The effect of tolterodine on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive containing ethinyl estradiol and levonorgestrel

Background: Tolterodine is an antimuscarinic agent for the treatment of ove ractive bladder. a chronic condition that is particularly common in women. Given the prevalence pattern of overactive bladder and the widespread use o f oral contraception, circumstances are likely to arise in which physicians may wish to prescribe tolterodine for patients already taking oral contrac eptives. Based on a search of MEDLINE from 1990 to 2001. there have been no studies of whether concomitant use of these agents entails a risk of drug- drug interaction or conception. Objective: This study investigated the effects of tolterodine on the pharma cokinetics and pharmacodynamics of a low-dose combination oral contraceptiv e (ethinyl estradiol 30 mug/levonorgestrel 150 mug). Methods: This was an open-label, randomized. 2-period crossover study in he althy women. Oral contraception was given for 21 days either alone or in co mbination with oral tolterodine 2 mg BID (on days 1-14) over two 28-day con traceptive cycles. Pharmacokinetic assessments were performed on day 14 bas ed on plasma levels of ethinyl estradiol and levonorgestrel up to 24 hours after dosing and serum tolterodine levels at 1 to 3 hours after dosing. The potential for pharmacodynamic interaction was assessed in terms of the ris k of failure of suppression of ovulation based on serum levels of estradiol and progesterone measured throughout each cycle. Results: Twenty-four healthy women (age, 23-41 years [mean, 30 years]; heig ht, 155-178 cm [mean, 167 cm], body weight, 51-75 kg [mean, 64 kg]) partici pated in the study. There was no evidence of a pharmacokinetic interaction between tolterodine and the steroid hormones in the oral contraceptive used , nor did the oral contraceptive show any relevant pharmacokinetic interact ion with tolterodine. Serum levels of estradiol and progesterone indicated suppression of ovulation in both treatment periods. Conclusion: In this selected population, coadministration of tolterodine di d not affect the contraceptive efficacy of a low-dose combination oral cont raceptive containing ethinyl estradiol and levonorgestrel.