T-Fovir

Approved Indications:

• Chronic Hepatitis B Virus (HBV) Infection:
• In adults and pediatric patients ≥2 years with compensated liver disease and evidence of active viral replication and persistent elevations in serum ALT or histological evidence of active disease.
• Human Immunodeficiency Virus Type 1 (HIV-1) Infection:
• In combination with other antiretroviral agents for adults and pediatric patients ≥2 years weighing ≥10 kg.

Important Off-Label/Clinically Accepted Uses:

• HIV Pre-Exposure Prophylaxis (PrEP):
• In combination with emtricitabine for at-risk individuals (MSM, serodiscordant couples, IV drug users).
• Post-Exposure Prophylaxis (PEP):
• Part of 3-drug regimen following occupational or non-occupational exposure to HIV.
• Prevention of Perinatal HIV Transmission:
• As part of maternal antiretroviral therapy in pregnancy.

Route of Administration: Oral
Form: Tenofovir Disoproxil Fumarate (TDF) 300 mg tablets

Adults:

• HIV-1 Infection & HBV: 300 mg once daily
• PrEP: 300 mg once daily, with emtricitabine 200 mg

Pediatric Dosing:

• ≥2 years (HIV-1 or HBV):
• Weight-based dosing using oral powder or tablets
• ≥35 kg: 300 mg once daily
• 17–34 kg: Dose adjusted per kg; use pediatric formulations

Renal Impairment:

• CrCl ≥50 mL/min: No adjustment
• CrCl 30–49 mL/min: 300 mg every 48 hours
• CrCl 10–29 mL/min (non-dialysis): 300 mg every 72–96 hours
• Hemodialysis: 300 mg every 7 days or after 12 hours of dialysis

Hepatic Impairment:

• No dosage adjustment required in mild to moderate hepatic impairment (Child-Pugh A or B). Use with caution in severe impairment.

Duration:

• Chronic treatment, reassessed periodically based on virological response and tolerance.

Tenofovir disoproxil is a prodrug of tenofovir, a nucleotide analog of adenosine 5′-monophosphate. Once absorbed, it is converted intracellularly to tenofovir diphosphate, the active metabolite. This compound competes with natural deoxyadenosine triphosphate for incorporation into viral DNA by the viral reverse transcriptase enzyme. Incorporation terminates DNA chain elongation, effectively halting replication of HIV-1 and HBV. It does not affect human DNA polymerase at therapeutic concentrations, which contributes to its selectivity and efficacy.

• Absorption: Rapidly absorbed with peak plasma concentrations in 1–2 hours. Oral bioavailability increases with high-fat meals (~39%).
• Distribution: Widely distributed to tissues; plasma protein binding ~7.2%.
• Metabolism: Not significantly metabolized by CYP enzymes; converted via esterases to active tenofovir.
• Excretion:
• Primarily renal (70–80%) via glomerular filtration and active tubular secretion.
• Half-life (plasma): ~17 hours
• Intracellular half-life (active metabolite): >60 hours

• Pregnancy: No longer assigned FDA letter category; however, human data from Antiretroviral Pregnancy Registry show no increased risk of birth defects. Considered safe in pregnancy when benefits outweigh risks.
• Lactation:
• Tenofovir is excreted into breast milk in small amounts.
• WHO supports breastfeeding in HIV-positive mothers receiving ART if safe alternatives are unavailable.
• No adverse effects reported in breastfed infants.

• Primary Class: Antiretroviral Agent
• Subclass: Nucleotide Reverse Transcriptase Inhibitor (NtRTI)

• Known hypersensitivity to tenofovir disoproxil or any component of the formulation
• Severe renal impairment (CrCl <10 mL/min), unless on hemodialysis
• Concurrent use with nephrotoxic agents without monitoring

• Renal Toxicity: May cause proximal renal tubulopathy or Fanconi syndrome; monitor renal function regularly.
• Lactic Acidosis/Severe Hepatomegaly with Steatosis: Rare but serious; discontinue if suspected.
• Hepatitis B Exacerbation: Acute worsening may occur upon discontinuation in HBV-infected patients.
• Bone Mineral Density Loss: Monitor bone health, especially in children, adolescents, and those at risk.
• Drug Resistance: Avoid monotherapy; always combine with other antiretrovirals to prevent resistance.

Common Adverse Effects:

• Gastrointestinal: Nausea, diarrhea, vomiting, flatulence
• Musculoskeletal: Back pain, bone pain, decreased bone density
• Neurological: Headache, dizziness, fatigue
• Renal: Mild increases in serum creatinine, proteinuria

Serious/Rare Effects:

• Lactic acidosis
• Fanconi syndrome
• Acute renal failure
• Hepatotoxicity
• Osteomalacia
• Immune reconstitution inflammatory syndrome (IRIS)

Onset: Typically within first few weeks; bone and renal effects may take months

Major Drug-Drug Interactions:

• Didanosine: Increased risk of pancreatitis, lactic acidosis; avoid combination
• Adefovir Dipivoxil: Increased nephrotoxicity risk; avoid co-administration
• Protease Inhibitors (e.g., atazanavir, ritonavir): May increase tenofovir levels; monitor toxicity
• Nephrotoxic Drugs (NSAIDs, aminoglycosides): Additive renal risk
• Ledipasvir/Sofosbuvir: Increases tenofovir exposure; monitor renal function

Metabolism Involvement:

• Does not use CYP450 pathways; minimal involvement with enzyme inducers/inhibitors

• FDA/CDC: Tenofovir disoproxil remains a recommended component in PrEP and ART, particularly where cost is a concern over Tenofovir alafenamide.
• WHO 2023 Guidelines: Tenofovir-based regimens (TDF + lamivudine or emtricitabine) remain first-line ART for adults and adolescents.
• EMA: Advises caution in long-term use due to renal and bone risks, especially in pediatric patients.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C–30°C.
• Humidity: Protect from excessive moisture; store in a tightly closed container.
• Light Protection: Keep in original packaging until use to protect from light.
• Handling: No refrigeration required; do not freeze.
• Oral Powder: Use within 60 days after opening; mix with soft foods (not liquid) for pediatric use.