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Continuous use oral contraceptive receives FDA regulatory approval
Wyeth Pharmaceuticals' Lybrel set to reach U.S. pharmacies this month
Clinicians now have a dedicated continuous use oral contraceptive. The Food and Drug Administration (FDA) has given final approval to Lybrel from Wyeth Pharmaceuticals of Collegeville, PA. The drug represents the first combination contraceptive pill designed to be taken 365 days a year, without a placebo phase or pill-free interval.
"I am excited about the fact that this approval is going to give a nod to something that we as clinicians have been doing for decades," says Robert Hatcher, MD, MPH, professor of gynecology and obstetrics at Emory University School of Medicine in Atlanta. "For many women, it makes a lot more sense than taking pills 21/7, 21/7, 21/7."
The drug, which received FDA approvable status in June 2006, is scheduled to reach U.S. pharmacy shelves this month, says Natalie de Vane, Wyeth spokeswoman. Since the drug represents a departure from the standard dosing schedule of regular oral contraceptives, look to Wyeth to provide information to clinicians and women about the new OC, she reports.
The new birth control pill comes in a 28-day pill pack with combination tablets that contain 90 mcg levonorgestrel and 20 mcg ethinyl estradiol. While the new drug may represent a step forward in birth control, its 28-day packaging may prove problematic, Hatcher observes. While a price has not yet been set for Lybrel, new drugs traditionally are the most expensive, he says. With the 28-day packaging, women will be forced to return for monthly refills, which can be difficult for patients served by family planning clinics. It is much harder for a person with an income of $15,000-$20,000, living below the poverty line, to return to the clinic, pick up her pills, and pay her copay 12 or 13 times a year, than for someone with a higher family income, says Hatcher.
"The high cost and the necessity of returning to the clinic every month are very unattractive features of this new pill," Hatcher states. "I predict that it will have minimal impact in programs serving less advantaged women."
Review research data
Results from recently published research regarding Lybrel's safety and efficacy indicate the drug has a safety profile and efficacy similar to cyclic OCs. A total of 2,402 women were enrolled in the drug's clinical trial; 2,134 took at least one dose of the study drug, and 921 completed the study.1 The study drug was supplied in 28-day pill packs; women took one pill daily for a period of 12 months with no pill-free intervals.
During the course of the study, which lasted more than 18 months, 19 women became pregnant while using the drug, yielding an on-treatment Pearl Index of 1.60 (95% CI = 0.96-2.49). Fifteen of these pregnancies were attributed to method failure (Pearl Index = 1.26; 95% CI = 0.71-2.08), and four were attributed to user failure (Pearl Index = 0.34; 95% CI = 0.09-0.86).
Women may be concerned that return to fertility may be affected by use of a continuous regimen pill. To evaluate the return to fertility among women planning to become pregnant after the use of Lybrel, researchers followed 21 women for up to 12 months following their last dose of treatment.2 Average duration of treatment with the drug was 197 days within the study group. The pregnancy rate was 57% (12/21) at three months and 81% (17/21) at 12 months after discontinuation, the scientists report. After the 12-month post-study follow-up, information was sought for the remaining four women who had not become pregnant. One woman conceived within 14 months of the last treatment for a total pregnancy rate of 86% (18/21). In the remaining three women who did not conceive, one woman ceased trying to become pregnant by 12 months, and the other two were lost to follow-up after 12 months, note the researchers.2 Eighteen pregnancies resulted in 17 live births and one spontaneous abortion. Data were obtained from 10 of the 17 newborns; all were uncomplicated term deliveries.
Counseling is key
Lybrel will add to what clinicians can offer women in terms of menstrual suppression, says Susan Wysocki, RNC, NP, president and CEO of the National Association of Nurse Practitioners in Women's Health. It will be welcomed by women who are willing to tolerate unscheduled bleeding in the first months of use, she says. Clinicians should counsel women that they will very likely have such unscheduled bleeding, she notes.
Most women will not achieve menstrual suppression until they have taken Lybrel for several months, says Wysocki. "Because there are no scheduled bleeding times, all the bleeding a woman will experience will be unscheduled," observes Wysocki. "Consider that the woman asking for Lybrel does not want to bleed, so she must know that it will take at least three to six months to achieve that goal."
While researchers in the clinical trial report that the incidence of uterine bleeding decreased with longer use, 21% of women had uterine bleeding by Pill Pack 13, with a median of four days of bleeding and three days of spotting per 28-day pill pack.1 More than three-quarters (77%) of women who experienced bleeding on Pill Pack 13 reported they were satisfied with the method, with 7% as neutral and 16% as dissatisfied.
"This suggests that there is a subset of women who may not achieve amenorrhea with prolonged use of continuous OC," researchers state in the published study. "The lack of amenorrheic outcome may lead to the discontinuation of OCs in these women."
One approach that may be effective in dealing with unscheduled bleeding with a continuous regimen pill is to stop use of pills for two to three days to intensify the withdrawal bleed, says Hatcher. In a prospective analysis comparing a 21/7-day regimen vs. a 168-day extended regimen of an OC drospirenone/ethinyl estradiol formulation, users who had breakthrough bleeding/spotting for at least seven consecutive days were randomized to undergo a three-day hormone-free interval vs. continuing active pills. Instituting a three-day hormone-free interval was significantly more effective in resolving unscheduled bleeding/spotting than continuing active pills, researchers report.3 Such an approach is not included in the Lybrel package insert, Hatcher notes.