Denosumab
Classification: BATC code: M05BX04
Summary
Studies about differences between men and women on the effect and safety of denosumab are lacking. Results from studies in only men or only women indicate that the effect of bone mineral density (BMD) is similar in both sexes.
Additional information
Pharmacokinetics and dosing
According to the original manufacturer, denosumab pharmacokinetics is similar in men and women [1]. No studies with a clinically relevant sex analysis regarding the dosing of denosumab have been found.
Effects
Well-powered trials evaluating clinical fracture risk reduction in male osteoporosis are lacking. To estimate the anti-fracture efficacy of denosumab in men, trials have used assumptions concerning drug efficacy derived from trials in postmenopausal women [2]. For instance, percentage change from baseline to month 12 in lumbar spine BMD in women in the FREEDOM trial (placebo 0.7 vs. denosumab 4.8) was comparable to men in the ADAMO trial (placebo 1.0 vs. denosumab 4.8) [2-4]. According to one reference [5] there is a small ongoing not yet published study of the effect of treatment with denosumab in men with primary osteoporosis.
Dose exposure-response relationship for denosumab was determined in patients with bone metastases from solid tumors. Patients (92 men, 281 women) received denosumab as single or multiple subcutaneous doses ranging from 30-180 mg administrated every 4 or 12 weeks for up to 3 years. Denosumab efficacy and potency did not differ between men and women [6].
Adverse effects
No studies with a clinical relevant sex analysis regarding adverse effects of denosumab have been found.
Reproductive health issues
Denosumab may cause fetal harm when a man treated with denosumab has unprotected sexual intercourse with a pregnant partner [7]. Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Updated: 2017-03-27
Date of litterature search: 2014-08-07
References
- PROLIA (denosumab). Summary of Product Characteristics. European Medicines Agency (EMA); 2014.
- Parthan A, Kruse M, Agodoa I, Silverman S, Orwoll E. Denosumab: a cost-effective alternative for older men with osteoporosis from a Swedish payer perspective. Bone. 2014;59:105-13. PubMed
- Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361:756-65. PubMed
- Orwoll E, Teglbjærg CS, Langdahl BL, Chapurlat R, Czerwinski E, Kendler DL et al. A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density. J Clin Endocrinol Metab. 2012;97:3161-9. PubMed
- Adler RA, Gill RS. Clinical utility of denosumab for treatment of bone loss in men and women. Clin Interv Aging. 2011;6:119-24. PubMed
- Doshi S, Sutjandra L, Zheng J, Sohn W, Peterson M, Jang G et al. Denosumab dose selection for patients with bone metastases from solid tumors. Clin Cancer Res. 2012;18:2648-57. PubMed
- Prolia (denosumab). DailyMed [www]. US National Library of Medicine. [updated 2014-06-01, cited 2014-08-07]. länk
- Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-05.] länk
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson