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2016年3月4日，美国FDA批准新药三合一复合剂（R/F/TAF）Odefsey®(emtricitabine，恩曲他滨200mg/rilpivirine，利匹韦林25 mg/tenofovir alafenamide 25mg or R/F/TAF)治疗HIV-1感染的患者。
恩曲他滨和tenofovir alafenamide来自吉利德，rilpivirine来自Janssen。Odefsey是基于TAF为基础的治疗，是吉利德获得的第二个关于TAF的FDA批准，也是单一片剂治疗HIV的最小片剂的代表。以TAF为基础的治疗第一个药物是在2015年11月5号FDA批准了Genvoya作为治疗12岁以上的儿童和成人HIV-1感染的指定用药。
Genvoya是一种包含elvitegravir, cobicistat, emtricitabine, 和tenofovir alafenamide的复合药物。 2015年11月23日，Genvoya获得EMA上市批准，患者为12周岁以上，体重大于35公斤的HIV-1携带者，同时患者所携带病毒并未发生对整合酶抑制剂、恩曲他滨或替诺福韦相联系的抗药突变。
Odefsey是完整方案治疗HIV-1的感染的12岁以及12岁以上的患者，且没有抗逆转录病毒治疗历史，且HIV-1 RNA水平小于或等于每毫升100 000份拷贝的患者，Odefsey 可以作为替代疗法对于那些稳定的抗逆转录病毒疗法病毒学抑制型（对于病毒抑制(HIV-1 RNA每毫升少于50份拷贝)，至少六个月，没有失败的治疗历史，也没有Odefsey子成分抵抗）患者。对于肌酐清除率大于或等于30毫升 /分钟的患者，Odefsey 无剂量调整要求。
Odefsey 在其产品标签有盒装警告，有脂肪变性，乳酸性酸中毒，严重肝肿大和急性加重期的乙型肝炎后期治疗等相关风险。
TAF是一种新奇的靶向药物，同时展现了高度的抗病毒活性，而剂量不足吉利德的Viread®(tenofovir disoproxil fumarate, TDF)剂量的十分之一，且TAF在血液中的含量比TDF减少90%，直接作用于癌细胞，更高效。
ODEFSEY Rx
Pharmacological Class:
Nucleoside analog reverse transcriptase inhibitors + non-nucleoside reverse transcriptase inhibitor.
Active Ingredient(s):
Emtricitabine 200mg, rilpivirine 25mg, tenofovir alafenamide (TAF) 25mg; tabs.
Company
Gilead Sciences, Inc.
Indication(s):
As a complete regimen for HIV-1 infection in patients who are antiretroviral treatment-naïve with HIV-1 RNA ≤100,000 copies/mL or to replace a stable antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA <50 copies/mL) for ≥6 months with no history of treatment failure and no known substitutions associated with resistance to any components of Odefsey.
Pharmacology:
Emtricitabine inhibits the activity of the HIV-1 reverse transcriptase (RT) by competing with the natural substrate deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA, which results in chain termination. Rilpivirine inhibits HIV-1 replication by non-competitive inhibition of HIV-1 RT. Tenofovir alafenamide, a phosphonoamidate prodrug of tenofovir, is intracellularly converted through hydrolysis. Tenofovir diphosphate inhibits HIV-1 replication by incorporation into viral DNA, which results in chain termination.
Legal Classification:
Rx
Contraindication(s):
Concomitant carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine, dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole, dexamethasone (more than a single dose), St. John’s wort.
Adults & Children:
<12yrs (<35kg): not established. ≥12yrs (≥35kg): 1 tab once daily with food. Severe renal impairment (CrCl <30mL/min): not recommended.
Warnings/Precautions:
Suspend therapy if lactic acidosis or hepatotoxicity (eg, hepatomegaly, steatosis) occurs. Not for treating chronic hepatitis B virus; test for HBV before starting therapy and closely monitor patients co-infected with HBV and HIV for several months after stopping treatment (discontinuing therapy may exacerbate HBV infection). Underlying hepatitis B or C, or marked elevations in liver-associated tests; monitor for hepatotoxicity. Consider monitoring LFTs in those without pre-existing hepatic dysfunction or other risks. Monitor CrCl, urine glucose, urine protein, serum phosphorus (in patients at risk for chronic renal disease); discontinue if significant renal dysfunction or Fanconi syndrome occurs). Prolongation of QTc interval with higher doses. Promptly evaluate if severe depressive symptoms occur. History of pathologic fracture or risk factors of osteoporosis or bone loss: consider monitoring bone mineral density (BMD); calcium/vitamin D supplement may be beneficial. Discontinue immediately if severe skin or hypersensitivity reactions develop. Pregnancy. Nursing mothers: not recommended.
Interaction(s)
See Contraindications. Avoid with concurrent or recent use of nephrotoxic agents. Concomitant antimycobacterials (eg, rifabutin): not recommended. May be potentiated by CYP3A or P-gp inhibitors, antagonized by CYP3A or P-gp inducers. Concomitant drugs that strongly affect P-gp activity (eg, cyclosporine) may lead to changes in TAF absorption. Concomitant with drugs known to prolong the QTc interval may increase risk of Torsade de Pointes; consider alternatives. May be potentiated by drugs that decrease renal function or compete for active tubular secretion (eg, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides, NSAIDs). Separate antacids by (≥2hrs before or 4hrs after) or H2-receptor antagonists by (≥12hrs before or ≥4hrs after) Odefsey. Concomitant azole antifungals (eg, fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole); monitor for breakthrough fungal infections. Concomitant macrolide or ketolide antibiotics (eg, clarithromycin, erythromycin, telithromycin); consider alternative (eg, azithromycin). Concomitant methadone; monitor.
Adverse Reaction(s)
Nausea, depressive disorders, insomnia, headache, diarrhea, fatigue; decreased BMD, new onset or worsening renal impairment, fat redistribution, immune reconstitution syndrome.
How Supplied:
Tabs—30
LAST UPDATED:
3/11/2016 |
