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Betametason – systemiskt

Klassificering: B

Preparat: BENTELAN 0,5 mg, Betametason AB Unimedic, Betametason Alternova, Betametason Evolan, Betamethasone American Regent, Betapred, Betnesol, CELESTAMINE N0,5 Tabletten, Celeston®, Celeston® bifas®

ATC kod: H02AB01

Sammanfattning

Det saknas publicerade kontrollerade studier om könsskillnader i effekt av betametason, förutom vid prevention av Respiratory Distress Syndrome (andnödssyndrom) hos för tidigt födda barn och resultaten där är motsägelsefulla.
 
En stor meta-analys har visat att höga dagsdoser av orala glukokortikoider ökar risken för benfraktur lika mycket hos kvinnor och män, oavsett ålder och underliggande sjukdom. En annan stor populationsbaserad studie visade dock en ökad risk för fraktur hos kvinnor som exponerats för orala glukokortikoider.
 
Kunskapsunderlaget avseende skillnader mellan kvinnor och män är mycket begränsat och motiverar inte olika dosering eller behandling.

Additional information

Pharmacokinetics and dosing

Healthy adults (2 men, 6 women) receiving betamethasone 8 mg i.v. and betamethasone phosphate 10.6 mg i.v. showed no apparent sex difference in any pharmacokinetic parameter. Body weight did not affect AUC or half-life [3].

Effects

No studies with a clinically relevant sex analysis regarding the effect of betamethasone have been found, except for use during pregnancy. In pregnancy, corticosteroid can be used to encourage fetal lung maturation where premature delivery is expected [4] as immature lung development can lead to respiratory distress syndrome (RDS) [5]. A systematic review and meta-analysis, including four studies using betamethasone and four studies using dexamethasone (in total 1109 boys, 968 girls), found no difference in the reduction of RDS between girls and boys (relative risk 0.57 vs. 0.50). However, all four trials with betamethasone showed a benefit only for boys, while all four trials with dexamethasone showed benefit only in girls [6]. In contrast to this, other studies [7, 8] have shown a beneficial response to betamethasone only in girls. One possible explanation to these contradictory findings may be heterogeneous groups with different average gestational ages and birth weights in the studies [6-8].

Adverse effects

A large meta-analysis of corticosteroid-induced osteoporosis in adults showed that oral corticosteroid treatment with doses above 5 mg/day (of prednisolone or equivalent) reduced bone mineral density and increased the risk of fracture during treatment, irrespective of age, sex, or underlying disease (66 studies with 2891 patients with BMD measures, 71.5% women and 23 studies with 558 with fractures in corticosteroid users, and 244 235 corticosteroid users with fractures in the General Practice Research Database) [1]. However, a study not included in the meta-analysis, retrospectively analyzed the population attributable risk of fracture in a cohort using oral corticosteroids (8192 men, 12034 women). Compared to the general population, corticosteroids users had a higher risk of fracture (RR 1.90), and women had a higher risk than men (RR 2.13) [2]. Another meta-analysis of glucocorticoid therapy in children (in total 287 patients with BMD measure, and 37 819 with fractures) showed corticosteroid use to be associated with reduced spine bone mineral density and no sex difference in the risk for fracture were seen [3].

Reproductive health issues

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

Other information

There has been concern that prenatal use of corticosteroids to increase lung maturation in premature infants is associated with long term effects, such as cognitive deficits [4]. A cross-sectional study evaluated children (117 boys, 105 girls) born to women at risk of preterm delivery   treated with synthetic betamethasone or dexamethasone as a single course during pregnancy. Cognitive testing was performed when the children were at age 8-11 years old along with a structured interview with the mothers. Boys born to women with a pathologic pregnancy with or without receiving glucocorticoid scored lower IQ than controls. No differences in IQ scores between groups were seen in girls [9]. A study of individuals aged 20-22 years (43 men, 38 women) who had antenatally been exposed to one course betamethasone for prevention of neonatal respiratory distress syndrome showed no effect on cognitive functioning [10]. Another observational study of long-term effects of antenatal corticosteroid use (betamethasone or dexamethasone) showed that boys had a higher risk of epilepsy than girls (OR 1.74 vs. 0.50). Children were followed up until their ninth birthday [11].

The effect of betamethasone on fetal heart rate and behavior in preterm twin pregnancy was analyzed in 18 pregnant women receiving 12 mg of betamethasone i.m. Betamethasone decreased basal fetal heart rate and body and breathing movements. The response in one fetus was highly associated with that in the co-twin, and independent of sex [7].

Försäljning på recept

Fler kvinnor än män hämtade ut tabletter eller injektionsvätska innehållande betametason (ATC-kod H02AB01) på recept i Sverige år 2015, totalt 123 532 kvinnor och 79 956 män. Det motsvarar 25 respektive 16 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 65-74 år hos kvinnor och åldersgruppen 70-84 år hos män. I genomsnitt var läkemedel inom denna ATC-kod 1,7 gånger vanligare hos kvinnor [12]. Hälften av försäljningen inom denna ATC-kod sker på recept, andra halvan går på rekvisition där det saknas könsspecifika användningsdata [13].

Uppdaterat: 2019-02-26

Litteratursökningsdatum: 2016-09-15

Referenser

  1. van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int. 2002;13:777-87. PubMed
  2. Donnan PT, Libby G, Boyter AC, Thompson P. The population risk of fractures attributable to oral corticosteroids. Pharmacoepidemiol Drug Saf. 2005;14:177-86. PubMed
  3. Hansen KE, Kleker B, Safdar N, Bartels CM. A systematic review and meta-analysis of glucocorticoid-induced osteoporosis in children. Semin Arthritis Rheum. 2014;44:47-54. PubMed
  4. Petersen MC, Nation RL, McBride WG, Ashley JJ, Moore RG. Pharmacokinetics of betamethasone in healthy adults after intravenous administration. Eur J Clin Pharmacol 1983;25(5):643-50 PubMed
  5. The United Kingdom Teratology Information Service (UKTIS) - Exposure in pregnancy. Corticosteroids in pregnancy. Newcastle upon Tyne: Public Health England. 2012 [cited 2016-09-15.] länk
  6. Crowther CA, McKinlay CJ, Middleton P, Harding JE. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes. Cochrane Database Syst Rev. 2015;7:CD003935. PubMed
  7. Roberge S, Lacasse Y, Tapp S, Tremblay Y, Kari A, Liu J et al. Role of fetal sex in the outcome of antenatal glucocorticoid treatment to prevent respiratory distress syndrome: systematic review and meta-analysis. J Obstet Gynaecol Can. 2011;33:216-26. PubMed
  8. Ballard PL, Ballard RA, Granberg JP, Sniderman S, Gluckman PD, Kaplan SL et al. Fetal sex and prenatal betamethasone therapy. J Pediatr. 1980;97:451-4. PubMed
  9. Papageorgiou AN, Colle E, Farri-Kostopoulos E, Gelfand MM. Incidence of respiratory distress syndrome following antenatal betamethasone: role of sex, type of delivery, and prolonged rupture of membranes. Pediatrics. 1981;67:614-7. PubMed
  10. Alexander N, Rosenlöcher F, Dettenborn L, Stalder T, Linke J, Distler W et al. Impact of Antenatal Glucocorticoid Therapy and Risk of Preterm Delivery on Intelligence in Term-Born Children. J Clin Endocrinol Metab. 2016;101:581-9. PubMed
  11. Dessens AB, Haas HS, Koppe JG. Twenty-year follow-up of antenatal corticosteroid treatment. Pediatrics. 2000;105:E77. PubMed
  12. Eriksson L, Haglund B, Ewald U, Odlind V, Kieler H. Short and long-term effects of antenatal corticosteroids assessed in a cohort of 7,827 children born preterm. Acta Obstet Gynecol Scand. 2009;88:933-8. PubMed
  13. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-09-15.] Socialstyrelsens statistikdatabas
  14. Conicse. Stockholm: eHälsomyndigheten. 2015 [cited 2016-03-23.] länk

Författare: Linnéa Karlsson Lind

Faktagranskat av: Mia von Euler

Godkänt av: Karin Schenck-Gustafsson