STRIBILD
Clinical safety rating: caution
Comprehensive clinical and safety monograph for STRIBILD (STRIBILD).
STRIBILD is a fixed-dose combination of elvitegravir (integrase strand transfer inhibitor), cobicistat (CYP3A inhibitor to boost elvitegravir), emtricitabine (nucleoside reverse transcriptase inhibitor), and tenofovir disoproxil fumarate (nucleotide reverse transcriptase inhibitor). Elvitegravir inhibits HIV-1 integrase, blocking integration of viral DNA into host genome. Emtricitabine and tenofovir inhibit HIV-1 reverse transcriptase.
| Metabolism | Elvitegravir is metabolized primarily by CYP3A; cobicistat is a CYP3A inhibitor and also metabolized by CYP3A and to a minor extent by CYP2D6; emtricitabine is minimally metabolized; tenofovir is not significantly metabolized. |
| Excretion | Elvitegravir: 94.8% in feces (parent drug and metabolites), 6.7% in urine. Cobicistat: 86.2% in feces, 8.2% in urine. Emtricitabine: 86% in urine (70% unchanged), 14% in feces. Tenofovir: 70-80% in urine (unchanged) via glomerular filtration and active tubular secretion. |
| Half-life | Elvitegravir: 12.9 h (boosted by cobicistat). Cobicistat: 3-4 h. Emtricitabine: 10 h. Tenofovir: 12-18 h (prolonged in renal impairment). Clinical context: Once-daily dosing maintains therapeutic concentrations. |
| Protein binding | Elvitegravir: 98-99% (albumin, alpha-1-acid glycoprotein). Cobicistat: 97-98%. Emtricitabine: <4%. Tenofovir: <0.7%. |
| Volume of Distribution | Elvitegravir: ~2.8 L/kg. Cobicistat: ~0.9 L/kg. Emtricitabine: 1.4 L/kg. Tenofovir: 1.3 L/kg. Indicates extensive tissue distribution, including lymphatic tissues. |
| Bioavailability | Oral: Elvitegravir absolute bioavailability unknown; boosted to therapeutic levels with cobicistat. Cobicistat: unknown. Emtricitabine: >90%. Tenofovir disoproxil: 25% (fumarate salt); tenofovir alafenamide component in Stribild: not applicable (Stribild contains TDF). |
| Onset of Action | Oral: Elvitegravir peak plasma concentration at 4h; antiviral effect begins within 24h of first dose. |
| Duration of Action | 24h (supports once-daily dosing due to boosted elvitegravir and long intracellular half-life of tenofovir diphosphate >60h). |
One tablet (150 mg elvitegravir, 150 mg cobicistat, 200 mg emtricitabine, 300 mg tenofovir disoproxil fumarate) orally once daily with food.
| Dosage form | TABLET |
| Renal impairment | Not recommended for CrCl <30 mL/min. For CrCl 30-49 mL/min, consider alternative regimen; if used, monitor renal function closely. No dose adjustment for CrCl ≥50 mL/min. |
| Liver impairment | No dose adjustment for mild to moderate hepatic impairment (Child-Pugh A or B); not recommended for severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Approved for patients weighing ≥35 kg: one tablet orally once daily with food. Not indicated for patients <35 kg. |
| Geriatric use | No specific dose adjustment; select dose with caution due to age-related renal impairment; monitor renal function and bone mineral density. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for STRIBILD (STRIBILD).
| Breastfeeding | Breastfeeding is not recommended for women with HIV in the US to avoid postnatal transmission. Emtricitabine and tenofovir are excreted in human milk at low levels; M/P ratios: emtricitabine ~0.01-0.02, tenofovir ~0.03. Elvitegravir and cobicistat are likely excreted in breast milk but data are insufficient. Potential for infant toxicity from cobicistat is unknown. Milk concentrations of emtricitabine are below 2% of maternal dose; tenofovir below 0.03%. |
| Teratogenic Risk | Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) is classified as Pregnancy Category B for emtricitabine/tenofovir DF and elvitegravir. Limited data in pregnant women show no increased risk of major birth defects in the first trimester. Cobicistat is not recommended for use during pregnancy due to decreased drug concentrations in the third trimester. Human data from the Antiretroviral Pregnancy Registry confirm no overall increased risk of teratogenicity for the component drugs, with sufficient first-trimester exposures to exclude a 2-fold increase in birth defects. Small increased risk of neural tube defects with efavirenz-containing regimens not seen with Stribild components. No evidence of fetal toxicity in animal studies. |
■ FDA Black Box Warning
Posttreatment acute exacerbation of hepatitis B in patients co-infected with HIV-1 and HBV. Monitor hepatic function for at least several months after discontinuation.
| Serious Effects |
["Concomitant use with drugs highly dependent on CYP3A for clearance (e.g., alfuzosin, sildenafil for PAH, ergot derivatives, cisapride, pimozide, midazolam, triazolam)","Concomitant use with rifampin","Concomitant use with St. John’s wort","Coadministration with adefovir dipivoxil"]
| Precautions | ["New onset or worsening renal impairment","Lactic acidosis/severe hepatomegaly with steatosis","Decreased bone mineral density","Immune reconstitution syndrome","Risk of resistance in treatment-experienced patients with prior integrase inhibitor failure"] |
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| Fetal Monitoring | HIV viral load and CD4 cell count should be monitored at baseline and throughout pregnancy, with viral load repeated every 2-4 weeks until suppression and then at least every 3 months. Renal function (serum creatinine, CrCl, urine protein) at baseline and periodically due to tenofovir DF. Liver function tests (ALT, AST) at baseline and as clinically indicated. Blood glucose monitoring for gestational diabetes. Fetal ultrasound to monitor growth and development. Consider dose adjustment timing in third trimester due to PK changes in pregnancy to maintain viral suppression. |
| Fertility Effects | No significant effects on fertility reported in clinical trials. Elvitegravir/cobicistat/emtricitabine/tenofovir DF does not impair spermatogenesis or oogenesis in animal studies. Limited human data suggest no adverse impact on male or female fertility. HIV-positive women on antiretroviral therapy may have improved fertility due to better health status. |