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.
Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) that is phosphorylated to emtricitabine triphosphate, which competes with the natural substrate deoxycytidine-5'-triphosphate and incorporates into viral DNA, causing chain termination. Tenofovir alafenamide is a nucleotide reverse transcriptase inhibitor (NtRTI) that is converted to tenofovir diphosphate, which inhibits HIV-1 reverse transcriptase by competing with the natural substrate deoxyadenosine-5'-triphosphate and incorporating into DNA, leading to chain termination.
| Metabolism | Emtricitabine is metabolized via oxidation and glucuronidation, with CYP enzymes minimally involved. Tenofovir alafenamide is metabolized by cathepsin A and carboxylesterase 1 to tenofovir; it is a substrate of P-glycoprotein and BCRP. |
| Excretion | Emtricitabine: primarily renal (86% unchanged) via glomerular filtration and active tubular secretion. Tenofovir alafenamide: metabolism to tenofovir, then renal (70-80% unchanged) via glomerular filtration and active tubular secretion; <1% fecal. |
| Half-life | Emtricitabine: terminal half-life ~10 hours (clinical context: supports once-daily dosing). Tenofovir alafenamide: terminal half-life ~0.5 hours (prodrug), but active tenofovir diphosphate intracellular half-life >60 hours in PBMCs (clinical context: supports once-daily dosing due to long intracellular persistence). |
| Protein binding | Emtricitabine: <4% bound to plasma proteins. Tenofovir alafenamide: ~80% bound to plasma proteins (mainly albumin). Tenofovir (active metabolite): <7% bound. |
| Volume of Distribution | Emtricitabine: Vd ~1.4 L/kg (extensive distribution into total body water). Tenofovir alafenamide: Vd ~0.8 L/kg (moderate distribution). |
| Bioavailability | Oral: emtricitabine ~93% (not significantly affected by food). Tenofovir alafenamide ~42% (fasting), increased to 65% with a high-fat meal (taken with food in clinical use). |
| Onset of Action | Oral: time to peak plasma concentration (Tmax) ~1-2 hours for both emtricitabine and tenofovir alafenamide; clinical antiviral effect begins within hours due to intracellular phosphorylation, but maximal suppression achieved after 1-2 weeks of dosing. |
| Duration of Action | Oral: duration of antiviral effect ~24 hours due to once-daily dosing; intracellular tenofovir diphosphate levels persist for >60 hours, allowing forgiveness if a dose is missed up to 24 hours late. |
One tablet (200 mg emtricitabine / 25 mg tenofovir alafenamide) orally once daily with food.
| Dosage form | TABLET |
| Renal impairment | Not recommended for patients with CrCl < 30 mL/min. For CrCl 30-50 mL/min: continue standard dose (no adjustment needed for tenofovir alafenamide). Emtricitabine requires dose interval adjustment if used alone, but as F/TAF fixed-dose, avoid if CrCl < 30 mL/min. No dose adjustment for CrCl ≥ 30 mL/min. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not recommended for severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Approved for patients weighing ≥ 25 kg. Dose: One tablet (200 mg emtricitabine / 25 mg tenofovir alafenamide) orally once daily with food. For children < 25 kg, use alternative formulations or dosing not available with this fixed-dose combination. |
| Geriatric use | No specific dose adjustment based on age alone. Monitor renal function closely; consider age-related renal impairment and adjust according to CrCl as per renal adjustment guidelines. |
| 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 | Both drugs are excreted in human milk; unknown M/P ratio. Risk of HIV transmission via breastfeeding; in resource-limited settings, WHO recommends breastfeeding on ART. Not recommended in US if alternatives available. |
| Teratogenic Risk | Insufficient human data; animal studies show no evidence of teratogenicity. Use during pregnancy only if clearly needed. Avoid in first trimester unless benefit outweighs risk. |
■ FDA Black Box Warning
WARNING: POST-TREATMENT ACUTE EXACERBATION OF HEPATITIS B and RISK OF DRUG RESISTANCE WITH USE FOR PrEP. Patients with HIV-1 and HBV coinfection who discontinue emtricitabine and tenofovir alafenamide should be closely monitored for severe acute exacerbations of hepatitis B. For PrEP, the drug must only be used in individuals confirmed to be HIV-1 negative; resistance may develop if used in undiagnosed HIV-1 infection.
| Common Effects | Hepatitis B |
| Serious Effects |
["Contraindicated in patients with unknown or positive HIV-1 status when used for PrEP","Contraindicated in patients with a history of hypersensitivity to emtricitabine, tenofovir alafenamide, or any component of the product"]
| Precautions | ["Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with NRTIs","Acute exacerbation of hepatitis B in coinfected patients upon discontinuation","New onset or worsening renal impairment; monitor serum creatinine and urine glucose/protein","Decreased bone mineral density; increased risk of fractures","Immune reconstitution syndrome","Risk of HIV-1 resistance if used for PrEP in undiagnosed infection"] |
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| Fetal Monitoring | Monitor renal function (serum creatinine, eGFR, urine glucose/protein) at baseline and periodically; monitor for anemia, lactic acidosis, hepatotoxicity. Fetal monitoring per standard obstetric care. |
| Fertility Effects | No clinically significant effects on fertility reported in animal or human studies. |