TENOFOVIR DISOPROXIL FUMARATE

Clinical safety rating: safe

Other nephrotoxic drugs increase risk of renal impairment Can cause renal impairment and decreased bone mineral density.

How it works

Nucleotide reverse transcriptase inhibitor; tenofovir diphosphate competitively inhibits HIV-1 and HBV reverse transcriptase and incorporates into viral DNA causing chain termination.

What the body does with it

Metabolism	Tenofovir disoproxil fumarate is a prodrug that is converted to tenofovir by plasma and tissue esterases; tenofovir is not significantly metabolized by CYP450 enzymes; eliminated renally by glomerular filtration and active tubular secretion.
Excretion	Renal: ~70-80% unchanged via glomerular filtration and active tubular secretion; minimal biliary/fecal (<1% as unchanged drug).
Half-life	Terminal elimination half-life: ~17 hours in HIV-infected patients; prolonged to ~28 hours in renal impairment (CrCl <50 mL/min).
Protein binding	<0.7% bound to plasma proteins (minimal).
Volume of Distribution	1.2-1.3 L/kg; suggests distribution into total body water, with extensive distribution into tissues (e.g., kidney, liver, lymphoid tissue).
Bioavailability	Oral: ~25% (under fasted conditions); increases to ~39% with high-fat meal.
Onset of Action	Oral: Not applicable (prodrug); active metabolite tenofovir diphosphate reaches steady-state intracellular concentrations in 7-14 days.
Duration of Action	Intracellular half-life of tenofovir diphosphate: ~60 hours, supporting once-daily dosing; plasma drug levels persist for >24 hours.

Classification & Brands

Dosing & administration

300 mg orally once daily with food.

Dosage form	TABLET
Renal impairment	CrCl ≥50 mL/min: 300 mg every 24 hours; CrCl 30-49 mL/min: 300 mg every 48 hours; CrCl 10-29 mL/min: 300 mg twice weekly; CrCl <10 mL/min or hemodialysis: not recommended; if benefit outweighs risk, 300 mg every 7 days.
Liver impairment	No dose adjustment required for mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, C).
Pediatric use	Approved for HIV-1 in patients ≥2 years weighing ≥10 kg: weight 10-14 kg: 150 mg once daily; 15-22 kg: 200 mg once daily; 23-28 kg: 250 mg once daily; >28 kg: 300 mg once daily. For chronic hepatitis B, approved in patients ≥12 years weighing ≥35 kg: 300 mg once daily.
Geriatric use	Use with caution due to age-related renal impairment; select dose based on renal function (CrCl). Start at lower end of dosing range if CrCl ≥50 mL/min; otherwise adjust per renal guidelines. Monitor renal function frequently.

Use during pregnancy

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 disoproxil fumarate is excreted into human breast milk. The M/P ratio is not established. Limited data suggest low infant exposure, but caution is recommended. Weigh benefits of breastfeeding against potential risk of infant exposure.
Teratogenic Risk	Tenofovir disoproxil fumarate is classified as FDA Pregnancy Category B. No increased risk of major birth defects or miscarriage has been observed in human studies. however, routine surveillance is recommended. For the first trimester, risk of major malformations is not significantly different from background rate. For the second and third trimesters, no specific fetal risks have been identified, but caution is advised due to potential for lactic acidosis and hepatic steatosis in the mother.

Warnings & precautions

■ FDA Black Box Warning

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases; post-treatment acute exacerbation of hepatitis B.

Side Effect Profile

Common Effects	Diarrhea Nausea Rash Weakness Vomiting Fatigue Abdominal pain Increased transaminase level in blood Decreased phosphate level in blood Pain Dizziness Depression Insomnia difficulty in sleeping Fever Itching
Serious Effects

Absolute Contraindications

Concomitant use with didanosine increases risk of toxicity; concomitant use with adefovir dipivoxil; hypersensitivity reaction to tenofovir or any component of the formulation.

Clinical Precautions

Precautions

New onset or worsening renal impairment; decrease in bone mineral density; redistribution/accumulation of body fat; immune reconstitution syndrome; coinfection with HIV and HBV risk of HBV exacerbation upon discontinuation.

Clinical Tips & Counseling

Drug interactions

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TENOFOVIR DISOPROXIL FUMARATE

Clinical safety rating: safe

Other nephrotoxic drugs increase risk of renal impairment Can cause renal impairment and decreased bone mineral density.

How it works

Nucleotide reverse transcriptase inhibitor; tenofovir diphosphate competitively inhibits HIV-1 and HBV reverse transcriptase and incorporates into viral DNA causing chain termination.

What the body does with it

Metabolism	Tenofovir disoproxil fumarate is a prodrug that is converted to tenofovir by plasma and tissue esterases; tenofovir is not significantly metabolized by CYP450 enzymes; eliminated renally by glomerular filtration and active tubular secretion.
Excretion	Renal: ~70-80% unchanged via glomerular filtration and active tubular secretion; minimal biliary/fecal (<1% as unchanged drug).
Half-life	Terminal elimination half-life: ~17 hours in HIV-infected patients; prolonged to ~28 hours in renal impairment (CrCl <50 mL/min).
Protein binding	<0.7% bound to plasma proteins (minimal).
Volume of Distribution	1.2-1.3 L/kg; suggests distribution into total body water, with extensive distribution into tissues (e.g., kidney, liver, lymphoid tissue).
Bioavailability	Oral: ~25% (under fasted conditions); increases to ~39% with high-fat meal.
Onset of Action	Oral: Not applicable (prodrug); active metabolite tenofovir diphosphate reaches steady-state intracellular concentrations in 7-14 days.
Duration of Action	Intracellular half-life of tenofovir diphosphate: ~60 hours, supporting once-daily dosing; plasma drug levels persist for >24 hours.

Classification & Brands

Dosing & administration

300 mg orally once daily with food.

Dosage form	TABLET
Renal impairment	CrCl ≥50 mL/min: 300 mg every 24 hours; CrCl 30-49 mL/min: 300 mg every 48 hours; CrCl 10-29 mL/min: 300 mg twice weekly; CrCl <10 mL/min or hemodialysis: not recommended; if benefit outweighs risk, 300 mg every 7 days.
Liver impairment	No dose adjustment required for mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, C).
Pediatric use	Approved for HIV-1 in patients ≥2 years weighing ≥10 kg: weight 10-14 kg: 150 mg once daily; 15-22 kg: 200 mg once daily; 23-28 kg: 250 mg once daily; >28 kg: 300 mg once daily. For chronic hepatitis B, approved in patients ≥12 years weighing ≥35 kg: 300 mg once daily.
Geriatric use	Use with caution due to age-related renal impairment; select dose based on renal function (CrCl). Start at lower end of dosing range if CrCl ≥50 mL/min; otherwise adjust per renal guidelines. Monitor renal function frequently.

Use during pregnancy

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 disoproxil fumarate is excreted into human breast milk. The M/P ratio is not established. Limited data suggest low infant exposure, but caution is recommended. Weigh benefits of breastfeeding against potential risk of infant exposure.
Teratogenic Risk	Tenofovir disoproxil fumarate is classified as FDA Pregnancy Category B. No increased risk of major birth defects or miscarriage has been observed in human studies. however, routine surveillance is recommended. For the first trimester, risk of major malformations is not significantly different from background rate. For the second and third trimesters, no specific fetal risks have been identified, but caution is advised due to potential for lactic acidosis and hepatic steatosis in the mother.

Warnings & precautions

■ FDA Black Box Warning

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases; post-treatment acute exacerbation of hepatitis B.

Side Effect Profile

Common Effects	Diarrhea Nausea Rash Weakness Vomiting Fatigue Abdominal pain Increased transaminase level in blood Decreased phosphate level in blood Pain Dizziness Depression Insomnia difficulty in sleeping Fever Itching
Serious Effects

Absolute Contraindications

Concomitant use with didanosine increases risk of toxicity; concomitant use with adefovir dipivoxil; hypersensitivity reaction to tenofovir or any component of the formulation.