Drug Interaction Report

GENERALLY AVOID: Hydroxyurea may potentiate the risk of toxicities associated with the use of didanosine (ddI), a nucleoside reverse transcriptase inhibitor (NRTI). Specifically, concurrent use of hydroxyurea and ddI, with or without stavudine (d4T), has been associated with an increased risk of pancreatitis and peripheral neuropathy, the former of which may be fatal. Although rare, the syndrome of lactic acidosis and severe hepatomegaly with steatosis (with or without pancreatitis) may also occur more frequently with the combination than with ddI alone. Investigators theorize that hydroxyurea may enhance the potency of nucleoside analogues, particularly ddI, by preferentially depleting intracellular deoxyadenosine triphosphate and, to a lesser extent, other deoxynucleoside triphosphates. This action results in increased incorporation of the active metabolites of ddI and other NRTIs into DNA synthesis and disruption of the process.

MANAGEMENT: In general, antiretroviral regimens containing ddI and hydroxyurea should probably not be prescribed if other treatment options are available. Close observation for signs and symptoms of toxicity is recommended if these drugs must be used together, particularly in patients with advanced HIV disease and/or elderly patients. Both drugs should be suspended if pancreatitis is suspected, and ddI discontinued permanently if pancreatitis is confirmed. Prompt withdrawal of these drugs is also essential in patients who develop peripheral neuropathy to avoid irreversible damage. Therapy with ddI may be reinstituted following resolution of neuropathy symptoms, but reduced dosages are recommended. Likewise, treatment should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity, and permanent discontinuation considered if the syndrome is confirmed. Patients should be advised to seek medical attention promptly if symptoms of toxicity occur such as nausea, vomiting, abdominal pain, fatigue, unexplained weight loss, tachypnea, dyspnea, motor weakness, numbness, tingling, and pain in hands and feet.

ADJUST DOSING INTERVAL: Didanosine bioavailability is decreased when administered with food. Loss of efficacy may result.

MANAGEMENT: Didanosine should be administered in the fasting state, at least 30 minutes before or more than 2 hours after eating.