ELVITEGRAVIR, COBICISTAT, EMTRICITABINE AND TENOFOVIR ALAFENAMIDE
Clinical safety rating: safe
Other nephrotoxic drugs increase risk of renal impairment Can cause renal impairment and decreased bone mineral density.
Elvitegravir is an HIV-1 integrase strand transfer inhibitor, blocking viral DNA integration. Cobicistat is a CYP3A inhibitor boosting elvitegravir exposure. Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI). Tenofovir alafenamide is a nucleotide reverse transcriptase inhibitor (NtRTI) that, after conversion to tenofovir, inhibits HIV reverse transcriptase.
| Metabolism | Elvitegravir: CYP3A (primary), glucuronidation (UGT1A1/3). Cobicistat: CYP3A (metabolized), CYP2D6 (minor). Emtricitabine: largely unchanged renal excretion; minimal hepatic metabolism via oxidation and glucuronidation. Tenofovir alafenamide: hydrolyzed to tenofovir by cathepsin A and CES1; tenofovir is renally excreted. |
| Excretion | Elvitegravir: 94% fecal, 6.7% renal; Cobicistat: 86% fecal, 8% renal; Emtricitabine: 86% renal (unchanged); Tenofovir alafenamide: 31% renal (as tenofovir), 46% fecal (as tenofovir alafenamide). |
| Half-life | Elvitegravir: 12.9 h; Cobicistat: 3.5 h; Emtricitabine: 10 h; Tenofovir alafenamide: 0.51 h (active metabolite tenofovir has half-life of 12-18 h). All half-lives are terminal elimination half-lives; once-daily dosing is supported by boosted pharmacokinetics. |
| Protein binding | Elvitegravir: ~99% bound to albumin and alpha-1 acid glycoprotein; Cobicistat: ~97-98% bound to albumin; Emtricitabine: <4% bound; Tenofovir alafenamide: ~80% bound to plasma proteins. |
| Volume of Distribution | Elvitegravir: 0.27 L/kg; Cobicistat: 0.16 L/kg; Emtricitabine: 0.57 L/kg; Tenofovir alafenamide: 0.24 L/kg. These values indicate distribution primarily into total body water with some tissue binding. |
| Bioavailability | Oral: Elvitegravir: ~10% (increased to 85-90% with cobicistat boosting); Cobicistat: ~65%; Emtricitabine: 93%; Tenofovir alafenamide: ~20% (higher with food). |
| Onset of Action | Oral: Antiviral effect begins within 2-4 weeks of therapy with maximal suppression typically by 24 weeks. |
| Duration of Action | Oral: 24 hours (once-daily dosing) due to boosted pharmacokinetics; missed dose should be taken as soon as possible if within 12 hours of scheduled time. |
One tablet (150 mg elvitegravir, 150 mg cobicistat, 200 mg emtricitabine, 10 mg tenofovir alafenamide) orally once daily with food.
| Dosage form | TABLET |
| Renal impairment | Not recommended for patients with CrCl < 30 mL/min. No dose adjustment for CrCl ≥ 30 mL/min. For patients with CrCl 15-29 mL/min, use emtricitabine/tenofovir alafenamide-containing regimen only if alternative not available, with reduced dose of emtricitabine/tenofovir alafenamide (consider separate components). |
| Liver impairment | No dose adjustment for mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Not recommended for severe hepatic impairment (Child-Pugh C). |
| Pediatric use | For patients weighing ≥ 35 kg: one tablet (same strength) once daily with food. Not recommended for patients weighing < 35 kg. |
| Geriatric use | No specific dose adjustment required; however, monitor renal function due to age-related decline and potential for decreased CrCl. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other nephrotoxic drugs increase risk of renal impairment Can cause renal impairment and decreased bone mineral density.
| FDA category | Animal |
| Breastfeeding | Unknown whether elvitegravir, cobicistat, or TAF are excreted in human breast milk. Emtricitabine is excreted in human milk. Tenofovir is excreted in human milk at low levels (M/P ratio not established for TAF; for TDF, M/P ratio ~0.5-1). Due to potential for HIV transmission and adverse effects in the infant, breastfeeding is not recommended for HIV-infected women. |
| Teratogenic Risk |
■ FDA Black Box Warning
Post-treatment acute exacerbation of hepatitis B (HBV) in patients co-infected with HIV-1 and HBV who discontinue products containing emtricitabine and/or tenofovir disoproxil fumarate. Cases of fatal renal impairment have been reported with tenofovir-containing products; tenofovir alafenamide has lower renal risk but caution advised.
| Common Effects | Hepatitis B |
| Serious Effects |
["Coadministration with drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious adverse events (e.g., alfuzosin, ranolazine, dronedarone, colchicine, lomitapide, lovastatin, simvastatin, sildenafil for pulmonary hypertension, ergot derivatives, midazolam oral, triazolam)","Coadministration with CYP3A inducers (e.g., rifampin, St. John's wort) due to loss of virologic response"]
| Precautions | ["Hepatotoxicity: monitor liver enzymes especially in HBV co-infection.","Renal impairment: assess CrCl before and during therapy; not recommended if CrCl <30 mL/min.","Lactic acidosis/severe hepatomegaly with steatosis: reported with NRTIs.","Bone mineral density decreases: monitor if history of fracture or osteoporosis.","Immune reconstitution syndrome: may occur with combination therapy.","Drug interactions: cobicistat is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates or drugs with narrow therapeutic index."] |
Loading safety data…
| Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (TAF) is classified as FDA Pregnancy Category B. There are no adequate and well-controlled studies in pregnant women. In animal studies, no evidence of teratogenicity was observed with elvitegravir, cobicistat, emtricitabine, or TAF. However, tenofovir disoproxil fumarate (TDF) has been associated with reduced fetal growth and bone effects; TAF results in lower tenofovir exposure. The Antiretroviral Pregnancy Registry monitors outcomes. First trimester: risk cannot be ruled out; use only if benefit outweighs risk. Second and third trimesters: no increased risk of major malformations reported in registry data. There is a potential for lactic acidosis and hepatic steatosis in pregnant women receiving nucleoside analogues. |
| Fetal Monitoring | Monitor maternal HIV RNA, CD4 count, liver function tests, renal function (serum creatinine, estimated creatinine clearance, urine glucose and protein) at baseline and periodically during pregnancy. Assess fetal growth and development via ultrasound. Monitor for lactic acidosis and hepatotoxicity. Check for anemia (due to emtricitabine). |
| Fertility Effects | No known significant effects on fertility. Animal studies with elvitegravir, cobicistat, emtricitabine, and TAF showed no impairment of fertility. No human data on fertility impact. |