近日 Mylan宣布，FDA批准Cimduo（Lamivudine and Tenofovir Disoproxil Fumarate Tablets），与其他抗逆转录病毒药物联合用于治疗成人和儿科患者的人类免疫缺陷病毒1型（HIV-1）感染。
批准日期：2018年8月3日，公司：Mylan Specialty L.P.
CIMDUO（拉米夫定和替诺福韦地索普西富马酸盐[lamivudine and tenofovir disoproxil fumarate]）片剂，用于口服
美国最初批准：2018年
警告：
后处理急性乙型肝炎的预防措施请参阅完整的BOXED警告的完整预定信息。
•据报道，共感染HBV和人类免疫缺陷病毒（HIV-1）且停用拉米夫定和替诺福韦地索普西富马酸盐的患者出现严重急性乙型肝炎急性加重。在这些患者中密切监测肝功能，并在适当时启动抗乙型肝炎治疗。
作用机制
CIMDUO是抗病毒药物3TC和TDF的固定剂量组合，具有抗HIV-1的抗病毒活性[见MICROBIOLOGY]。
适应症和用法
CIMDUO是拉米夫定（3TC）和替诺福韦地索普西富马酸盐（TDF）的两种药物组合，两者都是核（t）侧逆转录酶抑制剂，并与其他抗逆转录病毒药物联合用于治疗人类免疫缺陷病毒1型（HIV- 1）体重至少35千克的成人和儿科患者的感染。
剂量和给药
•测试：在开始和使用CIMDUO治疗期间，应对患者进行乙型肝炎病毒感染检测，并应获得估计的肌酐清除率，尿糖和尿蛋白。
•推荐剂量：每日一次口服一片，含或不含食物。
•肾功能损害：不建议CrCL低于50mL/min的患者或需要血液透析的终末期肾病患者。
剂量形式和强度
片剂：300mg拉米夫定和300mg替诺福韦地索普西富马酸盐（相当于245mg替诺福韦地索普西）。
禁忌症
•CIMDUO禁用于先前对本产品任何成分过敏的患者。
警告和注意事项
•乳酸性酸中毒/严重肝肿大伴脂肪变性：对于出现症状或实验室检查结果提示乳酸性酸中毒或明显肝毒性的患者，停止治疗。
•新发作或恶化的肾功能损害：可能包括急性肾功能衰竭和范可尼综合征。在开始用替诺福韦地索普西富马酸盐（CIMDUO的一种成分）治疗之前评估估计的肌酸酐清除率。在有肾功能不全风险的患者中，在开始使用替诺福韦治疗前和治疗期间定期评估估计的肌酐清除率，血清磷，尿糖和尿蛋白。避免在同时或最近使用肾毒性药物的情况下使用CIMDUO。
•在接受联合抗逆转录病毒疗法和基于干扰素和利巴韦林的治疗方案的HIV-1 / HCV合并感染患者中发生肝功能失代偿，有些致命。监测与治疗相关的毒性。停止使用CIMDUO作为医学上合适的，并考虑减少或停用干扰素α，利巴韦林或两者。
•胰腺炎：对有胰腺炎病史或其他胰腺炎危险因素的儿科患者慎用。在临床上适当停用CIMDUO。
•骨密度（BMD）降低：在HIV感染患者中观察到。考虑对有病理性骨折史或骨质疏松症或骨丢失的其他危险因素的患者进行BMD评估。
•免疫重建综合症：在HIV感染患者中观察到。可能需要进一步评估和治疗。
•体脂的再分配/积累：在接受抗逆转录病毒联合治疗的HIV感染患者中观察到。
•仅限三核苷的方案：已报告HIV感染患者的早期病毒学失败。仔细监测并考虑修改治疗方案。
不良反应
•最常见的不良反应（CIMDUO>10％）是头痛，疼痛，抑郁，腹泻和皮疹。
要报告疑似不良反应，请致电1-877-446-3679（1-877-4-INFO-RX）或FDA 1-800-FDA-1088或WWW.FDA.GOV/MEDWATCH联系Mylan。
药物相互作用
•Atazanavir：当与CIMDUO共同给药时，Atazanavir应与利托那韦共同给药。
•HIV-1蛋白酶抑制剂：当CIMDUO与阿扎那韦/利托那韦，地瑞纳韦/利托那韦或洛匹那韦/利托那韦共同作用时，监测有关替诺福韦毒性的证据。
•山梨糖醇：避免使用CIMDUO长期服用山梨糖醇。
用于特定人群
•哺乳期：由于可能传播艾滋病毒，不推荐母乳喂养。
包装提供/存储和处理
CIMDUO（拉米夫定和替诺福韦地索普西富马酸盐）片剂300mg/300mg是白色至灰白色，薄膜包衣的椭圆形片剂，一侧用“M112”压印，另一侧用平面压印。
它们提供如下：
NDC 49502-450-93
纸箱装有30片装有干燥剂，感应密封和防蛀帽的瓶子
NDC 49502-450-77
纸箱装有90片装有干燥剂，感应密封和防蛀帽的瓶子
储存在20°C至25°C（68°F至77°F）; 允许的偏差为15°C至30°C（59°F至86°F）。 [参见USP受控室温。]
在原始容器中分配。
完整说明附件：
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a300f04d-118f-4136-aaf3-ddfd00197f86

Cimduo(Lamivudine and Tenofovir Disoproxil Fumarate Tablets, for Oral Use)
CIMDUO™ (lamivudine and tenofovir disoproxil fumarate) is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adult and pediatric patients weighing at least 35 kg.
WARNING: POST TREATMENT ACUTE EXACERBATIONS OF HEPATITIS B
Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1) and have discontinued lamivudine or tenofovir disoproxil fumarate, components of CIMDUO. Monitor hepatic function closely in these patients and, if appropriate, initiate anti-hepatitis B treatment [see Warnings and Precautions (5.2)].
IMPORTANT SAFETY INFORMATION
CIMDUO is contraindicated in patients with a previous hypersensitivity reaction to any of the components contained in the formulation.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. Treatment should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
All patients with HIV-1 should be tested for the presence of chronic hepatitis B virus (HBV) before initiating antiretroviral therapy. Discontinuation of anti-HBV therapy, including lamivudine (3TC) and tenofovir disoproxil fumarate (TDF), may be associated with severe acute exacerbations of hepatitis. Patients infected with HBV who discontinue CIMDUO should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, resumption of anti-hepatitis B therapy may be warranted. See the full prescribing information for Important Differences Among Lamivudine-Containing Products.
TDF, a component of CIMDUO is principally eliminated by the kidney. Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of TDF.
It is recommended that estimated creatinine clearance be assessed in all patients prior to initiating therapy and as clinically appropriate during therapy with TDF. In patients at risk of renal dysfunction, it is recommended that estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein be assessed prior to initiation of TDF, and periodically during TDF therapy.
CIMDUO should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs (NSAIDs)).
In vitro studies have shown ribavirin can reduce the phosphorylation of pyrimidine nucleoside analogues such as 3TC, a component of CIMDUO. Although no evidence of a pharmacokinetic or pharmacodynamic interaction (e.g., loss of HIV-1/HCV virologic suppression) was seen when ribavirin was coadministered with 3TC in HIV-1/HCV co-infected patients, hepatic decompensation (some fatal) has occurred in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin. Patients receiving interferon alfa with or without ribavirin and 3TC should be closely monitored for treatment-associated toxicities, especially hepatic decompensation. See the full prescribing information for interferon and ribavirin.
In pediatric patients with a history of prior antiretroviral nucleoside exposure, a history of pancreatitis, or other significant risk factors for the development of pancreatitis, 3TC, a component of CIMDUO, should be used with caution. Treatment with CIMDUO should be stopped immediately if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur.
In clinical trials in HIV-1 infected adults, TDF was associated with slightly greater decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism, suggesting increased bone turnover relative to comparators. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher in subjects receiving TDF. The effects of TDF-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk are unknown.
Cases of osteomalacia associated with proximal renal tubulopathy, manifested as bone pain or pain in extremities and which may contribute to fractures, have been reported in association with the use of TDF.
Immune reconstitution syndrome has been reported in HIV-infected patients treated with combination antiretroviral therapy, including 3TC and TDF
In HIV-infected patients, redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving combination antiretroviral therapy.
Early virologic failure has been reported in HIV-infected patients treated with triple nucleoside-only regimens. Monitor carefully and consider treatment modification.
The most common adverse reactions (>10% with CIMDUO) are headache, pain, depression, diarrhea, and rash.