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Lamotrigine

Classification: C

Drug products: Crisomet, Labileno, Lamictal, Lamictal 25 mg disperguojamosios, Lamictal®, Lamocare, Lamotrigin 1A Farma, Lamotrigin 2care4, Lamotrigin Actavis, Lamotrigin Amneal, 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 seems similar in men and women. In one study, vertigo 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 are similar in men and women [1,2,3,]. 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. Totally 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 sex appear to be unnecessary [2,3].

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 [3,4]. During mid and late pregnancy, serum concentrations of lamotrigine may decline to 30-50% of pre-pregnancy levels, with an increased frequency of seizures [4,5]. Therefore, close monitoring of lamotrigine concentrations throughout the entire pregnancy and postpartum is recommended [6].

Effects

A randomized clinical trial (18 men, 27 women) studying possible clinical predictors of positive response to lamotrigine monotherapy in adults with refractory affective bipolar disorder found a relationship between the degree of lamotrigine response and male sex [7].

Adverse effects

In a randomized parallel study comparing placebo and 300 and 500 mg/day of lamotrigine, the overall adverse reaction profile for lamotrigine was similar between females and males. The only adverse reaction for which the reports were greater than 10% more frequent in females than males 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 [8].

Drug interactions

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 mikrogram) and no alternations in menstrual pattern were noted [5]. Swedish users, please consult Janusmed Interactions(Janusmed interaktioner).

Birth defects

Swedish users, please consult Janusmed Drugs and Birth Defects(Janusmed fosterpåverkan).

Updated: 2017-03-28

Date of litterature search: 2013-03-20

References

  1. Lamotrigine. DailyMed [www]. US National Library of Medicine. [updated 2012-10-01, cited 2013-03-18]. 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. Sabers A, Tomson T. Managing antiepileptic drugs during pregnancy and lactation. Curr Opin Neurol. 2009;22:157-61. PubMed
  5. Schenck-Gustafsson K, DeCola PR, Pfaff DW, Pisetsky DS, editor. Handbook of Clinical Gender Medicine. 1st ed. Karger; 2012.
  6. Pennell PB. 2005 AES annual course: evidence used to treat women with epilepsy. Epilepsia. 2006;47 Suppl 1:46-53. PubMed
  7. 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
  8. Alvestad S, Lydersen S, Brodtkorb E. Rash from antiepileptic drugs: influence by gender, age, and learning disability. Epilepsia. 2007;48:1360-5. PubMed
  9. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-30.] länk

Authors: Linnéa Karlsson Lind, Desirée Loikas

Reviewed by: Expertrådet för neurologiska sjukdomar, Ellen Vinge

Approved by: Mia von Euler