Dosing and uses of adefovir dipivoxil, Hepsera (adefovir)
Adult dosage forms and strengths
tablet
- 10mg
Chronic Hepatitis B
10 mg PO qDay
Renal Impairment
CrCl ≥ 50 mL/min: Dose adjustment not necessary
CrCl 30-49 mL/min: 10 mg PO q48hr
CrCl 10-29 mL/min: 10 mg PO q72hr
Hemodialysis: 10 mg qWeek following dialysis
Pediatric dosage forms and strengths
tablet
- 10mg
Chronic Hepatitis B
<12 years old: Not recommended
≥12 years old: Administer as in adults, 10 mg PO qDay
Renal Impairment
CrCl ≥ 50 mL/min: Dose adjustment not necessary
CrCl 30-49 mL/min: 10 mg PO q48hr
CrCl 10-29 mL/min: 10 mg PO q72hr
Hemodialysis: 10 mg qWeek following dialysis
adefovir dipivoxil, Hepsera (adefovir) adverse (side) effects
>10%
Hematuria (11% vs 10% in placebo-treated)
Asthenia (13% vs. 14% placebo)
Hepatitis exacerbation (25%)
1-10%
Nausea (5%)
Flatulence (4%)
Diarrhea (3%)
Dyspepsia (3%)
Headache (9%)
Rash (1-10%)
Pruritus (1-10%)
Dyspepsia (5-9%)
Cough (6-8%)
Rhinitis (5%)
Increased AST/ALt
Abnormal liver function
Renal failure
Renal insufficiency
Increased serum Cr (2-3%)
Hypophosphatemia
Postmarketing Reports
Metabolism and nutrition disorders: Hypophosphatemia
Gastrointestinal disorders: Pancreatitis
Musculoskeletal system and connective tissue disorders: Myopathy, osteomalacia (manifested as bone pain and may contribute to fractures), both associated with proximal renal tubulopathy
Renal and urinary disorders: Renal failure, Fanconi syndrome, proximal renal tubulopathy
Warnings
Black box warnings
Severe acute exacerbations of hepatitis reported following discontinuing drug; monitor hepatic function
Chronic use may result in nephrotoxicity in patients with renal impairment or in those at risk of renal dysfunction; dose adjustment may be required
Resistance to HIV NRTIs may emerge in patients with chronic hepatitis B in whom HIV infection is unrecognized or untreated
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, reported with nucleoside analogs alone or in combination with other antiretrovirals; obesity and prolonged nucleoside exposure may be risk factors
Contraindications
Hypersensitivity
Cautions
Discontinuation may result in severe acute exacerbation of hepatitis B
Patients who discontinue treatment: Monitor hepatic function for several months
Patients with renal dysfunction: Risk of nephrotoxicity (monitor and adjust dose accordingly)
Coadministration with drugs that reduce renal function may increase adefovir serum concentration
Do not administer with tenofovir (additive toxicity)
May increase HIV resistance in untreated patients who are HIV+
Risk of lactic acidosis, severe hepatomegaly with steatosis
To monitor fetal outcomes, Pregnancy Registry established: 1-800-258-4263
Pregnancy and lactation
Pregnancy category: C (Pregnancy Registry: 1-800-258-4263)
Lactation: Unknown if excreted in breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of adefovir dipivoxil, Hepsera (adefovir)
Mechanism of action
Acyclic nucleotide analog; inhibits HBV DNA polymerase; inhibition blocks reverse transcriptase activity, which in turn reduces viral DNA synthesis
Absorption
Bioavailability: 59%
Peak plasma time: 0.58-4 hr
Peak plasma concentration: 18.4±6.26 ng/mL
AUC: 220±70 ng•hr/mL
Distribution
Protein Bound: ≤ 4%
Vd: 317-467 mL/kg
Metabolism
Rapidily converted to adefovir from the diester prodrug, adefovir dipivoxiL
Metabolites: Adefovir (active)
Elimination
Half-life: 7.48±1.65 hr
Renal clearance: 231±48.9 mL/min
Excretion: Urine; renal glomerular filtration, active tubular secretion
Dialyzable: Yes
