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Lamotrigine kinetics within the menstrual cycle, after menopause, and with oral contraceptives

Objective: We prospectively evaluated the fluctuation of lamotrigine (LTG) clearance during the menstrual cycle. We also assessed the effect of postmenopausal status and investigated in detail the effect of oral contraceptives (OCs) on LTG clearance. Methods: Three groups of women with epilepsy using LTG monotherapy were evaluated. Women in the first group (n = 7) had a regular cycle and did not use OCs; the second group used a 1-phase combined OC (n = 7), and the third group (n = 7) was postmenopausal. Two menstrual cycles or at least 2 months (postmenopausal women) were assessed, monitoring LTG levels every other day. Results: The mean apparent LTG clearance in women of reproductive age not using OCs was 49 (SD 22.6, range 20.4–83.5) L/24 hours. No significant effect of endogenous hormones on LTG clearance was found. In women using OCs, the mean LTG clearance was 126 (SD 60.2, range 44.3–205) L/24 hours. There was an increase in LTG levels during the pill-free week, with maximum levels 54% (range 29%–129%) higher than baseline levels. LTG levels decreased to the baseline value within a mean of 8 days of starting OC use (SD 3.7, range 2.5–16.5). In the postmenopausal women, the mean clearance was 82 (SD 38.4, range 35.9–125) L/24 hours. Conclusions: We observed a higher mean lamotrigine (LTG) clearance in postmenopausal women compared with young women not using oral contraceptives (OCs) and confirmed that OC use may have a strong effect on LTG clearance. There was no significant fluctuation of LTG clearance during the menstrual cycle.