Adefovir Dipivoxil

Approved Indications:

• Chronic Hepatitis B Virus (HBV) Infection:
• Treatment of chronic HBV infection in adults and pediatric patients ≥12 years with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.
• Indicated for both HBeAg-positive and HBeAg-negative chronic hepatitis B.

Important Off-Label (Clinically Accepted) Uses:

• Lamivudine-Resistant HBV: Used in combination with lamivudine for patients who have developed lamivudine resistance (though newer agents like tenofovir are now preferred).
• Organ Transplant Recipients: Occasionally used to prevent HBV recurrence post-liver transplantation in specific cases when other options are not suitable.

Route: Oral. Take with or without food at the same time each day.

Adults:

• Chronic HBV: 10 mg once daily.

Pediatrics (≥12 years):

• 10 mg once daily.

Renal Impairment:

• Dose adjustment required based on creatinine clearance (CrCl):
• CrCl 20–49 mL/min: 10 mg every 48 hours
• CrCl 10–19 mL/min: 10 mg every 72 hours
• Hemodialysis: 10 mg every 7 days following dialysis
• Monitor renal function regularly during treatment.

Hepatic Impairment:

• No dosage adjustment needed.

Elderly:

• Use with caution due to age-related declines in renal function; adjust dose if needed.

Adefovir dipivoxil is an oral prodrug that is rapidly converted in vivo to adefovir, an acyclic nucleotide analog of adenosine monophosphate. Adefovir is phosphorylated intracellularly to the active diphosphate form, which inhibits HBV DNA polymerase by competing with the natural substrate deoxyadenosine triphosphate. It causes DNA chain termination after incorporation into viral DNA, thereby blocking viral replication. This results in reduced HBV DNA levels, decreased liver inflammation, and histologic improvement in chronic hepatitis B.

Absorption:

• Oral bioavailability ~59%.
• Peak plasma concentration reached ~0.6 to 4 hours after dosing.

Distribution:

• Volume of distribution: ~392 liters.
• Protein binding: <4%.

Metabolism:

• Minimal metabolism; primarily converted by ester hydrolysis to active adefovir.

Excretion:

• Primarily excreted unchanged in urine by glomerular filtration and active tubular secretion.
• Terminal half-life: ~7.5 hours.
• Renal clearance: ~100 mL/min.

Pregnancy:

• Previously FDA Pregnancy Category C. Limited human data; animal studies showed embryotoxicity at high doses. Use only if potential benefit justifies risk. Safer alternatives (e.g., tenofovir) are preferred during pregnancy.

Lactation:

• Unknown if adefovir is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment.

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

• Hypersensitivity to adefovir dipivoxil or any component of the formulation.

• Nephrotoxicity: Dose-dependent renal toxicity can occur, especially at higher doses. Monitor renal function closely.
• Lactic Acidosis & Hepatomegaly: Risk of lactic acidosis and severe hepatomegaly with steatosis; discontinue if suspected.
• HIV Resistance: May cause HIV resistance if used in undiagnosed or untreated HIV co-infection — test for HIV before starting.
• Post-Treatment Exacerbation: Acute severe exacerbations of hepatitis B may occur after discontinuation; monitor liver function for at least several months.
• Dose Adjustments: Carefully adjust doses in renal impairment to reduce risk of toxicity.

Common:

• Asthenia (weakness)
• Headache
• Abdominal pain
• Nausea
• Flatulence

Serious/Rare:

• Nephrotoxicity (increased serum creatinine, renal tubular dysfunction)
• Lactic acidosis
• Hepatomegaly with steatosis
• Exacerbation of hepatitis after discontinuation
• HIV resistance development in co-infected patients not receiving antiretroviral therapy

• Nephrotoxic Drugs: Concomitant use with other nephrotoxic agents (e.g., aminoglycosides, NSAIDs) may increase renal toxicity risk.
• HIV Medications: Monotherapy can lead to HIV resistance; do not use as a single agent in patients with HIV/HBV co-infection.
• Probenecid: May reduce renal clearance of adefovir; monitor for toxicity.
• No significant CYP450 interactions — not metabolized by liver enzymes.

• NICE & WHO: Adefovir is now less favored due to its lower potency and higher nephrotoxicity risk compared to first-line agents like tenofovir or entecavir.
• FDA: No major recent updates; still approved but largely replaced in most treatment guidelines by safer, more effective antivirals.
• Clinical Guidelines: Recommend regular renal monitoring and switching to alternative therapy if renal function deteriorates.

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C (59°F–86°F).
• Store in original container; protect from moisture and light.
• Keep bottle tightly closed.