Bidirectional Interaction between oral contraception and lamotrigine in women with epilepsy – role of progestins

ABSTRACT Purpose To investigate the effects of various progestins in combined oral contraceptives (COCs) on lamotrigine (LTG) serum concentrations and, vice versa, the potential impact of LTG on progestin serum levels during the menstrual cycle. Methods Twenty women with epilepsy (WWE) undergoing LTG monotherapy and COC (LTG group; mean ± SD [median; range] age 24.2 ± 4.6 [23.0; 18-37] years) as well as fourteen controls on COC (24.9 ± 5.6 [22.5; 20-39] years) were assessed for eligibility and all agreed to participate in the study and remained for data analyses. Results LTG levels differed significantly between phases of inactive pill and active pill use (p=0.004), particularly with drospirenon (p=0.018) and levonorgestrel (p=0.068) as progestogen component but not with gestoden (p=0.593). Furthermore, the LTG group showed significantly lower progestin levels during inactive pill when compared to active pill use with respect to levonorgestrel (p=0.042) and drospirenon (p=0.018) but not to gestoden (p=0.109). Progestin concentrations did not differ between patients and controls (p>0.05). Conclusions The findings suggest that drospirenon and levonorgestrel but not gestoden seem to reduce LTG serum concentrations when being co-administered in WWE which might be of importance concerning seizure risk. Vice versa, no effect of LTG on several progestins could be demonstrated, arguing against a potential loss of contraception safety with LTG.