Rezoven Tablet

Adefovir Dipivoxil is indicated 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.

Adefovir dipivoxil is a diester prodrug of adefovir. Adefovir is an acyclic nucleotide analog with activity against human hepatitis B virus (HBV). Adefovir 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 approximate oral bioavailability of adefovir from a 10 mg single dose is 59%. In vitro binding of adefovir to human plasma or human serum proteins is 4%. Adefovir is excreted through renal route by a combination of glomerular filtration and active tubular secretion.

The recommended dose of Adefovir in chronic hepatitis B patients with adequate renal function is 10 mg, once daily, taken orally, without regard to food.

The pharmacokinetics of adefovir was unchanged when adefovir dipivoxil was coadministered with lamivudine, trimethoprim/ sulfamethoxazole and acetaminophen. When adefovir dipivoxil was co-administered with ibuprofen (800 mg three times daily), increases in adefovir Cmax (33%), AUC (23%) and urinary recovery were observed due to higher oral bioavailability of adefovir.

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

The most common side effects of adefovir dipivoxil are weakness, headache, stomach pain and nausea. Severe acute exacerbations of hepatitis have been reported in patients who have discontinued anti-hepatitis B therapy, including therapy with adefovir dipivoxil. In patients at risk of or having underlying renal dysfunction, chronic administration of adefovir dipivoxil may result in nephrotoxicity. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with other antiretrovirals.

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Adefovir dipivoxil should be used during pregnancy only if clearly needed and after careful consideration of the risks and benefits. It is not known whether adefovir is excreted in human milk. Mothers should be instructed not to breast-feed if they are taking adefovir dipivoxil.

Patients who discontinued adefovir dipivoxil should be monitored at repeated intervals over a period of time for hepatic function. The patients at risk of or having underlying renal dysfunction should be monitored closely for renal function and may require dose adjustment.

Doses of adefovir dipivoxil 500 mg daily for 2 weeks and 250 mg daily for 12 weeks have been associated with gastrointestinal side effects. If overdose occurs the patient must be monitored for evidence of toxicity and standard supportive treatment applied as necessary.

Hepatic viral infections (Hepatitis B)

Pediatric use: Safety and effectiveness in pediatric patients have not been established.

Geriatric use: In general, caution should be exercised when prescribing to elderly patients since they have greater frequency of decreased renal or cardiac function due to concomitant disease or other drug therapy.

Dose Adjustment in Renal Impairment: the dosing interval of Adefovir should be adjusted in patients with baseline creatinine clearance <50 ml/min using the following suggested guidelines:

• CrCl ≤ 50 ml/min: 10 mg
• CrCl 20-49 ml/min: 10 mg every 48 hours
• CrCl 10-19 ml/min: 10 mg every 72 hours
• Haemodialysis patients: 10 mg every 7 days following dialysis

Store at cool and dry place. Protect from light and moisture. Keep all the medicines out of the reach of children.