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Oxkarbazepin

Klassificering: A

Preparat: Apydan, Apydan Extent, Oxcarbazepin Mylan, Oxcarbazepine STADA, Trileptal, Trileptal®

ATC kod: N03AF02

Substanser: oxkarbazepin

Sammanfattning

Inga könsrelaterade skillnader i effekt har observerats för oxkarbazepin. Vissa studier indikerar att kvinnor har en högre risk än män att utveckla hyponatremi vid oxkarbazepinbehandling.

Additional information

Pharmacokinetics and dosing

According to the pharmaceutical company, no sex-related pharmacokinetic differences have been observed in children, adults or the elderly [1, 2]. Pharmacokinetic studies in Chinese patients with epilepsy show contradictory results. One study involving children and adults (54 men, 24 women, mean age 37 years) found lower clearance of the active metabolite 10-monohydroxy derivative (MHD) in women than in men [3], while a study including only children (90 boys, 51 girls, mean age 8 years) did not find an association between MHD pharmacokinetics and patient’s sex [4].

Effects

The pharmaceutical company report that no important sex differences in the efficacy of oxcarbazepine in epilepsy patients were shown in clinical trials [2, 5]. No other published studies with a clinically relevant sex analysis regarding the effects of oxcarbazepine have been found.

Adverse effects

Adverse events were reported more frequently in women than men treated with carbamazepine or oxcarbazepine for treatment of trigeminal neuralgia or neuralgiform (36 men, 43 women). The probability of a toxic dose with oxcarbazepine for women were around 1200 mg and for men around 1800 mg [6].

Oxcarbazepine can induce hyponatremia and women may have a higher risk than men of developing hyponatremia. A suggested explanation to this might be sex-related differences in the mechanisms of sodium transport [7]. A register-based study in epilepsy patients (69 men, 289 women) showed that women treated with oxcarbazepine had a higher risk of hyponatremia than men (odds ratio 2.25) [8].

Reproductive health issues

The plasma concentrations of estrogens and progestogens may be decreased by coadministration of oxcarbazepine. The effect of hormone therapy may therefore be impaired [2]. Regarding drug-drug interactions aspects, please consult Janusmed Interactions (in Swedish, Janusmed interaktioner).

There are studies indicating that treatment with oxcarbazepine (as well as carbamazepine and valproic acid) is associated with sperm abnormalities in men with epilepsy [9-12]. The clinical relevance of this finding is unclear. However, it is possible that the epilepsy itself affect the sperm quality, since decreased levels have been seen even before AED treatment [13]. Semen quality, sexual function and sex hormones in men with epilepsy are not affected by treatment with lamotrigine, levetiracetam, or oxcarbazepine, according to a randomized controlled trial including 38 adult men with newly diagnosed epilepsy [13]. Reports of sexual dysfunction caused by levetiracetam or oxcarbazepine are limited to case reports. Larger studies suggest that lamotrigine, levetiracetam and oxcarbazepine can improve sexual function [13, 14]. 

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

Other information

Slightly more men than women were treated in inpatient care with the main diagnosis epilepsy (ICD-10 G40) in Sweden during 20192011, totally 2 8553389 men and 2 5592921 women. The prevalence was highest among the elderly in both sexes. In the age group 5045 year and older, the diagnosis was on average 1.31.4 times more common among men. In the younger age groups, the prevalence was similar in both women and men [15]. In a Swedish study, the incidence of unprovoked epileptic seizures/epilepsy was generally higher among men than women, especially in the age group 60 years and older. In the age group 1-9 year, the incidence was higher among girls [16].

Försäljning på recept

Något fler män än kvinnor hämtade ut läkemedel innehållande oxkarbazepin (ATC-kod N03AF02) på recept i Sverige år 2019, totalt 2 213 män och 1 909 kvinnor. Det motsvarar 0,4 respektive 0,4 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 5-14 år hos båda könen [17].

Uppdaterat: 2020-10-01

Litteratursökningsdatum: 2019-09-24

Referenser

  1. Trileptal (oxcarbazepine). Summary of Product Characteristics. Swedish Medical Products Agency (MPA) {updated 2019-04-15, cited 2019-09-24]. länk
  2. Trileptal (oxcarbazepine) DailyMed [www]. US National Library of Medicine. [updated 2019-01-04, cited 2019-09-24]. länk
  3. Yu Y, Zhang Q, Xu W, Lv C, Hao G. Population pharmacokinetic modeling of oxcarbazepine active metabolite in Chinese patients with epilepsy. Eur J Drug Metab Pharmacokinet. 2016;41(4):345-51. PubMed
  4. Lin WW, Li XW, Jiao Z, Zhang J, Rao X, Zeng DY et al. Population pharmacokinetics of oxcarbazepine active metabolite in Chinese paediatric epilepsy patients and its application in individualised dosage regimens. Eur J Clin Pharmacol. 2019;75(3):381-392. PubMed
  5. US Food and Drug Administration. Statistical Review - TRILEPTAL (oxcarbazepine). Drugs@FDA [www]. [updated 2001-11-20, cited 2019-10-09]. länk
  6. Besi E, Boniface DR, Cregg R, Zakrzewska JM. Comparison of tolerability and adverse symptoms in oxcarbazepine and carbamazepine in the treatment of trigeminal neuralgia and neuralgiform headaches using the Liverpool Adverse Events Profile (AEP). J Headache Pain. 2015;16:563. PubMed
  7. Grikiniene J, Volbekas V, Stakisaitis D. Gender differences of sodium metabolism and hyponatremia as an adverse drug effect. Medicina (Kaunas). 2004;40:935-42. PubMed
  8. Berghuis B, van der Palen J, de Haan GJ, Lindhout D, Koeleman BPC, Sander JW et al. Carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy. Epilepsia. 2017;58(7):1227-1233. PubMed
  9. Isojärvi JI, Löfgren E, Juntunen KS, Pakarinen AJ, Päivänsalo M, Rautakorpi I et al. Effect of epilepsy and antiepileptic drugs on male reproductive health. Neurology. 2004;62:247-53. PubMed
  10. Asadi-Pooya A, Farazdaghi M, Ashjazadeh N. Effects of carbamazepine on semen parameters in men with newly diagnosed epilepsy. Iran J Neurol. 2015;14(3):168-70. PubMed
  11. Svalheim S, Sveberg L, Mochol M, Taubøll E. Interactions between antiepileptic drugs and hormones. Seizure. 2015;28:12-7. PubMed
  12. Ocek L, Tarhan H, Uludağ FI, Sarıteke A, Köse C, Colak A et al. Evaluation of sex hormones and sperm parameters in male epileptic patients. Acta Neurol Scand. 2018;137(4):409-416. PubMed
  13. Wu D, Chen L, Ji F, Si Y, Sun H. The effects of oxcarbazepine, levetiracetam, and lamotrigine on semen quality, sexual function, and sex hormones in male adults with epilepsy. Epilepsia. 2018;59(7):1344-1350. PubMed
  14. Yogarajah M, Mula M. Sexual Dysfunction in Epilepsy and the Role of Anti-Epileptic Drugs. Curr Pharm Des. 2017;23(37):5649-5661. PubMed
  15. Statistikdatabas för diagnoser. Stockholm: Socialstyrelsen. 2019 [cited 2020-10-01.] länk
  16. Adelöw C, Andell E, Amark P, Andersson T, Hellebro E, Ahlbom A et al. Newly diagnosed single unprovoked seizures and epilepsy in Stockholm, Sweden: First report from the Stockholm Incidence Registry of Epilepsy (SIRE). Epilepsia. 2009;50:1094-101. PubMed
  17. Statistikdatabas för läkemedel. 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