VEMLIDY

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VEMLIDY (VEMLIDY).

How it works

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.

What the body does with it

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).

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VEMLIDY (VEMLIDY).

Breastfeeding	Tenofovir is excreted in human breast milk at low levels. The milk-to-plasma ratio is approximately 1.2 for tenofovir. However, data specific to tenofovir alafenamide are limited. Caution is advised; risk to the nursing infant is considered low.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Concomitant use with drugs that are P-glycoprotein or BCRP inducers (e.g., rifampin, St. John's wort)","Coadministration with another antiretroviral agent containing tenofovir (e.g., tenofovir disoproxil fumarate, emtricitabine/tenofovir)"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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VEMLIDY

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VEMLIDY (VEMLIDY).

How it works

What the body does with it

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).

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VEMLIDY (VEMLIDY).

Breastfeeding	Tenofovir is excreted in human breast milk at low levels. The milk-to-plasma ratio is approximately 1.2 for tenofovir. However, data specific to tenofovir alafenamide are limited. Caution is advised; risk to the nursing infant is considered low.
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.