Revised SPC: Fluconazole 400mg/200ml infusion bags (2mg/ml in 200ml infusion bags)

SPC includes additional pregnancy data showing no increase in overall risk of malformations associated with use of cumulative dose of ≤150mg in first trimester; one cohort study however suggests exposure associated with small increased risk of musculoskeletal malformations.

SPS commentary:

In one large observational cohort study, first trimester exposure to oral fluconazole was associated with a small increased risk of musculoskeletal malformations, corresponding to approximately 1 additional case per 1000 women treated with cumulative doses ≤450mg compared with women treated with topical azoles and to approximately 4 additional cases per 1000 women treated with cumulative doses over 450mg. The adjusted relative risk was 1.29 (95% CI 1.05 to 1.58) for 150mg oral fluconazole and 1.98 (95% CI 1.23 to 3.17) for doses over 450mg fluconazole.

 

The manufacturer states that fluconazole in standard doses and short-term treatments should not be used in pregnancy unless clearly necessary.

 

Section 4.4 has also been updated to note that studies have shown an increasing prevalence of infections with Candida species other than C. albicans, which are often inherently resistant (e.g. C. krusei and C. auris) or show reduced susceptibility to fluconazole (C. glabrata). Such infections may require alternative antifungal therapy secondary to treatment failure. Therefore, prescribers are advised to take into account the prevalence of resistance in various Candida species to fluconazole.

Source:

electronic Medicines compendium