Drug Interactions between estradiol topical and Lamictal

ADJUST DOSE: Coadministration with estrogens or progestins used for hormonal contraception or hormonal replacement therapy may significantly decrease the plasma concentrations and pharmacologic effects of lamotrigine due to induction of lamotrigine glucuronidation. The available evidence suggests that estrogens are the main cause of serum lamotrigine reductions and the data supporting the involvement of progestin-containing medications in this reduction are conflicting. In a pharmacokinetic study of 16 female volunteers taking an oral contraceptive containing 30 mcg of ethinyl estradiol and 150 mcg of levonorgestrel concomitantly with lamotrigine 300 mg per day, the clearance of lamotrigine increased approximately 2-fold. Additionally, the systemic exposure (AUC) and the maximum plasm concentration (Cmax) of lamotrigine decreased by 52% and 39%, respectively. In the same study, coadministration of lamotrigine did not impact the pharmacokinetics of the ethinyl estradiol component of the oral contraceptive. However, the AUC of levonorgestrel decreased by 19% and measurement of serum FSH, LH, and estradiol indicated some loss of suppression of the hypothalamic-pituitary-ovarian axis. The clinical significance is unknown. Measurement of serum progesterone indicated no hormonal evidence of ovulation.

MANAGEMENT: Plasma lamotrigine levels and pharmacologic response should be monitored more closely whenever estrogen- or progestin-containing medications are added to or withdrawn from therapy. The maintenance dose of lamotrigine will in most cases need to be increased by approximately 2-fold when used concomitantly with combined hormonal contraceptives in women not also taking an enzyme-inducing drug (e.g., carbamazepine, phenytoin, phenobarbital, primidone, rifampin). It is recommended that from the time that the combined hormonal contraceptive is started, the lamotrigine dose is increased by 50 to 100 mg/day every week, according to individual patient response. The manufacturer's labeling should be consulted for more detailed dosage recommendations. Patients should be advised to contact their physician if they experience loss of seizure control or symptoms of lamotrigine toxicity such as ataxia, nystagmus, increased seizures, irregular heartbeat, and changes in mental status. In patients receiving oral contraceptives, gradual transient increases in lamotrigine levels (approximately 2-fold increase) will occur during the pill-free week for women not also taking an enzyme-inducing drug. The increase in lamotrigine levels will be greater if the dose of lamotrigine is increased in the few days before or during the pill-free week. Patients should be instructed to promptly report changes in their menstrual pattern due to the potential for diminished contraceptive efficacy.