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近日,新型抗艾滋口服药Odefsey (emtricitabine, rilpivirine, tenofovir alafenamide)获FDA批准上市。
Odefsey是一种三合一复合剂（R/F/TAF），包括200mg恩曲他滨（emtricitabine）、25mg利匹韦林（rilpivirine）和25mg替诺福韦艾拉酚胺富马酸（TAF）
Odefsey是吉利德推出的第二款以TAF作为核苷类逆转录酶抑制剂的抗艾滋药物，具备低剂量强药效的优势。
Odefsey前体药物是TAF。TAF是一种新型核苷类逆转录酶抑制剂（NRTI），是吉利德已上市药物Viread（替诺福韦酯，TDF）的升级版。临床试验证实，TAF进入细胞效率明显高于TDF，而且可以在低于TDF十分之一剂量时，就具有非常高的抗病毒疗效，从而降低药物副作用，减轻肾损伤和骨质疏松。
批准日期：2016年3月6日 公司：吉利德科学公司
ODEFSEY®（恩曲他滨，rilpivirine，和替诺福韦alafenamide）片剂，供口服使用
最初美国批准：2016年
警告：
乳酸性酸中毒/脂肪变性和乙肝见完整的黑框警告的完整处方信息，治疗后急性发作期重度肝肿大。
乳酸性酸中毒和严重肝肿大伴脂肪变性，包括致命的情况下，已经报告了使用核苷类似物。
ODEFSEY没有被批准用于治疗慢性乙型肝炎病毒（HBV）感染的治疗。乙肝严重的急性加重有报道谁是病人合并感染HIV-1和HBV并有含恩曲他滨（FTC）和/或富马酸替诺福韦酯（TDF）停产的产品，并与ODEFSEY可能发生。肝功能应密切在这些患者进行监测。如果适当的话，抗乙肝治疗开始可能有必要。
作用机理
ODEFSEY是抗逆转录病毒药物恩曲他滨，rilpivirine，和替诺福韦alafenamide [见微生物学]固定剂量组合。
适应症和用法
ODEFSEY是恩曲他滨（FTC）和替诺福韦alafenamide（TAF）的三药物组合，两者的HIV核苷类似物逆转录酶抑制剂（NRTIs），和rilpivirine（RPV），非核苷逆转录酶抑制剂（NNRTI），并且被指示作为HIV-1感染的患者12岁，比年长的那些与HIV-1 RNA无抗逆转录病毒治疗史的初始治疗小于或等于每毫升10万份的治疗方案齐全;或替换一个稳定的抗逆转录病毒疗法在那些谁病毒学抑制（HIV-1的每毫升少于50拷贝的RNA），用于至少六个月与电阻相关联ODEFSEY的各个部件没有治疗失败的历史，没有已知的取代。
用法用量
测试：前ODEFSEY开始，患者应为乙型肝炎病毒感染进行测试，和肌酐清除率，尿糖，尿蛋白应获得。
推荐用量：口服一餐每天一次取一粒。
ODEFSEY开始后，替代疗法，以评估潜在的病毒学失败或出现反弹后，建议HIV-1 RNA和方案的耐受性增加监测。
患者低于每分钟30毫升肌酐清除率不推荐ODEFSEY：肾功能损害。
剂型和规格
片剂：200毫克FTC，25毫克RPV和25mg TAF。
禁忌症
当与药物可能发生在反应堆压力容器的血浆浓度显著降低，这可能导致病毒学应答和可能的阻力和交叉耐药性的损失共施用ODEFSEY是禁忌。
警告和注意事项
皮肤及过敏反应：
上市后含遥控飞行器方案，包括与嗜酸粒细胞增多和全身症状（DRESS）药品不良反应病例的经验中严重皮肤和过敏性反应的报道。立即停止治疗，如果过敏或皮疹与肝血清biochemistries全身症状或海拔开发，并密切监测临床状态，包括肝血清biochemistries。
同时使用ODEFSEY的与其他药物可降低RPV的接触可能导致的ODEFSEY的治疗效果和抗性的可能发展的损失。
用药物同时使用ODEFSEY与已知风险延长心电图QT间期可以增加尖端扭转的风险。
抑郁症：严重抑郁症的报道。紧急医疗评估，建议严重的抑郁症。
肝：肝不良事件已经报道了在接收含有遥控飞行器方案的患者。显示器前，并与ODEFSEY治疗的患者有潜在肝脏疾病或肝脏相关的测试显着升高时肝脏相关的测试。另外还要考虑监视肝相关的测试中患者无危险因素。
体内脂肪重新分配/积累：在接受抗逆转录病毒治疗的患者中观察到。
免疫重建综合征：可能需要进一步的评估和治疗。
新发或加重肾功能损害：评估肌酐清除率，尿糖，并在所有患者尿蛋白开始ODEFSEY治疗前和治疗过程中监控。监测患者的慢性肾脏病血清磷。
骨丢失和矿化缺陷：考虑监视BMD患者的病理性骨折或骨质疏松或骨流失的其他危险因素的历史。
不良反应
Rilpivirine：向反应堆压力容器（发生率大于或等于2％，等级2-4）最常见的不良反应是抑郁症，失眠，头痛。
恩曲他滨替诺福韦和Alafenamide：最常见的不良反应（发生率大于或等于10％，所有等级）是恶心。
要报告疑似不良反应，请联系吉利德科学公司1-800-GILEAD-5或FDA电话1-800-FDA-1088或www.fda.gov/medwatch。
药物相互作用
CYP3A4诱导剂或抑制剂：诱导或抑制CYP3A4的可能影响RPV的血浆浓度的药物。
P-糖蛋白（P-gp）的诱导剂或抑制剂：药物强烈影响的P-gp活性可以导致在TAF吸收的变化。
药物，增加胃pH值：药物，增加胃pH值可能会降低反应堆压力容器的血浆浓度。
特殊人群中使用
哺乳期：感染艾滋病毒的妇女应指示不进行母乳喂养，由于艾滋病毒传播的可能性。
儿科：不建议用于患者小于12岁或体重低于35公斤。
包装规格/储存与处理
ODEFSEY片剂是灰色，胶囊状，并涂有“GSI”模压在一侧和另一侧“255”膜。各瓶包含30个片剂（NDC 61958-2101-1），硅胶干燥剂，聚酯线圈，并用一防儿童闭合封闭。
存储低于30°C（86°F）。
保持容器密闭。
免除只能在原容器。
FDA Approves Odefsey(emtricitabine 200mg/rilpivirine 25mg/tenofovir alafenamide 25mg) for the Treatment of HIV-1
Gilead Sciences announced that the Food and Drug Administration (FDA) has approved Odefsey (emtricitabine/rilpivirine/tenofovir alafenamide [R/F/TAF]) tablets for the treatment of HIV-1 infection in certain patients.
Odefsey is indicated as a complete regimen for the treatment of HIV-1 in patients ≥12 years old who have no antiretroviral treatment history and HIV-1 RNA levels ≤100,000 copies/mL. It is also indicated as replacement for a stable antiretroviral regimen for those who are virologically suppressed (defined as HIV-1 RNA levels <50 copies/mL) for ≥6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Odefsey.
Odefsey combines emtricitabine and tenofovir alafenamide, both HIV nucleoside analog reverse transcriptase inhibitors (NRTIs), and rilpivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI).
The FDA approval was based on a bioequivalence study that showed Odefsey achieved similar blood drug levels of emtricitabine and TAF as Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide; Gilead Sciences) and similar drug levels of rilpivirine as Edurant (rilpivirine). Its safety, efficacy, and tolerability have been supported by clinical studies of rilpivirine-based therapy and F/TAF-based therapy in various patient populations with HIV: treatment-naive adults and adolescents, virologically suppressed adults who switched from PI-, NNRTI-, and INSTI-based regimens, and virologically suppressed adults with mild-to-moderate renal impairment.
Odefsey is the second tenofovir alafenamide-based regimen to be approved by the FDA and is also the smallest pill of any single-tablet regimen for the treatment of HIV.
Odefsey is available as 200mg/25mg/25mg strength tablets in 30-count bottles.
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 |
