Fluconazole/fluticasone propionate interaction
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First report of an interaction, leading to adrenal insufficiency and Cushing syndrome in a child: case report A 9-year-old girl developed adrenal insufficiency and Cushing syndrome during concomitant treatment with fluticasone propionate and fluconazole. The girl, who had cystic fibrosis (CF) and liver cirrhosis, was diagnosed with asthma and started inhaled fluticasone propionate 110 µg/actuation, two puffs twice daily, as well as prednisone. Four weeks later, fluticasone propionate was increased to 220 µg/actuation, two puffs twice daily. After a further 3 weeks, she presented with vaginal candidiasis and was prescribed a 5-day course of oral fluconazole 100mg. After 3 days of fluconazole, she developed polyuria and excessive thirst. Tests revealed a blood glucose level of greater than 600 mg/dL. The girl underwent dietary carbohydrate restriction, after which her glucose levels decreased slightly. Two days after the onset of symptoms, results of further tests were consistent with CF-related diabetes. She received insulin glargine and insulin aspart; however, her blood glucose levels remained elevated and she subsequently developed weight gain, hirsutism, a rounded face, violaceous striae and bruised easily. A 24-hour urine collection revealed no ketosteroids or free cortisol. Serum levels of cortisol and corticotropin were also suppressed. Her clinical condition was consistent with iatrogenic Cushing syndrome, coupled with hypothalamic-pituitary-adrenal axis suppression. Fluticasone propionate was withdrawn, and she received prednisone at tapering doses. Insulins were rapidly titrated to a stop. Two weeks after completing prednisone therapy, her HbA1c level had normalised and a tetracosactide stimulation test confirmed adequate adrenal reserve. Fluticasone propionate therapy was not restarted. Author comment: "Evaluation of this clinical outcome and use of a drug interaction probability scale indicate that this is a probable interaction." Hoover WC, et al. Rapid onset of iatrogenic adrenal insufficiency in a patient with cystic fibrosis-related liver disease treated with inhaled corticosteroids and a moderate CYP3a4 inhibitor. Annals of Pharmacotherapy 45: No. 78, Jul-Aug 2011. 803060416 Available from: URL: http://dx.doi.org/10.1345/aph.1q103 - USA
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Editorial comment: A search of AdisBase, Embase and Medline did not reveal any previous case reports of an interaction between fluconazole and fluticasone propionate. The WHO ADR database contained eight reports involving the concomitant use of fluconazole and fluticasone, including one report of a drug interaction.
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Reactions 24 Sep 2011 No. 1370
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