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Lamotrigine

Classification: C

Drug products: Crisomet, Labileno, Lamictal, Lamictal 25 mg disperguojamosios, Lamictal®, Lamocare, Lamotrigin 1A Farma, Lamotrigin 2care4, Lamotrigin Abacus Medicine, Lamotrigin Actavis, Lamotrigin Aristo, Lamotrigin Arrow, Lamotrigin Aurobindo, Lamotrigin Bluefish, Lamotrigin BMM Pharma, Lamotrigin Ebb, Lamotrigin EQL, Lamotrigin Hexal, Lamotrigin Medochemie, Lamotrigin Mylan, Lamotrigin Orifarm, Lamotrigin ratiopharm, Lamotrigin Teva

ATC code: N03AX09

Substances: lamotrigine

Summary

Analyses of differences between men and women in the antiepileptic effect of lamotrigine are lacking. One study has shown better response in men compared to women when treated with lamotrigine for bipolar affective disease.

Overall, adverse effects seem similar in men and women. In one study, dizziness was more often reported in women.

During pregnancy, the concentration of lamotrigine is lowered, and frequent therapeutic drug monitoring and dose escalation is needed. Post-partum, the dose needs to be normalized as to avoid overdosing.

Additional information

Pharmacokinetics and dosing

Population analysis shows that pharmacokinetics of lamotrigine is similar in men and women [1-3]. However, a meta-analysis found that the volume of distribution was 27% lower in women than men. This difference persisted even when the effect of weight was taken into account. In all, 22/289 women were receiving concomitant therapy with various oral contraceptives. But in this study, oral contraceptives exhibited little effect on the pharmacokinetics of lamotrigine [3]. Dose adjustment based on patient’s sex appear to be unnecessary [2, 3]. During pregnancy, elimination of lamotrigine is increased necessitating therapeutic drug monitoring and dose adjustment, se below.

Effects

A small U.S. randomized clinical trial (18 men, 27 women, aged 20-67 years) has analysed possible clinical predictors of positive response to lamotrigine monotherapy in adults with refractory affective bipolar disorder. Male sex was associated with good response to lamotrigine [4].

Adverse effects

In a randomized parallel study conducted by the pharmaceutical company comparing placebo and 300 and 500 mg/day of lamotrigine, the overall adverse reaction profile for lamotrigine was similar between women and men. The only adverse reaction for which the reports were greater than 10% more frequent in women than men was dizziness (difference = 16.5%) [1].

A retrospective analysis of patients on antiepileptic drug treatment showed fertile women to have a higher risk for skin reactions than men when treated with lamotrigine [5].

Reproductive health issues

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 [6]. 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 [6, 7]. 

During pregnancy, clearance of lamotrigine increases progressively until the 32nd gestational week when it may be 2-3 times higher than pre-pregnancy levels. This is caused by induction of glucuronidation. After delivery the lamotrigine elimination rate drops rapidly and reach the pre-pregnant levels within the first 2-3 weeks postpartum [3, 8]. During mid and late pregnancy, serum concentrations of lamotrigine may decline to 30-50% of pre-pregnancy levels, with an increased frequency of seizures [8, 9]. Therefore, close monitoring of lamotrigine concentrations throughout the entire pregnancy and postpartum is recommended [10].

Lamotrigine has little effect on mixed-function oxygenase enzymes, it would not be expected that estrogen and progestin clearance would be altered. Previous investigation suggests that lamotrigine has no effect on the clearance of ethinyl estradiol and levonorgestrel (30/150 µg) and no alternations in menstrual pattern were noted [9].  Regarding drug-drug interactions aspects, please consult Janusmed Interactions (in Swedish, Janusmed interaktioner).

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

Updated: 2020-09-30

Date of litterature search: 2019-09-20

References

  1. Lamictal (lamotrigine). DailyMed [www]. U.S. National Library of Medicine. [updated 2019-08-27, cited 2019-09-20]. länk
  2. Hussein Z, Posner J. Population pharmacokinetics of lamotrigine monotherapy in patients with epilepsy: retrospective analysis of routine monitoring data. Br J Clin Pharmacol. 1997;43:457-65. PubMed
  3. Grasela TH, Fiedler-Kelly J, Cox E, Womble GP, Risner ME, Chen C. Population pharmacokinetics of lamotrigine adjunctive therapy in adults with epilepsy. J Clin Pharmacol. 1999;39:373-84. PubMed
  4. Obrocea GV, Dunn RM, Frye MA, Ketter TA, Luckenbaugh DA, Leverich GS et al. Clinical predictors of response to lamotrigine and gabapentin monotherapy in refractory affective disorders. Biol Psychiatry. 2002;51:253-60. PubMed
  5. Alvestad S, Lydersen S, Brodtkorb E. Rash from antiepileptic drugs: influence by gender, age, and learning disability. Epilepsia. 2007;48:1360-5. PubMed
  6. 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
  7. Yogarajah M, Mula M. Sexual Dysfunction in Epilepsy and the Role of Anti-Epileptic Drugs. Curr Pharm Des. 2017;23(37):5649-5661. PubMed
  8. Sabers A, Tomson T. Managing antiepileptic drugs during pregnancy and lactation. Curr Opin Neurol. 2009;22:157-61. PubMed
  9. Schenck-Gustafsson K, DeCola PR, Pfaff DW, Pisetsky DS, editor. Handbook of Clinical Gender Medicine. 1st ed. Karger; 2012.
  10. Pennell PB. 2005 AES annual course: evidence used to treat women with epilepsy. Epilepsia. 2006;47 Suppl 1:46-53. PubMed
  11. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2019 [cited 2020-03-10.] länk

Authors: Linnéa Karlsson Lind

Reviewed by: Mia von Euler, Carl-Olav Stiller, Diana Rydberg

Approved by: Karin Schenck-Gustafsson