T-Fovir A

Approved Indications:

• Chronic Hepatitis B Virus (HBV) Infection
• In adults and pediatric patients (≥12 years or ≥25 kg) with compensated liver disease.
• HIV-1 Infection (in combination with other antiretrovirals):
• In adults and pediatric patients weighing ≥25 kg.
• As part of fixed-dose combination regimens (e.g., Descovy®, Biktarvy®, Genvoya®, Odefsey®) in treatment-naïve or virologically suppressed patients.

Off-Label or Clinically Accepted Uses:

• HBV Prophylaxis in Immunosuppressed Patients:
  Used in preventing HBV reactivation during immunosuppressive or cytotoxic therapy.

Adults and Pediatric Patients (≥25 kg):

• Chronic Hepatitis B Infection:
  Tenofovir Alafenamide 25 mg orally once daily with food.
• HIV-1 Infection (Fixed-dose combinations):
  Refer to specific combination product for exact dosing.
  Example:
• Descovy®: 25 mg Tenofovir Alafenamide + 200 mg Emtricitabine once daily.

Special Populations:

• Renal Impairment:
  No dose adjustment needed for eGFR ≥15 mL/min.
  Not recommended if eGFR <15 mL/min unless on chronic hemodialysis (administer after dialysis on dialysis days).
• Hepatic Impairment:
  No dose adjustment for mild/moderate impairment (Child-Pugh A or B).
  Not studied in severe hepatic impairment (Child-Pugh C); use with caution.

Administration Notes:

• Administer with food to enhance absorption.
• Do not chew or crush the tablet.

Tenofovir Alafenamide (TAF) is a phosphonamidate prodrug of tenofovir, a nucleotide reverse transcriptase inhibitor (NtRTI). After oral administration, TAF is metabolized intracellularly to the active metabolite, tenofovir diphosphate. This compound mimics natural deoxyadenosine triphosphate and competes with it for incorporation into viral DNA by reverse transcriptase. Once incorporated, it causes premature DNA chain termination, thereby inhibiting viral replication. TAF delivers higher intracellular concentrations of the active agent with lower plasma levels, improving safety over tenofovir disoproxil fumarate (TDF).

• Absorption:
  Oral bioavailability increases with food.
  Peak plasma concentration (Cmax) occurs ~1 hour post-dose.
• Distribution:
  High intracellular uptake into PBMCs.
  Plasma protein binding ~80%.
• Metabolism:
  Primarily metabolized by cathepsin A in PBMCs and hepatocytes to tenofovir.
  Minor CYP3A-mediated hepatic metabolism.
• Excretion:
  Primarily renal as unchanged tenofovir (~70%).
  Half-life of intracellular tenofovir diphosphate: ~150–180 hours.
  Plasma elimination half-life: ~0.5 hours.

• Pregnancy:
  No FDA-assigned letter category.
  Human data do not show increased risk of birth defects or miscarriage.
  Tenofovir Alafenamide is considered relatively safe when clinically indicated.
• Lactation:
  Tenofovir is excreted in human milk in low levels.
  No adverse effects reported in breastfed infants.
  Breastfeeding may be considered with appropriate maternal monitoring, particularly in HIV-negative HBV-positive mothers.
  For HIV-positive mothers, breastfeeding is generally discouraged in high-resource settings.

• Primary Class: Antiviral Agent
• Subclass: Nucleotide Reverse Transcriptase Inhibitor (NtRTI)
• Generation: Second-generation tenofovir prodrug

• Known hypersensitivity to Tenofovir Alafenamide or any component of the formulation
• Co-administration with strong P-gp inducers (e.g., rifampin, St. John's wort) that significantly reduce TAF plasma levels
• Severe renal impairment (eGFR <15 mL/min not on dialysis)

• Lactic Acidosis & Hepatomegaly with Steatosis:
  Reported with nucleoside analogs; monitor liver enzymes.
• HBV Reactivation:
  In HBV/HIV co-infected patients, discontinuation may lead to severe acute exacerbations of hepatitis B. Monitor liver function for several months after stopping.
• Renal Toxicity:
  Risk is significantly lower than with TDF but still present. Monitor renal function regularly, especially in at-risk patients.
• Bone Mineral Density Loss:
  Less reduction compared to TDF, but long-term use may still impact bone health. Monitor in patients with risk factors for osteoporosis.
• Immune Reconstitution Syndrome:
  May occur in HIV-infected individuals beginning antiretroviral therapy.

Common Adverse Effects:

• Gastrointestinal: Nausea, diarrhea, abdominal pain
• General: Fatigue, headache
• Metabolic: Weight gain (especially in combination ART)

Less Common or Serious Effects:

• Renal: Decreased creatinine clearance, proteinuria
• Hepatic: Elevated ALT/AST, hepatic steatosis
• Musculoskeletal: Mild decrease in bone mineral density
• Hematologic: Neutropenia (rare)

Rare/Severe:

• Lactic acidosis
• Hepatomegaly with steatosis
• Hypophosphatemia (more likely with TDF)

• Enzyme/Transporter Involvement:
  Substrate of P-glycoprotein (P-gp), BCRP; minor metabolism via CYP3A4.
• Major Interactions:
• P-gp Inducers: (e.g., rifampin, carbamazepine, phenytoin) ↓ TAF levels—avoid.
• Protease Inhibitors: (boosted regimens) ↑ TAF exposure—monitor toxicity.
• Anticonvulsants: May reduce efficacy—avoid or monitor closely.
• Alcohol/Food Interactions:
• Food increases absorption; recommended to take with food.
• No direct interaction with alcohol, but liver monitoring is advised.

• WHO & DHHS Guidelines:
• TAF is now preferred over TDF in patients with renal or bone risk.
• Incorporated in many first-line HIV treatment regimens.
• EMA/FDA Approvals:
• Expanded to include pediatric patients ≥25 kg for both HIV and HBV.
• New fixed-dose combinations (e.g., Symtuza®) include TAF.
• Safety Labeling Changes:
• Emphasized risk of weight gain when used with integrase inhibitors.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C.
• Humidity & Light: Store in original container; protect from moisture.
• Handling: Keep container tightly closed.
• Reconstitution/Refrigeration: Not applicable; oral solid dosage form.