Shortened pill-free interval delivered by new 20 mcg pill
Organon's Mircette scheduled for U.S. debut this summer
The array of low-dose pills expands with the summer debut of Mircette, a new 20 mcg oral contraceptive (OC) from Organon in West Orange, NJ. The new OC is the first pill to feature a shortened hormone-free interval. Its patented dosing regimen begins with 21 days of 20 mcg of the estrogen ethinyl estradiol and 150 mcg of the progestin desogestrel. The last seven days of the cycle start with two days of placebo pills, followed by five days of 10 mcg pills of ethinyl estradiol.
Family planning providers should look for Mircette to hit the shelves about the first of July, says Joel Krasnow, MD, associate director of medical services at Organon's U.S. affiliate. Mircette received U.S. Food and Drug Administration (FDA) approval in April, with the following months focused on bringing Organon's medical sales and support staff up to speed on the new contraceptive. Information on the new pill has just been presented at the annual clinical meeting of the Washington, DC-based American College of Obstetricians and Gynecologists.
Mircette now joins two other 20 mcg pills on the American marketplace: Alesse, a 20 mcg ethinyl estradiol/100 mcg levonorgestrel monophasic pill from Wyeth-Ayerst Laboratories in Philadelphia, and Loestrin 1/20, a 20 mcg ethinyl estradiol/1 mg norethindrone acetate OC from Parke-Davis of Morris Plains, NJ. The United States is the first country to see Mircette, Krasnow confirms.
Mircette's unique dosing regimen represents a further advance in contraceptive technology, he says. It follows such moves as the drop in estrogen doses, the introduction of triphasic pills, and the development of new progestins.
This new advance just makes sense, asserts Sarah Berga, MD, an associate professor of OB/ GYN and reproductive sciences at the University of Pittsburgh School of Medicine, Magee-Women's Hospital. Berga, an investigator in Mircette's clinical trials, asks why all seven days in the pill-free interval should be "uncovered," when that isn't really how the normal menstrual cycle works.
"In theory, it predisposes toward pregnancy, because by about day eight or nine of a normal menstrual cycle, the egg escapes the need for the gonadotropic stimulation that causes it to grow early on," she explains.
The shortening of the pill-free interval intrigues John Guillebaud, MA, FRCSE, FRCOG, MFFP, professor of family planning and reproductive health in the department of gynecology at the University College in London and medical director of the London-based Margaret Pyke Centre.
"The five days of ethinyl estradiol [used in the Mircette regimen] ought to oppose the effect of any follicle-stimulating hormone in promoting growth of a follicle in those women who are close to ovulation at the end of each pill-free interval," he says. Those women comprise about one-fifth of all pill-takers, according to research performed by Guillebaud and other investigators.1
While he has not seen the clinical data on Mircette, he says the shortening of the pill-free regimen is one approach to tackling what he terms as the "Achilles heel" of the birth control pill pack. Missed pills just prior and immediately following the traditional seven-day pill-free interval can easily cause breakthrough ovulation in some women, he notes. (See Contraceptive Tech nology Update, June 1995, pp. 69-71, for Guillebaud's theories on the pill-free interval.)
Mircette safe, effective
While initial results are scheduled to be published this summer, Krasnow says company-sponsored research shows that Mircette offers safe, effective birth control.
The efficacy trial included more than 1,000 women for a duration of 18 menstrual cycles, he says. Organon took a conservative approach in calculating Mircette's Pearl index, which is obtained by dividing the number of accidental pregnancies by the number of years of exposure to the risk of unintended pregnancy contributed by all women in the study.2
"We were fairly conservative in that in other studies, people exclude patients who miss pills," he says. "We included patients, even if they missed four or more pills. Missing four or more pills out of 21 is questionable to whether you're on the regimen; nevertheless, we got a Pearl index of 1.02 including all those people."
Breakthrough bleeding occurred in 3.5% of the 18 cycles, Krasnow says. The combination of incidences of breakthrough bleeding and spotting occurred in 12% of the cycles. The company again took a conservative view in compiling the bleed -ing statistics, including those women who missed four or more pills. The side effects experienced by women on the Mircette regimen are similar to those seen in other OCs, he says. No significant adverse effects, such as myocardial infarctions, were recorded during the clinical trial, he notes. "We have the expected incidences of bloating, nausea, and breast tenderness. We did not get any unexpected or unanticipated side effects."
Less than 3% of patients discontinued due to problems related to bleeding or menstrual symptoms, Krasnow says.
Who might benefit?
The low incidence of breakthrough bleeding with Mircette may prove to be an advantage for those women who experience such problems with other formulations, Berga says. That group may well benefit from the extra estrogen provided during the last five days of the pill pack, she surmises. Women who suffer from headaches during the pill-free interval in other OCs also may be candidates for Mircette's unique dosing regimen.
"The dose in the pill-free interval is very low," Berga says of the Mircette regimen. "In a way, it prevents estrogen levels from crashing."
It takes about two or three days for the estrogen levels from any OC to go away when it is stopped, Berga explains. The small amount of estrogen provided by the Mircette formulation during the last five days helps prevent the withdrawal headache some women experience. Further study of this issue is being done by Organon, Krasnow says.
Another set of women who may be served by Mircette's dosing regimen are those who have had a "breakthrough pregnancy" on an ultra- low dose regimen, Guillebaud suggests. Those women also could achieve contraception by "tricycling" any OC, which is the practice of taking three to four pills packs in a row, followed by a four-day pill-free interval, he says.
The trend in the past few years has been to start new contraceptors on the lowest possible dose of estrogen, in keeping with the FDA's recommendations on the subject. With Mircette, Organon has added another choice in the low-dose OC arena.
"I tend to start with a lower-dose 20 mcg preparation - that's my preference," Berga says. "But since there are so few on the market right now, if patients run into problems, I don't have a lot of alternatives. It's good to have another alternative."
References
1. Tayob Y, Robinson G, Adams J, et al. Ultrasound appearance of the ovaries during the pill-free interval. Brit J Fam Plann 1990; 16:94-96.
2. Hatcher RA, Trussell J, Stewart F, et al. Contraceptive Technology. 16th edition. New York: Irvington Publishers; 1994.
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