Drug-drug Interactions with Antifungal Agents

Fungal opportunistic infections continue to be seen in individuals with HIV despite the widespread use of HAART. Further, in some cases antiretroviral treatment-naive patients develop fungal infections prior to initiation of HAART.

In the current retrospective study, conducted at the University Hospital of Bordeaux, France, researchers describe drug-drug interactions encountered among adult patients receiving systemic antifungal treatment in the hospital's intensive care units (ICUs) and infectious diseases units (IDUs) between 1996 and 2001.

The investigators examined all episodes of treatment with antifungal agents and identified all prescribed concomitant medication for potential drug-drug interaction-related serious events occurring during treatment.

Results

• In 105 patients receiving antifungals, 150 treatment episodes occurred.

• Fluconazole (Diflucan) was used in 48% of the treatment episodes, amphotericin B (Fungizone) in 46%, itraconazole (Sporanox) in 4.7%, and flucytosine (Ancobon) in 1.3%.

• 116 potential drug-drug interactions were identified related to the use of amphotericin B (81.0%), fluconazole (17.2%), or itraconazole (1.7%).

• Of these, 22 were associated with clinical evidence of adverse interactions (hypokalemia, increased creatinine, or nephrotoxicity).

• All these clinical drug-drug interactions occurred with amphotericin B.

• Interactions were due to furosemide (Lasix; 36.4%), cyclosporine (Neoral and others; 31.8%), and hydrocortisone (18.2%).

• Potential drug-drug interactions were mostly commonly associated with leukemia (40.4%), HIV infection (24.6%), and cancer (10.5%).

Conclusion

Based on these findings, the study authors concluded, "In ICU and IDU, systemic antifungal treatments lead to many serious drug-drug interactions, mainly related to the type of antifungal used and to the pathology treated. Clinically serious drug-drug interactions seem more common with amphotericin."

10/12/07

Reference
F Depont, F Vargas, H Dutronc, and others. Drug-drug interactions with systemic antifungals in clinical practice. Pharmacoepidemiology & Drug Safety. September 19, 2007 [Epub ahead of print].