Drug Interactions between allopurinol and Videx EC

CONTRAINDICATED: Coadministration with allopurinol may significantly increase the plasma concentrations of didanosine. The proposed mechanism is allopurinol inhibition of didanosine first-pass metabolism via xanthine oxidase. In two patients with renal impairment (CrCl = 15 and 18 mL/min), allopurinol (300 mg/day) increased the area under the plasma concentration-time curve (AUC) of didanosine (200 mg single dose) by approximately 4-fold. In fourteen healthy volunteers, the mean AUC of didanosine (400 mg single dose) was increased about 2-fold by allopurinol (300 mg/day for 7 days). In one study, four patients treated with an antiretroviral regimen containing didanosine (four 100 mg chewable tablets/day) were able to maintain similar didanosine plasma levels and antiretroviral competency with half the dosage of didanosine during coadministration with allopurinol (300 mg/day). These effects persisted after several months of concomitant treatment.

MANAGEMENT: Because elevated plasma levels of didanosine may be associated with increased risk of serious adverse effects such as pancreatitis and peripheral neuropathy, as well as increased serum uric acid concentrations, the concomitant use of didanosine and allopurinol is considered contraindicated.