EMTRICITABINE; RILPIVIRINE; TENOFOVIR ALAFENAMIDE
Clinical safety rating: safe
Other nephrotoxic drugs increase risk of renal impairment Can cause renal impairment and decreased bone mineral density.
Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI); rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI); tenofovir alafenamide is an NRTI. Combination inhibits HIV-1 replication by blocking reverse transcriptase.
| Metabolism | Emtricitabine: minimal metabolism; Rilpivirine: metabolized primarily by CYP3A4; Tenofovir alafenamide: hydrolyzed to tenofovir by cathepsin A in hepatocytes and by carboxylesterase 1 in peripheral blood mononuclear cells, then further metabolized by intracellular kinases to tenofovir diphosphate. |
| Excretion | Emtricitabine: 86% renal (glomerular filtration and active tubular secretion), 14% fecal. Rilpivirine: 85% fecal (65% as parent drug), 6.1% renal (negligible unchanged). Tenofovir alafenamide: <1% renal; >80% fecal as metabolites; hydrolyzed intracellularly to tenofovir, which is eliminated renally (70-80% unchanged) via glomerular filtration and active tubular secretion. |
| Half-life | Emtricitabine: 10 h (healthy subjects); 8-9 h (HIV-1 infected, once-daily dosing achieves therapeutic plasma concentrations). Rilpivirine: 45 h (terminal, supports once-daily dosing). Tenofovir alafenamide: 0.51 h (parent); tenofovir metabolite: 32-37 h (intracellular, supports once-daily dosing). |
| Protein binding | Emtricitabine: <4% (no specific binding). Rilpivirine: 99.7% (plasma proteins, primarily albumin). Tenofovir alafenamide: ~80% (plasma proteins, primarily albumin). |
| Volume of Distribution | Emtricitabine: 1.4 L/kg (extensive distribution into tissues including PBMCs). Rilpivirine: 152 L (total, not weight-adjusted; extensive tissue distribution). Tenofovir alafenamide: 0.3 L/kg (moderate; concentrates in PBMCs and other target tissues). |
| Bioavailability | Emtricitabine: 93% (oral). Rilpivirine: 32% (oral with food, increases ~50% with normal-calorie meal). Tenofovir alafenamide: 25% (oral with food; increased 60% with high-fat meal). |
| Onset of Action | Oral: Emtricitabine: peak plasma concentration 1-2 h; Rilpivirine: peak 4-5 h; Tenofovir alafenamide: peak 0.5-1 h. Virologic suppression typically achieved within 4-8 weeks of once-daily dosing. |
| Duration of Action | Once-daily dosing maintains plasma and intracellular concentrations above therapeutic thresholds for 24 h. Rilpivirine has a long half-life allowing forgiveness of occasional delayed doses. Tenofovir alafenamide intracellular tenofovir-diphosphate half-life >60 h in PBMCs. |
One tablet (emtricitabine 200 mg, rilpivirine 25 mg, tenofovir alafenamide 25 mg) orally once daily with a meal.
| Dosage form | TABLET |
| Renal impairment | Not recommended in patients with CrCl <30 mL/min. No dose adjustment required for CrCl ≥30 mL/min. |
| Liver impairment | Contraindicated in Child-Pugh class B or C hepatic impairment. Use with caution in mild hepatic impairment (Child-Pugh class A). |
| Pediatric use | Approved for patients weighing ≥35 kg: one tablet (emtricitabine 200 mg, rilpivirine 25 mg, tenofovir alafenamide 25 mg) orally once daily with a meal. Not recommended for patients <35 kg. |
| Geriatric use | No specific dose adjustment recommended. 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 | Emtricitabine: Excreted in human milk, M/P ratio ~1.0 (animal data), infant dose ~2% of maternal dose. Rilpivirine: Excreted in human milk, M/P ratio ~0.5 (animal data), infant exposure low. Tenofovir alafenamide: Excreted in human milk in animals; human data not available. Breastfeeding not recommended in HIV+ women to avoid postnatal transmission; if used, benefits of breastfeeding vs. risk of transmission should be considered. |
| Teratogenic Risk |
■ FDA Black Box Warning
WARNING: POST-TREATMENT ACUTE EXACERBATION OF HEPATITIS B. Severe acute exacerbations of hepatitis B (HBV) have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine and/or tenofovir disoproxil fumarate, and may occur with tenofovir alafenamide. Hepatic function should be monitored closely in these patients.
| Common Effects | Hepatitis B |
| Serious Effects |
["Co-administration with rifampin, rifapentine, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, St. John's wort, or other strong CYP3A inducers","Severe hepatic impairment (Child-Pugh class C)","History of hypersensitivity to any component"]
| Precautions | ["Post-treatment acute exacerbation of hepatitis B (see boxed warning)","New onset or worsening renal impairment: monitor renal function before and during therapy","Risk of hepatotoxicity, especially in patients with underlying liver disease or coinfection with hepatitis C","Depressive disorders: monitor for depressive symptoms","Bone mineral density reductions and increased fracture risk with tenofovir alafenamide","Immune reconstitution syndrome","Fat redistribution and accumulation","Lactic acidosis and severe hepatomegaly with steatosis (rare)"] |
Loading safety data…
| Emtricitabine: No significant teratogenic risk in animal studies; human data from Antiretroviral Pregnancy Registry show no increased risk of major birth defects (first trimester prevalence 2.3%, second/third trimester 2.5%). Rilpivirine: No increased risk of birth defects; limited human data. Tenofovir alafenamide: No teratogenic risk observed in animals; human data show no increased birth defects. Overall, risk of major malformations is low across all trimesters, but data are limited. |
| Fetal Monitoring | Monitor HIV viral load and CD4 count regularly; assess liver function tests, renal function (serum creatinine, eGFR, urine protein), and bone density periodically. Screen for hepatitis B co-infection (TDF component). Fetal ultrasound for growth and anatomy as per standard obstetrical care; no specific fetal monitoring required. Consider drug interaction checks with concomitant medications. |
| Fertility Effects | No evidence of adverse effects on male or female fertility in animal studies. Emtricitabine, rilpivirine, and tenofovir alafenamide do not impair fertility in humans. HIV infection itself may reduce fertility. No impact on assisted reproductive technologies. |