By Brian Vastag

PHYSICIANS, WOMEN’S HEALTH advocates, and legislators are irate over the Food and Drug Administration’s (FDA) decision to bar emergency contraceptives from over-the-counter sales in the United States. The birth control pills, which reduce the risk of pregnancy to 1% when taken within 72 hours of intercourse, are available without a prescription in 33 countries.

In December 2003, the FDA’s Reproductive Health Drugs Advisory Committee voted 23-4 in favor of over-thecounter sales of Plan B (levonorgestrel), the progestin-only emergency contraceptive made by Barr Laboratories, Bala Cynwyd, Pa.

But in a May 6 letter, Steven Galson, MD, MPH, acting director of the FDA’s Center for Drug Evaluation and Research, stated that the company had presented insufficient data on the drug’s safety in adolescent girls younger than age 16 years. He also wrote that an amended application from Barr to make the drug available over the counter only to adolescent girls and women older than 16 years was incomplete.

The FDA typically follows the recommendations of its advisory committees, and a long-time spokeswoman was unable to recall another incident where the agency bucked an overwhelming vote. She insisted, however, that the decision was not precedent setting.

DECISION PROTESTED

Reaction was swift and trenchant. Protests organized by the National Organization of Women and other groups sprang up, where physicians were seen handing out Plan B prescriptions. Forty members of Congress wrote the FDA urging a reversal; many also asked the General Accounting Office to investigate the decision. Rep Carolyn Maloney (D, NY) introduced legislation that would force the FDA to affirm that its
decision was medically sound. A dozen other legislators demanded the resignation of Galson and Lester Crawford, DVM, PhD, the acting FDA commissioner. “It is appalling that a nation with one of the highest teen pregnancy rates in the industrialized world would deny women this safe contraceptive option,” saidmicrobiologist and US Congresswoman Louise Slaughter, MPH, (D, NY) at a press conference.

During a teleconference organized by the Planned Parenthood Federation of America, Paul Blumenthal, MD, MPH, associate professor of obstetrics and gynecology at the Johns Hopkins University School of Medicine, said that Plan B met the FDA’s over-the-counter requirements “in spades.” Users can recognize their own need for the drug; the potential for abuse is negligible; and contraindications, such as established pregnancy or vaginal bleeding, are easily recognized. “And even if [the user] is pregnant, it won’t hurt [the fetus],” said Blumenthal, reiterating the conclusion of every study of emergency contraception.

UNUSUAL DECISION

The FDA’s decision is even more unusual in light of comments made by one of its own officials, Daniel Davis, MD, MPH, medical officer in the division of reproductive and urological drugs. At the December advisory committee meeting, Davis presented the agency’s safety analysis.

“More than 15000 women from 29 countries in clinical trials using various doses of levonorgestrel . . . had been studied. This data . . . didnot uncover any deaths, cardiovascular problems, thromboembolic events, or serious adverse events,” he said. “In summary, the FDA review of the sponsor’s clinical trial safety data did not find any safety signals of concern.” Davis also noted that the rates of ectopic pregnancies, spontaneous abortions, and birth defects were lower among the small number of women who had used Plan B and become pregnant than among the general population.

SAFETY DATA IN ADOLESCENTS

While the agency cited the lack of safety data in adolescents in its decision, such data do exist. A clinical trial sponsored by Barr included 29 adolescent girls aged 14 to 16 years (of 585 participants); other, earlier studies of emergency contraception across the globe have enrolled several hundred 15- and 16-year-olds. “The safety of use in adolescents is certainly there,” said Scott Spears, MD, associate professor of pediatrics at the University of Wisconsin, Madison. “There aren’t a large number [of young adolescents] in the trials, but the biology of a 14-year-old is not different from [that of] a 16-year old.”

EARLY WORRY

Even before the FDA’s decision, advisory committee members and others worried that the FDA’s approval process had been hijacked by politics. In an April editorial, committee members Michael Greene, MD, and Alastair Wood, MD, and New England Journal of Medicine Editor-in-Chief Jeffrey Drazen, MD, wrote that “there is no medical dispute. Rather, the delay [in approval] results from the concern of some groups, without any supporting data, that the availability of the drug may have a corrupting influence on sexual behavior” (N Engl J Med. 2004;
350:1561-1562).

At the December meeting, however, attendees heard that easy availability of emergency contraception does not influence sexual behavior, except perhaps to encourage more use of condoms. After reviewing eight studies that provided participants with birth control education or education plus emergency contraceptives, Jin Chen, MD, PhD, from the FDA’s division of overthe- counter drug products, concluded that girls and women with access to emergency contraceptives “didn’t have more frequent unprotected sex, didn’t decrease condom use, didn’t switch to less effective contraception.” Spears, who consults with his university’s health clinic, said, “When teens have unprotected sex, it isn’t because they’re thinking of a pill they can take later. That’s not how the teen mind works.”

The latest clinical trial, from the University of Pittsburgh, reported that 15% of young women with emergency contraception on hand used it compared with 8% of those who needed a prescription. Women with easy access to Plan B also used the pills an average of 11 hours after unprotected sex, compared with an average of 22 hours for those who needed a prescription. Condom use was higher among those with the pills, too; they used condoms 77% of the time, compared with 62% among the education-only group ( J Pediatr Adolesc Gynecol. 2004;17:87-96).

AVOIDING ABORTIONS

Advocates of over-the-counter sales are also quick to point out the consequences of unwanted pregnancy, namely, millions of abortions. Of some 3 million unintended pregnancies in the United States each year, nearly half, or 1.4 million, end in abortion, according to the National Vital Statistics Report compiled by the Centers for Disease Control and Prevention. In a 2002 report, the nonprofit Guttmacher Institute concluded that emergency contraception prevented 51000 US abortions in 2000, when prescription access to the drug was spotty and the majority of pharmacies did not stock it.

Liza Siebel, director of public policy at women’s advocacy group Break the Cycle, argued that over-the-counter sales could prevent most of the 25000 annual pregnancies caused by sexual assault. “When a victim is raped, her biggest fear is often pregnancy,” said Siebel. A spokeswoman for Barr said that the company will return to the FDA for approval of over-the-counter marketing for adolescent girls and women aged 16 years or older. Younger girls would still need a prescription. The company had amended its original over-the-counter proposal with this plan, but the FDA did not evaluate the idea because the company had not submitted draft labeling.

The FDA will have 6 months to respond after Barr submits its request later this year.

What’s the Plan?

Each year, an estimated 2.4 million women worldwide use emergency contraception.

Early formulations included estrogen and progestin and were known to induce severe abdominal cramping. Current formulations include progestin only, substantially reducing the incidence of abdominal pain.

Package inserts advise women to take one 0.75-mg pill within 72 hours of unprotected sex and another pill 12 hours later. When initiated within 24 hours, the risk of pregnancy is 0.4%; it climbs to 2.7% when the first pill is taken 48 to 72 hours after sex; the effectiveness of emergency contraception continues declining thereafter. The best evidence shows that taking both doses simultaneously is just as effective as spacing them by 12 hours. “It also makes it more likely that they’ll take both of them,” said Scott Spears, MD, associate professor of pediatrics at the University of Wisconsin, Madison.

The pills work like regular oral contraceptives, by preventing ovulation or by preventing uterine implantation of an egg. The two pills are equivalent in dose to about 10 daily oral contraceptive pills, and a single use typically costs $20 to $30.

Emergency contraception is available in 101 countries. Sixty-eight, including the United States and Canada, require a prescription. The other 33 allow sales by pharmacists without a prescription, while Sweden and Norway are the only countries that allow unrestricted over-the-counter sales.

Five US states also allow sales by pharmacists without a prescription: Alaska, California, Hawaii, New Mexico, and Washington, which launched the trend in 1997. Pharmacists there dispense 2000 doses each month, but just 300 of 1150 statewide pharmacies (26%) have joined the program.

A number of sources maintain online information about emergency contraception. The Department of Health and Human Services provides a page of informational links on the Web (available at http://www.4woman.gov//faq/econtracep.htm). Planned Parenthood Federation of America offers information and helps locate health care professionals who prescribe emergency contraception (available at http://www.plannedparenthood.org/ec/). Princeton University also offers a large searchable database of emergency contraception educational materials (available at http://ec.princeton.edu/ecmaterials/default.asp).

©2004 American Medical Association. All rights reserved.