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Levonorgestrel and Ethinyl Estradiol Tablets (Lybrel™)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD, Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationship to this field of study.
The FDA has approved the first continuous, low dose, oral contraceptive for the prevention of pregnancy. This new contraceptive contains levonorgestrel and ethinyl estradiol and is marketed by Wyeth Pharmaceuticals, Inc., as Lybrel.
Levonorgestrel/ethinyl estradiol (LNG/EE) is indicated for the prevention of pregnancy in women who choose an oral contraceptive as the method of contraceptive.1
One tablet is taken daily without any interruption (no tablet-free days). If the woman is not on any current contraceptive, therapy should be started on Day 1 (within 24 hours) of the menstrual cycle. If the woman is on a cyclic combination oral contraceptive, therapy should be started on Day 1 of withdrawal bleeding and no more than 7 days after the last active tablet. Non-hormonal backup contraceptive method is not recommended. If the woman is on a progestin only pill, therapy should be initiated the day after taking the progestin pill and a backup method is recommended for the first 7 days of LNG/EE. A backup method is recommended for conversion from implants or injectable contraceptives.1
Lybrel is available as 28 day dispensing unit, each tablet containing LNG 90 mcg and EE 20 mcg.
Continuous delivery of hormones eliminates menstruation and associated symptoms. This may be preferable for certain women.
Unscheduled bleeding and spotting is more likely with continuous LNG/EE. Without regular menstruation it may be difficult to recognize pregnancy. Amenorrhea is induced in about 60% of women. It is uncertain how long after discontinuation of LNG/EE that conception is possible.
The efficacy and safety of continuous LNG/EE was shown in 2 one-year studies involving healthy women ages 18-49. One study which was done in Europe (n = 641) used a formulation that contained 100 mcg of LNG compared to 90 mcg in the second study which was done North America (n = 2134)1,2 and is the same dose marketed in the US. The primary efficacy endpoint was the number of unintended pregnancies during treatment which was measured as the number per 100 women-years of use (Pearl Index). The overall Pearl Indices in the North American study were 2.38 (95% CI: 1.51, 3.57) among women 35 years or less in all users and 1.55 (95% CI: 0.87, 2.56) in women who took the tablets as directed.2 About ¾ and ½ of women respectively, experience spotting only or bleeding by the second month. Bleeding and spotting tend to decline with continual use. However, 21% of women experienced uterine bleeding after 12 cycles of use with a median of 4 days of bleeding and 3 days of spotting per 28 days (2). Uterine bleeding was the primary reason for discontinuing therapy (18%). Amenorrhea was induced in 59% of women and absence of bleeding in 79%. Cost was not available at the time of this review.
Oral contraceptives have evolved from monthly regimens to every three months (ie, Seasonale® and Seasonique™) and now to continuous use (Lybrel™). These formulations give women the choice of monthly menstruation, 4 periods per year, or none per year. Women who have menstruation associated symptoms such as dysmenorrhea, menorrhagia, pelvic pain, migraine headaches, and even seizures may welcome a continuous oral contraceptive and consider these regimens an improvement in quality of life.3,4 Long-term safety and the return of fertility, after discontinuation of continuous regimens are not known.
1. Lybrel Product Information. Wyeth Pharmaceutical, Inc. May 2007.
2. Archer DF, et al. Contraception. 2006;74:439-445.
3. Archer DF. Contraception. 2006;74:359-66.
4. Wiegratz I, Kuhl H. Drugs. 2004;64:22447-22462.