TRUVADA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRUVADA (TRUVADA).
Truvada is a combination of emtricitabine and tenofovir disoproxil fumarate, both nucleoside reverse transcriptase inhibitors (NRTIs). Emtricitabine and tenofovir are phosphorylated to active metabolites that compete with endogenous nucleotides and incorporate into viral DNA, causing chain termination and inhibiting HIV-1 reverse transcriptase.
| Metabolism | Emtricitabine is minimally metabolized via oxidation and glucuronidation; tenofovir disoproxil fumarate is a prodrug that is rapidly converted to tenofovir, which undergoes limited metabolism and is primarily excreted renally. |
| Excretion | Tenofovir disoproxil fumarate: ~70-80% unchanged in urine via glomerular filtration and active tubular secretion. Emtricitabine: ~86% unchanged in urine via glomerular filtration and active tubular secretion; 14% as metabolites. Biliary/fecal: <1% each. |
| Half-life | Tenofovir: terminal half-life ~17 hours (range 12-24h), allowing once-daily dosing; intracellular half-life of active diphosphate >60 hours. Emtricitabine: terminal half-life ~10 hours (range 7-12h); intracellular triphosphate half-life ~39 hours. |
| Protein binding | Tenofovir: <0.7% bound to plasma proteins. Emtricitabine: <4% bound to plasma proteins. |
| Volume of Distribution | Tenofovir: 0.8 L/kg, indicating wide distribution into tissues. Emtricitabine: 1.4 L/kg, extensively distributed into total body water including cerebrospinal fluid. |
| Bioavailability | Oral tenofovir disoproxil fumarate: 25% (fed); emtricitabine: 93% (fasted or fed). |
| Onset of Action | Oral: Not applicable for acute effect; antiretroviral activity begins with first dose; plasma concentrations reach steady-state within 7 days for tenofovir and 4-7 days for emtricitabine. |
| Duration of Action | Supports once-daily dosing due to long intracellular half-lives; missed dose up to 24 hours does not significantly alter suppression; clinical trials show maintained viral suppression for 48 weeks. |
| Brand Substitutes | Tenof EM Tablet, Forstavir-EM Tablet, Tavin EM Tablet, Ricovir EM 200 mg/300 mg Tablet, Emfovir Tablet |
One tablet (200 mg emtricitabine/300 mg tenofovir disoproxil fumarate) orally once daily.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-49 mL/min: one tablet every 48 hours. CrCl <30 mL/min or hemodialysis: not recommended. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe impairment (Child-Pugh C). |
| Pediatric use | Weight ≥35 kg: one tablet (200 mg emtricitabine/300 mg tenofovir disoproxil fumarate) orally once daily. |
| Geriatric use | No specific dose adjustment; use with caution due to increased frequency of renal impairment. Monitor renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRUVADA (TRUVADA).
| Breastfeeding | Both emtricitabine and tenofovir are excreted in human milk. The M/P ratio is approximately 1.0 for emtricitabine and 2.5 for tenofovir. Theoretical risk of neonatal HIV transmission if mother is HIV-positive; otherwise considered acceptable for HBV prevention in mother. Use with caution. |
| Teratogenic Risk | Truvada (emtricitabine/tenofovir disoproxil fumarate) is classified as FDA Pregnancy Category B. Animal studies showed no evidence of teratogenicity. However, tenofovir exposure has been associated with reduced fetal growth and bone mineral density in some human cohorts, but no increase in birth defects. First trimester use carries low risk; second/third trimester exposure may cause transient neonatal bone effects. |
■ FDA Black Box Warning
Post-treatment acute exacerbation of hepatitis B (HBV) has been reported in HBV-coinfected patients who discontinue Truvada. Hepatic function should be monitored closely in these patients. Also, lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with use of nucleoside analogs.
| Serious Effects |
["Hypersensitivity to emtricitabine, tenofovir, or any component","Concurrent use with other tenofovir-containing or emtricitabine-containing products","In PrEP, individuals with unknown or positive HIV-1 status"]
| Precautions | ["Lactic acidosis/severe hepatomegaly with steatosis","Renal impairment, including acute renal failure and Fanconi syndrome","Bone toxicity, including osteomalacia and decreased bone mineral density","Risk of HIV-1 resistance in PrEP if undiagnosed HIV-1 infection or nonadherence","Immune reconstitution syndrome","Fat redistribution/accumulation"] |
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| Fetal Monitoring | Monitor renal function (serum creatinine, urine protein), liver function tests, hepatitis B status, and HIV viral load monthly during pregnancy. Fetal ultrasound for growth and bone density if prolonged use. Newborn should be monitored for lactic acidosis, renal function, and bone density if exposed in utero. |
| Fertility Effects | No adverse effects on fertility reported in animal or human studies. Truvada does not impair spermatogenesis or oogenesis. HIV/HBV treatment may improve fertility by controlling underlying infection. |