Requiring a physician's prescription for hormonal emergency contraceptive pills makes no sense. Unintended pregnancies remain endemic in the United States, and wider use of emergency contraceptive pills could substantially help. However, the prescription requirement poses an unnecessary barrier to prompt, effective use of this preventive therapy. According to the Durham-Humphrey Amendment of 1951, the default option for all new drugs is, in principle, over-the-counter, unless a drug is addictive or dangerous when self-administered. Clearly, hormonal emergency contraception is neither of these. Emergency contraceptive pills meet all the customary criteria for over-the-counter use: low toxicity, no potential for overdose or addiction, no teratogenicity, no need for medical screening, self-identification of the need, uniform dosage, and no important drug interactions. The Food and Drug Administration is authorized, and, by its own regulations, should be required to switch hormonal emergency contraception to over-the-counter status without delay. The current prescription requirement is not only gratuitous but also harmful to women's health because it impedes access to this important therapy.

^aFamily Health International, Research Triangle Park, North Carolina, USA
^bThe Center for Reproductive Law and Policy, New York, New York, USA

(Obstet Gynecol 2001:98:151-155. © 2001 by The American College of Obstetricians and Gynecologists.)

In the past several years, two emergency contraceptive pill regimens have been approved by the United States Food and Drug Administration (FDA). Both regimens consist of two doses of hormone taken 12 hours apart. The Yuzpe regimen (currently marketed as Preven, Gynétics, Somerville, NJ) contains both an estrogen, ethinyl estradiol, and a progestin, levonorgestrel, in each dose. The levonorgestrel regimen (marketed as Plan B, Women's Capital Corporation, Bellevue, WA) contains only levonorgestrel. Both regimens are currently available only by prescription. The prescription requirement limits access to the pills, which deters effective use of the treatment, and no medical justification exists for maintaining prescription status. In this article, we will describe the medical need and legal basis for an immediate switch to over-the-counter availability.

The Scope of the Problem

Unintended pregnancy is a major public health problem in the United States. Almost half of all United States women aged 15 to 44 years in 1994 have had at least one unplanned pregnancy at some time in their lives. Almost half of the 5.4 million pregnancies ending in 1994 were unintended and resulted in unwanted or mistimed births or in abortion. If current abortion rates persist, more than 40% of United States women will have had at least one induced abortion by menopause.¹ Although the unintended pregnancy rate has decreased in the past decade, the United States rate remains substantially higher than that in other developed countries and is particularly high among young, less educated, and poor women.¹ The consequences of unintended pregnancy can be serious, including maternal death and morbidity, low birth weight, birth defects, infant death, maternal and child abuse, and social and economic hardship for all involved.²

Emergency contraceptive pills have the potential to reduce the incidence of unintended pregnancy substantially. Most unintended pregnancies occur after an immediately apparent contraceptive failure—a condom breaks, oral contraceptive pills are missed, a spermicide tablet fails to melt—or after a couple fails to use any contraception at all. At least one of these events has been estimated to occur in more than 64 million menstrual cycles per year in the United States. If emergency contraceptive pills were used in three-quarters of these situations, unintended pregnancies and consequent abortions could be reduced by as much as half.³

These benefits can be realized, however, only if women have ready access to the therapy. Both emergency contraception products currently approved by the FDA are labeled for use within the first 72 hours after intercourse. Even within this time period, both regimens appear to be substantially more effective the sooner they are used: in one recent study, the chance of pregnancy was at least four times greater if emergency contraceptive pills were taken between 48 and 72 hours after coitus than if they were taken within less than 24 hours.⁴ Any delay in treatment reduces efficacy, leading to an increased risk of treatment failure and consequent unintended pregnancy.

Public Health Justification for Removing Prescription Requirement

Prescription status is a major barrier to access to emergency contraceptive pills. Women are often unable to see or contact a health care provider quickly to obtain a prescription, especially on weekends and in evenings when contraceptive accidents are most likely to occur. Allowing women to purchase emergency contraceptive pills directly over-the-counter is the most expedient way to ensure that women can obtain and use them immediately whenever the need arises.

Moreover, prescription status is medically unwarranted.⁵ As we describe below, the characteristics of both emergency contraceptive pill regimens make it highly unlikely that either safety or efficacy would be compromised if women could purchase and use them without first consulting a provider.⁶

Emergency contraceptive pills are nontoxic. The hormones contained in emergency contraceptive pills have been used in oral contraceptive pills by tens of millions of women around the world for 4 decades. Indeed, the oral contraceptive pill is arguably the most extensively studied medication in the history of pharmaceuticals. The incidence of serious complications of chronic use of these pills has proven to be extremely low. In the largest study of the two FDA-approved emergency contraception regimens reported to date, the most commonly reported complaints were nausea, breast tenderness, lower abdominal pain, fatigue, headache, heavier or lighter menstrual bleeding, dizziness, vomiting, and diarrhea (Table 1). ⁷ The few case reports of serious adverse events in emergency contraceptive pill users do not support a causal association.

Emergency contraceptive pills are certainly safer than many drugs currently sold over-the-counter in the United States. For example, hundreds of deaths are recorded yearly in the United States from overdoses of aspirin and other over-the-counter antipyretics and analgesics. To allow unrestricted access to aspirin while requiring a physician's prescription for emergency contraceptive pills makes no sense.

Emergency contraceptive pills carry no danger from overdosage or potential for addiction. Although an overdose of emergency contraceptive pills could lead to the side effects previously mentioned, no deaths, suicides, or other serious consequences of an acute overdose of either hormone have been reported. Indeed, a study by the World Health Organization found menstrual irregularities to be the most notable side effect of levonorgestrel used repeatedly for postcoital contraception.⁸ The hormones contained in the two approved products are not addictive. In fact, the side effects, although temporary and not serious, might be expected to deter frequent use.

Emergency contraceptive pills are not teratogenic and pose no danger in pregnancy. Extensive research over 4 decades has confirmed that use of hormonal contraception during early pregnancy carries no risk of damage to an embryo.⁹ The FDA removed warnings about possible teratogenic effects from labeling of oral contraceptive pills several years ago, and approved labeling of emergency contraceptive pills also does not carry this warning. Guidelines from expert organizations do not require a pregnancy test before treatment with emergency contraceptive pills,¹⁰ nor does FDA-approved labeling of the Plan B product.

The regimens for emergency contraceptive pills have been proved effective. Unlike many other drugs that are switched from prescription to over-the-counter status, such as ibuprofen, the dose of hormones used in over-the-counter emergency contraception would be identical to that currently used in the prescription regimens. The existing efficacy data that justify distribution of these regimens by prescription therefore would be directly applicable to the over-the-counter products.

The treatment is identical for all women. Both currently approved regimens of emergency contraceptive pills consist of two equal doses taken 12 hours apart. Because this dose is applicable to all women, professional expertise is not needed to determine the correct dose. In this respect, emergency contraceptive pills are much simpler than medications currently sold over-the-counter, which require tailoring of dose based on patient characteristics (such as age) or therapeutic response.

The instructions are simple and easy to follow. Women should take one dose as soon as possible, and a second identical dose 12 hours later. In contrast, many over-the-counter medicines have more complicated instructions for use.

Screening to recognize the indication for therapy is irrelevant. The only indication for use of emergency contraceptive pills is unprotected intercourse. Identification of this indication does not require professional expertise.

The package labels for the two products approved by the FDA list a number of contraindications (Table 2). However, other than pregnancy, none of these contraindications are supported by medical evidence.⁹ These lists appear to have been adapted from package labeling for oral contraceptive pills, which is inappropriate given the different patterns of use. No reason exists to believe that contraindications to oral contraceptive pills, which are used daily over months or years, should apply to emergency contraceptive pills, which are used in a single 12-hour period and which contain a much lower total hormone dose. These contraindications should be removed from the labeling of emergency contraceptive pills.

Pregnancy is a legitimate contraindication to use of emergency contraceptive pills, but only because the treatment is ineffective during pregnancy, and not because it places the woman or the embryo at risk. Pregnancy can usually be ruled out by a woman herself without examination by, or even consultation with, a medical professional. In cases of doubt, she can use an over-the-counter pregnancy test or see her health care provider.

Professional monitoring of emergency contraception therapy is unnecessary. The duration of treatment with emergency contraceptive pills is short (12 hours), and the elimination half life of each of the two hormones is less than 24 hours. Side effects are self-limited and generally mild. Severe symptoms, if they occur, are usually managed with over-the-counter analgesics or antiemetics. If emergency contraceptive pills fail, a woman will eventually recognize on her own that she is pregnant. Professional monitoring will neither reduce the incidence of side effects nor increase the efficacy of therapy, and it is unnecessary.

No important drug interactions have been demonstrated. Evidence suggests that the efficacy of routine oral contraceptive pills may be reduced by concomitant use of certain medications, such as rifampin and certain anticonvulsant drugs, and possibly by use of the nutritional supplement St. John's Wort. Similar interactions may occur with emergency contraceptive pills as well. However, no conclusive information is available on how or even whether the dose should be adjusted for women taking these drugs. The prescription requirement for emergency contraceptive pills does not resolve the problem posed by this lack of knowledge. Once data on this matter become available, labeling of emergency contraceptive pills could be modified to advise women taking these drugs to alter the dose appropriately or to consult their physicians. Contraceptive steroids are not known to have substantial effects on activity of other drugs.

Legal Basis for Switching to Over-The-Counter

Since 1938, the Food, Drug and Cosmetic Act (21 United States Code [USC] §§ 301 et seq., 1999) has required approval by the FDA of human drugs placed on the United States market. In its original form (Pub. L. No. 75-717, 52 Stat. 1040, 1938), the Act did not authorize classification of drugs as over-the-counter or by prescription only.¹¹ Rather, the original Act presumed that most drugs would be directly available to consumers without a prescription. Hence, the Act permitted distribution only of drugs containing directions likely to be understood by ordinary consumers. Despite this lack of statutory authority, the FDA permitted approval of drugs that lacked adequate directions for lay use, if those drugs were distributed by prescription only.¹¹

In 1951, Congress passed the Durham-Humphrey Amendment, which expanded the kinds of drugs that could be approved (Pub. L. No. 82-215, 65 Stat. 648, 1951).⁶ The Amendment explicitly authorized the FDA to approve drugs that cannot be used safely without medical supervision; however, it specified that these drugs must be distributed by prescription and include appropriate labeling directed to the physician and pharmacist.⁶ The Amendment requires prescription-only distribution of any drug which is "habit forming," "not safe for use except under the supervision of a practitioner licensed by law to administer such drug," or "limited by an approved [new drug application] to use under the professional supervision of a practitioner licensed by law to administer such drug" (21 USC 353(b), 1999). Importantly, all other drugs may be sold over-the-counter, which remains, in principle, the default option.

In practice, the manufacturer initially determines in its new drug application whether a drug should be available for prescription or over-the-counter distribution (21 USC 355(c), 1999). However, once a prescription drug has been made available, the FDA has explicit authority to switch the drug to over-the-counter if the prescription restriction is unnecessary (21 USC § 353(b)(3), 1999). Such a switch may be undertaken on the FDA's own initiative, may be sought by any interested person through a citizen's petition, or may be sought by the manufacturer or distributor (21 Code of Federal Regulations [CFR] § 310.200(b), 1999; 21 USC 355, 1999). Once the FDA has undertaken review of a prescription drug's marketing status, the agency is required to switch the drug to over-the-counter status if the prescription limitation is not necessary (21 CFR § 310.200(b), 1999).

The distributors of Preven and Plan B have not sought approval from the FDA to sell these products over-the-counter. Nonetheless, numerous public health and reproductive health advocates, as well as drug manufacturers and members of the FDA, have questioned whether the prescription restriction on these drugs is justified by health concerns. The FDA will soon consider this question pursuant to a citizen's petition submitted February 2001, by more than 70 organizations, including the American Public Health Association.

The FDA follows a number of well-established criteria in determining whether a prescription restriction is necessary for protection of the public health. In short, a prescription drug should be switched to over-the-counter status if: the drug is safe for self-medication, the drug is effective when self-administered, the condition to be treated is self-diagnosable, and the drug's labeling is tailored to self-administration (21 CFR § 310.200(b), 1999; 21 CFR § 330.10(a)(4), 1999). As described above, both regimens of emergency contraceptive pills clearly fulfill all these criteria. Accordingly, once the FDA completes its review, it will be authorized and, indeed, required by federal regulations to switch these products to over-the-counter status.

Movement Toward Over-The-Counter

Family planning programs in the United States and abroad are already moving to "over-the-counter-like" distribution approaches for emergency contraceptive pills. Of note, Planned Parenthood Federation of America Inc., has endorsed prescription of emergency contraceptive pills by telephone, as well as provision of emergency contraceptive pills in advance, so that patients may keep the pills at home in case of future need. These approaches are similar to over-the-counter distribution in that the patient is not examined before she takes the pills; in the case of advance provision, she may not have had any screening or counseling by a medical professional for weeks, months, or even years before pill use. Planned Parenthood affiliate clinics and other reproductive health service clinics around the country have instituted these practices with no known problems. A trial having pharmacists in Washington state dispense emergency contraception has been a resounding success.

Other countries are dropping the prescription requirement as well. Levonorgestrel for emergency contraception has been available without a prescription in France since June, 1999, and no adverse events have been reported. On October, 2000, emergency contraceptive pills became available over-the-counter in Norway. In addition, the British Department of Health has announced its plan to offer hormonal emergency contraception without a physician's prescription.

Some critics of easy access to emergency contraception worry that over-the-counter availability will undermine women's use of ongoing contraception. Evidence from Scotland¹² and Ghana has been reassuring concerning advance provision of emergency contraception. A study among high-risk women in San Francisco found advance provision to be associated with greater use of emergency contraception, a shift away from hormonal methods, and increased use of condoms.

The requirement for a prescription to obtain emergency contraceptive pills hurts women's health by posing an unnecessary obstacle to the prompt, effective use of this important therapy. Rather than improving women's health, this requirement indirectly contributes to the epidemic of unintended pregnancies and induced abortions in this country. These outcomes are both antithetical to the mission of the FDA and damaging to public health. No medical reason exists to maintain prescription status for emergency contraceptive pills, as professional intervention is not necessary to ensure safe and correct use. Following the medical principle of "primum non nocere," the prescription requirement for emergency contraceptive pills should be dropped.⁵

References

1. Henshaw SK. Unintended pregnancy in the United States. Fam Plann Perspect 1998;30:24-9, 46.

2. Brown SS, Eisenberg L, eds. The best intentions. Washington, DC: National Academy Press, 1995.

3. Trussell J, Stewart F, Guest F, Hatcher RA. Emergency contraceptive pills: A simple proposal to reduce unintended pregnancies. Fam Plann Perspect 1992;24:269-73.

4. Piaggio G, von Hertzen H, Grimes DA, Van Look PF. Timing of emergency contraception with levonorgestrel or the Yuzpe regimen. Task Force on Postovulatory Methods of Fertility Regulation. Lancet 1999;353:721.

5. Ellertson C, Trussell J, Stewart FH, Winikoff B. Should emergency contraceptive pills be available without prescription? J Am Med Womens Assoc 1998;53:226-9, 232.

6. Jacobs LR. Prescription to over-the-counter drug reclassification. Am Fam Physician 1998;57:2209-14.

7. Task Force on Postovulatory Methods of Fertility Regulation. Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception. Lancet 1998;352:428-33.

8. United Nations Development Programme/United Nations Population Fund/World Health Organization/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Task Force on Post-Ovulatory Methods of Fertility Regulation. Efficacy and side effects of immediate postcoital levonorgestrel used repeatedly for contraception. Contraception 2000;61:303-8.

9. Raman-Wilms L, Tseng AL, Wighardt S, Einarson TR, Koren G. Fetal genital effects of first-trimester sex hormone exposure: A meta-analysis. Obstet Gynecol 1995;85:141-9.

10. American College of Obstetricians and Gynecologists. Practice patterns. Emergency oral contraception. Number 3, December, 1996 (replaces Number 2, October, 1996). Int J Gynaecol Obstet 1997;56:290-7.

11. Juhl RP. Prescription to over-the-counter switch: A regulatory perspective. Clin Ther 1998;20(Suppl C):C111-7.

12. Glasier A, Baird D. The effects of self-administering emergency contraception. N Engl J Med 1998;339:1-4.

Address reprint requests to: David A. Grimes, MD, Family Health International, PO Box 13950, Research Triangle Park, NC 27709; E-mail: dgrimes@fhi.org

Received January 9, 2001.
Accepted March 23, 2001.