Adefovir (Hepsera®)

Class: Adefovir is a nucleoside phosphonate (ANP) anti-viral agent.

Antiviral Activity: Adefovir has activity against HIV but is not used due to nephrotoxicity. Adefovir also has activity against hepatitis B.

Mechanism of Action: Nucleotide Analog Reverse Transcriptase Inhibitor (NRTI)

Adefovir dipivoxil is converted to the active metabolite adefovir diphosphate. Adefovir diphosphate competes with deoxyadenosine 5' triphosphate for incorporation into viral DNA. Adefovir diphosphate lacks a 3' hydroxyl group and results in viral DNA chain termination.

Mechanism of Resistance: Resistance to NRTI’s occurs through two mechanisms; decreased incorporation of NRTI’s into the viral DNA and increased excision of NRTI’s from the viral DNA. The development of resistant hepatitis B is rare.

Pharmacodynamics: The IC50 of adefovir was 0.2-1.2 µM for HBV and 1 – 0.4-30 µM for HIV.

Pharmacokinetics: Maximum concentrations are reached in a median of 1.75 hours. Plasma protein binding in vitro is less than 4%. Adefovir likely undergoes both glomerular filtration and active tubular secretion

Adverse Effects: The most frequently observed adverse effects associated with adefovir are asthenia, abdominal pain, and headache. Nephrotoxicity and hypophosphatemia have also been seen.

Dosage: Tablet – 10mg (30 tablet bottle)

Adult dose - 10 mg orally. The dosage for children has not yet been established.

Disease state based dosing: Dosage adjustment is recommended in patients with moderate or severe renal dysfunction. Patients requiring hemodialysis should receive adefovir dipivoxil at a dose of 10 mg every 7 days post hemodialysis.

No dosage adjustment is required for hepatic impairment.

Contraindications/Warnings/Precautions: Monitor for severe, acute exacerbations of hepatitis after discontinuing adefovir. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of NRTIs.

Drug Interactions: Adefovir is a substrate of p-glycoprotein and therefore may interact with other medications that are substrates of p-glycoprotein.

Pregnancy: Category C: Risk unknown. Human studies inadequate.

Monitoring Requirements: Serum phosphorous, serum creatinine and BUN

Brand names/Manufacturer: Hepsera® Gilead Sciences Inc