Drug Interactions between fluconazole and nitrofurantoin

MONITOR: The concomitant administration of nitrofurantoin and fluconazole may increase the risk of hepatic and pulmonary toxicity. The mechanism is unknown. A 73-year-old patient who had been taking nitrofurantoin for 5 years developed respiratory symptoms (fatigue, dyspnea, cough, pleuritic pain, and tracheal pain) and hepatic enzyme elevations 2 months after fluconazole 150 mg/week was added to his regimen. A diagnosis of pulmonary fibrosis was made after chest X-rays and respiratory tests were performed. The patient also took multiple other drugs including terazosin, cimetidine, fluticasone nasal spray, diphenhydramine, ibuprofen, fluocinonide ointment, multivitamin, vitamin E, calcium-vitamin D, aspirin, calcium polycarbophil, and docusate, and drank moderate amounts of alcohol. Symptoms improved gradually after discontinuation of nitrofurantoin and fluconazole. Nitrofurantoin alone is known to cause pulmonary toxicity (usually pulmonary fibrosis or interstitial pneumonitis) and both drugs individually have been associated with hepatic toxicity.

MANAGEMENT: Until more information is available it may be advisable to monitor patients for signs of adverse pulmonary and hepatic effects during concomitant administration. Patients should be advised to notify their physician if they develop cough, dyspnea, fatigue, or pain.