Adefovir Dipivoxil

Indications

Adefovir Dipivoxil is used for: Chronic hepatitis B

Adult Dose

Chronic Hepatitis B Adult: PO:10 mg, once daily.

Child Dose

Chronic Hepatitis B Child: Oral <12 years old: Not recommended >12 years old: Administer as in adults, 10 mg PO once daily.

Renal Dose

Renal impairment: Haemodialysis patients: 10 mg every 7 days after dialysis. CrCl (ml/min) 30-49 10 mg every 48 hr. 10-29 10 mg every 72 hr.

Administration

Taken orally, without regard to food.

Contra Indications

Adefovir Dipivoxil is contraindicated in patients with previously demonstrated hypersensitivity to any of the components of the product.

Precautions

Severe acute exacerbations of hepatitis reported following discontinuation drug; monitoring 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 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 Monitoring Parameters Monitor liver function tests every 3 months, and viral markers for hepatitis B every 3–6 months during treatment (continue monitoring for at least 1 year after discontinuation—recurrent hepatitis may occur on discontinuation). Monitor renal function before treatment then every 3 months, more frequently in patients receiving nephrotoxic drugs.

Pregnancy-Lactation

Pregnancy Prospective pregnancy data from APR are not sufficient to adequately assess risk of birth defects, miscarriage or adverse maternal or fetal outcomes; adefovir disoproxil (ADV) use during pregnancy has been evaluated in a limited number of individuals reported to APR and the number of exposures to adefovir is insufficient to make a risk assessment compared to a reference population; estimated background rate for major birth defects is 2.7% in the U.S. reference population of Metropolitan Atlanta Congenital Defects Program (MACDP); estimated rate of miscarriage is not reported in APR; all pregnancies have a background risk of birth defect, loss, or other adverse outcomes Animal data In animal reproduction studies with oral ADV, no adverse developmental effects were observed at exposures (Cmax) 23 times higher in rats and 40 times higher in rabbits than those at recommended human dose (RHD) Lactation It is not known whether adefovir is present in human breast milk, affects human milk production, or has effects on breastfed infant The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from drug or from underlying maternal condition

Interactions

Increased risk of nephrotoxicity with nephrotoxic drugs e.g. aminoglycosides, ciclosporin, NSAIDs, vancomycin, tacrolimus. Ibuprofen increases bioavailability of adefovir. Contraindicated (0) Serious - Use Alternative (2) bacitracin tenofovir DF

Adverse Effects

Side effects of Adefovir Dipivoxil : >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 Potentially Fatal: Lactic acidosis, severe hepatomegaly with steatosis, hepatotoxicity, nephrotoxicity.

Mechanism of Action

Adefovir dipivoxil is an acyclic nucleoside reverse transciptase inhibitor. The diester function is hydrolyzed and subsequently phosphorylated to the active adefovir diphosphate. The active metabolite inhibits HBV DNA polymerase (reverse transcriptase) and hence inhibits viral replication. It can be used in patients with lamivudine-resistant hepatitis B.