Overview
11 DESCRIPTION Adefovir dipivoxil is a diester prodrug of adefovir. Adefovir is an acyclic nucleotide analog with activity against human hepatitis B virus (HBV). The chemical name of adefovir dipivoxil is 9-[2-[[bis[(pivaloyloxy)methoxy]-phosphinyl]-methoxy]ethyl]adenine. It has a molecular formula of C 20 H 32 N 5 O 8 P, a molecular weight of 501.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Adefovir is an antiviral drug [See Microbiology ( 12.4 )]. 12.3 Pharmacokinetics Adult Subjects The pharmacokinetics of adefovir have been evaluated in healthy volunteers and patients with chronic hepatitis B. Adefovir pharmacokinetics are similar between these populations. Absorption Adefovir dipivoxil is a diester prodrug of the active moiety adefovir. Based on a cross study comparison, the approximate oral bioavailability of adefovir from adefovir dipivoxil is 59%. Following oral administration of a 10 mg single dose of adefovir dipivoxil to chronic hepatitis B patients (N=14), the peak adefovir plasma concentration (C max ) was 18.4 ± 6.26 ng/mL (mean ± SD) and occurred between 0.58 and 4.00 hours (median = 1.75 hours) post dose.
Indications
- 1 INDICATIONS AND USAGE Adefovir dipivoxil tablets are indicated for the treatment of chronic hepatitis B in patients 12 years of age and older with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. This indication is based on histological, virological, biochemical, and serological responses in adult patients with HBeAg+ and HBeAg- chronic hepatitis B with compensated liver function, and with clinical evidence of lamivudine-resistant hepatitis B virus with either compensated or...
Common Doses
- 10 mg
- 10 mL
- 50 mL
Dosage
2 DOSAGE AND ADMINISTRATION One tablet containing 10 mg adefovir dipivoxil once daily orally with or without food. ( 2.1 ) Dose adjustment in renal impairment for adults ( 2.2 ) Creatinine Clearance (mL/min) Creatinine clearance calculated by Cockcroft-Gault method using lean or ideal body weight. Greater than or equal to 50 30 to 49 10 to 29 Hemodialysis Patients Recommended dose and dosing interval 10 mg every 24 hours 10 mg every 48 hours 10 mg every 72 hours 10 mg every 7 days following dialysis No dose recommendations for ( 2.
Black Box Warning
WARNING: SEVERE ACUTE EXACERBATIONS OF HEPATITIS, NEPHROTOXICITY, HIV RESISTANCE, LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS Severe acute exacerbations of hepatitis have been reported in patients who have discontinued anti-Hepatitis B therapy including adefovir dipivoxil tablets. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-Hepatitis B therapy. If appropriate, resumption of anti-Hepatitis B therapy may be warranted [See Warnings and Precautions (5. 1 ) ].
Contraindications
- 4 CONTRAINDICATIONS Adefovir dipivoxil tablets are contraindicated in patients with previously demonstrated hypersensitivity to any of the components of the product. Adefovir dipivoxil tablets are contraindicated in patients with previously demonstrated hypersensitivity to any of the components of the product. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: Severe acute exacerbations of Hepatitis [ S ee Boxed Warning , Warnings and Precautions (5.1) ] Nephrotoxicity [See Boxed Warning , Warnings and Precautions (5.2) ] Most common adverse reaction (incidence greater than 5%) in compensated liver disease patients were asthenia, headache, abdominal pain and nausea. ( 6.1 ) The most common adverse reaction in pre- and post- transplantation lamivudine-resistant liver disease patients was increased creatinine. ( 6.
Interactions
- 7 DRUG INTERACTIONS Since adefovir is eliminated by the kidney, coadministration of adefovir dipivoxil with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either adefovir and/or these coadministered drugs [See Clinical Pharmacology ( 12.3) ]. Patients should be monitored closely for adverse events when adefovir dipivoxil is coadministered with drugs that are excreted renally or with other drugs known to affect renal function [ See Warnings and Precautions (5.2) ] .