TENOFOVIR DISOPROXIL FUMARATE 300MG TABLET

Indications

• HIV infection in combination with other antiretroviral drugs
• Chronic hepatitis B infection with compensated liver disease
• Chronic hepatitis B infection with decompensated liver disease

Dosage

Children: For children weighing up to 30 kg: 1 mg/kg twice daily. For children weighing 30-59 kg: 30 mg twice daily.

Adults: 245 mg once daily by mouth.

Mechanism of action

Tenofovir disoproxil is converted intracellularly to tenofovir diphosphate, which competes with natural deoxyadenosine triphosphate for incorporation into viral DNA. This incorporation causes chain termination and inhibits viral replication. The drug targets the reverse transcriptase enzyme, which is crucial for the replication of HIV and hepatitis B virus.

Pharmacodynamics

As an NRTI, tenofovir disoproxil exhibits a dose-dependent effect on viral replication. It effectively reduces viral load in patients with HIV and chronic hepatitis B. The drug's efficacy is enhanced when used in combination with other antiretroviral agents, leading to improved outcomes in managing these viral infections.

Pharmacokinetics

Tenofovir disoproxil is well absorbed in the gastrointestinal tract, with peak plasma concentrations occurring approximately 1-2 hours after oral administration. It has a half-life of about 12-18 hours, allowing for once-daily dosing. The drug is primarily eliminated via renal excretion, and dosage adjustments are recommended for patients with renal impairment.

Contra-indications

• Hypersensitivity to peanut or soya products
• Renal impairment with creatinine clearance less than 50 mL/minute

Adverse effects

• Abdominal distension
• Proximal renal tubulopathy
• Fatigue
• Dizziness
• Somnolence

Interactions

• Ciclosporin - unknown effect on exposure
• Eltrombopag - unknown effect on exposure
• Ledipasvir with sofosbuvir - unknown effect on exposure
• Leflunomide - unknown effect on exposure
• Teriflunomide - unknown effect on exposure
• Velpatasvir - unknown effect on exposure
• Voxilaprevir with sofosbuvir and velpatasvir - potentially increases concentration

Precautions

• Caution in elderly patients due to limited information
• Monitor renal function and serum phosphate before treatment and periodically thereafter
• Counsel patients regarding the impact on driving and skilled tasks due to potential dizziness and fatigue

Pregnancy

Manufacturer advises avoidance during pregnancy due to limited safety data.

Breast-feeding

Manufacturer advises caution; consult relevant guidelines.

Storage

Store below 30°C, in a dry place, away from direct light.

Formulations

• Tablets: 245 mg
• Granules: 132 mg (approx. equivalent to 245 mg when reconstituted)

Indications

• HIV-1 infection
• Chronic hepatitis B virus infection

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing recommendations.

Adults: Refer to the relevant clinical guidelines or the BNF for specific dosing recommendations.

Mechanism of action

Tenofovir disoproxil fumarate is converted to its active form, tenofovir, which competes with natural deoxynucleotides for incorporation into viral DNA by reverse transcriptase. This incorporation results in chain termination, preventing further viral replication. It also has a similar mechanism against HBV, inhibiting viral replication.

Pharmacodynamics

Tenofovir exhibits a dose-dependent inhibition of HIV-1 and HBV replication. The drug is effective against a broad range of HIV-1 subtypes and has been shown to have a high barrier to resistance. Its antiviral activity is measured by its ability to reduce viral load in patients, leading to improved immune function as indicated by increases in CD4+ T-cell counts.

Pharmacokinetics

After oral administration, tenofovir disoproxil fumarate is rapidly absorbed and converted to tenofovir. It has a bioavailability of approximately 25% when taken with food. The drug is primarily eliminated by the kidneys, with a half-life of about 17 hours. Steady-state concentrations are achieved within 2 days of dosing. Renal function should be monitored as tenofovir can cause nephrotoxicity.

Adverse effects

• Nausea
• Diarrhea
• Headache
• Fatigue
• Rash
• Renal impairment
• Bone mineral density loss
• Lactic acidosis

Interactions

• Didanosine
• Acyclovir
• Cidofovir
• Rifampicin
• St. John's Wort

Precautions

• Monitor renal function regularly
• Assess for signs of lactic acidosis
• Evaluate bone mineral density in long-term use
• Use with caution in patients with pre-existing renal impairment

Pregnancy

Tenofovir disoproxil fumarate is classified as category B. Animal studies have not shown teratogenic effects, but clinical data in pregnant women are limited. Use only if clearly needed.

Breast-feeding

Tenofovir is excreted in human milk. The decision to continue breastfeeding or discontinue the drug should consider the benefits of breastfeeding against the mother's need for the drug.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets: 300 mg