2018年7月25日，强生公司旗下杨森医药公司的HIV感染新药Symtuza（D/C/F/TAF，800mg/150mg/200mg/10mg）获得美国FDA批准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，这是继Symtuza获得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感染者后再次传来喜讯。
  近年来，HIV-1感染者人数日益攀升，联合国艾滋病规划署 (UNAIDS) 的统计数据显示2017年全球感染HIV的人数高达3690万（180万为新感染患者），其中仅2170万感染者接受抗病毒治疗。这些年HIV治疗领域虽然取得了长足的发展，但是研究人员仍在寻找可以在大多数HIV感染者中维持病毒学抑制，并且方便给药、患者服药依从性好的治疗方案。
  Symtuza的获批无疑给HIV-1感染者带来了新的希望，而且也使其成为美国市场上首个也是唯一一个把已被证明疗效持久、具有对耐药的高度基因屏障的达芦那韦和可以改善肾功能、骨密度特性的替诺福韦艾拉酚胺集中于同一片药物内的单一片剂方案（STR）。
  此次Symtuza获批是基于AMBER和EMERALD这两个为期48周、关键性的III期临床试验。其中AMBER研究是针对既往未接受ARV治疗的HIV-1成人感染者，EMERALD研究是针对已实现病毒学抑制的HIV-1成人感染者；AMBER研究是将Symtuza与D/C+F/TDF方案进行比较，EMERALD研究将Symtuza与继续接受增强型蛋白酶抑制剂（bPI）+F/TDF方案进行比较。
  其中AMBER研究数据显示：Symtuza与对照组相比，病毒学抑制率为91.4%比88.4%，病毒学失败率为4.4%比3.3%，但是Symtuza耐受性较好，不良事件导致的治疗中断较对照方案少（2% vs 4%）验。EMERALD研究结果显示：Symtuza与对照组相比，病毒学抑制率为94.9%比93.7%，病毒学失败率为0.8%比0.5%，两组均没有患者因病毒学失败中止治疗。令人兴奋的是这两项临床试验都显示，接受Symtuza治疗的患者的骨密度指数和某些肾功能指标与对照组相比有显著提高，不过这些骨密度变化的长期临床意义尚不清楚。

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
file:///C:/Users/Administrator/AppData/Local/Microsoft/Windows/Temporary%20Internet%20Files/Content.IE5/10IHCP4N/symtuza_pi.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