Adefovir Dipivoxil
Pronunciation: (a-DEF-oh-vir dye-piv-OX-il)Class: Antiviral agent
Trade Names:Hepsera- Tablets 10 mg
Pharmacology
Inhibits hepatitis B virus (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.
Pharmacokinetics
Absorption
Bioavailability of adefovir is approximately 59%. C max is approximately 18.4 ng/mL, and T max is approximately 1.75 h.
Distribution
Up to 4% is protein bound. Vd is approximately 352 to 392 mL/kg (IV doses at steady state).
Metabolism
Adefovir dipivoxil (prodrug) is rapidly converted to adefovir (active).
Elimination
The terminal elimination half-life is approximately 7.48 h; 45% of dose is recovered as adefovir in the urine over 24 h. Adefovir is renally excreted by a combination of glomerular filtration and active tubular secretion.
Special Populations
Renal Function ImpairmentC max , AUC, and half-life increased in those with moderate or severe renal function impairment or with end-stage renal disease. Dosing interval modification is recommended.
Hepatic Function ImpairmentNo changes in pharmacokinetics were observed in patients with moderate and severe hepatic function impairment. No dosage adjustment is required.
ElderlyPharmacokinetics have not been studied.
ChildrenPharmacokinetics in children 12 to 18 yr of age are comparable with those observed in adults.
Indications and Usage
Treatment of chronic hepatitis B in patients 12 yr of age and older with evidence of active viral replication and evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.
Contraindications
Standard considerations.
Dosage and Administration
Adults and Children 12 yr of age and olderPO 10 mg daily.
Renal Function ImpairmentAdultsPO For CrCl 50 mL/min or more, 10 mg daily; for CrCl 30 to 49 mL/min, 10 mg every 48 h; for CrCl 10 to 29 mL/min, 10 mg every 72 h; for hemodialysis patients, 10 mg every 7 days following dialysis. No dosing recommendations are available for nonhemodialysis patients with CrCl below 10 mL/min. No clinical data are available for dosing recommendations in adolescent patients with renal function impairment.
General Advice
- Administer without regard to food.
Storage/Stability
Store tablets at controlled room temperature (59° to 86°F).
Drug Interactions
Drugs that reduce renal function, ibuprofenMay increase plasma concentrations of adefovir.
Laboratory Test Interactions
None well documented.
Adverse Reactions
CNS
Asthenia (13%); headache (9%).
GI
Abdominal pain (9%); nausea (5%); flatulence (4%); diarrhea, dyspepsia (3%).
Genitourinary
Fanconi syndrome, proximal renal tubulopathy, renal failure (postmarketing).
Lab Tests
Decreased serum phosphorous, increased serum creatinine.
Metabolic-Nutritional
Hypophosphatemia (postmarketing).
Musculoskeletal
Myopathy, osteomalacia (postmarketing).
Precautions
WarningsHepatitisAcute exacerbations have occurred in patients who have discontinued antihepatitis B therapy, including adefovir. Monitor hepatic function closely with clinical and laboratory follow-up for at least several months in patients who discontinue antihepatitis B therapy. Resumption of antihepatitis B therapy may be warranted. HIV resistanceMay emerge in unrecognized or untreated HIV infection. Offer HIV antibody testing to all patients prior to initiating therapy. Lactic acidosis/hepatomegalyLactic acidosis and hepatomegaly with steatosis (including fatal cases) have been reported with use of nucleoside analogs alone or in combination with other antiretrovirals. NephrotoxicityChronic administration of adefovir in patients at risk of or having underlying renal function impairment may result in nephrotoxicity. Close monitoring is required. Dosage adjustment may be necessary. |
MonitorMonitor renal function in all patients during treatment, especially those with preexisting or other risk factors for renal impairment. Monitor patients for evidence of lactic acidosis or pronounced hepatotoxicity and steatosis; suspend therapy in patients who develop clinical or laboratory findings suggestive of these conditions. Monitor hepatic function at repeated intervals with both clinical and laboratory follow-up for at least several months in patients discontinuing therapy; closely monitor patients after stopping therapy. Prior to starting therapy, offer HIV antibody testing to all patients. |
Pregnancy
Category C .
Lactation
Undetermined.
Children
Safety and efficacy not established in children younger than 12 yr of age.
Elderly
Select dose with caution, reflecting greater frequency of decreased hepatic, renal, or cardiac function and comorbidity.
Renal Function
Dosage adjustments may be necessary. No data are available for making dosing recommendations in patients younger than 18 yr of age with renal function impairment.
Clinical resistance
Resistance to adefovir can result in viral load rebound, which may result in exacerbation of hepatitis B and, in patients with hepatic function impairment, may lead to liver decompensation and possible death. To reduce the risk of resistance in patients with lamivudine-resistant HBV, use adefovir dipivoxil combined with lamivudine; do not use adefovir dipivoxil monotherapy. To reduce the risk of resistance in patients receiving adefovir dipivoxil monotherapy, consider modifying treatment if serum HBV DNA levels remain above 1,000 copies/mL with continued treatment.
Overdosage
Symptoms
GI adverse reactions.
Patient Information
- Advise patient to review the patient information leaflet carefully before starting therapy and to read and check for new information each time the medication is refilled.
- Review dosing schedule with patient.
- Advise patient that tablets can be taken without regard to food, but can be taken with food if GI upset occurs.
- Advise patient that if a dose is missed, to take it as soon as remembered on that day. Caution patient not to take more than 1 dose of adefovir in a day, and not to take 2 doses at the same time to catch up.
- Caution patient not to change the dose or stop taking unless advised by health care provider. Advise patient that stopping therapy may result in severe exacerbation of hepatitis.
- Advise patient to get an HIV test before starting therapy and any time after that when there is a chance of exposure to HIV.
- Advise patient that medication will not cure hepatitis B infection or any other viral infection (eg, HIV) and to continue to take other antiviral medications as prescribed.
- Advise patient that this therapy will not prevent transmission of hepatitis B to others, and to avoid spreading hepatitis B to others: do not share needles or injection equipment; do not share personal items that have blood or body fluids on them (eg, toothbrushes, razor blades); do not have any kind of sex without protection (eg, condoms, dental dams).
- Advise patient that it is not known if adefovir can prevent cirrhosis, liver failure, or liver cancer that may develop as a result of hepatitis B infection.
- Instruct patient to immediately report any of the following to health care provider: appetite loss; cold feeling, especially in arms and legs; difficulty breathing; dizziness; fast or irregular heart beat; generalized body discomfort; light-colored bowel movements or very dark-colored urine; light-headedness; stomach pain with nausea and vomiting; unexplained drowsiness; unusual muscle pain; yellowing of the skin or eyes.
Copyright © 2009 Wolters Kluwer Health.
