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Pulmonary and Hepatic Toxicity Due to Nitrofurantoin and Fluconazole Treatment

Assistant Professor, Department of Clinical Pharmacy, University of Colorado Health Sciences Center, Denver, CO

Bennett L Parnes, MD

Associate Professor, Department of Family Medicine; Associate Professor, Division of Geriatrics, Department of Medicine, University of Colorado Health Sciences Center

Reprints: Sunny A Linnebur PharmD BCPS, Department of Clinical Pharmacy, University of Colorado Health Sciences Center, 4200 East Ninth Ave., Campus Box C238, Denver, CO 80262-0238, fax 303/315-4630, sunny.linnebur{at}uchsc.edu

OBJECTIVE: To reemphasize potential risks associated with chronic nitrofurantoin use and to report a case of combined pulmonary and hepatic toxicity precipitated from acute use of fluconazole concomitantly with chronic nitrofurantoin.

CASE SUMMARY: A 73-year-old white man taking nitrofurantoin 50 mg/day for 5 years developed combined hepatic and pulmonary toxicity after taking fluconazole acutely for onychomycosis. Two months after starting fluconazole, the patient's hepatic enzymes showed elevation 5 times the upper limits of normal. In addition, the patient reported fatigue, dyspnea on exertion, pleuritic pain, burning trachea pain, and a cough. Chest X-rays showed bilateral pulmonary disease consistent with nitrofurantoin toxicity. Both drugs were determined to be the cause of the patient's pulmonary and hepatic toxicity, so they were discontinued. Pulmonary function tests measured after discontinuation were abnormal and also consistent with nitrofurantoin toxicity. The patient's hepatic and pulmonary toxicity resolved upon discontinuation of both drugs and use of inhaled corticosteroids.

DISCUSSION: Changes in hepatic enzyme measurement, pulmonary function measurements, and chest X-rays indicate that our patient developed hepatic and pulmonary toxicity due to his drug therapy. An objective causality assessment revealed that these adverse events were probably due to fluconazole given with nitrofurantoin. Either drug may have caused the hepatic toxicity. However, it is possible that pharmacokinetic changes induced by an interaction with fluconazole precipitated the nitrofurantoin-induced pulmonary toxicity.

CONCLUSIONS: Our patient developed pulmonary and hepatic toxicity after starting fluconazole in combination with chronic nitrofurantoin. A potential drug interaction of unknown mechanism may have been the cause of the toxicities.

Key Words: fluconazole, hepatic toxicity, nitrofurantoin, pulmonary toxicity

Published Online, February 13, 2004. www.theannals.com, DOI 10.1345/aph.1D306