.61 mg), mannitol (4.8 mg), monobasic sodium phosphate dihydrate (0.34 mg), polysorbate 80 (0.4 mg), sodium chloride (2.47 mg), sodium citrate (0.12 mg) and Water for Injection, USP. Sodium hydroxide is added as necessary to adjust pH.</p><p style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 0.8em; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;">Each 10 mg/0.1 mL prefilled syringe delivers 0.1 mL (10 mg) of drug product. Each 0.1 mL of HUMIRA contains adalimumab (10 mg), mannitol (4.2 mg), polysorbate 80 (0.1 mg), and Water for Injection, USP.</p><p style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 0.8em; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;">Each 10 mg/0.2 mL prefilled syringe delivers 0.2 mL (10 mg) of drug product. Each 0.2 mL of HUMIRA contains adalimumab (10 mg), citric acid monohydrate (0.26 mg), dibasic sodium phosphate dihydrate (0.31 mg), mannitol (2.4 mg), monobasic sodium phosphate dihydrate (0.17 mg), polysorbate 80 (0.2 mg), sodium chloride (1.23 mg), sodium citrate (0.06 mg) and Water for Injection, USP. Sodium hydroxide is added as necessary to adjust pH.</p><p style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 0.8em; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><b>Neulasta (Pegfilgrastim)</b> is provided in two presentations:</p><ul style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; counter-reset: a 0; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; list-style: inside none; margin: 12.3611px 24.7361px; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><li style="background-attachment: initial; background-clip: initial; background-color: initial; background-origin: initial; background-position: 0px 7px; background-repeat: no-repeat; background-size: initial; background: url("../../images/orange-list.a2de725cdb0b.png") 0px 7px no-repeat !important; border: none; box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; list-style: none circle; margin: 0px; overflow-wrap: break-word; padding: 0px 0px 0px 15px; vertical-align: baseline;">Neulasta for manual subcutaneous injection is supplied in 0.6 mL prefilled syringes. The prefilled syringe does not bear graduation marks and is designed to deliver the entire contents of the syringe (6 mg/0.6 mL).</li><li style="background-attachment: initial; background-clip: initial; background-color: initial; background-origin: initial; background-position: 0px 7px; background-repeat: no-repeat; background-size: initial; background: url("../../images/orange-list.a2de725cdb0b.png") 0px 7px no-repeat !important; border: none; box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; list-style: none circle; margin: 0px; overflow-wrap: break-word; padding: 0px 0px 0px 15px; vertical-align: baseline;">On-body injector (OBI) for Neulasta is supplied with a prefilled syringe containing 0.64 mL of Neulasta in solution that delivers 0.6 mL of Neulasta in solution when used with the OBI for Neulasta. The syringe does not bear graduation marks and is only to be used with the OBI for Neulasta.</li></ul><p style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 0.8em; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;">The delivered 0.6 mL dose from either the prefilled syringe for manual <b>subcutaneous </b>injection or the OBI for Neulasta contains 6 mg pegfilgrastim (based on protein weight) in a sterile, clear, colorless, preservative-free solution (<b>pH 4.0</b>) containing acetate (0.35 mg), polysorbate 20 (0.02 mg), sodium (0.02 mg), and sorbitol (30 mg) in Water for Injection, USP.</p><p style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 0.8em; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><b>NEUPOGEN (filgrastim)</b> injection is a sterile‚ clear‚ colorless‚ preservative-free liquid containing filgrastim at a specific activity of 1.0 ± 0.6 × 10<span class="Sup" style="border: 0px; box-sizing: border-box; display: inline; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; overflow-wrap: break-word; padding: 0px; vertical-align: super;">8</span> U/mg (as measured by a cell mitogenesis assay). The product is available in single-dose vials for subcutaneous or intravenous use and prefilled syringes for subcutaneous use. The single-dose vials contain either 300 mcg/mL or 480 mcg/1.6 mL of filgrastim. The single-dose prefilled syringes contain either 300 mcg/0.5 mL or 480 mcg/0.8 mL of filgrastim. The NEUPOGEN drug product has a <b>pH of 4.0</b>. See table below for product composition of each single-dose vial or prefilled syringe.</p><div class="scrollingtable" style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 25px; overflow-wrap: break-word; overflow-y: auto; padding: 0px; vertical-align: baseline;"><div class="scrollingtable" style="border: 0px; box-sizing: border-box; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 25px; overflow-wrap: break-word; overflow-y: auto; padding: 0px; vertical-align: baseline;"><table style="border-collapse: collapse; border-spacing: 0px; border: 0px; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 10px 0px 20px; max-width: 600px; overflow-wrap: break-word; padding: 0px; vertical-align: baseline; width: 85%;"><colgroup style="box-sizing: border-box; overflow-wrap: break-word;"><col align="left" style="box-sizing: border-box; overflow-wrap: break-word;" valign="top" width="20%"></col><col align="center" style="box-sizing: border-box; overflow-wrap: break-word;" valign="top" width="20%"></col><col align="center" style="box-sizing: border-box; overflow-wrap: break-word;" valign="top" width="20%"></col><col align="center" style="box-sizing: border-box; overflow-wrap: break-word;" valign="top" width="20%"></col><col align="center" style="box-sizing: border-box; overflow-wrap: break-word;" valign="top" width="20%"></col></colgroup><thead style="border: 0px; box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><tr class="First Last" style="background-color: #eef9ff; border: 0px; box-sizing: border-box; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><th align="left" class="Lrule" style="background: rgb(43, 120, 159); border: 1px solid rgb(0, 0, 0); box-sizing: border-box; color: white; font-family: pt_sansbold, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; text-align: center; vertical-align: baseline;"></th><th align="center" style="background: rgb(43, 120, 159); border: 1px solid rgb(0, 0, 0); box-sizing: border-box; color: white; font-family: pt_sansbold, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; text-align: center; vertical-align: baseline;">300 mcg/mL Vial</th><th align="center" style="background: rgb(43, 120, 159); border: 1px solid rgb(0, 0, 0); box-sizing: border-box; color: white; font-family: pt_sansbold, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; text-align: center; vertical-align: baseline;">480 mcg/1.6 mL Vial</th><th align="center" style="background: rgb(43, 120, 159); border: 1px solid rgb(0, 0, 0); box-sizing: border-box; color: white; font-family: pt_sansbold, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; text-align: center; vertical-align: baseline;">300 mcg/0.5 mL Syringe</th><th align="center" class="Rrule" style="background: rgb(43, 120, 159); border: 1px solid rgb(0, 0, 0); box-sizing: border-box; color: white; font-family: pt_sansbold, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; text-align: center; vertical-align: baseline;">480 mcg/0.8 mL Syringe</th></tr></thead><tfoot style="border: none; box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><tr style="background-color: #eef9ff; border: none; box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><td align="left" colspan="5" style="background-color: white; border: none; box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;"><dl class="Footnote" style="border: 0px; box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; overflow-wrap: break-word; overflow: hidden; padding: 0px; vertical-align: baseline; width: 512.903px;"><dt style="border: 0px; box-sizing: border-box; float: left; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; overflow-wrap: break-word; padding: 0px; vertical-align: baseline; width: 10.25px;"><a href="https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=97cc73cc-b5b7-458a-a933-77b00523e193#footnote-reference-3" name="footnote-3" style="border: 0px; box-sizing: border-box; color: #1d86bb; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; overflow-wrap: break-word; padding: 0px; text-transform: uppercase; vertical-align: baseline;">*</a></dt><dd style="border: none; box-sizing: border-box; float: left; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; list-style-type: none; margin: 0px; overflow-wrap: break-word; padding: 0px 0px 0px 15px; vertical-align: baseline; width: 502.639px;">quantity sufficient to make.</dd></dl></td></tr></tfoot><tbody style="border: 0px; box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><tr class="First" style="background-color: #eef9ff; border: 0px; box-sizing: border-box; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><td align="left" class="Lrule" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">filgrastim</td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">300 mcg</td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">480 mcg</td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">300 mcg</td><td align="center" class="Rrule" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">480 mcg</td></tr><tr style="border: 0px; box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><td align="left" class="Lrule" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">acetate</td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">0.59 mg</td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">0.94 mg</td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">0.295 mg</td><td align="center" class="Rrule" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">0.472 mg</td></tr><tr style="background-color: #eef9ff; border: 0px; box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><td align="left" class="Lrule" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">polysorbate 80</td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">0.04 mg</td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">0.064 mg</td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">0.02 mg</td><td align="center" class="Rrule" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">0.032 mg</td></tr><tr style="border: 0px; box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><td align="left" class="Lrule" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">sodium</td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">0.035 mg</td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">0.056 mg</td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">0.0175 mg</td><td align="center" class="Rrule" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">0.028 mg</td></tr><tr style="background-color: #eef9ff; border: 0px; box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><td align="left" class="Lrule" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">sorbitol</td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">50 mg</td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">80 mg</td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">25 mg</td><td align="center" class="Rrule" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">40 mg</td></tr><tr style="border: 0px; box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><td align="left" class="Lrule" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">water for Injection</td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;"></td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;"></td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;"></td><td align="center" class="Rrule" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;"></td></tr><tr class="Last" style="background-color: #eef9ff; border: 0px; box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><td align="left" class="Lrule" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">USP q.s. ad<a class="Sup" href="https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=97cc73cc-b5b7-458a-a933-77b00523e193#footnote-3" name="footnote-reference-3" style="border: 0px; box-sizing: border-box; color: #1d86bb; display: inline; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; overflow-wrap: break-word; padding: 0px; text-transform: uppercase; vertical-align: super;">*</a></td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">1 mL</td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">1.6 mL</td><td align="center" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">0.5 mL</td><td align="center" class="Rrule" style="border: 1px solid rgb(0, 0, 0); box-sizing: border-box; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; font-weight: inherit; line-height: inherit; margin: 0px; min-width: 75px; overflow-wrap: break-word; padding: 6px; vertical-align: top;">0.8 mL</td></tr></tbody></table><b>REMICADE<span class="Bold" style="border: 0px; box-sizing: border-box; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px; overflow-wrap: break-word; padding: 0px; vertical-align: baseline;"><span class="Sup" style="border: 0px; box-sizing: border-box; display: inline; font-family: inherit; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px; overflow-wrap: break-word; padding: 0px; vertical-align: super;">®</span></span> (infliximab)</b> for injection is supplied as a sterile, preservative-free, white, <b>lyophilized powder</b> for <b>intravenous</b> infusion after reconstitution and dilution. Following reconstitution with 10 mL of Sterile Water for Injection, USP, the final concentration is 10 mg/mL and the resulting <b>pH is approximately 7.2.</b> Each single-dose vial contains 100 mg infliximab, dibasic sodium phosphate, dihydrate (6.1 mg), monobasic sodium phosphate, monohydrate (2.2 mg), polysorbate 80 (0.5 mg), and sucrose (500 mg).</div><div class="scrollingtable" style="border: 0px; box-sizing: border-box; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 25px; overflow-wrap: break-word; overflow-y: auto; padding: 0px; vertical-align: baseline;"><b>RITUXAN (rituximab)</b> injection is a sterile, preservative-free, clear, colorless solution for intravenous infusion. RITUXAN is supplied at a concentration of 10 mg/mL in either 100 mg/10 mL or 500 mg/50 mL single-dose vials. Each mL of solution contains 10 mg rituximab, polysorbate 80 (0.7 mg), sodium chloride (9 mg), sodium citrate dihydrate (7.35 mg), and Water for Injection, USP. The <b>pH is 6.5</b>.</div><div class="scrollingtable" style="border: 0px; box-sizing: border-box; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 25px; overflow-wrap: break-word; overflow-y: auto; padding: 0px; vertical-align: baseline;"><br /></div><div class="scrollingtable" style="border: 0px; box-sizing: border-box; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 25px; overflow-wrap: break-word; overflow-y: auto; padding: 0px; vertical-align: baseline;"><b>MISTAKES MIGHT HAPPEN. FOR ACCURACY AND DETAILS, PLEASE REVIEW THE RELATED SCIENTIFIC ARTICLES AND PRODUCT INSERTS.</b></div></div><div class="scrollingtable" style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-size: 14px; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 25px; overflow-wrap: break-word; overflow-y: auto; padding: 0px; vertical-align: baseline;"><br /></div><div class="scrollingtable" style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-size: 14px; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 25px; overflow-wrap: break-word; overflow-y: auto; padding: 0px; vertical-align: baseline;"><br /></div><div class="scrollingtable" style="background-color: white; border: 0px; box-sizing: border-box; color: #222222; font-family: pt_sansregular, Arial, sans-serif; font-feature-settings: inherit; font-kerning: inherit; font-optical-sizing: inherit; font-size: 14px; font-stretch: inherit; font-variant-alternates: inherit; font-variant-east-asian: inherit; font-variant-numeric: inherit; font-variant-position: inherit; font-variation-settings: inherit; line-height: inherit; margin: 0px 0px 25px; overflow-wrap: break-word; overflow-y: auto; padding: 0px; vertical-align: baseline;"><br /></div></div></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-13300753327234666252024-02-03T03:14:00.000-08:002024-02-03T03:14:21.400-08:00OVERVIEW: Pfizer's Biosimilar Products<p>Here is a list of Pfizer's biosimilar products:</p><p><b>Proper Name Proprietary Name Reference Approval</b></p><p>Infliximab-dyyb Inflectra REMICADE (infliximab) 2016</p><p>Filgrastim-aafi Nivestym NEUPOGEN (filgrastim) 2018</p><p>Epoetin alfa-epbx Retacrit EPOGEN/PROCRIT (epoetin alfa) 2018</p><p>Rituximab-pvvr Ruxience RITUXAN (rituximab) 2019</p><p>Trastuzumab-qyyp Trazimera HERCEPTIN (trastuzumab) 2019</p><p>Bevacizumab-bvzr Zirabev AVASTIN (bevacizumab) 2019</p><p>Adalimumab-afzb Abrilada HUMIRA (adalimumab) 2019</p><p>Pegfilgrastim-apgf Nyvepria NEULASTA (pegfilgrastim) 2020</p><p><br /></p><p>As of Feb 2, 2024, the competitors of Pfrizer's first biosimilar product, INFLECTRA is summarized as follows:</p><p><b><u>Reference Product: Infliximab (Remicade)</u></b></p><p><b>Product Proper Name Proprietary Applicant BLA Strength Presentation Route</b></p><p>Reference Infliximab Remicade Centocor Inc. 103772 100 mg, single dose vial, i.v.</p><p>Biosimilar Infiximab-AXXQ Avsola Amgen Inc. 761086 100 mg, single dose vial, i.v.</p><p>Biosimilar Infiximab-DYYB Inflectra Celltrion Inc. 12554 100 mg, single dose vial, i.v.</p><p>Biosimilar Infiximab-ABDA Renflexis Samsung Bioepis 761054 100 mg, single dose vial, i.v.</p><p>Biosimilar Infliximab-QBTX Ixifi Pfizer Inc. 761072 100 mg, single dose vial, i.v.</p><p>The approval date for Avsola is 12/06/2019, Inflectra 04/05/2016, Renflexis Renflexis 04/21/2017 and Ixifi 12/13/2017. </p><p><b><u>Reference Product: Infliximab-DYYB (Zymfentra)</u></b></p><p>Reference Infliximab-DYYB Zymfentra Celltrion, Inc. 761358 120 mg/ml pre-filled syringe</p><p> autoinjector, subcutaneous</p><p>approval date: 10/20/2023.</p><p><br /></p><p>As of Feb 2, 2024, the competitors of Pfrizer's biosimilar product approved in 2020, NEUPOGEN is summarized as follows:</p><p><b><u>Reference Product: Filgrastim (NEUPOGEN) ; Approval: 1991</u></b></p><p><b>Product Proper Name Proprietary Applicant BLA Strength Presentation </b></p><p>Reference Filgrastim NEUPOGEN Amgen 103353 300mcg/1ml vial</p><p>Reference Filgrastim NEUPOGEN Amgen 103353 480mcg/1.6ml vial</p><p>Reference Filgrastim NEUPOGEN Amgen 103353 300mcg/0.5ml syringe</p><p>Reference Filgrastim NEUPOGEN Amgen 103353 400mcg/0.8ml syringe</p><p>Biosimilar Filgrastim-aafi NIVESTYM Pfizer 761080 300mcg/1ml vial (i.v. & s.c.)</p><p>Biosimilar Filgrastim-aafi NIVESTYM Pfizer 761080 480mcg/1.6ml vial (i.v. & s.c.)</p><p>Biosimilar Filgrastim-aafi NIVESTYM Pfizer 761080 300mcg/0.5ml syringe (s.c.)</p><p>Biosimilar Filgrastim-aafi NIVESTYM Pfizer 761080 400mcg/0.5ml syringe (s.c.)</p><p>Biosimilar Filgrastim-ayow RELEUKO Kashiv Bios. 761082 300mcg/1ml vial (i.v. & s.c.)</p><p>Biosimilar Filgrastim-ayow RELEUKO Kashiv Bios. 761082 480mcg/1.6ml vial (i.v. & s.c.)</p><p>Biosimilar Filgrastim-ayow RELEUKO Kashiv Bios. 761082 300mcg/0.5ml syringe (s.c.)</p><p>Biosimilar Filgrastim-ayow RELEUKO Kashiv Bios. 761082 400mcg/0.5ml syringe (s.c.)</p><p>Biosimilar Figrastim-sndz ZARXIO Sandoz Inc. 125553 300mcg/1ml vial (i.v. & s.c.)</p><p>Biosimilar Figrastim-sndz ZARXIO Sandoz Inc. 125553 480mcg/1ml vial (i.v. & s.c.)</p><p><br /></p><p>In addition to these Biosimilars, NEUPOGEN also faces a limited competition from GRANIX (tbo-filgrastim) and NEULASTA/NEULASTA ONPRO (pegfilgrastim) together with their biosimilars. NEUPOGEN, GRANIX and NEULASTAs' indications are summarized as follows:</p><p><br /></p><p><b><span style="font-size: medium;">INDICATIONS ANDA USE - NEUPOGEN, GRANIX and NEULASTA</span></b></p><p><b>NEUPOGEN is a leukocyte growth factor indicated to</b></p><p>• Decrease the incidence of infection‚ as manifested by febrile <b>neutropenia</b>‚ in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever</p><p>• Reduce the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML) </p><p>• Reduce the duration of <b>neutropenia</b> and neutropenia-related clinical sequelae‚ e.g.‚ febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation (BMT) </p><p>• Mobilize autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis</p><p>• Reduce the incidence and duration of sequelae of severe <b>neutropenia</b> (e.g.‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia</p><p>• Increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome) </p><p><b>GRANIX (tbo-filgrastim) is a leukocyte growth factor indicated</b> in adult and pediatric patients 1 month and older for reduction in the duration of severe <b>neutropenia</b> in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia. </p><p><b>Neulasta is a leukocyte growth factor indicated to: </b></p><p>• Decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. </p><p>• Increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Subsyndrome of Acute Radiation Syndrome). </p><p><br /></p><p>MISTAKES MIGHT HAPPEN DURING THE PREPARATION OF THIS ARTICLE. FOR ACCURACY AND DETAILS, PLEASE CHECK WITH FDA PURPLEBOOK AND RELATED INFORMATION SOURCES. </p><p><b>Reference</b></p><p>1. <a href="https://biosimilars.pfizerpro.com/">https://biosimilars.pfizerpro.com/</a></p><p><br /></p><p><br /></p><p><br /></p>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-36991941661396094362024-02-02T04:02:00.000-08:002024-02-02T04:02:56.888-08:00Overview: mRNA vaccine - its key players, manufacturing and development process<div>mRNA vaccines have been at the forefront of medical innovation, especially during the COVID-19 pandemic. Here are general ideas of mRNA manufacturing and development process, and its key players:</div><div><br /></div><div><b><span style="font-size: medium;">MANUFACTURING OF A mRNA VACCINE</span></b></div><div><br /></div><div>The manufacturing process for mRNA vaccines is fascinating and represents a significant leap in medical technology. Here is a summary of its manufacturing process:</div><div><br /></div><div><b>In Vitro Synthesis: </b>Unlike traditional protein expression, where cloning and amplification steps are time-consuming, mRNA is produced through an enzymatic in vitro synthesis process. This means there’s no need to remove cells or host cell proteins. The simplicity of this process allows for rapid adaptation to new protein targets, making it highly versatile.</div><div><br /></div><div><b>mRNA Sequence Insertion: </b>The heart of mRNA vaccine production lies in inserting a snippet of RNA code into a small DNA molecule within a cell. This process can be used for any mRNA sequence, making it remarkably flexible.</div><div><br /></div><div><b>Reactor Tank Growth:</b> Once the RNA code is inserted, the cell quickly grows more mRNA in a reactor tank. This streamlined approach contrasts with the customized, iterative setups required for conventional vaccines.</div><div><br /></div><div><b>Purification and Formulation:</b> Downstream processing involves purifying the mRNA product. One of the key advantages of mRNA vaccines is their sequence-independent manufacturing, which simplifies both upstream and downstream steps. This includes <b>lipid nanoparticle</b> (<b>LNP</b>) formulation and fill/finish processes.</div><div><br /></div><div><b><span style="font-size: medium;">DEVELOPMENT OF A mRNA VACCINE</span></b></div><div><br /></div><div>The development of mRNA vaccines involves several crucial steps:</div><div><br /></div><div><b>Design: </b>At the onset of the COVID-19 pandemic, researchers rapidly sequenced the SARS-CoV-2 virus using state-of-the-art genomic sequencers. Scientists identified the spike protein gene as the vaccine candidate. The spike protein is important for the virus to attach to host cells.</div><div><br /></div><div>Using in-vitro protocols, scientists create mRNA that mimics our natural biological processes. They separate the two strands of plasmid DNA and use RNA polymerase to transcribe the spike protein gene into a single mRNA molecule. This process closely resembles how our genes are transcribed. mRNA is a molecule that carries instructions from DNA to
the cell's protein-making machinery.</div><div><p data-sourcepos="9:1-9:18"><strong>Production: </strong>The designed mRNA is then produced in
large quantities in the laboratory. This is done using a process called
in vitro transcription (IVT). IVT uses enzymes to copy the mRNA
sequence from a DNA template. The resulting mRNA is then purified to
remove any unwanted contaminants.</p><p data-sourcepos="15:1-15:19"><strong>Formulation: </strong>The purified mRNA is then formulated into
a vaccine. This involves packaging the mRNA in a protective delivery
system, such as lipid nanoparticles (LNPs). LNPs are tiny spheres made
of fat molecules that help to protect the mRNA from degradation and
deliver it to cells. </p><p data-sourcepos="15:1-15:19">most mRNA vaccines currently require ultra-cold storage to prevent degradation.</p><p data-sourcepos="20:1-20:27"><strong>Preclinical testing: </strong>Once the vaccine has been formulated, it
is tested in animals to assess its safety and efficacy. This is called
preclinical testing.</p><p data-sourcepos="26:1-26:23"><strong>Clinical trials: </strong>Clinical trials are studies that are conducted in humans to test the safety and efficacy of a vaccine.</p><p data-sourcepos="26:1-26:23"><strong>Regulatory approval: </strong>If a vaccine is safe and effective in clinical trials, it can be submitted to regulatory agencies for approval.</p></div><div><br /></div><div><span style="font-size: medium;">SOME KEY PLAYERS</span></div><div><br /></div><div><b><a href="https://www.biontech.com/int/en/home.html" target="_blank">BioNTech</a>:</b> A German biotechnology company that collaborated with Pfizer to develop one of the first authorized mRNA COVID-19 vaccines1.</div><div><br /></div><div><a href="https://www.modernatx.com/en-US" target="_blank"><b>Moderna Therapeutics</b>:</a> An American biotech company that developed another highly effective mRNA COVID-19 vaccine.</div><div><br /></div><div><a href="https://www.pfizer.com/" target="_blank"><b>Pfizer:</b> </a>Partnered with BioNTech to produce the BNT162b2 COVID-19 vaccine, which is an mRNA-based vaccine.</div><div><br /></div><div><b><a href="https://www.greenlightbiosciences.com/" target="_blank">GreenLight Biosciences:</a> </b>GreenLight Biosciences is a US company, headquartered in Lexington, Massachusetts. They are a public-benefit corporation. Products include Calaritha, Varroa destructor mite-control product and a pipeline of other RNA-based solutions.</div><div><br /></div><div><b><a href="https://www.strandtx.com/" target="_blank">Strand Therapeutics:</a> </b>Strand Therapeutics is a US company. Based in Boston, Massachusetts, they focus on developing programmable mRNA therapeutics for various diseases, with a current emphasis on cancer.</div><div><br /></div><div><span style="font-size: large;">T</span>hese companies have played pivotal roles in advancing mRNA technology for both vaccines and therapeutics. Additionally, there are ongoing clinical trials exploring mRNA-based treatments for various diseases, including cancer and cardiovascular conditions. The potential of mRNA technology continues to expand, and researchers and industry players are actively enhancing their tools and technologies to harness its power.</div><div><br /></div><div><b><span style="font-size: medium;">HOW DOES A mRNA VACCINE WORK?</span></b></div><div><br /></div><div class="separator" style="clear: both; text-align: center;"><iframe allowfullscreen="" class="BLOG_video_class" height="454" src="https://www.youtube.com/embed/w4sUuFBEo2g" width="545" youtube-src-id="w4sUuFBEo2g"></iframe></div><br /><div><br /></div><div><b><br /></b></div><div><b>This article describes the general aspects of mRNA vaccine manufacturing and development. For accuracy and details for particular products, please check with the related scientific articles and patent applications, and related resources. </b></div><div><b><br /></b></div><div><br /></div><div><b><span style="font-size: medium;">REFERENCE</span></b></div><div><br /></div><div>Ivana Knezevic, Development of mRNA Vaccines: Scientific and Regulatory Issues, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910833/" target="_blank">Vaccines (Basel)</a>. 2021 Feb; 9(2): 81 </div><div><br /></div><div>Yongjun Liang, et al, Development and Delivery Systems of mRNA Vaccines, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354200/" target="_blank">Front Bioeng Biotechnol.</a> 2021; 9: 718753.</div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-29088831825160381502024-02-01T09:49:00.000-08:002024-02-01T09:49:46.795-08:00Impact of Continuous Manufacturing Processes on the Viral Safety of Therapeutic Proteins<p><b>Shifting Therapeutic Protein Drug Substance Manufacturing Paradigms</b></p><div class="col-md-8 col-md-push-2" role="main"><p>While traditional therapeutic protein manufacturing involves producing the protein in engineered cells followed by purification to remove product- and process-related impurities, including potentially infectious viral particles (such as retrovirus-like particles, RVLPs). Guidance document ICH Q5A takes a three-pronged approach to address viral safety risks: i) starting material testing (i.e., cell bank testing), ii) raw materials and intermediates testing, and iii) viral clearance testing during the purification process. The purification process includes both non-dedicated (i.e., chromatography) and dedicated virus clearance steps (i.e., chemical inactivation and virus filtration) to effectively clear RVLPs (and any possible viral contaminants) from the final drug product.</p><p>The emerging continuous manufacturing approach necessitates new strategies. <b>This integration of production and purification allows for shorter processing times, reduced manual intervention, and a reduction in facility size</b> through the use of smaller tanks, bioreactors, and columns. However, continuous manufacturing continuously purifies the protein during production, posing unique challenges for ensuring viral safety. Regulatory frameworks and testing methods developed for traditional methods may not directly translate to continuous manufacturing, hence the need for ongoing research and collaboration between manufacturers and regulators to establish robust viral safety measures for this innovative approach.</p><p><b>CDER Researchers' Study</b></p><div _ngcontent-ng-c568490658="" class="avatar-gutter ng-tns-c568490658-138 ng-star-inserted"><recitations-gutter _ngcontent-ng-c568490658="" _nghost-ng-c1710824384="" class="ng-tns-c568490658-138 ng-trigger ng-trigger-hideElement ng-star-inserted" style="opacity: 1;"><div _ngcontent-ng-c1710824384="" class="resize-observable"></div></recitations-gutter></div><div _ngcontent-ng-c568490658="" class="response-container-content ng-tns-c568490658-138" selection=""><div _ngcontent-ng-c4025454317="" class="response-content ng-trigger ng-trigger-responsePopulation ng-tns-c568490658-138"><message-content _ngcontent-ng-c4025454317="" _nghost-ng-c3817193527="" class="model-response-text ng-tns-c4025454317-137 ng-star-inserted" id="message-content-id-r_f6ad1cb23430e043" style="height: auto;"><div _ngcontent-ng-c3817193527="" class="markdown markdown-main-panel" dir="ltr" style="--animation-duration: 600ms; --fade-animation-function: cubic-bezier(0.05, 0.7, 0.91, 1);"><p data-sourcepos="1:1-1:412">Continuous manufacturing (CM) presents unique challenges for ensuring viral safety due to its dynamic nature compared to traditional batch processing. To address this, CDER researchers identified three key steps in CM: capture chromatography, viral inactivation, and viral filtration. They adapted existing batch-based methods to these continuous steps, developing small-scale models for studying their effectiveness.</p>
<p data-sourcepos="3:1-3:53">One focus area was <b>continuous capture chromatography</b>, which uses multiple columns cycled through various stages. Initial concerns existed about its impact on viral safety. However, side-by-side comparisons with batch processing showed similar viral clearance capabilities, suggesting minimal impact and the feasibility of using simulated batch-based models for evaluation.</p>
<p data-sourcepos="5:1-5:169">This research highlights the ongoing efforts to ensure viral safety in continuous manufacturing and the development of appropriate testing methods for this innovative manufacturing approach.</p><p data-sourcepos="1:1-1:221">Similar to capture chromatography, <b>continuous viral filtration</b> in continuous manufacturing raises concerns due to its unique operating features. These include longer processing times, fluctuating product streams, and continuous flow instead of pressure. Researchers addressed this by developing two small-scale models mimicking specific aspects of continuous filtration.</p><p data-sourcepos="3:1-3:105">One model simulated longer processing times and volume throughput. Over four days, it maintained pressure within limits and effectively cleared the viral surrogate, demonstrating the feasibility of long-term continuous filtration.</p><p data-sourcepos="5:1-5:193">The other model focused on dynamic product streams, replicating fluctuations in protein and virus concentration. While pressure was affected, viral clearance remained robust, suggesting minimal impact on safety.</p><p data-sourcepos="5:1-5:169">
</p><p data-sourcepos="7:1-7:184">These protein-specific models provide a starting point for understanding continuous filtration and can be adapted to different systems, ensuring viral safety as continuous manufacturing technology advances.</p><p data-sourcepos="7:1-7:184"><b>Conclusion</b></p></div></message-content></div></div><p data-sourcepos="1:1-1:297">As continuous manufacturing gains traction for therapeutic proteins, limited research exists on ensuring their viral safety. This study provides valuable insights for both internal and external stakeholders, shedding light on potential concerns and methods for safe development using continuous manufacturing. With increasing submissions incorporating continuous manufacturing elements, readily available FDA expertise and public examples become crucial for successful implementation and regulatory evaluation. This research aligns with the Emerging Technology Program's goals, paving the way for safe and efficient continuous manufacturing adoption.</p><p> <strong style="font-size: small;">Figure 1.</strong><span style="font-size: small;"> Comparison of batch manufacturing to continuous manufacturing. (Credit: FDA)</span></p><hr /><div alt="Figure 1. Comparison of batch manufacturing to continuous manufacturing" class="align-center embedded-entity" data-embed-button="media_browser" data-entity-embed-display="media_image" data-entity-type="media" data-entity-uuid="c51d0552-f2a6-4f04-bc94-e11d50ca55ad" data-langcode="en" title="Figure 1. Comparison of batch manufacturing to continuous manufacturing"><img alt="Figure 1. Comparison of batch manufacturing to continuous manufacturing" class="img-responsive" height="455" loading="lazy" src="https://www.fda.gov/files/figure1-impact.png" title="Figure 1. Comparison of batch manufacturing to continuous manufacturing" width="667" /></div><p><br /></p><div class="callout"><h2><br /></h2></div><h3><br /></h3><div><br /></div><div><b>Original Document: Impact of Continuous Manufacturing Processes on the Viral Safety of Therapeutic Proteins, FDA website, Feb. 01, 2024. (For accuracy and details, please visit <a href="https://www.fda.gov/drugs/regulatory-science-action/impact-continuous-manufacturing-processes-viral-safety-therapeutic-proteins" target="_blank">FDA website</a>.)</b></div></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-59400130118355046182024-02-01T05:55:00.000-08:002024-02-01T05:55:45.309-08:00Antibody Manufacturing Process: An Overview<p><span style="font-family: arial;"><span style="font-size: large;">T</span>he antibody manufacturing process, regardless of the specific antibody like ustekinumab, can be broadly divided into <strong>upstream</strong> and <strong>downstream</strong> processing:</span></p>
<p data-sourcepos="5:1-5:24"><strong><span style="font-family: arial;">Upstream Processing:</span></strong></p>
<ol data-sourcepos="7:1-19:0">
<li data-sourcepos="7:1-11:0">
<p data-sourcepos="7:4-7:29"><strong><span style="font-family: arial;">Cell Line Development:</span></strong></p>
<ul data-sourcepos="8:5-11:0">
<li data-sourcepos="8:5-8:106"><span style="font-family: arial;">Isolate specific B cells producing the desired antibody from immunized animals or humanized systems.</span></li>
<li data-sourcepos="9:5-9:97"><span style="font-family: arial;">Create immortalized cell lines (hybridoma or recombinant) that stably produce the antibody.</span></li>
<li data-sourcepos="10:5-11:0"><span style="font-family: arial;">Optimize cell line growth and antibody production in bioreactors.</span></li>
</ul>
</li>
<li data-sourcepos="12:1-15:0">
<p data-sourcepos="12:4-12:37"><strong><span style="font-family: arial;">Cell Culture and Fermentation:</span></strong></p>
<ul data-sourcepos="13:5-15:0">
<li data-sourcepos="13:5-13:140"><span style="font-family: arial;">Large-scale cultivation of
the selected cell line in controlled bioreactors with optimal
conditions for efficient antibody production.</span></li>
<li data-sourcepos="14:5-15:0"><span style="font-family: arial;">Monitoring and adjusting various parameters like nutrients, pH, temperature, and oxygen levels.</span></li>
</ul>
</li>
<li data-sourcepos="16:1-19:0">
<p data-sourcepos="16:4-16:33"><strong><span style="font-family: arial;">Harvest and Clarification:</span></strong></p>
<ul data-sourcepos="17:5-19:0">
<li data-sourcepos="17:5-17:73"><span style="font-family: arial;">Harvesting the cell culture broth containing the produced antibody.</span></li>
<li data-sourcepos="18:5-19:0"><span style="font-family: arial;">Removing cellular debris and other impurities through centrifugation and filtration.</span></li>
</ul>
</li>
</ol>
<p data-sourcepos="20:1-20:26"><strong><span style="font-family: arial;">Downstream Processing:</span></strong></p>
<ol data-sourcepos="22:1-23:44" start="4">
<li data-sourcepos="22:1-23:44">
<p data-sourcepos="22:4-22:32"><strong><span style="font-family: arial;">Capture and Purification:</span></strong></p>
<ul data-sourcepos="23:5-25:0">
<li data-sourcepos="23:5-23:106"><span style="font-family: arial;">Employing chromatography techniques to capture the target antibody with high specificity and purity.</span></li>
<li data-sourcepos="24:5-25:0"><span style="font-family: arial;">Sequential steps like protein A chromatography, ion exchange, and size exclusion chromatography.</span></li>
</ul>
</li>
<li data-sourcepos="26:1-30:0">
<p data-sourcepos="26:4-26:37"><strong><span style="font-family: arial;">Concentration and Formulation:</span></strong></p>
<ul data-sourcepos="27:5-30:0">
<li data-sourcepos="27:5-27:72"><span style="font-family: arial;">Concentrating the purified antibody solution to the desired level.</span></li>
<li data-sourcepos="28:5-28:104"><span style="font-family: arial;">Adding stabilizing excipients (salts, sugars) and buffers to maintain stability and functionality.</span></li>
<li data-sourcepos="29:5-30:0"><span style="font-family: arial;">Sterile filtration and filling into vials or syringes.</span></li>
</ul>
</li>
<li data-sourcepos="31:1-34:0">
<p data-sourcepos="31:4-31:23"><strong><span style="font-family: arial;">Quality Control:</span></strong></p>
<ul data-sourcepos="32:5-34:0">
<li data-sourcepos="32:5-32:86"><span style="font-family: arial;">Extensive testing to ensure the final product meets stringent quality standards.</span></li>
<li data-sourcepos="33:5-34:0"><span style="font-family: arial;">Purity, potency, activity, and absence of contaminants are rigorously assessed.</span></li>
</ul>
</li>
</ol>
<p data-sourcepos="35:1-35:34"><strong><span style="font-family: arial;">Critical Steps and Parameters:</span></strong></p>
<ul data-sourcepos="37:1-40:69">
<li data-sourcepos="37:1-37:123"><span style="font-family: arial;"><strong>Cell line stability and performance:</strong> Maintaining consistent antibody production throughout the manufacturing process.</span></li>
<li data-sourcepos="38:1-38:142"><span style="font-family: arial;"><strong>Bioreactor conditions:</strong> Precise control of pH, temperature, nutrients, and oxygen levels for optimal cell growth and antibody production.</span></li>
<li data-sourcepos="39:1-39:115"><span style="font-family: arial;"><strong>Purification efficiency:</strong> Minimizing losses while ensuring high purity and specificity of the target antibody.</span></li>
<li data-sourcepos="40:1-40:69"><span style="font-family: arial;"><strong>Sterility and control of contaminants:</strong> Preventing contamination throughout the process to ensure a safe and pure product.</span></li>
<li data-sourcepos="41:1-42:0"><span style="font-family: arial;"><strong>Process consistency and scalability:</strong> Establishing robust and reproducible protocols for large-scale manufacturing.</span></li>
</ul>
<p data-sourcepos="43:1-43:321"><span style="font-family: arial;">It's important to note that this is a simplified overview, and the specific steps and parameters involved may vary depending on the specific antibody and desired characteristics. Additionally, advancements in technologies are constantly evolving, influencing the manufacturing process for improved efficiency and quality.</span></p><p data-sourcepos="43:1-43:321"><br /></p><p data-sourcepos="43:1-43:321"><br /></p><p data-sourcepos="43:1-43:321"></p><div class="separator" style="clear: both; text-align: center;"><br /></div><div class="separator" style="clear: both; text-align: center;"><br /></div><div class="separator" style="clear: both; text-align: center;"><a href="https://www.astrazeneca.com/content/dam/az/wscd/covid-19/manufacturingmonoclonalantibodies_v3.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="450" data-original-width="800" height="366" src="https://www.astrazeneca.com/content/dam/az/wscd/covid-19/manufacturingmonoclonalantibodies_v3.png" width="651" /></a></div><br /><div class="separator" style="clear: both; text-align: center;"><br /></div><br /><b>Picture Credit: AstraZeneca</b><p></p><p data-sourcepos="43:1-43:321"><br /></p><p data-sourcepos="43:1-43:321"><br /></p>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-42040653778475171842024-02-01T04:57:00.000-08:002024-02-02T11:54:15.502-08:00Players in Biosimilar Industry<p><b> Alvotech</b> is a prominent player in the biosimilar industry, but many other companies are also vying for a share of this rapidly growing market. Here are some of the key players to watch:</p>
<p data-sourcepos="3:1-3:18"><strong>Major players:</strong></p>
<ul data-sourcepos="5:1-13:114">
<li data-sourcepos="5:1-6:21"><strong>Amgen:</strong> A
large American multinational biotechnology company that has developed
and commercialized biosimilars for several high-profile drugs, including Enbrel, Humira, and Rituxan.</li>
<li data-sourcepos="7:1-8:31"><strong>Samsung Bioepis:</strong> A South Korean biopharmaceutical company that is a subsidiary of Samsung Group. It has a strong biosimilars portfolio and has partnered with several other companies to commercialize its products.</li>
<li data-sourcepos="9:1-10:22"><strong>Biogen:</strong> An American multinational biotechnology company that has developed and commercialized several biosimilars, including Rituxan and Neupogen.</li>
<li data-sourcepos="11:1-12:22"><strong>Pfizer:</strong> An American multinational pharmaceutical company that has developed and commercialized several biosimilars, including Inflectra and Eprex/Januvia.</li>
<li data-sourcepos="13:1-13:114"><strong>Merck:</strong> An American multinational pharmaceutical company that has developed and commercialized several biosimilars, including Lucentis and Renvela.</li>
<li data-sourcepos="15:1-17:0"><strong>Sandoz:</strong> A Swiss multinational pharmaceutical company that is a subsidiary of Novartis. It has a strong biosimilars portfolio and is one of the world's leading suppliers of biosimilars.</li>
</ul>
<p data-sourcepos="18:1-18:21"><strong>Emerging players:</strong></p>
<ul data-sourcepos="20:1-26:161">
<li data-sourcepos="20:1-21:39"><strong>Momenta Pharmaceuticals:</strong> An American biopharmaceutical company that is developing and commercializing biosimilars for several high-profile drugs. (Momenta was recently acquired by Johnson & Johnson.) </li><li data-sourcepos="20:1-21:39"><strong><a href="https://fujifilmdiosynth.com/" target="_blank">Fujifilm Diosynth Biologies</a>:</strong> A Japanese biopharmaceutical company that is contract manufacturing biosimilars for several other companies.</li>
<li data-sourcepos="24:1-25:36"><strong><a href="https://celltrionhealthcare.com/en-us/" target="_blank">Celltrion Healthcare</a>:</strong> A South Korean biopharmaceutical company that is developing and commercializing biosimilars for several high-profile drugs.</li>
<li data-sourcepos="26:1-26:161"><strong>Dr. Reddy's Laboratories:</strong>
An Indian multinational pharmaceutical company that is developing and
commercializing biosimilars for several high-profile drugs.</li>
<li data-sourcepos="28:1-30:0"><strong>Epirus Biopharmaceuticals:</strong> An American biopharmaceutical company that is developing biosimilars for several high-profile drugs. However, it was closed. Epirus has filed for Chapter 7 bankruptcy protection, handed its Remicade (infliximab) biosimilar to <a href="https://www.rellife.com/web/lifesciences/home" target="_blank">Reliance Life Sciences</a>.</li>
</ul>
<p data-sourcepos="31:1-31:253">These are just a few of the many players in the biosimilar industry. The landscape is constantly evolving, and new companies are emerging all the time. As biosimilars become more widely adopted, we can expect to see even more competition in this market.</p>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-81594785703088655382024-02-01T04:31:00.000-08:002024-02-01T04:36:00.666-08:00REVIEW: STELARA® (ustekinumab) injection<div><span style="font-size: large;">U</span>stekinumab, a human IgG1κ monoclonal antibody, is a human interleukin-12 and -23 antagonist. Based on DNA recombinant technology, ustekinumab is produced in a murine cell line. The manufacturing process contains steps for the clearance of viruses. Ustekinumab is comprised of 1326 amino acids and has an estimated molecular mass that ranges from 148,079 to</div><div>149,690 Daltons.</div><div><br /></div><div>Ustekinumab is a human IgG1қ monoclonal antibody that binds with specificity to the p40 protein subunit used by both the IL-12 and IL-23 cytokines. IL-12 and IL-23 are naturally occurring cytokines that are involved in inflammatory and immune responses, such as natural killer cell activation and CD4+ T-cell differentiation and activation. In in vitro models, ustekinumab was shown to disrupt IL-12 and IL-23 mediated signaling and cytokine cascades by disrupting the interaction of these cytokines with a shared cell-surface receptor chain, IL-12Rβ1. The cytokines IL-12 and IL-23 have been implicated as important contributors to the chronic inflammation that is a hallmark of Crohn’s disease and ulcerative colitis. In animal models of colitis, genetic absence or antibody blockade of the p40 subunit of IL-12 and IL-23, the target of ustekinumab, was shown to be protective.</div><div><br /></div><div>In a small exploratory study, a decrease was observed in the expression of mRNA of its molecular targets IL-12 and IL-23 in lesional skin biopsies measured at baseline and up to two weeks post-treatment in subjects with psoriasis.</div><div><br /></div><div>In both study UC-1 (induction) and study UC-2 (maintenance), a positive relationship was observed between exposure and rates of clinical remission, clinical response, and endoscopic improvement. The response rate approached a plateau at the ustekinumab exposures associated with the recommended dosing regimen for maintenance treatment.</div><div><br /></div><div><b>STELARA® (ustekinumab) injection Initial U.S. Approval: 2009</b></div><div><br /></div><div>STELARA® (ustekinumab) injection is a sterile, preservative-free, colorless to light yellow solution and may contain a few small translucent or white particles with pH of 5.7- 6.3.</div><div><br /></div><div><b>INDICATIONS</b></div><div><br /></div><div>STELARA® is a human interleukin-12 and -23 antagonist indicated for the treatment of: Adult patients with:</div><div>• moderate to severe plaque psoriasis (Ps) who are candidates for phototherapy or systemic therapy.</div><div>• active psoriatic arthritis (PsA).</div><div>• moderately to severely active Crohn’s disease (CD).</div><div>• moderately to severely active ulcerative colitis.</div><div>Pediatric patients 6 years and older with:</div><div>• moderate to severe plaque psoriasis, who are candidates for phototherapy or systemic therapy.</div><div>• active psoriatic arthritis (PsA).</div><div><br /></div><div><b>DOSAGE AND ADMINISTRATION</b></div><div><br /></div><div>The psoriasis subcutaneous recommended dosage depends on body weight. For example, weight greater than 100 Kg: 90 mg administered subcutaneously initially and 4 weeks later, followed by 90 mg administered subcutaneously every 12 weeks; weight range (Kg) less than or equal to 100 kg: 45 mg administered subcutaneously initially and 4 weeks later, followed by 45 mg administered subcutaneously every 12 weeks. Even lower dosages are recommended for pediatric patients.</div><div><br /></div><div><b>DOSAGE FORMS AND STRENGTHS</b></div><div><b><br /></b></div><div>STELARA® (ustekinumab) is a colorless to light yellow solution and may contain a few small translucent or white particles.</div><div><br /></div><div><u>Subcutaneous Injection</u></div><div>• Injection: 45 mg/0.5 mL or 90 mg/mL solution in a single-dose prefilled syringe</div><div>• Injection: 45 mg/0.5 mL solution in a single-dose vial</div><div><br /></div><div><u>Intravenous Infusion</u></div><div>• Injection: 130 mg/26 mL (5 mg/mL) solution in a single-dose vial</div><div><br /></div><div><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEiNP4TtyF1ukNgzy6RfyjpbQDaeZCDQ2_CzbFsSPz6UkTsnesK4RibJ6RZ5Bvv1xsHbIhxmZnyqRtXZyzp-pRSHUjF0NeAea0xnOwmyaiJpWKL_vYtyCtiGmyrIinNMrKZbAgns_7HeNd0EWjSvT1EeJf94oRSjxfMCXJq6x2XoC6PjSnidE6vw" style="margin-left: 1em; margin-right: 1em;"><img alt="" data-original-height="242" data-original-width="795" height="185" src="https://blogger.googleusercontent.com/img/a/AVvXsEiNP4TtyF1ukNgzy6RfyjpbQDaeZCDQ2_CzbFsSPz6UkTsnesK4RibJ6RZ5Bvv1xsHbIhxmZnyqRtXZyzp-pRSHUjF0NeAea0xnOwmyaiJpWKL_vYtyCtiGmyrIinNMrKZbAgns_7HeNd0EWjSvT1EeJf94oRSjxfMCXJq6x2XoC6PjSnidE6vw=w609-h185" width="609" /></a></div><br /><br /></div><div><br /></div><div><b>PK</b></div><div><br /></div><div>• Tmax (healthy subjects): 8.5 days</div><div>• Steady-state serum concentrations of ustekinumab (subjects with psoriasis, multiple doses): Week 28</div><div>• Apparent accumulation in serum ustekinumab concentration over time when given subcutaneously every 12 weeks: No</div><div>• half-life (mean): 14.9+/-4.6 to 45.6+/-89.2 days across all psoriasis studies following subcutaneous administration.</div><div><br /></div><div>• The metabolic pathway of ustekinumab has not been characterized. As a human IgG1κ monoclonal antibody, ustekinumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.</div><div><br /></div><div><b>ADVERSE REACTIONS</b></div><div><br /></div><div>Most common adverse reactions are:</div><div>• Psoriasis (≥3%): nasopharyngitis, upper respiratory tract infection, headache, and fatigue.</div><div>• Crohn’s Disease, induction (≥3%): vomiting. </div><div>• Crohn’s Disease, maintenance (≥3%): nasopharyngitis, injection site erythema, vulvovaginal candidiasis/mycotic infection, bronchitis, pruritus, urinary tract infection, and sinusitis. </div><div>• Ulcerative colitis, induction (≥3%): nasopharyngitis </div><div>• Ulcerative colitis, maintenance (≥3%): nasopharyngitis, headache, abdominal pain, influenza, fever, diarrhea, sinusitis, fatigue, and nausea</div><div><br /></div><div><b>MARKET</b></div><div><br /></div><div>Authorization paves way for biosimilar competition in the approximately
€2.5 billion (US$2.7 billion) EU ustekinumab market as soon as possible
after expiry of intellectual-property rights in July 2024.</div><div>(<a href="https://investors.alvotech.com/news-releases/news-release-details/stada-and-alvotech-secure-approval-uzpruvo-europes-first" target="_blank">Alvotech news release</a>, January 10, 2024)</div><div><p data-sourcepos="1:1-1:256">As of today, February 1st, 2024, <strong>one ustekinumab biosimilar is approved in the EU market</strong>. This biosimilar, named <strong>Uzpruvo</strong>, was developed by Alvotech and commercially licensed to STADA. It received marketing authorization in the EU in September 2023.</p><p data-sourcepos="3:1-3:112">Technically, there are 0 ustekinumab biosimilars curretly approved and actively available in the US market.<strong> </strong>However, on October 26, 2023, the FDA approved the first ustekinumab biosimilar called Wezlana (ustekinumab-auub). It's important to note that due to a patent lawsuit, Wezlana's launch is delayed. The applicant for Wezlana (ustekinumab-auub) in the US is Pfizer Inc. The biosimilar was developed by Samsung Bioepis. </p><p data-sourcepos="3:1-3:112">Samsung Bioepis reported that it has signed a settlement and license agreement with Johnson
& Johnson (“J&J”) in the United States relating to SB17, Samsung
Bioepis’s ustekinumab biosimilar to J&J’s STELARA®. If SB17 is
approved by the FDA, the license period in the United States will begin
on February 22, 2025. (<a href="https://www.goodwinlaw.com/en/insights/blogs/2023/12/janssen-and-samsung-bioepis-settle-stelara-ustekinumab-litigation" target="_blank">Goodwin</a>, Dec. 13, 2023)</p><p data-sourcepos="3:1-3:112">On the other hand, Alvotech and Teva Pharmaceuticals Inc. announced that they reached a settlement and license agreement with
Johnson & Johnson regarding AVT04, Alvotech’s proposed biosimilar to
STELARA (ustekinumab) in the United States. “According to the
settlement agreement, AVT04 (ustekinumab) can be marketed in the US,
subject to regulatory approval, no later than February 21, 2025.” (<a href="https://www.goodwinlaw.com/en/insights/blogs/2023/06/alvotech-and-teva-reach-ustekinumab-stelara-settlement-with-jj" target="_blank">Goodwin</a>. June 13, 2023) </p><p data-sourcepos="3:1-3:112">On May 23, 2023, Amgen settled patent lawsuit over biosimilar of J&J's big-selling Stelara. Amgen said that the settlement terms are
confidential, but it will allow the company to sell its biosimilar of
Stelara "no later than January 1st, 2025." (<a href="Amgen settles patent lawsuit over biosimilar of J&J's big-selling Stelara" target="_blank">Reuters</a>, May 23, 2023)</p><p data-sourcepos="3:1-3:112"><br /></p><p data-sourcepos="3:1-3:112"><b>(The content of this article may not be 100% accurate. Please google for updates and details.)</b></p><p data-sourcepos="3:1-3:112"><br /></p><p data-sourcepos="3:1-3:112"><br /></p><p data-sourcepos="1:1-1:256"><br /></p></div><div><br /></div><div><br /></div><div><br /></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-74776738663863398872024-01-31T12:31:00.000-08:002024-01-31T12:31:04.565-08:00REVIEW: VONJO- pacritinib citrate capsule<div><span style="font-size: large;">V</span>ONJO contains pacritinib citrate. Pacritinib is an oral kinase inhibitor with activity against wild type Janus associated kinase 2 (JAK2), mutant JAK2V617F, and FMS-like tyrosine kinase 3 (FLT3), which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. MF is often associated with dysregulated JAK2 signaling. Pacritinib has higher inhibitory activity for JAK2 compared to JAK3 and TYK2. At clinically relevant concentrations, pacritinib does not inhibit JAK1. Pacritinib exhibits inhibitory activity against additional cellular kinases (such as CSF1R and IRAK1) the clinical relevance of which is unknown.It is a citrate salt.</div><div><br /></div><div><b>Appl. No. N208712 Applicant Holder: CTI BIOPHARMA CORP</b></div><div><br /></div><div><br /></div><div>News released on Mar 6, 2023: </div><h1 class="press-release-header__title">CTI BioPharma Reports Fourth Quarter and Full Year 2022 Financial Results </h1><div><b>Highlights:</b></div><div><ul type="disc"><li>FDA approval of VONJO (pacritinib) for the treatment
of adults with intermediate or high-risk primary or secondary
(post-polycythemia vera or post-essential thrombocythemia) myelofibrosis
with a platelet count below 50 × 109/L.</li><li><span class="xn-money">$54 million</span> in net sales in the first nine months following VONJO launch.</li><li>Over 1,000 patients commercially treated with VONJO in 2022.</li><li>Inclusion
in the National Comprehensive Cancer Network® (NCCN®) Clinical Practice
Guidelines in Oncology for Myeloproliferative Neoplasms, with a
recommendation for VONJO as a: First-line treatment option for
higher-risk myelofibrosis patients with platelet counts </li></ul></div><div><br /></div><div><b>INDICATIONS AND USAGE: </b>treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF) with a platelet count below 50 × 109/L.</div><div><br /></div><div><b>DOSAGE AND ADMINISTRATION: </b>200 mg / 100 mg orally twice daily; taken with or without food.</div><div><br /></div><div>Monitoring for Safety is important e.g. CBC, coagulation testing, ECG, prior to and during the treatment.</div><div><br /></div><div><b>ADVERSE REACTIONS</b></div><div><br /></div><div>The following clinically significant adverse reactions are described elsewhere in the labeling:</div><div><br /></div><div>Hemorrhage</div><div>Diarrhea</div><div>Thrombocytopenia</div><div>Prolonged QT Interval</div><div>Major Adverse Cardiac Events</div><div>Thrombosis</div><div>Secondary Malignancies</div><div>Risk of Infection</div><div><br /></div><div>Dose Modification is needed for Adverse Reactions such as diarrhea, thrombocytopenia, hemorrhage, and prolonged QT interval.</div><div><br /></div><div><b>API</b></div><div><br /></div><div><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEiO_3zskBZ8k-H4HQHfGS67jffBjPQviXXJ3bsx_--dCR1l5BlBTkHcSfhbJLbEaNj6Vwo4M1N_mLtQgGjEb2S4OZWzse8yq_U2uMZDIW2ToTojmzoe6XuU2nS-dy-gZmHvo6MKlqDiABl8vhxtvvUDoKq_P-lTXlYeKGETEIGUAsmisjoXXQAF" style="margin-left: 1em; margin-right: 1em;"><img alt="" data-original-height="153" data-original-width="387" height="171" src="https://blogger.googleusercontent.com/img/a/AVvXsEiO_3zskBZ8k-H4HQHfGS67jffBjPQviXXJ3bsx_--dCR1l5BlBTkHcSfhbJLbEaNj6Vwo4M1N_mLtQgGjEb2S4OZWzse8yq_U2uMZDIW2ToTojmzoe6XuU2nS-dy-gZmHvo6MKlqDiABl8vhxtvvUDoKq_P-lTXlYeKGETEIGUAsmisjoXXQAF=w430-h171" width="430" /></a></div><br />Slightly or not soluble in water.</div><div><br /></div><div><b>COMPOSITION / EXCIPIENTS</b></div><div><br /></div><div><b>VONJO</b> capsule is for oral administration. Each capsule contains 100 mg of pacritinib equivalent to 140.65 mg of pacritinib citrate and the inactive ingredients are microcrystalline cellulose NF, polyethylene glycol 8000 (PEG 8000) NF, and magnesium stearate NF. The gelatin capsule is bovine derived. The capsule shell contains gelatin, titanium dioxide, black iron oxide, erythrosine, red iron oxide, and printing ink containing shellac, propylene glycol, titanium dioxide, sodium hydroxide, and povidone.</div><div><b><br /></b></div><div><b>PD</b></div><div>Pacritinib inhibited the phosphorylation of signal transducer and activator of transcription 5 (STAT5) protein in a dose-dependent manner (ex vivo) in expanded erythroid progenitor cells derived from healthy subjects. </div><div><br /></div><div><b>PK</b></div><div>Pharmacokinetics of pacritinib increases in a less than dose-proportional manner. VONJO 200 mg twice daily accumulates 386% and reaches steady-state within a week.</div><div><b>Tmax: </b>4-5 h.</div><div><b>Food Effect: </b>no siginificant effect. (200 mg with a high fat meal)</div><div><b>Plasma Protein Binding: </b>98.8%</div><div><b>Metabolism: </b>CYP3A4 isozyme, metabolite - M1 and M2.</div><div><b>Half-life: </b>27.7 h</div><div><b>Excretion: </b>Following a single oral administration of radiolabeled pacritinib 400 mg in healthy adult subjects, 87% of the radioactivity was recovered in feces, and 6% was recovered in urine. No unchanged drug was excreted in feces and 0.12% of unchanged drug was excreted in urine.</div><div><br /></div><div><b>ORANGE BOOK PATENTS</b></div><div>8153632 (EXP 01/17/2029) - a chemical</div><div>8980873 (EXP 03/25/2030) - a crystal structure (X-ray diffraction peak)</div><div>9573964 (EXP 05/05/2028) - a method of treating a condition</div><div><br /></div><div><br /></div><div><br /></div><div><br /></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-33496069.post-71868237705316608632024-01-31T02:28:00.000-08:002024-01-31T02:28:58.677-08:00REVIEW: AUGTYRO (Repotrectinib Capsule) <div><b>US Appl. No.:</b> N218213 <b>Applicant Holder</b>: Bristol Myer Squibb Co. </div><div><br /></div><div><span style="font-size: large;">R</span>epotrectinib is an inhibitor of proto-oncogene tyrosine-protein kinase ROS1 (ROS1) and of the tropomyosin receptor tyrosine kinases (TRKs) TRKA, TRKB, and TRKC. Repotrectinib exhibited anti-tumor activity in cultured cells expressing ROS1 fusions and mutations including SDC4-ROS1, SDC4-ROS1G2032R, CD74-ROS1, CD74-ROS1G2032R, CD74 ROS1D2033N, and CD74-ROS1L2026M. </div><div><br /></div><div>Pfizer’s Xalkori and Roche’s Rozlytrek are currently approved to target it. Bristol Myers believes Augtyro has an opportunity to roughly double the size of the ROS1 market, which the company has estimated to be around $500 million to $600 million, based on annual revenue from Xalkori and Rozyltrek. (Jonathan Gardner, FDA approves new Bristol Myers drug for lung cancer, www.biopharmadive.com, Nov. 16, 2023)</div><div><br /></div><div><br /></div><div><b>INDICATIONS AND USAGE</b></div><div><br /></div><div>AUGTYRO is indicated for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). </div><div><br /></div><div><b>API</b></div><div>Repotrectinib is a kinase inhibitor. The molecular formula for repotrectinib is C18H18FN5O2 and the molecular weight is 355.37 Daltons. Repotrectinib is a white to off-white powder, slightly or insoluble in water.</div><div><br /></div><div><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEhCKzE0XsO5Qg6AgvLLvXlZMluhmr67gzLoiAV7SIvj5Ga0wQAa1OnuGnsWT3gmhPSf3LbQPHMjI75933Sfh-wgUHdQIa5xw607k9f67N70KS_rOvofMDJjqI0XaPs5XmhVzDMIvdwr-E7-xoPOtIHig0iSlUiFMniCV76KPSXgWOHcRGTRElx9" style="margin-left: 1em; margin-right: 1em;"><img alt="" data-original-height="191" data-original-width="290" height="211" src="https://blogger.googleusercontent.com/img/a/AVvXsEhCKzE0XsO5Qg6AgvLLvXlZMluhmr67gzLoiAV7SIvj5Ga0wQAa1OnuGnsWT3gmhPSf3LbQPHMjI75933Sfh-wgUHdQIa5xw607k9f67N70KS_rOvofMDJjqI0XaPs5XmhVzDMIvdwr-E7-xoPOtIHig0iSlUiFMniCV76KPSXgWOHcRGTRElx9" width="320" /></a></div><br /><br /></div><div><br /></div><div><br /></div><div><br /></div><div><br /></div><div><b>EXCIPIENTS</b></div><div><br /></div><div>AUGTYRO (repotrectinib) capsules for oral use are supplied as printed hard shell capsules containing 40 mg of repotrectinib. Inactive ingredients are microcrystalline cellulose, sodium lauryl sulfate, croscarmellose sodium, and colloidal silicon dioxide. The white opaque capsule shell contains gelatin and titanium dioxide. The printing ink contains shellac and FDC blue #2 aluminum lake.</div><div><br /></div><div><b>DOSAGE AND ADMINISTRATION </b></div><div><br /></div><div>Select patients for the treatment of locally advanced or metastatic NSCLC with AUGTYRO based on the presence of ROS1 rearrangement(s) in tumor specimens. An FDA-approved test to detect ROS1 rearrangements for selecting patients for treatment with AUGTYRO is not currently available. </div><div><br /></div><div>Prior to initiating AUGTYRO, discontinue strong and moderate CYP3A inhibitors for 3 to 5 elimination half-lives of the CYP3A inhibitor.</div><div><br /></div><div>Prior to initiation of AUGTYRO, evaluate liver function tests including bilirubin and uric acid level.</div><div><br /></div><div>The recommended dosage of AUGTYRO is 160 mg taken orally once daily with or without food for 14 days, then increase to <b>160 mg twice daily</b> and continue until disease progression or unacceptable toxicity.</div><div><br /></div><div>Dosage Modifications are needed for adverse reactions.</div><div><br /></div><div><b>Administration</b> </div><div><br /></div><div>Take AUGTYRO at approximately the same time each day with or without food</div><div><br /></div><div><b>PK</b></div><div><br /></div><div>Repotrectinib Cmax and AUC0-inf increases approximately dose proportional over the single dose range of 40 mg to 240 mg. Steady state PK was time-dependent with an autoinduction of CYP3A4. Steady state is achieved within 14 days of daily administration of 160 mg. </div><div><br /></div><div><b>Absorption </b></div><div>The geometric mean (CV%) <b>absolute bioavailability</b> of repotrectinib is 45.7% (19.6%). </div><div><b>Tmax:</b> 2 to 3 hours post a single oral dose of 40 mg to 240 mg under fasted conditions</div><div><b>Food Effect:</b> No clinically significant</div><div><b>Plasma protein blinding:</b> 95.4% in vitro</div><div><b>Repotrectinib elimination:</b> time-dependent due to autoinduction of CYP3A4. </div><div><b>Mean terminal half-life:</b> 50.6 h for patients with cancer following a single dose. </div><div><b>Steady state terminal half-life: </b>35.4 h for patients with cancer. </div><div><b>Metabolism:</b> Repotrectinib is primarily metabolized by CYP3A4 followed by secondary glucuronidation. </div><div><b>Excretion: </b>Following a single oral 160 mg dose of radiolabeled repotrectinib, 4.84% (0.56% as unchanged) was recovered in urine and 88.8% (50.6% unchanged) in feces.</div><div><br /></div><div><b>ADVERSE REACTIONS </b></div><div><br /></div><div>The following clinically significant adverse reactions are described elsewhere in the labeling: </div><div> Central Nervous System Adverse Reactions</div><div> Interstitial Lung Disease (ILD)/Pneumonitis</div><div> Hepatotoxicity</div><div> Myalgia with Creatine Phosphokinase Elevation</div><div> Hyperuricemia</div><div> Skeletal Fractures</div><div> Embryo-Fetal Toxicity</div><div><br /></div><div><b>ORANGE BOOK PATENTS (AS OF 01/31/2024)</b></div><div>9714258 (Exp 01/23/2035): Chemical</div><div>10294242(Exp 07/05/2036): A crystalline polymorph form</div><div>11452725(Exp 07/24/2036): A method of treating a cancer</div>Unknownnoreply@blogger.com0