BICTEGRAVIR, 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.
Bictegravir is an HIV-1 integrase strand transfer inhibitor that blocks viral DNA integration into host genome. Emtricitabine is a nucleoside reverse transcriptase inhibitor that terminates viral DNA chain elongation. Tenofovir alafenamide is a nucleotide reverse transcriptase inhibitor that incorporates into viral DNA causing chain termination.
| Metabolism | Bictegravir is primarily metabolized by CYP3A and UGT1A1. Emtricitabine is minimally metabolized by oxidation and glucuronidation. Tenofovir alafenamide is metabolized by cathepsin A in PBMCs and by CES1 in hepatocytes; systemic metabolism limited via CYP3A. |
| Excretion | Bictegravir: 60% feces (as parent), 35% urine (as parent); Emtricitabine: 86% urine (70% unchanged, 14% metabolites), 14% feces; Tenofovir alafenamide: <1% urine (as parent), >80% feces (as tenofovir), renal elimination of tenofovir (through active tubular secretion) accounts for ~30-50% of a TAF dose. |
| Half-life | Bictegravir: 17.3 h (HIV-1 patients); Emtricitabine: 10 h (HIV-1 patients); Tenofovir alafenamide: 0.51 h (rapid conversion to tenofovir); Tenofovir (active metabolite): 32-37 h (cellular half-life in PBMCs). |
| Protein binding | Bictegravir: >99% bound to human plasma proteins; Emtricitabine: <4% (low binding); Tenofovir alafenamide: ~80% bound to plasma proteins. |
| Volume of Distribution | Bictegravir: Vd/F ~1.1 L/kg; Emtricitabine: Vd/F ~1.4 L/kg; Tenofovir alafenamide: Vd/F ~0.4 L/kg. |
| Bioavailability | Bictegravir: 68% (fed state); Emtricitabine: 93% (fasted or fed); Tenofovir alafenamide: 40-50% (fasted), 30-40% (fed), lower when taken with high-fat meal. |
| Onset of Action | Oral: Antiviral effect begins within 24 hours; maximal suppression achieved by 2-4 weeks. |
| Duration of Action | 24 hours; once-daily dosing maintains therapeutic concentrations due to long intracellular half-life of tenofovir diphosphate and bictegravir pharmacokinetics. |
One tablet (50 mg bictegravir, 200 mg emtricitabine, 25 mg tenofovir alafenamide) orally once daily.
| Dosage form | TABLET |
| Renal impairment | Not recommended for CrCl <30 mL/min. No dose adjustment for CrCl ≥30 mL/min. |
| Liver impairment | No dose adjustment for mild or moderate hepatic impairment (Child-Pugh A or B). Not recommended for severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Approved for adolescents ≥35 kg: same as adult dosing (one tablet once daily). For children <35 kg: not approved. |
| Geriatric use | No dose adjustment required; monitor renal function due to age-related decline in 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 | FTC and TAF are excreted in human breast milk; data for BIC are unknown. The milk-to-plasma ratio for FTC is approximately 2.0; for tenofovir (from TAF), it is approximately 0.15. Because of the potential for HIV transmission, viral resistance, and adverse effects in the infant, breastfeeding is not recommended. |
| Teratogenic Risk |
■ FDA Black Box Warning
Post-treatment acute exacerbation of hepatitis B: Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine and/or tenofovir disoproxil fumarate. Monitor hepatic function closely in these patients for at least several months. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
| Common Effects | Hepatitis B |
| Serious Effects |
["Coadministration with rifampin","Coadministration with dofetilide","Coadministration with St. John's wort"]
| Precautions | ["Risk of hepatitis B exacerbation upon discontinuation in HBV-coinfected patients","Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, reported with nucleoside analogs","Immune reconstitution syndrome","New onset or worsening renal impairment: Tenofovir alafenamide may cause renal toxicity; assess serum creatinine, CrCl, urine glucose and urine protein before and during therapy","Decreased bone mineral density observed with tenofovir alafenamide; consider monitoring in patients with osteoporosis history","Drug interactions: Avoid coadministration with rifampin, St. John's wort, carbamazepine; monitor with methadone, hormonal contraceptives"] |
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| Evidence from Antiretroviral Pregnancy Registry shows no increased risk of major birth defects for bictegravir (BIC), emtricitabine (FTC), or tenofovir alafenamide (TAF) when used in the first trimester (prevalence 2.6%, 3.0%, and 3.1% respectively, compared to background 2.8%). For second and third trimesters, no increased fetal risks have been identified, but data are limited. Animal studies at human equivalent doses showed no teratogenicity for BIC or FTC; TAF showed no adverse developmental effects at exposures 13-28 times human dose. |
| Fetal Monitoring | Monitor HIV viral load and CD4 count at each trimester (baseline, 1st, 2nd, 3rd trimester). Assess renal function (serum creatinine, eGFR, urine protein) and hepatic function (ALT, AST, bilirubin) at baseline and every trimester. Perform pregnancy ultrasound for fetal growth and anatomy. Monitor for bone mineral density effects if prolonged use. Check for signs of lactic acidosis or hepatotoxicity during pregnancy. |
| Fertility Effects | No adverse effects on male or female fertility have been observed in animal studies at clinically relevant exposures. In humans, no specific fertility studies have been conducted; however, effective antiretroviral therapy improves overall health, which may normalize fertility in people with HIV. |
| Food/Dietary | No significant food interactions. Bioavailability of bictegravir and tenofovir alafenamide is enhanced with food, but not required. Avoid grapefruit juice? No known interaction; however, in general, avoid excessive grapefruit juice intake due to potential CYP3A inhibition. No other dietary restrictions. |
| Clinical Pearls | Bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy) is a complete HIV-1 regimen; no additional antiretrovirals needed. Monitor renal function (serum creatinine, eGFR) at baseline and periodically. Avoid coadministration with rifampin, St. John's wort, or other inducers of CYP3A or uridine diphosphate glucuronosyltransferase (UGT) 1A1. Bictegravir has a high barrier to resistance; no need for baseline resistance testing if no history of prior failure. Assess for hepatitis B coinfection before initiation; discontinuing therapy may cause severe HBV exacerbation. |
| Patient Advice | Take one tablet once daily with or without food. · Do not miss doses; adherence is critical to maintain viral suppression and avoid resistance. · Notify your doctor immediately if you experience signs of lactic acidosis (unusual muscle pain, difficulty breathing, severe tiredness) or liver problems (dark urine, yellowing skin/eyes, abdominal pain). · This drug does not cure HIV or prevent transmission; use condoms and practice safe sex. · Inform all healthcare providers you are taking this medication, as it may interact with other drugs. · Do not start new medications (prescription, OTC, or herbal) without consulting your doctor. · Kidney function monitoring is required; stay well hydrated. · If you have hepatitis B, do not stop this medication without medical supervision due to risk of severe liver flare. |