Lamotrigine (Lamictalâ, GlaxoSmithKine) is a phenyltriazine antiepileptic agent registered in Singapore in 1993.

A significant degree of drug interaction was reported in a recent clinical pharmacology study that investigated the effects of combined oral contraceptive (COC) pill, Microgynon 30® (contains ethinyloestradiol 30 mcg & levonorgestrel 150 mcg) on the pharmacokinetics of lamotrigine and vice versa.

The study was conducted in healthy young female subjects. These subjects received Microgynon 30® and lamotrigine (titrated up to 300 mg) in accordance to standard prescribing information.

a) Decrease in lamotrigine serum levels
It was found that lamotrigine exposure was substantially reduced in the presence of the COC in an average of 52% and 39% in AUC and Cmax, respectively.

During the ‘pill-free' week of COC, the pre-dose serum lamotrigine concentrations increased to approximately 2-fold higher than during Microgynon 30® co-administration.

b) Effect on COC
Lamotrigine has a modest reduction effect in levonorgestrel plasma concentrations (mean decrease of 19% AUC and 12% Cmax) and minimal effect on ethinyloestradiol pharmacokinetics. Changes in serum follicle-stimulating hormone and luteinising hormone have been observed. The impact of these changes on ovarian ovulatory activity is unknown.

There have been reports of breakthrough seizures, unexpected pregnancies and menstrual bleeding disorders occurring with the concomitant use of Lamictal® and hormonal preparations.

Other oral contraceptive and HRT treatments have not been studied but they may similarly affect the pharmacokinetic parameters of lamotrigine.

Physicians should exercise appropriate clinical management of women starting or stopping hormonal contraceptives during Lamictal® therapy and dose adjustment for lamotrigine may be necessary. Patients should be advised to promptly notify their physicians if they experience changes in their menstrual pattern.

The local package insert for Lamictal® has been amended to reflect the above findings.