Adefovir Dipivoxil

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 decompensated liver function.

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. ( 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to adefovir dipivoxil during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258- 4263. Risk Summary Prospective pregnancy data from the APR are not sufficient to adequately assess the risk of birth defects, miscarriage or adverse maternal or fetal outcomes.

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. 5 WARNINGS AND PRECAUTIONS Severe acute exacerbations of hepatitis: Monitor hepatic function closely at repeated intervals for at least several months in patients who discontinue adefovir dipivoxil. ( 5.1 ) Nephrotoxicity: Monitor renal function during therapy for all patients, particularly those with pre-existing or other risks for renal impairment. Dose adjustment may be required. ( 5.2 ) HIV Resistance: Offer HIV testing to all patients prior to initiating adefovir dipivoxil. Untreated HIV may result in HIV resistance. ( 5.3 ) Lactic acidosis and severe hepatomegaly with steatosis: If suspected, suspend treatment. ( 5.4 ) Coadministration with Other Products: Do not administer adefovir dipivoxil concurrently with VIREAD ® or other tenofovir-containing products. 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 )