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Prednisone

Classification: C

Drug products: Deltison®, Lodotra, Prednison Streuli

ATC code: H02AB07

Substances: prednisone

Summary

Large controlled studies on sex differences of the mineral corticoid effect of prednisone are lacking.

A small study on children with congenital adrenal hyperplasia treated with corticosteroids including prednisone, showed that boys but not girls had earlier onset of puberty, measured by the Tanner’s scale. In another study, prednisone-treated boys had lower height and weight as adults compared to placebo, while no difference between treated girls or placebo was seen.
 
A large meta-analysis have shown that high daily doses of oral glucocorticoids increase the risk of bone fractures to a similar degree in men and women, regardless of age and underlying disease. However, another large population-based study found a higher risk of fracture in women than men exposed to oral corticosteroids.

Additional information

Pharmacokinetics and dosing

Prednisone is both a pro-drug to prednisolone and an inactive metabolite of prednisolone. Therefore, the pharmacokinetics of prednisone could be attributed to prednisolone. Prednisolone pharmacokinetics was investigated in healthy white and black men and women (16 men, 16 women) receiving a single oral dose 0.27 mg/kg of prednisone (precursor to prednisolone). Clearance of free prednisolone normalized for bodyweight was higher in men than in women, regardless of race [4]. Contrary to this, another smaller study (4 men, 4 women) observed a higher total and free clearance in women after receiving prednisolone 0.075-1.5 mg/kg [5].

The pharmacokinetics of total and unbound prednisone and prednisolone was studied in adult diabetic and non-diabetic kidney transplant recipients (30 men, 8 women). Men had a higher affinity constant than women for prednisolone bound to corticosteroid binding globulin. However, due to the small number of women in this study, it is not possible to conclude if sex the influence prednisone pharmacokinetics [6].

Effects

The impact of glucocorticoid-induced growth impairment has been investigated in several studies. Growth and pubertal development in children with congenital adrenal hyperplasia (CAH) on treatment with hydrocortisone acetate, cortisone acetate, or prednisone has been investigated (8 boys, 10 girls). Growth was evaluated according to Tanner’s standards. Boys had earlier onset of puberty, but not girls, and the authors speculate that this might be due to induction through hypothalamic stimulation by androgens [7].Growth in children with cystic fibrosis was studied in a randomized, double-blind trial (126 boys, 98 girls; ages 6-14). Children were randomized to low-dose prednisone or placebo. After 18 years of age, prednisone-treated boys had lower mean height and weight than placebo-treated boys, while prednisone-treated girls reached similar heights and weights as placebo-treated girls [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].No effect of low-dose prednisone on BMD was seen in RA patients overall (16 men, 164 women). However, a post hoc analysis of the study, including the 109 women who were postmenopausal, showed that a dose of 5 mg/day or less reduced hip BMD [9].

Reproductive health issues

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

Updated: 2019-02-26

Date of litterature search: 2017-02-20

References

  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. Magee MH, Blum RA, Lates CD, Jusko WJ. Prednisolone pharmacokinetics and pharmacodynamics in relation to sex and race. J Clin Pharmacol. 2001;41:1180-94. PubMed
  5. Meffin PJ, Brooks PM, Sallustio BC. Alterations in prednisolone disposition as a result of time of administration, gender and dose. Br J Clin Pharmacol. 1984;17:395-404. PubMed
  6. Ionita IA, Ogasawara K, Gohh RY, Akhlaghi F. Pharmacokinetics of total and unbound prednisone and prednisolone in stable kidney transplant recipients with diabetes mellitus. Ther Drug Monit. 2014;36:448-55. PubMed
  7. Hochberg Z, Schechter J, Benderly A, Leiberman E, Rosler A. Growth and pubertal development in patients with congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency. Am J Dis Child. 1985;139:771-6. PubMed
  8. Lai HC, FitzSimmons SC, Allen DB, Kosorok MR, Rosenstein BJ, Campbell PW et al. Risk of persistent growth impairment after alternate-day prednisone treatment in children with cystic fibrosis. N Engl J Med. 2000;342:851-9. PubMed
  9. Chung CP, Russell AS, Segami MI, Ugarte CA. The effect of low-dose prednisone on bone mineral density in Peruvian rheumatoid arthritis patients. Rheumatol Int. 2005;25:114-7. PubMed
  10. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2017-03-02.] länk

Authors: Linnéa Karlsson Lind

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson

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