Although anterior uveitis is a frequent complication of rifabutin therapy [1], it occurs infrequently with rifabutin prophylaxis (300 mg/d) [2]. This condition, however, has been seen during concomitant administration of rifabutin and either fluconazole or clarithromycin; this suggests that a drug interaction may be responsible for this complication [3]. We describe a patient with human immunodeficiency virus infection who developed anterior uveitis while receiving rifabutin prophylaxis during itraconazole therapy.

A 49-year-old man with a history of Pneumocystis carinii pneumonia and bilateral cytomegalovirus retinitis was hospitalized with anterior uveitis of the left eye. He had been receiving rifabutin prophylaxis (300 mg/d) for 6 months. One month before hospitalization, treatment with itraconazole (600 mg/d) was initiated for Aspergillus fumigatus pneumonia. Because of low itraconazole plasma levels after 3 weeks of treatment, the dose was increased to 900 mg/d 1 week before the onset of ophthalmic symptoms. At admission, trough serum levels of itraconazole and its metabolite were appropriate (516 µg/L and 645 µg/L, respectively). As expected, trough serum levels of rifabutin and its LM565 metabolite (153 ng/mL and 50 ng/mL, respectively) were higher (serum levels of rifabutin are usually lower than 50 ng/mL 24 hours after oral administration of 300 mg of the drug). Rifabutin prophylaxis was discontinued, and the patient was treated with topical steroids and a cycloplegic agent. Results of ophthalmic examination returned to normal after 5 days.

Itraconazole, an orally active triazole antifungal drug, appears to be well tolerated but can inhibit the metabolism of other drugs, such as digoxin and cyclosporine. No interaction between rifabutin and itraconazole has been reported. Our case report suggests a kinetic interaction between itraconazole and rifabutin that resulted in an increase in serum rifabutin levels and a risk for developing uveitis. Serum levels of rifabutin should be closely monitored in patients receiving rifabutin prophylaxis during itraconazole therapy. If uveitis develops in such patients, rifabutin-related uveitis should be suspected and rifabutin therapy should be stopped immediately.