NATIONAL HARBOR, MD. – Delayed-release dimethyl fumarate (DMF) coadministered with norgestimate/ethinyl estradiol, a commonly used progesterone-estrogen combination oral contraceptive, did not alter the OC’s pharmacokinetics or pharmacodynamics, according to the results of a small study.
The safety profile of the coadministered preparation is similar to the profile of DMF (Tecfidera, Biogen) alone, Dr. Bing Zhu said in a poster session at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Dr. Bing Zhu
The findings indicate that women with relapsing-remitting multiple sclerosis (RRMS) who are of childbearing age and who are being treated with DMF can use OCs without having to modify the contraceptive dose, said Dr. Zhu, who is an employee of Biogen, Cambridge, Mass.
The study involved healthy women aged 18-45 years (mean age about 31 years) who were able to conceive. All received a daily OC (Ortho-Cyclen; 250 mcg norgestimate, 35 mcg ethinyl estradiol). After 28 days, those with progesterone levels less than 3 ng/mL were randomized to a 28-day regimen of either the daily dose of OC (n = 39) or OC along with DMF (240 mg twice daily), designated period 1, with crossover to the other treatment for a further 28 days (period 2). Blood samples were collected during the first 24 hours for pharmacokinetic measurements and at 2, 3, and 4 weeks for pharmacodynamic determinations.
The primary objective was the pharmacokinetics of norgestimate, as determined by measuring the levels of its main metabolite, norelgestromin. Secondary objectives included pharmacodynamics, as determined by the levels of serum progesterone and the safety/tolerability of DMF.
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Plasma concentrations of norelgestromin and ethinyl estradiol were identical over time in the OC and OC + DMF groups in period 1, as was serum progesterone.
Treatment-emergent adverse events were similar in type and severity in both groups. Most were mild. The prevalent adverse events included flushing and gastrointestinal disorders accompanied by nausea and vomiting. Adverse events occurred in 10 of the 39 (26%) subjects who received the OC and in 26 of the 39 (67%) subjects who received the OC + DMF. Discontinuation because of adverse events occurred in 8% and 15% of subjects who received the OC and the OC + DMF, respectively. There were no deaths.
“The results suggest that women of childbearing potential treated with DMF are able to use a combined OC for contraception without dose modification,” said Dr. Zhu.
The study findings were recently published (Neurology. 2016 Apr 5;86:Suppl P2.097).
The study was funded by Biogen. Dr. Zhu is a Biogen employee.