Pharmacology Update

Levonorgestrel/Ethinyl Estradiol Tablets (Seasonale)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

The FDA has approved the first 91-day oral contraceptive. The product is taken for 12 weeks (84 days), followed by 1 week of inactive tablets, resulting in 1 menstrual period every 3 months. This new oral contraceptive contains a common estrogen (ethinyl estradiol) and progestin (levonorgestrel) and is marketed by Duramed Pharmaceuticals Inc as Seasonale.

Indications

Levonorgestrel/ethinyl estradiol (Seasonale) is indicated for the prevention of pregnancy in women.1

Dosage

One active tablet is taken daily for 84 consecutive days followed by 7 days of inactive tablets. The tablets should be taken at the same time of the day each day. The first cycle should begin on the first Sunday after the onset of menstruation or if menstruation begins on a Sunday.1

Potential Advantages

The number of scheduled menstrual cycles is reduced from once monthly to once every 3 months.

Potential Disadvantages

There is a higher frequency of intermenstrual bleeding and/or spotting compared to 28-day cycle regimens, although these tend to decrease with each successive cycle.1,2 More subjects discontinue Seasonale compared to a 28-day regimen due to unacceptable intermenstrual bleeding/spotting, 7.7% vs 1.8%.1 Also, unintentional pregnancies may go undetected for longer periods of time due to the longer interval between menstrual cycles.

Comments

Seasonale is the first 91-day oral contraceptive. The active ingredients, ethinyl estradiol and levonorgestrel, are the same and contain the same daily doses as the commonly used contraceptives Levlen and Nordette. In the case of Seasonale, women take 3 uninterrupted cycles of active drug. In a 1-year study, 4 pregnancies occurred over 809 completed 91-day cycles. This represents an overall use-efficacy (typical user efficacy) pregnancy rate of 1.98 per 100 women-years of use.1 When Seasonale (4 cycles) was compared to a 28-day regimen Nordette (13 cycles), the Pearl Index based in method failure was 0.55 per 100 women compared to 1.45 for Nordette.2 The primary advantages for women are fewer scheduled menstrual cycles compared to a 28-day regimen. The primary disadvantage is higher frequency of intermenstrual bleeding and/or spotting, particularly in the first cycle. Percent of subjects with 7 or more days of bleeding and/or spotting in the first cycle of Seasonale was 65% compared to 38% in users of the first 4 cycles of a 28-day regimen.1 Similarly, the percentage of patients with 20 or more days of bleeding and/or spotting was 35% and 6%, respectively. However, over 1 year of use the total days (withdrawal and intermenstrual) were similar.1 Seasonale is priced comparably to other branded oral contraceptives. Its wholesale cost is about $96 for a 91-day cycle compared to about $89 for 3 28-day cycles of Nordette. The company is expected to seek FDA approval of a low-dose formulation of Seasonale in 2004.3

Clinical Implications

Seasonale provides an option for women who elect to have a fewer number of scheduled menstrual cycles. However, some may find the higher frequency of intermenstrual bleeding and/or spotting unacceptable.

Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente, and Assistant Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are associate editors of Internal Medicine Alert.

References

1. Seasonale Product Information. Barr Laboratories, Inc. September 2003.

2. Anderson FD, et al. Contraception. 2003;68(2):89-96.

3. FDC Report. The Pink Sheet. 2003;65(37):38-39.