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. |
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 | 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 | Tenofovir is present in human milk at low levels; M/P ratio not reported. No adverse effects observed in breastfed infants; caution recommended. |
| 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. |
■ 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 |
["Coadministration with drugs that are potent inducers of P-glycoprotein and BCRP (e.g., rifampin, St. John's wort) which may lead to loss of virologic response and resistance"]
| 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"] |
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| 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. |