The net effects of drug interactions with lamotrigine are summarized in Table 3 (see also DOSAGE AND ADMINISTRATION).
Oral Contraceptives :
†In 16 female volunteers, an oral contraceptive preparation containing 30 mcg ethinylestradiol and 150 mcg levonorgestrel increased the apparent clearance of lamotrigine (300 mg/day) by approximately 2-fold with a mean decrease in AUC of 52% and in Cmax of 39%. In this study, trough serum lamotrigine concentrations gradually increased and were approximately 2-fold higher on average at the end of the week of the inactive preparation compared to trough lamotrigine concentrations at the end of the active hormone cycle.
Gradual transient increases in lamotrigine plasma levels (approximate 2-fold increase) occurred during the week of inactive hormone preparation (‚Äúpill-free‚ÄĚ week) for women not also taking a drug that increased the clearance of lamotrigine (carbamazepine, phenytoin, phenobarbital, primidone, or rifampin). The increase in lamotrigine plasma levels will be greater if the dose of lamotrigine is increased in the few days before or during the "pill-free" week. Increases in lamotrigine plasma levels could result in dose-dependent adverse effects (see PRECAUTIONS: Oral Contraceptives).
In the same study, co-administration of lamotrigine (300 mg/day) in 16 female volunteers did not affect the pharmacokinetics of the ethinylestradiol component of the oral contraceptive preparation. There was a mean decrease in the AUC and Cmaxof the levonorgestrel component of 19% and 12%, respectively. Measurement of serum progesterone indicated that there was no hormonal evidence of ovulation in any of the 16 volunteers, although measurement of serum FSH, LH, and estradiol indicated that there was some loss of suppression of the hypothalamic≠ pituitary-ovarian axis.
The effects of doses of lamotrigine other than 300 mg/day have not been studied in clinical trials.
The clinical significance of the observed hormonal changes on ovulatory activity is unknown. However, the possibility of decreased contraceptive efficacy in some patients cannot be excluded. Therefore, patients should be instructed to promptly report changes in their menstrual pattern (e.g., break-through bleeding).
Dosage adjustments will be necessary for most women receiving estrogen-containing oral contraceptive preparations (see DOSAGE AND ADMINISTRATION: Special Populations: Women and Oral Contraceptives).