Drug products: Florinef, Florinef Acetaat, Florinef®
ATC code: H02AA02
Substances: fludrocortisone, fludrocortisone acetate
No controlled or prospective studies examining sex differences in fludrocortisone efficacy, safety or pharmacokinetics have been identified. Limited observational data has indicated that women might be more prone to overtreatment with mineralocorticoids in Addison’s disease than men, and that this might contribute to an increased relative risk of cardiovascular disease. However, the available evidence is too weak to permit definitive conclusions.
No pharmacokinetic studies comparing differences in exposure of fludrocortisone between men and women have been identified. Limited observational data has generally indicated that average daily doses of fludrocortisone administered to men and women with autoimmune Addison’s disease are roughly equal [1, 2], with one population-based study demonstrating marginally higher fludrocortisone doses prescribed to men with this condition in clinical practice .
No controlled studies examining sex differences in fludrocortisone efficacy have been identified. Observational data including comparisons between men and women is very limited and does not provide meaningful guidance for conventional clinical purposes.
A large proportion of patients receiving fludrocortisone are subject to concomitant treatment with a glucocorticoid agent, which typically also contributes to mineralocorticoid effects. Thus, administered doses of glucocorticoids can affect dosing requirements of fludrocortisone in individual patients. The specific effects of fludrocortisone might therefore be difficult to isolate in clinical practice, which may contribute to the paucity of clinical trials examining fludrocortisone effects specifically.
A few studies examining sex differences in fludrocortisone-induced mineralocorticoid receptor stimulation effects other than those usually deemed clinically relevant have been identified. One example of this is provided by a placebo-controlled study in healthy volunteers, including 40 men and 40 women, examining potential improvements of spatial memory after single doses of 0.4 mg fludrocortisone . Similar improvements in men and women were demonstrated in this study after identical doses.
No prospective studies addressing the issue of sex differences in the adverse effects of fludrocortisone have been identified.
The same interpretational challenges as described above regarding widespread concomitant treatment with glucocorticoids is likely to apply to the characterization of adverse effects of fludrocortisone treatment specifically. A comprehensive, population-based retrospective cohort study reviewing the medical records of 1500 patients with autoimmune Addison’s disease in Sweden, found a more pronounced association between daily fludrocortisone doses >0.1 mg and risk of cardiovascular disease in women than in men . The authors hypothesized that women might be disproportionately subjected to mineralocorticoid overtreatment as a result of lower constitutive levels of aldosterone, but the results were arguably prone to confounding and should be interpreted with caution.
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2020-09-14
Reviewed by: Diana Rydberg, Carl-Olav Stiller
Approved by: Karin Schenck-Gustafsson