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
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.
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 . 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.
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 .
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%) .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 .
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 . 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 .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 . 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).
Date of litterature search: 2019-09-20
Reviewed by: Mia von Euler, Carl-Olav Stiller, Diana Rydberg
Approved by: Karin Schenck-Gustafsson