Página 1 De 8 Uptodate®: 'Emergency Contraception'

UpToDate®: 'Emergency contraception' Página 1 de 8 ® ©2005 UpToDate Emergency contraception Mimi Zieman, MD Robert L Barbieri, MD UpToDate performs a continuous review of over 330 journals and other resources. Updates are added as important new information is published. The literature review for version 13.2 is current through April 2005; this topic was last changed on April 25, 2005. The next version of UpToDate (13.3) will be released in October 2005. INTRODUCTION — Emergency contraception (also known as postcoital contraception) typically refers to the administration of drugs to prevent pregnancy in women who have had recent unprotected intercourse (including sexual assault), or to those who have had a failure of another method of contraception (eg, broken condom) (show table 1). Advisory committees to the United States Food and Drug Administration (FDA) have recommended that emergency contraception (Plan B, levonorgestrel only) be made available without prescription, as in many other countries [1]. Arguments for this approach are that women will have easier access to treatment; thus, they will be more likely to use it and can begin treatment sooner when it is most effective [2,3]. This should reduce the number of unplanned pregnancies and pregnancy terminations (see "Advance planning" below). The major argument against over-the-counter status is that the opportunity for evaluation and counseling by a health care provider is lost. An office encounter could be used to determine whether nonconsensual sex occurred and discuss risk and prevention of sexually transmitted infections, use of regular contraception, and prepregnancy issues. However, studies have shown that most women are able to use emergency contraception appropriately without formal evaluation and counseling by a health care provider [4]. After considering both sides of the argument, both the American Medical Association and the American College of Obstetricians and Gynecologists supported over-the-counter availability of emergency contraception. In May 2004 the FDA considered this issue but did not give approval; instead they requested increased safety information for girls under 16 or restriction of nonprescription availability for girls in this age group [5]. Limited available data suggest adolescents use emergency contraception appropriately and tolerate the drug about as well as adults [6-9]. The available methods for and efficacy of emergency contraception are reviewed here. Long- term methods of contraception are discussed separately. (See "Overview of contraception" and see "Overview of the use of oral contraceptives"). BACKGROUND RISK OF PREGNANCY — There are many factors which affect a woman's fertility. In general, the risk of pregnancy after an episode of coitus without effective contraception is shown in Table 1A (show table 1A). These data represent the rate of pregnancy in a population of young couples in their mid-20's. Given the uncertainty in timing of ovulation, emergency contraception is offered, when indicated, without regard to timing of the menstrual cycle. MECHANISM — The mechanism of action is uncertain. Emergency contraceptives may act by inhibiting ovulation, interfering with tubal transport, preventing implantation, or possibly causing regression of the corpus luteum. Since these drugs are administered within hours of UpToDate®: 'Emergency contraception' Página 2 de 8 intercourse and implantation does not occur until approximately seven days after ovulation, use of emergency contraception cannot interrupt a pregnancy. a woman is considered pregnant once a conceptus has implanted [10]. The only FDA approved drug that interrupts pregnancy once implantation has occurred is the antiprogestin mifepristone. (See "Mifepristone for the medical termination of pregnancy"). PREPARATIONS — Several options are available for emergency contraception (show table 2) [11,12]. Ethinyl estradiol plus levonorgestrel — A regimen of ethinyl estradiol (100 mcg) and levonorgestrel (0.5 mg) taken twice, 12 hours apart (the Yuzpe regimen), reduces the number of anticipated pregnancies by 75 to 80 percent [13]. Stated differently, if 100 women have unprotected intercourse during the second or third week of their menstrual cycle, it is likely that eight will become pregnant; approximately two will become pregnant with proper use of the Yuzpe regimen and six of the eight pregnancies (75 percent) will be prevented [14]. In 1998, the United States Food and Drug Administration (FDA) approved marketing (by prescription) of the Preven Emergency Contraceptive Kit, which includes four combination tablets, each containing 50 mcg of ethinyl estradiol and 0.25 mg of levonorgestrel, and a pregnancy test to rule out pregnancy before taking the tablets. Instructions are to take two of the tablets as soon as possible within 72 hours of intercourse, and the other two tablets twelve hours later. However, recent research suggests that emergency contraception is still effective up to 120 hours after intercourse, therefore the 120 hour limit is used by many providers, such as Planned Parenthood. The manufacturer of Preven stopped production in 2004 in order to focus marketing on Plan B, a levonorgestrel-only product for emergency contraception, which is more effective and better tolerated than the combined preparation (see below). Where licensed regimens are not available, an oral contraceptive such as Ovral (two tablets twelve hours apart) or Lo/Ovral (4 tablets twelve hours apart) can be used (show table 3). Nausea and vomiting are the major side effects of the Yuzpe regimen. Meclizine 50 mg, taken one hour before the first dose, reduces nausea and vomiting but can cause some sedation [15]. A randomized study comparing metoclopramide (10 mg) and placebo taken one hour before each dose found metoclopramide significantly reduced the frequency of nausea from 56 to 28 percent; the reduction in vomiting was of borderline significance, 22 versus 11 percent [16]. There are no absolute contraindications to use of this regimen and, while not specifically studied, there does not appear to be harm to the fetus if the drugs are taken and the pregnancy continues. If the estrogen-progestin pills are vomited within one hour of ingestion and an antiemetic was not given prophylactically, then an antiemetic can be given and the estrogen-progestin dose repeated. Alternatively, levonorgestrel can be administered for emergency contraception (see below). Modified Yuzpe regimen — The Yuzpe regimen was not derived from systematic studies evaluating the optimum dose, timing, or type of progestin for emergency contraception. The only trial of modified Yuzpe regimens found that they were slightly less effective, although promising. This multicenter study enrolled 2041 women within 72 hours of unprotected intercourse and randomly assigned them to receive the standard Yuzpe regimen (100 mcg ethinyl estradiol plus 0.5 mg levonorgestrel for two doses 12 hours apart), a variant that substituted 2.0 mg norethindrone for the levonorgestrel, or only the first dose of Yuzpe (norgestrel was substituted for levonorgestrel and placebo pills were given in place of the second dose at 12 hours) [17]. Among 1973 women who had complete follow-up, 58 pregnancies occurred; 43 were considered method failures and 15 user failures. Failure rates were lowest with the standard Yuzpe regimen, although not significantly (show table 4). Nausea and vomiting were lowest with single dose therapy. Further investigation is needed before modified regimens can be recommended; however, this may not be possible since over 12,000 women would have to be enrolled for a study to have enough power to determine whether the small differences detected in this trial were significant. UpToDate®: 'Emergency contraception' Página 3 de 8 Levonorgestrel — Levonorgestrel, 0.75 mg given twice 12 hours apart, may be more effective and better tolerated than an estrogen-progestin regimen [18,19]. This was illustrated in a controlled trial in which 2000 women with regular menses who requested emergency contraception after unprotected coitus were randomly assigned to either levonorgestrel or the Yuzpe regimen [19]. The crude pregnancy rates were 1.1 and 3.2 percent, respectively. The proportion of pregnancies prevented (compared with the expected number) was 85 percent with the levonorgestrel regimen and 57 percent with the Yuzpe regimen. Nausea and vomiting were significantly less common with the levonorgestrel. The reduction in side effects and improved efficacy are significant benefits of the progestin-only regimen. In addition, it is an effective alternative for women with a history of thrombosis or who are otherwise unable to take estrogen preparations. If the levonorgestrel is vomited within one hour of administration, consider giving an antiemetic agent and then repeating the emergency contraception dose. The United States FDA has approved marketing of Plan B (by prescription), a pill pack that contains two 0.75 mg tablets of levonorgestrel to be taken twelve hours apart. The cost is comparable to the Preven kit (approximately $20) [20]. An advisory committee to the FDA recommended Plan B be made available without a prescription, but the FDA rejected this recommendation and requested increased safety information for girls under 16 or restriction of nonprescription availability for girls in this age group [5]. Other regimens also appeared to be effective in preliminary studies. Further trials confirming efficacy need to be performed before these regimens

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