EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE
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) that is phosphorylated to emtricitabine triphosphate, which inhibits HIV reverse transcriptase by competing with natural substrate and causing chain termination. Tenofovir disoproxil fumarate is a prodrug of tenofovir, an acyclic nucleoside phosphonate diester analog of adenosine monophosphate; it inhibits HIV reverse transcriptase and hepatitis B virus polymerase by incorporating into DNA and causing chain termination after conversion to tenofovir diphosphate.
| Metabolism | Emtricitabine is minimally metabolized; tenofovir disoproxil fumarate is converted to tenofovir by esterases and then to tenofovir diphosphate intracellularly. Tenofovir is eliminated renally by glomerular filtration and active tubular secretion. |
| Excretion | Emtricitabine: 86% excreted unchanged in urine via glomerular filtration and active tubular secretion; 14% metabolized to 3'-sulfoxide diastereomers and glucuronide conjugates, with <1% excreted in feces. Tenofovir disoproxil fumarate: Tenofovir is eliminated by a combination of glomerular filtration and active tubular secretion, with 70-80% of the dose recovered as unchanged tenofovir in urine within 72 hours; renal excretion is the primary route. |
| Half-life | Emtricitabine: Terminal elimination half-life is approximately 10 hours (range 8-14 hours) in patients with normal renal function; prolonged to >200 hours in severe renal impairment. Tenofovir: Terminal elimination half-life of tenofovir is approximately 17 hours (range 12-18 hours) in patients with normal renal function; prolonged in renal impairment. Clinically, the long half-life supports once-daily dosing. |
| Protein binding | Emtricitabine: <4% bound to plasma proteins (minimal). Tenofovir: <0.7% bound to plasma proteins (minimal). Neither drug binds to alpha-1-acid glycoprotein or albumin significantly. |
| Volume of Distribution | Emtricitabine: Apparent volume of distribution is approximately 1.4 L/kg (range 1.0-1.7 L/kg), indicating extensive distribution into total body water and tissues. Tenofovir: Volume of distribution at steady state is approximately 1.3 L/kg (range 1.0-1.6 L/kg), suggesting distribution into most body tissues including genital tract, lymphoid tissue, and PBMCs. |
| Bioavailability | Oral bioavailability: Emtricitabine: approximately 93% (range 88-98%) in healthy subjects; unaffected by food. Tenofovir disoproxil fumarate: Oral bioavailability of tenofovir is approximately 25% (range 20-30%) under fasting conditions; increased to 40-50% when administered with a high-fat meal. For the fixed-dose combination tablet, administration with or without food does not significantly affect overall exposure. |
| Onset of Action | Oral administration: Time to peak plasma concentration (Tmax) for emtricitabine is 1-2 hours; for tenofovir, 1-2 hours following oral absorption of tenofovir disoproxil fumarate. Antiviral effect begins within hours of first dose, with maximal suppression of HIV-1 RNA achieved within 2-4 weeks. |
| Duration of Action | Due to the long half-life of both components, the antiviral effect persists for at least 24 hours after a single oral dose, supporting once-daily dosing. Steady-state concentrations are achieved within 7 days of daily dosing. No significant accumulation beyond steady state. |
| Molecular Weight | Emtricitabine: 247.24 Da; Tenofovir disoproxil fumarate: 635.52 Da (tenofovir disoproxil: 519.44 Da; fumarate: 116.07 Da) |
One tablet (200 mg emtricitabine/300 mg tenofovir disoproxil fumarate) orally once daily.
| Dosage form | TABLET |
| Renal impairment | CrCl >= 50 mL/min: One tablet q24h. CrCl 30-49 mL/min: One tablet q48h. 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 hepatic impairment (Child-Pugh C). |
| Pediatric use | Children weighing ≥35 kg: One tablet (200/300 mg) orally once daily. For children <35 kg, use weight-based dosing of individual components or alternative formulations. |
| Geriatric use | No specific dose adjustment recommended; select dose based on renal function (CrCl) as elderly patients often have decreased renal function. |
| 1st trimester | Data from the Antiretroviral Pregnancy Registry show no increased risk of major birth defects with first-trimester exposure. However, use only if clearly needed due to limited data. |
| 2nd trimester | Considered safe in pregnancy for HIV treatment and pre-exposure prophylaxis (PrEP) when benefit outweighs risk. No known fetal toxicity. |
| 3rd trimester | Safe for use; tenofovir disoproxil fumarate can cause reduced bone mineral density in neonates but clinical significance is minimal. Emtricitabine is not associated with significant adverse effects. |
Clinical note
Other nephrotoxic drugs increase risk of renal impairment Can cause renal impairment and decreased bone mineral density.
| FDA category | Animal |
| Placental transfer | Both emtricitabine and tenofovir cross the placenta. Tenofovir has moderate transfer (cord blood levels ~60% of maternal), emtricitabine has high transfer (cord blood levels ~100% of maternal). |
■ 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 emtricitabine/tenofovir disoproxil fumarate. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue the drug.
| Common Effects | Hepatitis B |
| Serious Effects |
Hypersensitivity to any componentConcurrent use with other tenofovir-containing productsSevere renal impairment (CrCl <30 mL/min) for fixed-dose combination
| Precautions | New onset or worsening renal impairment: Assess creatinine clearance before and during therapy; avoid with CrCl <30 mL/min if using for PrEP or adjust dose if treating HIV., Lactic acidosis/severe hepatomegaly with steatosis: including fatal cases, especially in females and obese patients., Bone toxicity: Decreases in bone mineral density observed; consider monitoring in patients with pathological fractures., Immune reconstitution syndrome: may occur, including autoimmune disorders., Fat redistribution: central obesity, dorsocervical fat accumulation, peripheral wasting, breast enlargement, cushingoid appearance., Risk of HIV-1 transmission reduction: PrEP does not eliminate risk; adherence is critical. |
Loading safety data…
| Breastfeeding | Both drugs are secreted into human breast milk at low levels. In HIV-infected women, breastfeeding is not recommended to avoid transmission. In HIV-negative women on PrEP, the risk to the infant is considered low, but data are limited. |
| Lactation Rating | L3 |
| Teratogenic Risk | No increased risk of birth defects or fetal toxicity has been observed in human pregnancies exposed to emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) during the first trimester. The Antiretroviral Pregnancy Registry reports a prevalence of birth defects of 2.3% with first-trimester exposure, similar to the background rate. Sufficient prospective data exist to exclude a major teratogenic risk. For second and third trimesters, no evidence of fetal harm has been reported, but data are limited. |
| Fetal Monitoring | Monitor maternal HIV-1 viral load, CD4 count, and hepatic function (including ALT, AST) throughout pregnancy. Assess renal function (serum creatinine and calculated creatinine clearance) at baseline and periodically given tenofovir's potential for renal toxicity. Monitor for signs of lactic acidosis or hepatomegaly with steatosis. Fetal monitoring includes ultrasound to assess growth and development, especially if maternal disease progression occurs. Perform HIV-1 viral load testing at delivery to guide neonatal prophylaxis. |
| Fertility Effects | No adverse effects on fertility have been reported with emtricitabine and tenofovir disoproxil fumarate in human studies. In animal studies, no significant effects on mating, fertility, or reproductive performance were observed. There is no evidence that FTC/TDF impairs fertility in men or women. |
| Food/Dietary | None clinically significant. May be taken with or without food. High-fat meals slightly increase absorption but no dose adjustment needed. |
| Clinical Pearls | Monitor renal function (SCr, CrCl, urine glucose, urine protein) before and during therapy. CrCl <30 mL/min is a contraindication for TDF. Test for HBV co-infection before initiation; discontinuation may cause severe HBV exacerbation. Coadministration with nephrotoxic drugs increases AKI risk. Avoid in CrCl <30 if using TDF component. Dose adjustment needed for CrCl 30-49: extended interval. |
| Patient Advice | Take one tablet daily at approximately the same time with or without food. · Do not stop or miss doses; stopping can worsen hepatitis B infection. · Report symptoms of lactic acidosis (unusual tiredness, muscle pain, stomach pain, trouble breathing) or liver problems (yellow skin/eyes, dark urine, light stools). · Get regular kidney function tests as advised. · Use effective contraception; discuss pregnancy risks and breastfeeding. · Not for use as PEP or PrEP in individuals with CrCl <30 mL/min. · Avoid NSAIDs like ibuprofen without consulting doctor due to kidney risk. · Store at room temperature, keep out of reach of children. |