TENOFOVIR ALAFENAMIDE
Clinical safety rating: safe
Other nephrotoxic drugs increase risk of renal impairment Can cause renal impairment and decreased bone mineral density.
Tenofovir alafenamide is a nucleotide reverse transcriptase inhibitor that, after intracellular conversion to tenofovir diphosphate, inhibits HIV-1 and HBV reverse transcriptase 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 (CatA) in peripheral blood mononuclear cells and by carboxylesterase 1 (CES1) in hepatocytes; it also undergoes minimal CYP3A-mediated metabolism. It is not a substrate for renal transporters or P-glycoprotein. |
| Excretion | Renal elimination: ~70% unchanged via glomerular filtration and active tubular secretion; fecal: 2–5%; biliary: <1%. |
| Half-life | Terminal elimination half-life: 0.51 hours for tenofovir alafenamide, but active metabolite tenofovir diphosphate has intracellular half-life ~150–180 hours in PBMCs, supporting once-daily dosing. |
| Protein binding | ~80% bound to plasma proteins (albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Vd: 83–96 L (approximately 1.2 L/kg) indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability: ~40% (fasted) to 50% (with high-fat meal) due to efflux transport; food increases AUC by ~60%. |
| Onset of Action | Oral: antiviral effect detectable within 1–2 hours; maximal suppression of HBV DNA or HIV RNA occurs over weeks. |
| Duration of Action | Oral: clinical antiviral effect persists for 24 hours with once-daily dosing due to long intracellular half-life of tenofovir diphosphate. |
| Molecular Weight | 477.3 |
25 mg orally once daily with food for HIV-1 infection; 25 mg orally once daily for chronic hepatitis B.
| Dosage form | TABLET |
| Renal impairment | CrCl >=15 mL/min: no adjustment; CrCl <15 mL/min or on hemodialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B or C: not recommended. |
| Pediatric use | For HIV-1: age >=12 years and weight >=35 kg: 25 mg orally once daily with food. |
| Geriatric use | No specific dose adjustment; monitor renal function due to age-related decline. |
| 1st trimester | No evidence of increased risk of major birth defects; use if benefit outweighs risk. |
| 2nd trimester | No evidence of fetal harm; use if indicated. |
| 3rd trimester | No evidence of fetal harm; use if indicated. |
Clinical note
Other nephrotoxic drugs increase risk of renal impairment Can cause renal impairment and decreased bone mineral density.
| FDA category | Animal |
| Placental transfer | Passes placenta; cord blood concentrations ~50% of maternal plasma. |
| Breastfeeding | Minimal excretion into breast milk; infant dose <1% of therapeutic dose. Consider benefit of breastfeeding versus risk of infant exposure. |
■ FDA Black Box Warning
WARNING: POST-TREATMENT ACUTE EXACERBATION OF HEPATITIS B. Discontinuation of anti-hepatitis B therapy may result in severe acute exacerbations of hepatitis B. Patients with hepatitis B infection who discontinue tenofovir alafenamide should be closely monitored with clinical and laboratory follow-up for at least several months.
| Common Effects | Hepatitis B |
| Serious Effects |
Hypersensitivity to tenofovir alafenamide or any component
| Precautions | New onset or worsening renal impairment: increased risk in patients with underlying renal disease or taking nephrotoxic agents, Lactic acidosis/severe hepatomegaly with steatosis: reported with nucleoside analogs, Decreases in bone mineral density: observed in HIV-treated patients, Immune reconstitution syndrome: may occur when used in combination with antiretrovirals, Risk of hepatitis B exacerbation upon discontinuation |
| Food/Dietary |
Loading safety data…
| Lactation Rating | L2 |
| Teratogenic Risk | Human data on tenofovir alafenamide (TAF) in pregnancy are limited. Animal studies show no teratogenicity at exposures up to 20 times human exposure. In the Antiretroviral Pregnancy Registry, there is no evidence of increased risk of major birth defects with first-trimester exposure (prevalence 2.7 per 100 live births). However, spontaneous abortions and preterm labor have been reported. Risk is considered low, but use only if clearly needed. |
| Fetal Monitoring | Monitor maternal liver function tests, renal function (serum creatinine, eGFR), and urine protein. Monitor fetal growth via ultrasound in third trimester. In HIV-positive women, monitor maternal HIV viral load and CD4 count. Newborn should be tested for HIV infection after birth. |
| Fertility Effects | No direct effect on fertility observed in animal studies. In humans, no significant impairment of male or female fertility reported. However, underlying disease (e.g., HIV) may affect fertility. |
| TAF should be taken with a meal—high-fat meals increase absorption. No specific food restrictions, but consistent intake with food is recommended to maintain steady drug levels. Grapefruit is not known to interact with TAF. |
| Clinical Pearls | Tenofovir alafenamide (TAF) has lower renal and bone toxicity compared to tenofovir disoproxil fumarate (TDF). Monitor renal function and serum phosphate at baseline and periodically. TAF is a substrate of P-glycoprotein; avoid co-administration with strong P-gp inducers (e.g., rifampin, St. John's wort). Do not use TAF in patients with eGFR <15 mL/min unless on hemodialysis. Dose reduction recommended for eGFR 15-29 mL/min. TAF is not recommended in patients with decompensated cirrhosis (Child-Pugh B or C) for hepatitis B treatment. |
| Patient Advice | Take TAF with food to improve absorption. · Do not miss doses; if a dose is missed, take it as soon as remembered unless it is almost time for the next dose – do not double up. · Do not breastfeed while taking TAF if you have HIV, as HIV can be transmitted through breast milk. · Report symptoms of lactic acidosis (unusual muscle pain, trouble breathing, stomach pain with nausea/vomiting) or hepatotoxicity (yellowing of skin/eyes, dark urine, light stools) immediately. · TAF does not prevent the transmission of HIV or hepatitis B to others; use condoms and avoid sharing needles. · Avoid St. John's wort and rifampin while on TAF, as they reduce drug levels. · If you have chronic hepatitis B, do not stop TAF without consulting your doctor, as your hepatitis may worsen. · You may experience weight gain – discuss healthy lifestyle changes with your doctor. |