A double-blind, placebo-controlled evaluation of the effect of oral doses of rizatriptan 10 mg on oral contraceptive pharmacokinetics in healthy female volunteers

Rizatriptan (MAXALT(TM)), a potent oral 5-HT1B/1D agonist with a rapid onse t of action, is available now for the acute treatment of migraine. This stu dy examined the pharmacokinetic and clinical interaction between rizatripta n 10 mg and the components (ethinyl estradiol [EE] 35 mu g and norethindron e [NET] 1.0 mg) of a well-established oral contraceptive combination produc t, ORTHO-NOVUM 1/35. Levels of sex hormone binding globulin (SHBG), a prote in increased by EE to which NET binds, were also examined. In this two-peri od crossover study 20 healthy young female subjects received a coadministra tion of 8 days of rizatriptan treatment (6 days of single-dose 10 mg rizatr iptan and 2 days of multiple-dose rizatriptan, 10 mg q 4 hours for three do ses, giving a total daily dose of 30 mg on Days 7 and 8) or matching placeb o along with their daily dose (one tablet) of ORTHO-NOVUM 1/35 within their oral contraceptive cycle, plasma was sampled for EE, NET and SHBG concentr ations. Safety evaluations included routine laboratory safety studies, phys ical examinations, and monitoring for ECG vital signs, and adverse events. There were no statistically significant differences in any of the pharmacok inetic parameters of EE or NET between the rizatriptan and placebo treatmen t periods, thus indicating that rizatriptan had no meaningful effect on the disposition of either the EE or the NET component of ORTHO-NOVUM 1/35. The SHBG concentration did not change throughout the entire study Clinically, coadministration of rizatriptan with ORTHO-NOVUM 1/35 was well tolerated. B lood pressure, heart rate, and temperature showed no consistent trend or cl inically important changes. Adverse events following coadministration of ri zatriptan with ORTHO-NOVUM 1/35 were similar to those reported when placebo was given with ORTHO-NOVUM 1/35. The findings of this study indicate that there is little potential for dosages as high as 30 mg/day the maximum reco mmended dosing schedule, of rizatriptan to alter the plasma concentrations of oral contraceptives. (C)2000 the American College of Clinical Pharmacolo gy.