Adefovir Dipivoxil

Fatal cases of lactic acidosis and severe hepatomegaly with steatosis have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis). Disease-related concerns:

Severe, acute exacerbation of hepatitis B may occur upon discontinuation. Exacerbations may occur in up to 25% of patients and usually within 12 weeks and may be self-limited or resolve upon resuming treatment; risk may be increased with advanced liver disease or cirrhosis. Monitor liver function several months after stopping treatment; reinitiation of antihepatitis B therapy may be required. Ethanol should be avoided in hepatitis B infection due to potential hepatic toxicity.

May cause the development of HIV resistance in chronic hepatitis B patients with unrecognized or untreated HIV infection. Determine HIV status prior to initiating treatment with adefovir.

Use with caution in patients with renal dysfunction or in patients at risk of renal toxicity (including concurrent nephrotoxic agents or NSAIDs). Chronic administration may result in nephrotoxicity. Dosage adjustment is required in adult patients with renal dysfunction or in patients who develop renal dysfunction during therapy; no data available for use in children ≥12 years or adolescents with renal impairment. Calculation of creatinine clearance in all patients is recommended prior to initiating therapy. Concurrent drug therapy:

Do not use concurrently with tenofovir (Viread®) or any product containing tenofovir (eg, Truvada, Atripla, Complera). Other warnings/precautions:

Current clinical hepatitis B practice guidelines do not recommend adefovir for initial use in the management of chronic HBV due to high rate of resistance with long-term use; other antiviral agents with a high barrier to drug resistance are preferred (eg, tenofovir or entecavir). In the setting of lamivudine-resistant HBV, adefovir (including when combined with lamivudine) is also not a preferred strategy to manage antiviral resistance; consult current clinical practice guidelines for recommendations (AASLD [Terrault 2016]). If used, combination therapy with lamivudine should be used to decrease the risk of resistance in patients with lamivudine-resistant HBV.