Acute onset of pancreatitis with concomitant use of tenofovir and didanosine.

OBJECTIVE: To report a case of pancreatitis associated with the combined use of didanosine and tenofovir. CASE SUMMARY: A 51-year-old white man with HIV was initiated on antiretroviral therapy with didanosine 250 mg/day, tenofovir 300 mg/day, lamivudine 300 mg/day, stavudine 60 mg/day, and efavirenz 600 mg/day. Didanosine was prescribed at a reduced dosage due to the known interaction with tenofovir. Despite this dosage adjustment, the patient developed acute pancreatitis 10 weeks after antiretrovirals were initiated. Pancreatitis resolved spontaneously after antiretroviral discontinuation. DISCUSSION: Our report of didanosine-induced pancreatitis secondary to concurrent use with tenofovir is the third reported case that utilized a reduced didanosine dosage. Five previous pancreatitis reports have been described using full-strength didanosine with tenofovir. The exact mechanism of action for this interaction is unknown. Utilizing the Naranjo probability scale to assess causality, a possible adverse drug reaction was determined. CONCLUSIONS: Tenofovir and didanosine may be used cautiously in antiretroviral combination therapy. Reduced didanosine dosage (250 mg) should be used to reduce serum didanosine concentrations and subsequent toxicities. Practitioners should be aware that a significant drug interaction with resulting pancreatitis may occur even when a reduced dosage is prescribed.

Effect of tenofovir on didanosine absorption in patients with HIV.

OBJECTIVE: To evaluate the pharmacokinetic interaction between tenofovir and didanosine when used in combination as a highly active antiretroviral therapy regimen. DATA SOURCES: Literature retrieval was accessed through MEDLINE (1966-January 2003) using the terms tenofovir and didanosine. Abstracts from recent meetings, including the International AIDS Society, Interscience Conference on Antimicrobial Agents and Chemotherapy, and the Infectious Diseases Society of America, were reviewed for relevant abstracts and poster presentations. DATA SYNTHESIS: Pharmacokinetic studies evaluating the concurrent use of tenofovir and didanosine have been performed in healthy volunteers. Tenofovir 300 mg administered concurrently with 400 mg didanosine results in a 48-64% increase in the didanosine maximum plasma concentration and AUC with no significant alterations in the tenofovir pharmacokinetic parameters. Tenofovir 300 mg and didanosine 250 mg has been compared with didanosine 400 mg alone. The results demonstrated equivalent didanosine AUCs. CONCLUSIONS: When used concurrently, tenofovir significantly increases the maximum plasma concentration and the AUC of didanosine. Additional data in HIV-infected patients are needed to determine the long-term toxicities of this combination therapy. Didanosine dose reduction should be considered when these 2 agents are used concurrently.