Thalidomide does not alter the pharmacokinetics of ethinyl estradiol and norethindrone

Abstract

Objective: To evaluate the effect of thalidomide on the plasma pharmacokinetics of ethinyl estradiol (INN, ethinylestradiol) and norethindrone (INN, norethisterone).

Methods: Ten women who had undergone surgical sterilization were enrolled in an open-label crossover study conducted in the Georgetown University Clinical Research Center. The pharmacokinetics of single doses of 0.07 mg ethinyl estradiol and 2 mg norethindrone were measured at baseline and after 3 weeks of 200 mg thalidomide. Compliance with the thalidomide regimen was assessed with use of Medication Event Monitoring System (MEMS) caps.

Results: No changes were observed in the pharmacokinetics of ethinyl estradiol or norethindrone with thalidomide therapy. The mean +/- SD area under the plasma concentration-time curve (AUC0-infinity) for ethinyl estradiol was 6580 +/- 1100 ng.h/L at baseline and 5970 +/- 1560 ng.h/L after the thalidomide regimen (paired t test, P > .05). The values for norethindrone were 103 +/- 54 micrograms.h/L and 107 +/- 58 micrograms.h/L (paired t test, P > .05). No changes were observed for other pharmacokinetic parameters assessed for either ethinyl estradiol or norethindrone. No accumulation of thalidomide was seen after 21 days of therapy: day 1 AUC0-infinity 41.1 +/- 13.9 micrograms.h/mL; day 21 AUC0-infinity 59.6 +/- 27.3 micrograms.h/mL (paired t test, P > .05). No changes were observed for other pharmacokinetic parameters assessed for thalidomide between days 1 and 21. Thalidomide was well tolerated but caused variable degrees of sedation. The average thalidomide compliance rate was 97%.

Conclusions: The pharmacokinetics of thalidomide do not change with 3 weeks of daily dosing. Thalidomide does not alter the pharmacokinetics of ethinyl estradiol or norethindrone. Therefore there is no drug interaction between thalidomide and these 2 drugs. The efficacy of oral contraceptives containing ethinyl estradiol and norethindrone should not be affected by concomitant thalidomide therapy.

PIP: An open-label crossover study was conducted to evaluate the effect of thalidomide on the plasma pharmacokinetics of ethinyl estradiol (INN, ethinyl estradiol) and norethindrone (INN, norethisterone) among 10 women who had undergone surgical sterilization at Georgetown University Clinical Research Center. The pharmacokinetics of single doses of 0.07 mg ethinyl estradiol and 2 mg norethindrone were measured at baseline and after 3 weeks of 200 mg thalidomide. Compliance with the thalidomide regimen was assessed with the use of Medication Event Monitoring System caps. The results showed that there were no changes in the pharmacokinetics of ethinyl estradiol or norethindrone with thalidomide therapy. Furthermore, no changes were seen for other pharmacokinetic parameters assessed for thalidomide between days 1 and 21. Thalidomide was well tolerated, but caused variable degrees of sedation. The average compliance rate of thalidomide was 97%. This study concluded that there was no drug interaction between thalidomide and the other two drugs (ethinyl estradiol and norethindrone). The efficacy of oral contraceptives containing ethinyl estradiol and norethindrone should not be affected by concomitant thalidomide therapy.