VEMLIDY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VEMLIDY (VEMLIDY).
VEMLIDY (tenofovir alafenamide) is a nucleotide analog reverse transcriptase inhibitor. It is a prodrug that is converted intracellularly to tenofovir, which inhibits HIV reverse transcriptase by incorporating into viral DNA and causing chain termination.
| Metabolism | Metabolized by cathepsin A in PBMCs and CES1 in hepatocytes to form tenofovir. Minimal CYP450 involvement. |
| Excretion | Primarily renal (67% unchanged via glomerular filtration and active tubular secretion) and biliary/fecal (22%), with minor metabolism (12%). |
| Half-life | Approximately 12.9 hours; supports once-daily dosing. |
| Protein binding | Approximately 80% bound to human plasma proteins. |
| Volume of Distribution | Approximately 1.5 L/kg; indicates extensive tissue distribution, including penetration into hepatic cells. |
| Bioavailability | Oral: Approximately 25% under fasting conditions; increased by ~30% with high-fat meal. |
| Onset of Action | Oral: Inhibition of HBV replication observed within 2–4 weeks. |
| Duration of Action | 24 hours; maintains antiviral effect throughout dosing interval due to long intracellular half-life of active metabolite (tenofovir diphosphate). |
| Molecular Weight | 476.94 Da |
25 mg orally once daily with food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR >=15 mL/min. Not recommended in end-stage renal disease (ESRD) (GFR <15 mL/min) unless on hemodialysis; if on hemodialysis, administer after dialysis. |
| Liver impairment | No dose adjustment required for Child-Pugh A, B, or C cirrhosis. |
| Pediatric use | Approved for pediatric patients >=12 years and weighing >=35 kg: 25 mg orally once daily with food. |
| Geriatric use | No specific dose adjustment recommended; caution due to age-related renal impairment. |
| 1st trimester | Limited human data; animal studies show no evidence of fetal harm. Use only if clearly needed. |
| 2nd trimester | No well-controlled studies in pregnant women; use only if potential benefit justifies risk to fetus. |
| 3rd trimester | No well-controlled studies in pregnant women; use only if potential benefit justifies risk to fetus. |
Clinical note
Comprehensive clinical and safety monograph for VEMLIDY (VEMLIDY).
| Placental transfer | Tenofovir alafenamide and its metabolite tenofovir cross the placenta in humans, achieving detectable levels in cord blood. Animal studies show transfer of tenofovir across the placenta. |
| Breastfeeding | It is not known if tenofovir alafenamide is excreted in human milk. However, tenofovir, the metabolite, is present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for VEMLIDY and any potential adverse effects on the breastfed infant from the drug or underlying maternal condition. |
■ FDA Black Box Warning
Severe acute exacerbation of hepatitis B has been reported in patients who are coinfected with HBV and HIV-1 and have discontinued VEMLIDY. Hepatic function should be monitored closely in these patients.
| Serious Effects |
Hypersensitivity to tenofovir alafenamide or any component of the formulation
| Precautions | Exacerbation of hepatitis B upon discontinuation, Risk of lactic acidosis and severe hepatomegaly with steatosis, Renal impairment: monitor renal function and avoid use in patients with CrCl <15 mL/min, Bone mineral density reduction and osteomalacia, Immune reconstitution syndrome, Decrease in hepatic function in patients with decompensated cirrhosis |
| Food/Dietary | Take with a meal containing about 400-600 calories. High-fat meals increase absorption significantly. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Tenofovir alafenamide (VEMLIDY) is classified as FDA Pregnancy Category B. No increased risk of major birth defects has been observed in human studies. First trimester: limited data but no evidence of teratogenicity. Second and third trimesters: No increased risk of fetal adverse outcomes reported; however, placental transfer occurs. Use only if clearly needed. |
| Fetal Monitoring | Monitor hepatic function (ALT, AST, bilirubin) at baseline and periodically during therapy. Assess renal function (serum creatinine, estimated creatinine clearance) before initiating and routinely during treatment. Monitor for hepatitis B exacerbation if therapy is discontinued. No specific fetal monitoring is required beyond routine prenatal care. |
| Fertility Effects | No data on the effect of tenofovir alafenamide on female or male fertility. Animal studies showed no impairment of fertility. Clinical relevance in humans is unknown. |
| Clinical Pearls | Monitor renal function prior to and during therapy; not recommended in patients with estimated creatinine clearance <15 mL/min. Test for HIV before initiating, as tenofovir alafenamide can select for HIV resistance. May be used in patients with decompensated cirrhosis (Child-Pugh B/C). |
| Patient Advice | Take with food to increase absorption. · Do not skip doses or stop without consulting your doctor. · Report any signs of lactic acidosis (unexplained muscle pain, trouble breathing, stomach pain) or liver problems (dark urine, jaundice). · Get regular blood tests to monitor kidney function and hepatitis B status. · Use effective contraception if of childbearing potential; discuss pregnancy plans. |