2018年7月18日，四合一HIV新药Symtuza（darunavir/cobicistat/emtricitabine/tenofovir alafenamide D/C/F/TAF，800mg/150mg/200mg/10mg）获美国FDA批准上市，作为一种完整治疗方案，用于既往未接受治疗（初治）以及某些已实现病毒学抑制的HIV-1成人感染者。
Symtuza是一种新的基于darunavir的每日一次单一片剂方案（STR），结合了蛋白酶抑制剂darunavir（地瑞那韦，D）、药代动力学增效剂cobicistat（可比司他，C）、核苷类逆转录酶抑制剂emtricitabine（恩曲他滨，F）及替诺福韦艾拉酚胺（tenofovir alafenamide，TAF）。其中后3种活性药物成分来自于吉利德科学公司。
此次批准，使Symtuza成为美国市场首个也是唯一一个将darunavir已被证明的疗效持久性和对耐药的高度基因屏障以及TAF改善肾功能和骨密度特性集中于同一片药物内的单一片剂方案（STR），将为HIV-1成人感染者提供一种新的治疗选择。此前，Symtuza已获欧盟和加拿大批准，用于体重至少40公斤的12岁及以上青少年及成人HIV-1感染者的治疗。
用药方面，Symtuza的推荐剂量为:每日一次，每次一片，与食物同服。在肌酐清除率低于30mL/分钟或存在严重肝损害的患者中，不推荐使用Symtuza。
根据处方信息，在接受Symtuza治疗之前或开始治疗时，应对患者进行乙型肝炎病毒（HBV）感染和肾功能的检测，并在治疗期间检测肾功能作为临床适用。

Symtuza(Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Tablets)
description
Trade name: SYMTUZA
Active substance: DARUNAVIR; COBICISTAT; EMTRICITABINE; TENOFOVIR ALAFENAMIDE
NDC: 59676-800-30, 59676-800-99
Dosage form: TABLET
Dosage: 800MG; 150MG; 200MG; 10MG
Packing specification: 30 Tablets
Market Status: Prescription
TE code: None
RLD: TBD
RS: No
Approval time: 07/17/2018
Application No.: NDA210455
Licensee: Janssen Therapeutics
Licensee Address: Division of Janssen Products, LP, Titusville NJ 08560
Manufacturer: Patheon Inc
Manufacturer Address: 2100 Syntex Ct Mississauga ON L5N 7K9, Canada
Indications: HIV Infection
Manual: PDF
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SYMTUZA Rx
Generic Name and Formulations:
Darunavir 800mg, cobicistat 150mg, emtricitabine 200mg, tenofovir alafenamide 10mg; tabs.
Company:
Janssen Pharmaceuticals, Inc.
Monograph added.
Indications for SYMTUZA:
As a complete regimen for the treatment of HIV-1 infection in adults who are antiretroviral treatment-naïve or virologically-suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen for ≥6 months and have no known substitutions associated with resistance to darunavir or tenofovir.
Adult:
Test for HBV infection prior to initiation. 1 tab once daily with food. May split tab into 2 pieces if unable to swallow; consume entire dose immediately. Severe renal (CrCl <30mL/min) or severe hepatic impairment: not recommended.
Children:
<18yrs: not established.
Contraindications:
Concomitant alfuzosin, ranolazine, dronedarone, carbamazepine, phenobarbital, phenytoin, colchicine (in renal/hepatic impairment), rifampin, lurasidone, pimozide, ergots, cisapride, St. John’s wort, elbasvir/grazoprevir, lovastatin, simvastatin, sildenafil (for PAH), oral midazolam, triazolam.
Boxed Warning:
Post-treatment acute exacerbation of hepatitis B.
Warnings/Precautions:
Test for HBV before starting antiretroviral therapy. Discontinuation of emtricitabine and/or tenofovir disoproxil may be associated with severe acute exacerbations of hepatitis B. Closely monitor patients co-infected with HBV and HIV for several months after stopping treatment; if appropriate, anti-HBV therapy may be warranted (esp. in those with advanced liver disease or cirrhosis). Underlying chronic hepatitis, cirrhosis, or pre-treatment elevated transaminases: consider increased AST/ALT monitoring; interrupt or discontinue if evidence of new or worsening liver dysfunction occurs. Discontinue immediately if severe skin reactions develop. New onset or worsening renal impairment. Assess SCr (monitor closely if >0.4mg/dL), estimated CrCl, urine glucose, urine protein in all patients, and serum phosphorus (in chronic kidney disease) before initiating and during therapy. Suspend therapy if lactic acidosis or hepatotoxicity (eg, hepatomegaly, steatosis) occurs. Sulfonamide allergy. Diabetes (may need insulin or oral hypoglycemics dose adjusted). Immune reconstitution syndrome. Fat redistribution. Hemophilia. Elderly. Pregnancy (use alternatives), nursing mothers: not recommended.
Pharmacological Class:
HIV-1 protease inhibitor + CYP3A inhibitor + nucleoside analog reverse transcriptase inhibitors.
Interactions:
See Contraindications. Not recommended with other antiretroviral agents, rivaroxaban, voriconazole, rifabutin, rifapentine, simeprevir, everolimus, salmeterol, avanafil, ticagrelor. Concomitant drugs that reduce renal function or compete for active tubular secretion may potentiate emtricitabine, tenofovir (eg, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides, high-dose or multiple NSAIDs). May potentiate antiarrhythmics, digoxin, dasatinib, nilotinib (see full labeling), apixaban, clonazepam, SSRIs, TCAs, trazodone, itraconazole, ketoconazole, colchicine (see full labeling), antipsychotics, quetiapine (consider alternative antiretrovirals; if necessary, reduce quetiapine to ⅙ of current dose and monitor), β-blockers, calcium channel blockers, fentanyl, oxycodone, immunosuppressants, tramadol (reduce dose), PDE5 inhibitors (see full labeling), sedatives/hypnotics, IV midazolam; monitor. Concomitant other statins (eg, atorvastatin (max 20mg/day), fluvastatin, pitavastatin, pravastatin, rosuvastatin (max 20mg/day): start at low dose, titrate and monitor. Concomitant antibacterials (eg, clarithromycin, erythromycin, telithromycin), CYP3A-inducing anticonvulsants that are not contraindicated (eg, eslicarbazepine, oxcarbazepine), CYP3A-inducing corticosteroids (eg, systemic dexamethasone or others): consider alternatives. Concomitant vincristine, vinblastine: consider temporarily withholding cobicistat-containing regimen if significant hematologic or GI adverse events develop. Concomitant hormonal contraceptives (eg, drosperinone): monitor for hyperkalemia; other estrogen based contraceptives: consider additional or alternative (non-hormonal) contraception. Discontinue bosentan ≥36hrs prior to initiation of Symtuza; resume after ≥10 days following initiation. Concomitant artemether/lumefantrine; monitor effects. Concomitant buprenorphine, buprenorphine/naloxone, methadone; use lowest initial or maintenance dose and titrate. Monitor INR with warfarin.
Adverse Reactions:
Diarrhea, rash, nausea, fatigue, headache, abdominal discomfort, flatulence; lab abnormalities.
Note:
Enroll pregnant patients exposed to Symtuza in the Antiretroviral Pregnancy Registry (APR) at (800) 258- 4263.
Generic Availability:
NO
How Supplied:
Tabs—30