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. |
| Molecular Weight | 589.54 Da (for the fixed-dose combination; emtricitabine 247.25 Da, tenofovir disoproxil fumarate 635.52 Da, reported as the sum of the two active components) |
| 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 | Use only if clearly needed. There are limited human data, but animal studies have shown reproductive toxicity. No evidence of teratogenicity in humans at therapeutic doses. |
| 2nd trimester | Use only if clearly needed. No known increased risk of malformations. Monitor for anemia and lactic acidosis. |
| 3rd trimester | Use may be considered if benefits outweigh risks. Cases of lactic acidosis and hepatic steatosis have been reported with nucleoside analogues. Monitor liver function and lactate levels. |
Clinical note
Comprehensive clinical and safety monograph for TRUVADA (TRUVADA).
| Placental transfer | Both emtricitabine and tenofovir cross the placenta. Emtricitabine reaches cord blood levels approximately equal to maternal levels; tenofovir cord blood levels are about 60% of maternal levels. |
| Breastfeeding | Emtricitabine and tenofovir disoproxil fumarate are excreted into human milk. The effects on the nursing infant are unknown. Due to the potential for HIV transmission via breastfeeding and adverse effects in the infant, breastfeeding is not recommended for HIV-positive mothers. In HIV-negative mothers, caution is advised. |
■ 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 disoproxil fumarate, or any component of the formulationCo-administration with other antiviral agents containing emtricitabine, tenofovir, or lamivudineCo-administration with adefovir dipivoxil
| 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 |
| Food/Dietary | No significant food interactions. Truvada may be taken with or without food. A high-fat meal may slow absorption but does not affect overall exposure. Avoid grapefruit juice as it may alter drug levels (minimal clinical significance). |
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| Lactation Rating | L4 (Possibly Hazardous) |
| 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. |
| 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. |
| Clinical Pearls | Truvada (emtricitabine/tenofovir disoproxil fumarate) is indicated for HIV-1 pre-exposure prophylaxis (PrEP) and in combination with other antiretrovirals for HIV-1 treatment. For PrEP, confirm HIV-negative status before initiation and every 3 months thereafter. Monitor renal function (serum creatinine, urine glucose, urine protein) at baseline and periodically; tenofovir can cause proximal tubulopathy and decreased bone mineral density. In HIV treatment, always use as part of a fully suppressive regimen; avoid in patients with CrCl <30 mL/min. Dose adjust in renal impairment: for PrEP, if CrCl <60 mL/min, do not initiate; for treatment, reduce dose if CrCl 30-49 mL/min. Emtricitabine/tenofovir has activity against HBV; monitor for HBV flares upon discontinuation. Drug interactions: avoid concurrent or recent use of nephrotoxic agents (e.g., aminoglycosides, NSAIDs, IV vancomycin). |
| Patient Advice | Take Truvada exactly as prescribed, typically one tablet daily, with or without food. · For PrEP, it takes about 7 days for maximum protection for anal sex and 21 days for vaginal sex; use condoms consistently during this period. · Do not miss doses; if you miss a dose, take it as soon as you remember unless it's almost time for the next dose—then skip the missed dose. · Get tested for HIV every 3 months while taking Truvada for PrEP; if you become HIV-positive, you must stop Truvada and switch to a full HIV treatment regimen. · Report symptoms of kidney problems: decreased urination, swelling in legs or ankles, or back pain. · Do not take Truvada if you have untreated hepatitis B; discuss with your healthcare provider. · Avoid taking NSAIDs (like ibuprofen or naproxen) regularly without consulting your provider, as they may increase risk of kidney damage. · Store Truvada at room temperature (15-30°C / 59-86°F), away from moisture and heat. |