Emergency Contraceptive Kit (Preven—Gynetics, Inc.)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
The FDA has approved the first "morning after pill," Gynetics Inc.’s Preven Emergency Contraceptive Kit. Although high-dose oral contraceptives have been used in this role for years, Preven’s formulation is the most widely used and now the first approved product in the United States for this indication. The combination of levonorgestrel, progestin, and ethinyl estradiol, an estrogen, was introduced many years ago by AA Yuzpe and is often referred to as the Yuzpe regimen. It has been the standard regimen, in addition to levonorgestrel and ethinyl estradiol. Preven also includes a home pregnancy test to rule out existing pregnancy.
The tablets in the kit are indicated for the prevention of pregnancy in women after known or suspected contraceptive failure or unprotected intercourse.
The initial two tablets must be taken as soon as possible but within 72 hours of intercourse. The remaining two tablets are taken 12 hours later. If the patient should vomit within one hour of taking either dose, she should contact her physician and may consider repeating the tablets.1 An anti-nausea drug such as meclizine may be considered prophylactically one hour before the first dose.2 Patients should be advised that emergency contraceptive kits do not protect against sexually transmitted infections such as HIV.
Preven is supplied as four tablets each containing 50 mcg of ethinyl estradiol and 0.25 mg of levonorgestrel. In addition, a pregnancy test is included that detects the presence of human chorionic gonadotropin in the urine.
Several oral contraceptives have been regarded as safe and effective as emergency contraceptive regimens. However, Preven is the only product available in a convenient dosage form. Preven works to delay or prevent ovulation, thereby preventing fertilization. It is, therefore, fundamentally different and perhaps more acceptable to some patients than abortifactients such as RU486.
While Preven is safe and effective, it may be less effective then levonorgestrel (0.75 mg) alone, which is not available in the United States. Results from a large (n = 1998) randomized trial indicated that ethinyl estradiol (100 mcg) and levonorgestrel (0.50 mg) are less effective than levonorgestrel (0.75 mg) alone.3 The crude pregnancy rate was 1.1% (11/976) in the levonorgestrel group and 3.2% (31/976) in the levonorgestrel/ethinyl estradiol group. The proportion of prevented pregnancy was 85% for levonorgestrel and 57% for the combination. In addition, nausea and vomiting were higher in the combination group (50.5% vs 23.1% and 18.8% vs 5.6%, respectively). A slight delay in the time to next menses has been reported. A slight delay in the time to next menses has also been reported.3
Preven is an effective form of emergency contraception. While the precise mechanism of action is not clear, it is believed that this product may act by inhibiting ovulation, alter tubal transport of sperm and/or ova, and inhibit implantation.1 Use of the kit is expected to reduce the expected incidence of pregnancy by about 75%, with a confidence interval of 66-82%.4 This is based on an analysis of seven studies. A recent study, however, suggested that the efficacy may be lower, 57%.3 Efficacy may be greatest if the tablets are taken within 24 hours of unprotected intercourse and declines with time.1,3 Preven should be started within 72 hours. The probability of pregnancy depends on the timing of intercourse and ovulation. There is a 15% chance of pregnancy when unprotected intercourse occurs three days before ovulation, 30% one or two days before, and 12% on the day of ovulation. The probability approaches zero more than two days after ovulation.4
Preven is a safe, effective, and convenient form of emergency contraception. It costs about $20 per kit. Other dosage forms used for emergency contraception include Ovral (2 tablets per dose), Lo-Ovral (4 tablets per dose), and Nordette, Triphasil, Levlen, or Trilevlen (4 tablets per dose). One study suggests that Preven may not be as effective as levonorgestrel. Unfortunately, levonorgestrel at emergency contraceptive doses is not available in the United States. The closest would be 20 tablets per dose of Ovrette.2
There are an estimated 3.5 million unintended pregnancies occuring in the United States annually and about one-half of them are believed to be the result of contraceptive failure. Current products for emergency contraception include various oral contraceptives, emergency insertion of an intrauterine device, and now, Preven. Emergency contraception provides a cost-effective method to reduce the incidence of unintended pregnancies. Greater availability of emergency contraception may reduce the considerable medical and social costs of unintended pregnancies.5 A recent study indicated that emergency contraceptive options are underused. This is primarily due to lack of awareness among younger patients presenting for pregnancy termination. Jamieson and associates estimated that 38% of the surgical pregnancy terminations could have been avoided with the use of emergency contraceptive pills.6
1. Preven Product Information. Gynetics Inc. September 1998.
2. Anonymous. Med Lett 1998;40:102-103.
3. Task Force on Postovulatory Methods of Fertility. Lancet 1998;352(9126):428-433.
4. Trussell J, et al. Contraception 1998;57(6):363-369.
5. Trussell J, et al. Am J Public Health 1997:87(6): 932-937.
6. Jamieson MA, et al. J Pediatr Adolesc Gynecol 1999;12(1):11-15.