Drug Interactions between dapsone and didanosine

MONITOR: Limited data suggest that didanosine may reduce the therapeutic efficacy of dapsone in the prophylaxis of Pneumocystis jiroveci pneumonia, formerly known as Pneumocystis carinii pneumonia (PCP). A report of 57 HIV-infected patients treated with didanosine describes an increased incidence of treatment failure in patients receiving dapsone compared to those receiving pentamidine or sulfamethoxazole-trimethoprim (SMX-TMP). Specifically, treatment failure occurred in 11/28 patients receiving dapsone, 1/12 patients receiving aerosolized pentamidine, and 0/17 patients receiving SMX-TMP. Four of the dapsone patients died of respiratory failure. The rate of dapsone treatment failure in this report was significantly higher than that observed in a previous study by the same group in which only 2 of 162 patients developed PCP during dapsone prophylaxis. The authors theorized that buffers in the didanosine formulation may have impaired the dissolution and absorption of dapsone by raising gastric pH. However, a subsequent pharmacokinetic study found no significant effect of buffered didanosine or the antacid buffers themselves or other excipients on the plasma concentrations of a single 100 mg dose of dapsone. Another study in seven healthy volunteers also reported no significant change in the single-dose pharmacokinetics of dapsone during coadministration with antacids. In addition, a retrospective analysis found no association between the use of drugs that increase gastric pH and dapsone failure in the prophylaxis of PCP.

MONITOR: The risk of peripheral neuropathy may be increased during concomitant use of didanosine and dapsone. These agents are individually neurotoxic and may have additive effects during coadministration. However, clinical data are lacking.

MANAGEMENT: Clinicians should be aware of the potential for diminished effects of dapsone during coadministration with didanosine, although the interaction is not well established. Some clinicians have suggested taking dapsone at least 2 hours before or 6 hours after didanosine, but more recent data suggest that this may not be necessary. Patients should be advised of the possibility for increased risk of neurotoxicity, and monitored closely for symptoms of neuropathy such as visual disturbances, loss of fine motor function, and burning, tingling, pain, or numbness in the hands and feet. Consideration should be given to immediate discontinuation of these medications in patients who develop peripheral neuropathy to limit further damage. If necessary, therapy should generally be reinstituted only after resolution of neuropathy symptoms or return of symptoms to baseline status. In some cases, reduced dosages may be required.