Continuous regimen OCs: Will U.S. see new pill?
Pill designed with no pill-free intervals
(Editor’s note: This article discusses products not yet approved by the Food and Drug Administration.)
Many of your patients may now be using the extended regimen oral contraceptive (OC) Seasonale (Barr Labs, Pomona, NY), where an active pill is taken for 84 days, followed by seven days of placebo pills. But what if there was a pill that would offer continuous dosing with no pill-free intervals?
The Food and Drug Administration (FDA) is reviewing a request from Wyeth Pharmaceuticals of Madison, NJ, for approval of such an OC: Lybrel, a pill with 0.09 mg levonorgestrel and 0.02 mg ethinyl estradiol. If approved, the pill would be the first combination oral contraceptive approved designed to be taken daily, 365 days a year, without a placebo phase.
Research on Lybrel was just presented at the annual meeting of the American Society for Reproductive Medicine (ASRM) in Montreal.1-4 The efficacy data indicate that the pill was well tolerated and demonstrated the ability to inhibit menses by incrementally inducing amenorrhea (absence of bleeding or spotting) and no bleeding (absence of bleeding, with or without spotting) with increased duration of use. The regimen offers women a safe and effective contraceptive option that reduces the number of bleeding days and symptoms commonly associated with the menses, researchers conclude.1
"Overall, the amount of bleeding is small," says Jeffrey Jensen, MD, MPH, professor of obstetrics and gynecology at Oregon Health & Science University in Portland and an investigator in the clinical trial. "Women don’t become anemic, and hemoglobin actually increases."
Would women be interested in such a pill? In a national survey, 59% of women polled said they would be interested in not menstruating every month, and one-third would choose never to have a period.5
Lybrel’s efficacy rate appears to be consistent with currently available oral contraceptive products. The efficacy data presented at the ASRM meeting were based on the experiences of 2,134 women who took at least one dose of study drug. Nineteen women became pregnant during use of the regimen. While the Pearl index for the continuous-use regimen will be calculated from pooled results of all phase three studies, the Pearl index for the data presented at the meeting was 1.60 (95% CI, 0.96, 2.49) based on 15,461 pill packs and 13 pill packs per year.1
The drug’s safety profile appears consistent with currently approved cyclic oral contraceptives. Six serious adverse events were reported during the study: two cases of cholecystitis, with single appearances of the following conditions: deep vein thrombosis/pulmonary embolism, ectopic pregnancy, prolonged vaginal bleeding, and enlarged uterine fibroids.1
Researchers noted a steady increase from baseline in the percentage of participants who reported amenorrhea and no bleeding: 44.8% and 70.8%, respectively, by pill pack seven. Counseling regarding bleeding and spotting is an important part of success with a continuous dosing regimen, says Jensen.
"Although all patients expect to achieve amenorrhea, the experience from every study done with combined OC regimens demonstrate that most women experience a decrease in bleeding days and a substantial increase in spotting days for several months," Jensen observes. "Women who continue with the regimen can expect that their bleeding patterns will improve over time, but it may be six to 12 months before amenorrhea occurs."
At the ASRM meeting, researchers presented data showing that Lybrel significantly alleviates cycle-related symptoms.4 During the three-month, open-label substudy, participants with a history of cycle-related symptoms or premenstrual syndrome (PMS) reported a decrease in symptoms compared to baseline by the first pill pack, and they continued to report a decrease in symptoms during the two subsequent pill packs.
What advantages can a continuous dosing regimen offer for women who have cycle-related symptoms? Such a regimen may be particularly advantageous for women who suffer pain, mood, or behavioral symptoms linked to their menstrual cycles such as premenstrual syndrome and dysmenorrhea, says Ellen Freeman, PhD, professor of obstetrics and gynecology at the University of Pennsylvania in Philadelphia and lead author of the study.
"The continuous regimen appears to significantly reduce these symptoms," she explains. "Other women for various reasons may want to control the timing of their periods or eliminate them entirely."
References
- Archer DF, Jensen JT, Johnson JV, et al. Efficacy and safety of a continuous-use regimen of levonorgestrel/ethinyl estradiol: North American Phase 3 study results. Fertil Steril 2005; 84(supp1):S168.
- Archer DF, Kovalevsky G, Ballagh S, et al. Effect on ovarian activity of a continuous-use regimen of oral levonorgestrel/ ethinyl estradiol. Fertil Steril 2005; 84(supp1): S24.
- Johnson JV, Grubb GS. Endometrial histology in subjects on a continuous-use regimen of levonorgestrel/ethinyl estradiol: Results of a Phase 3 study. Fertil Steril 2005; 84(supp1): S170-S171.
- Freeman EW, Borisute H, Deal L, et al. A continuous-use regimen of levonorgestrel/ethinyl estradiol significantly alleviates cycle-related symptoms: Results of a Phase 3 study. Fertil Steril 2005; 84(supp1):S25.
- Andrist LC, Arias RD, Nucatola D, et al. Women’s and providers’ attitudes toward menstrual suppression with extended use of oral contraceptives. Contraception 2004; 70:359-363.
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