Levetiracetam
Classification: AATC code: N03AX14
Summary
Controlled studies on differences between men and women regarding effect of levetiracetam are lacking.
The present evidence concerning differences between men and women is limited and do not motivate differentiation in dosing or treatment.
Additional information
Pharmacokinetics and dosing
There is no evidence for relevant sex differences in levetiracetam pharmacokinetics [1]. According to clinical studies done by the original manufacturer (12 men, 11 women), levetiracetam Cmax and AUC were 20% higher in women than men. However, clearances adjusted for body weight were comparable [2]. Another study found no significant sex differences in pharmacokinetic parameters of levetiracetam in children aged 2.3-46.2 months [3].
In pregnancy, decreasing concentrations are found already from the first trimester and up to 40-60% in the third trimester (increased renal elimination or enzymatic hydrolysis). The inter-individual variation is large and a fast normalization is seen after delivery [4].
Effects
No studies with a clinically relevant sex analysis regarding the effects of levetiracetam have been found.
Adverse effects
A clinical trial (30 men, 27 women) found no apparent sexual or endocrine side effects of levetiracetam treatment in men and women (age 18-45 years). Men treated with levetiracetam had lower free testosterone and androstenedione levels than healthy controls, but this was also seen in men treated with either carbamazepine or lamotrigine. This could thus be a difference between persons with and without epilepsy, and not a specific drug effect. Menstrual disturbances were more commonly reported in the epilepsy group than in the control group, but there were no difference in menstrual disturbances between treated women and controls. According to ASEX scores (Arizona Sexual Experience Scale), women using levetiracetam were more satisfied with their sexual lives than healthy controls without epilepsy while no differences were found in men. The etiology of this improvement in women is unclear [5]. A cross-sectional cohort study found no impact of levetiracetam monotherapy for 6 months on serum concentrations of sex-steroid hormones in pre-pubertal children. However, this study had a small sample size (7 boys and 3 girls on levetiracetam). There is reason to assume that levetiracetam monotherapy for 6 months does not result in clinically relevant endocrine side effects in prepubertal children [6].
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: 2013-03-06
References
- Levetiracetam. Summary of Product Characteristics. European Medicines Agency. [updated 2014-01-08, cited 2016-04-04]. länk
- Levetiracetam. DailyMed [www]. US National Library of Medicine. [updated 2011-12-01, cited 2013-03-06]. länk
- Tomson T, Landmark CJ, Battino D. Antiepileptic drug treatment in pregnancy: changes in drug disposition and their clinical implications. Epilepsia. 2013;54:405-14. PubMed
- Glauser TA, Mitchell WG, Weinstock A, Bebin M, Chen D, Coupez R et al. Pharmacokinetics of levetiracetam in infants and young children with epilepsy. Epilepsia. 2007;48:1117-22. PubMed
- Svalheim S, Taubøll E, Luef G, Lossius A, Rauchenzauner M, Sandvand F et al. Differential effects of levetiracetam, carbamazepine, and lamotrigine on reproductive endocrine function in adults. Epilepsy Behav. 2009;16:281-7. PubMed
- Rauchenzauner M, Bitsche G, Svalheim S, Tauboll E, Haberlandt E, Wildt L et al. Effects of levetiracetam and valproic acid monotherapy on sex-steroid hormones in prepubertal children--results from a pilot study. Epilepsy Res. 2010;88:264-8. PubMed
- Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-30.] länk
Reviewed by: Expertrådet för neurologiska sjukdomar, Ellen Vinge
Approved by: Karin Schenck-Gustafsson