Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Topiramat

Klassificering: C

Preparat: Topamac, Topamax, Topimax, Topimax®, Topiramat 1A Farma, Topiramat 2care4, Topiramat Actavis, Topiramat Bluefish, Topiramat Ebb, Topiramat Orifarm, Topiramat Orion, Topiramat ratiopharm

ATC kod: N03AX11

Substanser: topiramat

Sammanfattning

Inga skillnader mellan könen avseende effekt eller säkerhet har observerats för topiramat.

Studier visar motsägande resultat gällande könsskillnader i viktminskning under pågående behandling med topiramat.

Under graviditet kan koncentrationen av topiramat minska med 30–40 %.

Additional information

Topiramate is used in focal epilepsy with or without generalization, in primary generalized tonic-clonic seizures, and as a migraine prophylactic.

Pharmacokinetics and dosing

More than 80% of topiramate is eliminated renally. No sex difference in half-life has been observed (11 men/boys, 15 women/girls) [1]. However, in women/girls, the volume of distribution of topiramate is about 50% less than in men/boys, this is attributed to the higher percentage of body fat in women/girls. This difference is not considered to be clinically relevant [1, 2]. The clearance of topiramate in adults is not influenced by patient’s sex or race [3]. No sex differentiation in dosing has been recommended [4]. Topiramate metabolism may increase during pregnancy, see below.

Effects

Studies conducted by the pharmaceutical company have shown no impact of patient’s sex on effectiveness and safety of topiramate, regardless of indication [3]. Five randomized, double-blind, placebo-controlled trials of topiramate as add-on therapy in patients with medically intractable partial-onset seizures showed no difference in efficacy by patient’s sex. However, women represented only 20% of the 534 patients studied [5]. An observational study in pediatric patients (43 boys, 70 girls) with migraine treated for at least three months with topiramate found no association between effect and patient’s sex [6].

Adverse effects

Treatment with topiramate may cause weight loss. Some studies suggest that there are no sex differences in weight loss in adults (13 men, 36 women) [7], while other studies indicate that women were more likely to lose weight than men after treatment during 12 months [8, 9].

Paresthesia is a common adverse event of topiramate treatment. A study based on survey data and register data (12 men and 148 women with migraine, 96 men and 64 women with epilepsy) shows that women were twice as likely as men in reporting paresthesia (odds ratio 2.1). Patients with migraine reported more paresthesia than patients with epilepsy (odds ratio 3.5), which may be due to faster titration protocol in migraine than in epileptic patients [8].

Reproductive health issues

Topiramate may reduce the plasma concentration of estrogens and progestins. Regarding drug-drug interactions aspects, please consult Janusmed Interactions (in Swedish, Janusmed interaktioner).

Physiologic changes during pregnancy can alter antiepileptic pharmacokinetics and total antiepileptic concentration. Pharmacokinetics of some antiepileptic drugs are more pronounced, probably due to pregnancy-related differential effects on cytochrome P450 enzymes and pregnancy-related changes in the volume of distribution [9]. Topiramate serum concentrations have been reported to decline by up to 30-40% during the third trimester of pregnancy, but with a considerable interindividual variation [10]. Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Försäljning på recept

Fler kvinnor än män hämtade ut läkemedel innehållande topiramat (ATC-kod N03AX11) på recept i Sverige år 2019, totalt 5 330 kvinnor och 2 226 män. Det motsvarar 1,1 respektive 0,4 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 25–59 år hos båda könen. I genomsnitt var läkemedel innehållande topiramat 2,6 gånger vanligare hos kvinnor [11].

Uppdaterat: 2020-09-08

Litteratursökningsdatum: 2019-09-23

Referenser

  1. Vovk T, Jakovljević MB, Kos MK, Janković SM, Mrhar A, Grabnar I. A nonlinear mixed effects modelling analysis of topiramate pharmacokinetics in patients with epilepsy. Biol Pharm Bull. 2010;33:1176-82. PubMed
  2. Sachdeo RC. Topiramate Clinical profile in epilepsy. Clin Pharmacokinet. 1998;34(5):335-46. PubMed
  3. Topiramate. DailyMed [www]. US National Library of Medicine. [updated 2019-05-07, cited 2019-09-23]. länk
  4. Topimax (topiramat). Summary of Product Characteristics. Swedish Medical Products Agency [updated 2019-04-10, cited 2019-09-23]. länk
  5. Morrell MJ. The new antiepileptic drugs and women: efficacy, reproductive health, pregnancy, and fetal outcome. Epilepsia. 1996;37 Suppl 6:S34-44. PubMed
  6. Yoo IH, Kim W, Kim H, Lim BC, Hwang H, Chae JH et al. Factors Associated with Favorable Outcome of Topiramate Migraine Prophylaxis in Pediatric Patients. J Clin Neurol. 2017;13(3):281-286. PubMed
  7. Verrotti A, Scaparrotta A, Agostinelli S, Di Pillo S, Chiarelli F, Grosso S. Topiramate-induced weight loss: a review. Epilepsy Res. 2011;95:189-99. PubMed
  8. Sedighi B, Shafiei K, Azizpour I. Topiramate-induced paresthesia is more frequently reported by migraine than epileptic patients. Neurol Sci. 2016;37(4):585-9. PubMed
  9. Legato MJ, editor. Principles of Gender-Specific Medicine. Academic Press Inc; 2004.
  10. 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
  11. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2019 [cited 2020-03-10.] länk

Författare: Linnéa Karlsson Lind

Faktagranskat av: Mia von Euler, Carl-Olav Stiller, Diana Rydberg

Godkänt av: Karin Schenck-Gustafsson