Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Fludrokortison

Klassificering: B

Preparat: Florinef, Florinef Acetaat, Florinef®

ATC kod: H02AA02

Substanser: fludrokortison, fludrokortisonacetat

Sammanfattning

Inga kontrollerade eller prospektiva studier som undersökt könsskillnader avseende effekter, biverkningar eller farmakokinetiken av fludrokortison har identifierats. Begränsade observationella data har indikerat att kvinnor i högre utsträckning än män kan bli föremål för översubstitution med mineralkortikoider vid Addisons sjukdom och att detta kan bidra till en relativ kardiovaskulär riskökning. Det befintliga evidensläget är emellertid alltför svagt för att tillåta några definitiva slutsatser.

Additional information

Pharmacokinetics and dosing

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 [3].

Effects

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 [4]. Similar improvements in men and women were demonstrated in this study after identical doses.

Adverse effects

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 [3]. 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.

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Försäljning på recept

Nästan lika många kvinnor och män hämtade ut tabletter innehållande fludrokortison (ATC-kod H02AA02) på recept i Sverige år 2019, totalt 1 783 män och 1 740 kvinnor. Det motsvarar 4 respektive 3 personer per tiotusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 75 år och äldre hos båda könen. I åldersgruppen 75 år och äldre var tabletter innehållande fludrokortison i genomsnitt 1,6 gånger vanligare hos män [5].

Uppdaterat: 2020-10-06

Litteratursökningsdatum: 2020-09-14

Referenser

  1. Puglisi S, Rossini A, Tabaro I, Cannavò S, Ferrau' F, Ragonese M et al. What factors have impact on glucocorticoid replacement in adrenal insufficiency: a real-life study. J Endocrinol Invest. 2020. PubMed
  2. Dalin F, Nordling Eriksson G, Dahlqvist P, Hallgren Å, Wahlberg J, Ekwall O, Söderberg S, Rönnelid J, Olcén P, Winqvist O, Catrina SB, Kriström B, Laudius M, Isaksson M, Halldin Stenlid M, Gustafsson J, Gebre-Medhin G, Björnsdottir S, Janson A, Åkerman AK, Åman J, Duchen K, Bergthorsdottir R, Johannsson G, Lindskog E, Landin-Olsson M, Elfving M, Waldenström E, Hulting AL, Kämpe O, Bensing S. Clinical and Immunological Characteristics of Autoimmune Addison Disease: A Nationwide Swedish Multicenter Study. J Clin Endocrinol Metab. 2017;102(2):379-389. PubMed
  3. Skov J, Sundström A, Ludvigsson JF, Kämpe O, Bensing S. Sex-Specific Risk of Cardiovascular Disease in Autoimmune Addison Disease-A Population-Based Cohort Study. J Clin Endocrinol Metab. 2019;104(6):2031-2040. PubMed
  4. Piber D, Schultebraucks K, Mueller SC, Deuter CE, Wingenfeld K, Otte C. Mineralocorticoid receptor stimulation effects on spatial memory in healthy young adults: A study using the virtual Morris Water Maze task. Neurobiol Learn Mem. 2016;136:139-146. PubMed
  5. Statistikdatabas för läkemedel. Stockholm: Socialstyrelsen. 2019 [cited 2020-03-10.] länk

Författare: Gustaf Beijer

Faktagranskat av: Diana Rydberg, Carl-Olav Stiller

Godkänt av: Karin Schenck-Gustafsson