TENOFOVIR ALAFENAMIDE FUMARATE
Clinical safety rating: safe
Other nephrotoxic drugs increase risk of renal impairment Can cause renal impairment and decreased bone mineral density.
Tenofovir alafenamide fumarate is a nucleotide reverse transcriptase inhibitor. It is a prodrug that is hydrolyzed intracellularly to tenofovir diphosphate, which inhibits HIV reverse transcriptase and hepatitis B virus polymerase by competing with the natural substrate deoxyadenosine 5'-triphosphate and by DNA chain termination after incorporation into viral DNA.
| Metabolism | Tenofovir alafenamide is primarily metabolized by cathepsin A in peripheral blood mononuclear cells and hepatocytes, and by carboxylesterase 1 in hepatocytes. It is not a substrate of CYP450 enzymes. |
| Excretion | Following oral administration, approximately 32% of the tenofovir alafenamide dose is excreted unchanged in urine via active tubular secretion and glomerular filtration; the remainder is eliminated as metabolites, primarily through fecal excretion (approximately 47%) and minor biliary elimination, with less than 1% excreted unchanged in feces. |
| Half-life | Terminal elimination half-life is approximately 0.51 hours (range 0.37-0.77 hours) for tenofovir alafenamide, while the active metabolite tenofovir diphosphate has a prolonged intracellular half-life of approximately 150-180 hours in PBMCs, supporting once-daily dosing. |
| Protein binding | Approximately 80% bound to plasma proteins, primarily to albumin (HSA) and, to a lesser extent, alpha-1-acid glycoprotein (AAG). |
| Volume of Distribution | Volume of distribution at steady state is approximately 0.88 L/kg (range 0.72-1.02 L/kg), indicating extensive distribution into extravascular tissues, including lymphoid tissue where active metabolite accumulates. |
| Bioavailability | Absolute bioavailability of tenofovir alafenamide following oral administration is approximately 40% (range 30-50%) under fed conditions; administration with a high-fat meal reduces AUC by approximately 15-20% compared to fasting state, but food does not significantly affect clinical efficacy. |
| Onset of Action | Oral administration: The time to peak plasma concentration (Tmax) is 0.5-1 hour post-dose; antiviral effect (HIV RNA reduction) is typically observed within 1-2 weeks of initiating therapy. |
| Duration of Action | The antiviral effect of once-daily dosing provides sustained suppression of HIV replication with intracellular tenofovir diphosphate concentrations maintained above the inhibitory threshold over 24 hours, allowing for once-daily administration. |
| Molecular Weight | 534.5 Da |
25 mg orally once daily with food.
| Dosage form | TABLET |
| Renal impairment | If CrCl ≥15 mL/min: no adjustment; CrCl <15 mL/min or hemodialysis: not recommended. |
| Liver impairment | Child-Pugh A or B: no adjustment; Child-Pugh C: not recommended. |
| Pediatric use | For patients weighing ≥25 kg: 25 mg orally once daily; for <25 kg: safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; monitor renal function due to age-related decline. |
| 1st trimester | Use is generally avoided unless benefit outweighs risk. Human data limited; animal studies show no teratogenicity at systemic exposures similar to human therapeutic exposure. HIV/HBV treatment may be continued. |
| 2nd trimester | Available data show no increased risk of major birth defects. Use is acceptable for treatment of HIV and HBV infection if clinically indicated. |
| 3rd trimester | No evidence of fetal harm. Continue therapy for HIV/HBV to prevent vertical transmission. Monitor for adverse effects specifically in the newborn (e.g., lactic acidosis, hepatic steatosis). |
Clinical note
Other nephrotoxic drugs increase risk of renal impairment Can cause renal impairment and decreased bone mineral density.
| FDA category | Animal |
| Placental transfer | Tenofovir alafenamide crosses the placenta. In ex vivo human placental perfusion studies, transfer of TAF is low (approximately 10% of maternal concentration). In vivo, cord blood concentrations are about 50-60% of maternal concentrations, indicating moderate placental transfer. The active metabolite, tenofovir diphosphate, accumulates in placental tissue. |
■ FDA Black Box Warning
No boxed warning currently exists for tenofovir alafenamide fumarate; however, tenofovir-containing products have warnings regarding lactic acidosis/severe hepatomegaly with steatosis and post-treatment acute exacerbation of hepatitis B.
| Common Effects | Hepatitis B |
| Serious Effects |
Concomitant use with drugs that are potent P-glycoprotein and/or BCRP inducers (e.g., rifampin, St. John's wort) resulting in loss of efficacy and possible resistanceKnown hypersensitivity to tenofovir alafenamide or any component of the formulation
| Precautions | New onset or worsening renal impairment, Lactic acidosis and severe hepatomegaly with steatosis, Exacerbation of hepatitis B upon discontinuation, Decreased bone mineral density, Immune reconstitution syndrome, Fat redistribution, Drug interactions with inducers of P-glycoprotein or BCRP |
| Food/Dietary |
Loading safety data…
| Breastfeeding | Tenofovir alafenamide is present in human milk at low concentrations. The estimated daily infant dose is <0.1% of the maternal dose and <1% of the pediatric dose for neonates. No adverse effects observed in breastfed infants. In HIV infection, breastfeeding is not recommended due to risk of postnatal transmission. For HBV, benefits of breastfeeding likely outweigh risks, but consultation with specialist advised. |
| Lactation Rating | L2 (Possibly Compatible) |
| Teratogenic Risk | Insufficient human data; animal studies show no evidence of teratogenicity at clinically relevant exposures. Risk cannot be excluded; use only if benefit outweighs risk. |
| Fetal Monitoring | Monitor renal function (serum creatinine, estimated GFR, urinalysis), hepatic function, and bone density during therapy. Assess HIV/HBV viral load and CD4 count periodically. |
| Fertility Effects | No evidence of impaired fertility in animal studies. Human data limited; unlikely to significantly affect fertility. |
| No significant food interactions; take with or without food. Avoid alcohol due to potential hepatotoxicity. |
| Clinical Pearls | TAF has lower renal and bone toxicity compared to TDF; monitor renal function (CrCl) before and during therapy; contraindicated in CrCl <15 mL/min (unless on dialysis); adjust dose in CrCl 15-29 mL/min; concomitant use with nephrotoxic drugs increases renal risk; may cause LFT elevations; test for HBV before initiating ART because TAF is active against HBV and discontinuation may cause HBV flare. |
| Patient Advice | Take exactly as prescribed, once daily with or without food. · Do not miss doses; if missed, take as soon as remembered unless close to next dose, then skip the missed dose. · Tell your doctor if you have kidney or liver disease, or hepatitis B infection. · Report symptoms of lactic acidosis (unusual muscle pain, trouble breathing, stomach pain with nausea/vomiting) or hepatotoxicity (yellow skin/eyes, dark urine, light stools). · Do not stop this medication without talking to your doctor, especially if you have hepatitis B. |