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Active ingredient: Adefovir Dipivoxil - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

  • Antiviral Agents
  • Reverse Transcriptase Inhibitors

Dosage Forms

  • Tablet (10 mg)

Brands / Synonyms

Adefovir; Adefovir pivoxil; Adefovirdipivoxl; ADV; Hepsera; PMEA; Preveon

Indications

For the treatment of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.

Pharmacology

Adefovir dipivoxil a diester prodrug of adefovir. Adefovir is an acyclic nucleotide analog with activity against human hepatitis B virus (HBV). The concentration of adefovir that inhibited 50% of viral DNA synthesis (IC50) in vitro ranged from 0.2 to 2.5 μM in HBV transfected human hepatoma cell lines. The combination of adefovir with lamivudine showed additive anti-HBV activity.

Mechanism of Action

Adefovir dipivoxil is a prodrug of adefovir. Adefovir is an acyclic nucleotide analog of adenosine monophosphate which is phosphorylated to the active metabolite adefovir diphosphate by cellular kinases. Adefovir diphosphate inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate deoxyadenosine triphosphate and by causing DNA chain termination after its incorporation into viral DNA. The inhibition constant (Ki) for adefovir diphosphate for HBV DNA polymerase was 0.1 μM. Adefovir diphosphate is a weak inhibitor of human DNA polymerases α and γ with Ki values of 1.18 μM and 0.97μM, respectively.

Absorption

Approximate oral bioavailability is 59%.

Toxicity

Renal tubular nephropathy characterized by histological alterations and/or increases in BUN and serum creatinine was the primary dose-limiting toxicity associated with administration of adefovir dipivoxil in animals. Nephrotoxicity was observed in animals at systemic exposures approximately 3–10 times higher than those in humans at the recommended therapeutic dose of 10 mg/day.

Biotrnasformation / Drug Metabolism

Following oral administration, adefovir dipivoxil is rapidly converted to adefovir. Forty-five percent of the dose is recovered as adefovir in the urine over 24 hours at steady state following 10 mg oral doses. Adefovir is not a substrate of the cytochrome P450 enzymes.

Contraindications

HIV infection, kidney problems, liver transplant, allergies. This medication should be used only when clearly needed during pregnancy.

Drug Interactions

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription products you may use, especially of: aminoglycosides (e.g., gentamicin, amikacin), amphotericin B, cyclosporine, non-steroidal anti-inflammatory drugs (e.g., ibuprofen), tacrolimus, vancomycin. Do not start or stop any medicine without doctor or pharmacist approval.

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