Ethinyl Estradiol, Not Progestogens, Reduces Lamotrigine Serum Concentrations

Reimers, Arne
Helde, Grethe
Brodtkorb, Eylert

*Department of Clinical Pharmacology, St. Olavs Hospital, Trondheim, Norway
†Department of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
‡Department of Neurology and Clinical Neurophysiology, St. Olavs Hospital, Trondheim, Norway

Address corresponding and reprint requests to Dr. A. Reimers at Department of Clinical Pharmacology, St. Olavs Hospital, University Hospital in Trondheim, 7006 Trondheim, Norway. E-mail: [email protected]

Accepted May 2, 2005.

Epilepsia 46(9):p 1414-1417, September 2005.

Summary

Purpose

To study the interaction between lamotrigine (LTG) and hormonal contraception.

Methods

LTG serum concentrations of female patients using either no hormonal contraception (n = 18), an ethinyl estradiol (EE)-containing (n = 11), or a progestogen (PG)-only–containing compound (n = 16) were analyzed. Patients were recruited prospectively, and blood samples were drawn during drug fasting and at steady-state conditions. Comedication with enzyme inducers, valproate, topiramate, or sertraline was not allowed. Some patients changed groups and thus served as their own controls. Samples were analyzed by a gas chromatography/ mass spectroscopy method. The Mann–Whitney U test was used for statistical comparison of the groups.

Results

The LTG serum concentration-to-dose ratio (CDR), expressed as (mg/L)/(mg/d) was significantly lower in women using EE than in the control group (mean ± SD, 0.010 ± 0.004 vs. 0.017 ± 0.006; p = 0.003). The CDR in women using PG was 0.02 ± 0.007, which was not statistically different from controls. No difference was found in CDR between women using either oral, topical, or parenteral PG. Five women switched from the control to the EE group and experienced a considerable reduction in CDR. An increase of the CDR toward control level was seen in the two women who changed from EE to PG.

Conclusions

It is the EE component of oral contraceptives that interacts with LTG. The PG-only compounds did not alter LTG serum concentrations in this study. These findings should be considered when counselling women with epilepsy in the childbearing ages.