Interaction between lamotrigine and hormone replacement therapies
The Netherlands Pharmacovigilance Centre Lareb received a report in September 2022 about an interaction between lamotrigine and hormone replacement therapy for menopausal symptoms. The product information of lamotrigine warns about this possible interaction, but the product information of hormone replacement therapies does not. This information will now be added.
Lamotrigine is a drug used to treat epilepsy or to prevent depressive episodes in patients with bipolar disorder. Hormone replacement therapies for menopausal complaints usually consist of an estrogenic and a progestagenic hormone. These drugs replace the endogenous production of these hormones in women during or after menopause. This reduces menopausal symptoms.
Report received by the Netherlands Pharmacovigilance Centre Lareb
The report that Lareb received, describes a woman who has been taking lamotrigine for a long period of time to treat depressive episodes. In 2022 she started the hormone replacement therapy Femoston (estradiol/dydrogesterone) for the treatment of menopausal symptoms. After 5 months, the patient noticed that the depressive symptoms were getting worse and she contacted her healthcare provider. Eventually, treatment with Femoston was discontinued. The lamotrigine blood levels were significantly lower during treatment with Femoston than several weeks after discontinuing the drug.
Estrogens are probably involved in the mechanism
In the body lamotrigine is converted to an inactive substance by several enzymes, including the enzyme UGT1A4. Estradiol, an estrogen, can increase the expression of this enzyme in the body. This may cause a decrease in lamotrigine blood levels when using estradiol or other estrogens.
Lareb has informed the Medicines Evaluation Board (MEB) about the report. The MEB has discussed this in the European network. There it was decided to add the possible interaction with lamotrigine to the product information of hormone replacement therapies.