Upon completion, the participant should be able to:

1. Describe the use of hormonal products in emergency contraception;
2. Recognize the limitations in the acceptance of wider application of emergency contraception therapy;
3. Identify the knowledge gaps by pharmacists and consumers in the use of emergency contraceptives;
4. Describe the structure of collaborative practice arrangements in emergency contraception; and,
5. Discuss the development of emergency contraception from off-label use to OTC status and the role of the FDA and individual states in this process.

INTRODUCTION

Determination by the Food and Drug Administration (FDA) in 2003 to postpone its decision on a proposal to switch a form of an emergency contractive product to non-prescription status inflamed passions on both sides of the abortion debate and has highlighted a legal and ethical dilemma for many pharmacists. Emergency, or postcoital, contraception is the use of a drug, usually a high dose oral contraceptive product, or device, typically an IUD, to prevent pregnancy after sexual intercourse (coitus) has taken place. Emergency contraceptives (ECs) are also known, inappropriately, as “morning after” pills.

At its December 16, 2003 meeting, the FDA’s advisory committees on Reproductive Health Drugs and Nonprescription Drugs voted 23-5 that a proposed over-the-counter (OTC) distribution program for Barr Laboratories’ emergency contraceptive product, Plan B, was adequate with respect to consumer access and safe use in a non-prescription setting. FDA ordinarily follows the recommendations of its advisory committees. However, in May, 2004, the agency issued a “non-approved” letter to the sponsor.¹ The letter noted that its application did not provide adequate data to support the use of Plan B by young adolescent women without the intervention of a physician. The letter also pointed out that the sponsor’s amendment of its application to allow marketing of Plan B by prescription order to young women under 16 years of age was incomplete and concluded that there was insufficient information to do a complete review. (In late August, 2005, FDA decided to delay a decision on Barr’s revised application for approval of OTC sales of Plan B for women over 16, citing novel practical and regulatory issues²).

Independent of FDA’s ultimate decision and the controversy surrounding the proposed extension of emergency contraception access, the expanded application of ECs to medical practice is limited by inadequate knowledge about their availability and correct use. In the United States, both consumers, especially adolescents, and health care professionals demonstrate information gaps on the proper use of ECs. Consequently, ECs are infrequently requested by women and infrequently prescribed by physicians.³ Pharmacists, who should be in a position to provide essential information about their use, are often poorly prepared and may also be reluctant to do so for ethical/moral reasons. Since some states already permit ECs to be dispensed by pharmacists without a prescription, and more states are considering doing so, adequate knowledge is essential for providing appropriate care. This lesson is intended to review the use of ECs in preventing pregnancy and will discuss issues of expanding access.

CONTRACEPTIVES AND REPRODUCTIVE FUNCTION

Normal reproductive function depends on a complex interaction between the endocrine system and its target organs.⁴ The hypothalamus, a critical brain region for endocrine and behavioral regulation, secretes a peptide, gonadotropin-releasing hormone (GnRH), also known as luteinizing hormone releasing hormone, which regulates luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion from the pituitary gland. LH and FSH promote maturation of the ova (egg) and stimulate secretion of estrogen and progesterone from the ovaries.

During the menstrual cycle, a single egg is released from the ovaries each month during ovulation. In the follicular phase of the cycle, FSH stimulates the growth of ovarian follicles. By the seventh day, one follicle becomes dominant and begins to mature.⁴ The maturing follicle begins to secrete estrogen, which regulates further production of FSH and LH, and prepares the endometrium of the uterus for possible implantation of a fertilized egg. When the estrogen produced by the ovaries reaches its plateau, the hormone induces a surge in LH production. Continued maturation of the follicle also requires FSH. Within 32-44 hours of onset of the LH surge, the dominant follicle ruptures and the egg is released (ovulatory phase). The egg then moves along the fallopian tube toward the uterus. After ovulation, the follicle breaks down into the "corpus luteum" (yellow body) and begins to produce progesterone (luteal phase). This phase corresponds with the functional life span of the corpus luteum, which secretes progesterone and estradiol for about 14 days, then degenerates unless pregnancy has occurred. The corpus luteum supports implantation of the fertilized ovum by secreting progesterone in increasing quantities, peaking 6-8 days after the LH surge. The progesterone halts release of all other eggs until the following cycle and maintains the thick lining of the uterus in preparation for pregnancy. The egg is viable for fertilization for only approximately 1 day after release from the follicle. Within approximately one week, the fertilized egg implants at the endometrium, the innermost layer of the uterus. If the egg is not fertilized as it moves down the fallopian tube, progesterone production diminishes causing the endometrium to shed and pass through the vagina, a process referred to as menstruation.

Many methods have been used since antiquity to produce contraception (including use of herbal, mineral and animal products and extracts, and household products and beverages).⁵ Hormonal extracts were shown in the 1920s to render rabbits infertile when it was demonstrated that progesterone could prevent release of an egg from the ovary. In 1949, the first synthetic progestins were synthesized, and combinations of progesterone and estrogen were marketed as early as 1957 to promote “menstrual regulation” and infertility.⁶ High doses of estrogen/progestins found in oral contraceptives suppress GnRH, FSH and LH release, and inhibit ovulation and impair follicular maturation.⁷ Oral contraceptives were first marketed in the United States in 1960, with approval of Searle’s Enovid, a combination of mestranol (150 µg) and norethynodrel (10 mg).⁶

Although only recently approved for emergency contraception (see below), oral contraceptive regimens have been used since the mid-1960’s to prevent pregnancy in rape victims.8 Estrogenic ovarian extracts were used decades earlier by veterinarians to prevent pregnancy in dogs and horses that had mated without their owner’s “consent.”⁸

EMERGENCY CONTRACEPTION

The first widely used emergency contraceptive method used in humans is referred to as the “Yuzpe Regimen,”named for the Canadian researcher, A. Albert Yuzpe, who published the original studies in 1974 showing that oral contraceptives are safe and effective when used for emergency contraception.⁹ The Yuzpe regimen consists of a combination of 100 µg of ethinyl estradiol combined with 1.0 mg of dl-norgestrel. This was equivalent to two Ovral tablets, which were available in Canada at the time the studies were conducted. The first dose was taken within 72 hours of coitus with a second identical dose taken 12 hours later, and this standard protocol continues to be used today. It should be noted, however, that the original Yuzpe regimen was not based on systemic/rigorous clinical evidence, but rather upon results of an empirical study. Pharmacists should be aware that other protocols have been shown to be successful (see below) and it is not necessary to adhere rigidly to the standard Yuzpe regimen.

Initially, the use of the Yuzpe formula in the United States was restricted to off-label use of oral contraception products in hospital emergency rooms, reproductive health clinics, and University health centers.^4,10 In the last two decades of the 20th Century, the Yuzpe formula or later equivalents have been used by hundreds of thousands of American women to prevent pregnancy.⁴

Estimates (see below) place the efficacy of ECs in reducing the risk of pregnancy at approximately 75% and proponents of ECs claim that their use could reduce the rate of induced abortions by a million or more per year as well as reduce the number of unwanted live births. Data suggest that approximately half of all pregnancies are unintended.¹¹ (In 1999, there were 6.23 million pregnancies in the United States. By extrapolation, more than 3 million pregnancies each year are likely to be unintended, with 1.31 million resulting in induced abortions.) In particular, US teen pregnancy rates exceed those of other developing nations¹²; 78% of teen pregnancies are unintended and 48% result in abortions.¹³

In the mid-to-late 1990s, access to ECs in the United States expanded due to a number of factors.⁴ In November 1994, the Center for Reproductive Law & Policy filed a citizen petition asking the FDA to require manufacturers of certain combined oral contraceptive products to amend their labeling and patient package inserts to include information regarding the use of these products for postcoital emergency contraception; that is, to approve their previously off-label use. In 1996, the Reproductive Health Technologies Project and the Office of Population Research at Princeton University established a national toll-free telephone hotline providing consumer information about emergency contraception and referrals to health professionals, and subsequently launched a media campaign to increase awareness about EC.

Despite these pressures, FDA declined to exercise its discretion to require the relabeling of these products for emergency contraception, and denied the petition. However, the agency decided to present the issue of safety and effectiveness of combined oral contraceptives for postcoital emergency use to its Advisory Committee for Reproductive Health Drugs. The committee met on June 28, 1996, to consider this issue and unanimously concluded that four regimens were safe and effective for postcoital emergency contraception.¹⁰

In contrast to the situation in 2003, FDA agreed with the committee’s conclusion and in 1997 approved four regimens for postcoital emergency contraception. The agency, relying on experience in Europe and New Zealand in which only one serious adverse event could be reasonably traced to ECs use over a 12-year period, concluded that the therapy was safe. The approved regimens were all existing oral contraceptive products (Levlen/Tri-Levlen, Ovral/Lo Ovral, Nordette, and Triphasil). These products contained 30-50 µg of ethinyl estradiol and 300-500 µg of norgestrel or 125-150 µg of levonorgestrel, with the recommended dose that paralleled the Yuzpe regimen (2-4 tablets [100-120 µg of ethinyl estradiol, 500-600 µg of levonorgestrel] within 72 hours of unprotected coitus, followed by a second identical dose 12 hours later).

FDA concluded that this regimen decreased the likelihood of pregnancy by 74%.^14,15 The statistical meta-analysis indicated that if 100 women have unprotected coitus once during the second or third week of their menstrual cycle, about eight will become pregnant, but if the same women use emergency contraception after unprotected coitus, only two will become pregnant. The agency also found no evidence that the medication would have an adverse effect on an established pregnancy. Other oral contraceptive products have since received approval, including dedicated products (see below).

Despite the potential benefits, as noted earlier, ECs are infrequently prescribed by US physicians. The use of ECs is more widespread in other countries. For example, the United Kingdom approved ECs in 1984 and more than 4 million prescriptions were written within the next decade.¹⁵ Recent estimates suggest that as many as 5 million women in the United States could be expected to use ECs annually.⁴

EMERGENCY CONTRACEPTION THERAPY

The typical candidate for emergency contraception is a woman of child-bearing age who has had unprotected sexual intercourse or contraceptive failure. Unprotected sex could be the result of intentional non-use of a condom, non-consensual sexual contact, condom failure, slippage or incorrect insertion of an IUD or diaphragm, missed doses of birth control pills, or other contraceptive errors (see Table 1). The woman who is most likely to seek emergency contraception is less than 25 years old, has been sexually active for several years, has used contraceptive measures previously, has never been pregnant and is concerned that a primary contraceptive method, typically a condom, may have failed.⁴ ECs are effective for at least 72 hours after intercourse. There is a common misperception among the lay public and some health care professionals (see below) that ECs are only effective for 24 hours (hence, the term “morning after” pill) and this knowledge gap is a serious impediment to the more frequent–and correct–use of ECs. The two primary methods of providing emergency contraception in the United States are oral hormonal therapy and the use of an intrauterine device (IUD).⁴⁷

Table 1. Indications for Emergency Contraception

• A woman was sexually assaulted.
• No contraceptive measure was used during intercourse.
• A couple erred in practicing abstinence or coitus interruptus.
• A condom broke, slipped, or leaked.
• A diaphragm or cervical cap was inserted improperly, became dislodged, removed too early, or a tear was discovered.
• An IUD was totally or partially expelled.
• A woman missed two or more active oral contraceptive tablets in a row during the pill cycle, or missed one or more progestin-only tablet, or missed one or more combination tablet immediately before or after a hormone free interval.
• A woman was more than 2 weeks late for a contraceptive injection.
• A woman was exposed to a possible teratogen.

Adapted from: http://www.pharmacist.com/pdf/emer_contra.pdf

Hormonal Therapy
Use.—Hormonal ECs likely prevent pregnancy via a complex action at many sites along the hypothalamic/pituitary/ovarian axis. The ECs may affect ovulation, fertilization, transport, and/or implantation of the egg.^14-18 The main mechanisms of action appear to be inhibition of follicular development and ovulation, and, as a consequence, corpus luteum formation. The ECs may also alter the cervical mucus and inhibit sperm penetration. Emergency contraceptive tablets could have effects on the endometrium that, theoretically, could affect implantation. However, most evidence indicates that EC methods are ineffective in preventing implantation or disrupting further development of the implanted egg after 5-6 days.^17,18 In summary, ECs are more likely to work by inhibiting or delaying ovulation rather than affecting implantation or fetal development; many criticisms of the use of ECs are based on assumption that implantation of the fertilized egg is impaired (see below).

Hormonal ECs are comprised of a progestin (usually levonorgestrel) and frequently an estrogen (usually ethinyl estradiol), and typically are a high dose (ie, multiple tablets) of an existing oral contraceptive product (see table 2 and http://ec.princeton.edu/worldwide/default.asp). The original Yuzpe formula contained 1.0 mg of dl-norgestrel; most modern preparations contain 0.5 mg of levonorgestrel, the active "l" isomer. Ordinarily, the woman seeking to prevent conception takes a dose of 2-20 oral contraceptive tablets within 72 hours of coitus, with a second identical dose taken 12 hours later. Two products (Plan B and Preven) are stand-alone preparations that are specifically prescribed for emergency contraception.

Adapted from: http://ec.princeton.edu/questions/dose.html

*Total dose of estrogen or progestin taken at one time contained in the stated number of pills.
^†Number of pills taken at once within 120 hours of unprotected intercourse with an identical number taken 12 hours later, unless otherwise indicated.
^‡Progestin in this product is dl-norgestrel; dose is expressed as the active isomer, levonorgestrel.
^§May also be taken as a single dose consisting of twice as many tablets with no additional dose 12 hours later.
^║No longer marketed in the United States.

Studies suggest that the methods are more effective the sooner they are used after unprotected coitus, and there appears to be a linear inverse relationship between efficacy and the time from sexual intercourse to treatment.^15,19 That is, pregnancy rates rise as treatment is delayed. However, the Yuzpe regimen (and Plan B) retain their effectiveness if the treatment is extended to 120 hours after intercourse,^19,20 although they may be slightly less effective than if used within the 72-hour window.¹⁶ This suggests two important factors for pharmacists to consider when counseling women who are contemplating emergency contraception treatment: (1) a woman should begin therapy as soon as possible after the need is recognized; and (2) the 72-hour time frame for starting emergency contraception therapy should be considered a guideline only, and treatment should not be withheld from those who present after 72 hours. Women should also be notified that ECs protect only against previous sexual activity and will not protect them from getting pregnant if coitus is attempted again later in the same cycle. Similarly, women should be reminded that ECs will not protect them from sexually transmitted diseases.

Side Effects and Contraindications
The main side effects associated with these methods are those normally expected from oral contraceptives. Nausea and vomiting are the most common effects, occurring in approximately 50% of users¹⁵; some clinicians give an anti-emetic such as meclizine (25-50 mg), dimenhydrinate (50 mg), diphenhydramine (25-50 mg), trimethobenzamide (250 mg) or promethazine (25 mg) to women using ECs to reduce nausea and vomiting.^14,16 Other common side effects include breast tenderness, fatigue, abdominal pain, and headache.^14,16 Most preparations will not ordinarily significantly delay menses in women who are regular, although some disruption of the menstrual cycle may be noted. There appears to be no increased risk of birth defects among oral contraceptive users who do become pregnant.

While there are no recognized absolute contraindications to the use of ECs, pharmacists should be mindful that when hormones are used as ECs, they are taken in very high doses, albeit for a short time. The known contraindications for daily oral contraceptive use–blood clots, stroke, pulmonary embolism, heart disease, high blood pressure, diabetes with vessel involvement, estrogen-sensitive tumors, severe headaches, liver disease and known allergy to any of the components–should serve as a precaution.^14,16 Mild hypertension and diabetes are not considered to be contraindications since these conditions in an active pregnancy carry a higher risk of morbidity than one-time emergency contraceptive use.¹⁴

The hormonal components of ECs are metabolized by the cytochrome P450 (CYP) enzyme pathways. Ethinyl estradiol undergoes hepatic metabolism by CYP3A4. Drugs known to induce CYP3A4 (eg, phenytoin, primidone, barbiturates, carbamazepine, ethosuximide, topiramate, methosuximide, rifampin, and griseofulvin) and St. John’s Wort can lead to decreased plasma levels of ethinyl estradiol¹⁶ and potentially cause failure of emergency contraception. However, the high doses of hormones used in emergency contraception may make this less likely, and there is no conclusive information on dose adjustment.²¹ Other reports suggest that certain antibiotics may decrease ethinyl estradiol blood levels by interfering with enterohepatic elimination.

Dedicated Products
Plan B is one of two dedicated emergency contraception products. (The other is Preven consisting of four light-blue emergency contraceptive pills, each containing levonorgestrel 0.25 mg and ethinyl estradiol 0.05 mg, dosed 2 tablets stat and repeated 12 hours later. Preven is available as an Emergency Contraceptive Kit consisting of a patient information booklet, a urine pregnancy test, and four emergency contraceptive tablets). Plan B, the product that was proposed for OTC status, consists of two tablets of 0.75 mg levonorgestrel. Plan B differs from the Yuzpe regimen in several ways. First, it contains only a progestin. One tablet is taken within 72 hours of unprotected sex, and the second 12 hours later. However, a single dose of 1.5 mg (2 tablets) may be as effective as two consecutive 0.75 mg doses.¹⁹

The risk of pregnancy from unprotected sex when Plan B is used correctly is estimated to be approximately 1.5%, suggesting that it is at least as effective as the Yuzpe combination.²² In addition, Plan B may be better tolerated than the estrogen/progestin combination. In a multicenter, randomized, blind clinical trial of more than 4000 women, nausea (15%) and vomiting (1%) were less frequent with the progestin-only Plan B regimen.^19,23 Pregnancy was prevented even if the single-dose levonorgestrel regimen was used 5 days after coitus. Research suggests that replacement of the Yuzpe regimen with levonorgestrel could improve the acceptability of hormonal emergency contraception and should therefore be considered in family planning programs.

Other Therapies
Other products that have been used for emergency contraception include the androgen, danazol, and the progesterone antagonist, mifepristone (RU-486). Mifepristone, which differs from the estrogen/progestin products, is an antagonist of progesterone and glucocorticoid receptors.²⁴ As a result, it exerts contraceptive activity by inhibiting the effects of progestins and disrupts follicular maturation. Some studies indicate that it may be more effective and produce less vomiting than the progestin/estrogen combinations;¹⁹ however, its acceptance for emergency contraception is even more controversial due to its other clinical use in inducing abortions.

Copper-releasing IUDs are also effective for emergency contraception reportedly preventing more than 99% of expected pregnancies when used within 5 days of coitus, and potentially maintaining activity when inserted 7 days after sexual contact.¹⁷

PRACTITIONER AND CONSUMER KNOWLEDGE

Consumers
Emergency contraceptive measures have been used for more than three decades to prevent pregnancy, yet they are infrequently prescribed and used. One major obstacle preventing more frequent use of ECs is a poor awareness of their efficacy and availability by both consumers and health care professionals.

One recent survey reported that only 1% of women aged 18-44 have ever used emergency contraceptive methods, a proportion that did not change between 1994 and 1997. Most women surveyed did not know that these methods are available in the United States, and only 11% knew enough about them to use them correctly.³

Another survey conducted in California in 2004 by the Kaiser Family Foundation confirmed the need for patient education about emergency contraception noting that only 2% of adult women have ever taken ECs.²⁵ Other major findings of the survey included:

• Only slightly more than half of women (57%) knew that emergency contraception is available in the United States;
• Half of adults who have heard of emergency contraception believe that the only option is RU-486;
• Only 1 in 10 women heard about emergency contraception from a health care professional (TV was the major source) and this was not increased significantly (13%) in women who had a gynecological visit within the past year; and,
• 53% of women said they would be more likely to use ECs if they were available directly from a pharmacist.

Another survey in California of 371 postpartum women from an inner city hospital revealed that 3% had used emergency contraception, 36% had heard of it but only 7% knew the correct timing for use. Two-thirds of the population indicated a willingness to use emergency contraception in the future. Factors positively associated with knowledge included being a teenager or more than 30 years old, annual income over $20,000, prior use of condoms, and history of an elective abortion.²⁶ Among those who had heard of emergency contraception, only 44% thought it was safe. One-third did not know that ECs are available in the United States or that a prescription is required. Most knew that ECs would not prevent sexually transmitted infections (81%). Significantly, only 16% of those familiar with ECs knew both the correct timing for use and that a prescription is required to obtain them. Most women were equally likely to have learned of ECs through a health care provider (31%), peers (31%), or the media (30%). Eighteen percent reported objections to the use of ECs due to moral or religious beliefs.

Poor consumer knowledge is not only a West coast phenomenon. A survey conducted in Boston also found that fewer than half of women knew the correct timing of ECs, and 44% knew that they were available only by prescription.²⁷ Only one-fourth of the women had discussed emergency contraception therapy with a health care professional. The cited studies have also consistently found that the knowledge gap is larger in Latina and African-American communities.

Pharmacists
Since consumers are in need of information about ECs, there is an obvious role for pharmacists to supply appropriate care, especially if the products attain greater status. Unfortunately, data suggest that pharmacists are not adequately prepared to provide this service.

A telephone survey of pharmacists conducted by Planned Parenthood in New York City in 1998 demonstrated some deficiencies in pharmacists’ knowledge.²⁸ Thirty-eight percent of pharmacists had no awareness of emergency contraception methods. This level of awareness was far below that of other health practitioners, including nurse practitioners and physician’s assistants. Moreover, almost two-thirds of pharmacists provided poor or erroneous information about this subject. For example, few pharmacists correctly identified the time frame during which emergency contraception could be achieved by high-dose oral contraception tablets, with many answering that drugs must be administered within 24 hours. Eleven percent of pharmacists surveyed reported that ECs were either unavailable or illegal in the United States.

In a Pennsylvania study, a “mystery shopper” contacted pharmacists seeking information about ECs.²⁹ When asked if there was something she could ask her doctor for, 28% of pharmacists replied “I don’t know.” Only one-third of the pharmacists knew the correct time frame (72 hrs) for using ECs. Thirteen percent claimed not to know about their side effects. Moreover, only about a third of pharmacists said they could fill a prescription for an emergency contraceptive on that day; this is significant since a delay reduces the efficacy of such therapy. Of those who could not fill a prescription, almost 80% said it was not in stock; the rest replied it was against store policy, cited moral or ethical reasons, or gave no reason. In South Dakota, only 5% of surveyed pharmacists could correctly answer three questions on ECs dealing with their mechanisms and side effects.³⁰ In addition, only 25% of pharmacists felt comfortable counseling women on emergency contraceptive methods; another 42% responded that their comfort level depended on the situation.

Reports of problems with obtaining ECs from pharmacies in a timely manner can also be found in other studies. In New Mexico, two research assistants posing as women needing emergency contraception, visited 89 pharmacies in Albuquerque presenting a prescription for either Plan B or Preven.³¹ The assistants recorded the availability of the products in the pharmacies. The drugs were in stock at only 11% of the visits. Of the pharmacists that did not stock the products, 53% reported they could obtain them within 24 hours. The most common reason cited by pharmacy providers for not stocking the products was the lack of prescriptions received for them (65%). Overall, timely availability of emergency contraception products, either in stock or within 24 hours, was greater on weekdays than on weekends; the research assistant could obtain emergency contraception within 24 hours 46% of the time if she came on a weekday compared with only 12% of the time if she came on a weekend. Corporate policy against stocking emergency contraception was cited by only 6% of pharmacy providers. Few pharmacy providers expressed ethical concerns when visited by the research assistants, however, the research assistants suspected that sometimes pharmacists reported an inability to order emergency contraception when, in fact, they were simply reluctant to do so, perhaps for moral reasons that they were unwilling to discuss. The authors concluded that a lack of availability at the pharmacy constitutes a major barrier to emergency contraception access.

Similarly, a review of pharmacies by the New York City Council Investigation Division in 2002 revealed that 55% of pharmacies in New York City carried at least one brand of ECs and an additional 16% would be able to order it.³² However, almost 30% of pharmacies indicated that they neither carried nor would order an EC pill. The percentage of pharmacies in the “not carried” group was somewhat lower among chains than independents (22% vs. 29%). The Council advocated a possible legal response to the problem of accessibility, recommending legislation requiring pharmacies that do not stock ECs to post signage indicating such in or near the prescription counter in order to avoid potential embarrassing situations for women seeking these products.

EXPANDING ECS AVAILABILITY

As noted earlier, emergency contraception has been available as an off-label use of oral contraceptives since at least the mid-1960s and some oral contraceptive products were approved for this use in 1996. Traditionally, these products could be obtained in clinics offering reproductive health information (eg, family planning clinics) and in many hospitals which provide services to rape victims. Certain states (eg, New York, Alabama) require state-funded public health clinics to provide ECs.

More recent developments have expanded the scope of access to ECs and the pharmacist’s role in providing these emergency measures. As of early 2006, at least eighteen states (AK, CA, DE, DC, KS, ME, MA, MI, MO, NH, NM, RI, SD, TN, VT, WA, WI) permit sales of ECs without a physician’s prescription, and three (IL, MD, NJ) have proposed legislation.⁴⁸ A typical model involves a collaborative practice arrangement between a pharmacy and a physician.

The prototype program is found in the State of Washington, which first permitted collaborative practice agreements in 1979.³³ In 1998, Washington enacted a pilot program to provide ECs to women through pharmacies. In the Washington program, the physician and pharmacist submit a completed, signed practice protocol to the Board of Pharmacy, which reviews the protocol and may grant prescriptive authority, limited to the therapy and procedures described in the protocol, for up to 2 years. (A sample protocol can be found at: http://www.pharmcare.org/cem/3-1-2-2.asp). Pharmacists receive training on issues such as therapeutic and dispensing information, informed consent for EC use, how to ensure privacy in a pharmacy setting, client counseling, and referral for ongoing contraceptive care. Generally, the patient needs to answer two questions in order to receive ECs³⁴: whether she has had unprotected coitus in the past 120 hours (verifying the need for ECs) and whether she has had a normal menstrual period within the past 4 weeks (ensuring that she is not already pregnant). All pharmacists submitting a protocol for prescriptive authority under the project must have attended a training session. In addition, they are provided with a sample informed consent form, and a list of reproductive health organizations for ongoing contraceptive care, sexually transmitted disease diagnosis and treatment, and sexual assault counseling and treatment. Charges for the prescription and consultative service vary by pharmacy, but averaged $30 to $40 in 2001.

The project also implemented a media campaign to let women know they can receive ECs directly from pharmacists and provides a list of names of participating pharmacies on an emergency contraceptive hotline and a website.³³ The initiative received an extremely positive response. As of 2001, more than 1500 pharmacists and pharmacy students had been trained and certified to provide emergency contraception. At any given time, the service is provided in approximately 180 pharmacies in Washington, including multiple locations of nine retail or grocery pharmacy chains.³⁵ More than 50,000 women in Washington have obtained ECs through pharmacies since the program was initiated with pharmacists dispensing approximately 1200 prescriptions per month; the abortion rate has reportedly dropped by 30% since the program’s inception.34 In the Washington program, women were able to receive ECs directly from a pharmacist in instances where they might not have otherwise obtained it easily. Surveys of these women indicated that:

• 15% chose a pharmacy because they did not have a regular health care provider;
• 48% obtained ECs after 6:00 p.m. on a weeknight or on the weekend; and,
• 55% would have waited to see if they were pregnant (35%) or did not know what they would have done (20%) if they could not have gone directly to a pharmacist for ECs.

California also has a collaborative practice agreement permitting women to obtain ECs from pharmacies.³⁶ Prior to initiating emergency contraception, pharmacists must complete an EC training program, which includes but is not limited to: how to handle sensitive communications, quality assurance, referral to additional services, and documentation. Pharmacists must provide each recipient of ECs with a standardized “Fact Sheet” that has been approved by the California State Board of Pharmacy. The fact sheet provides consumer information on the use, safety, and effectiveness of ECs and provides a phone number for family planning and pregnancy information for women who do not have or cannot afford a physician.

New Mexico also approved emergency contraceptive prescribing by pharmacists in 2003.³⁷ The New Mexico plan differs from the other plans in that a single statewide protocol was approved for all pharmacists who receive emergency contraceptive training, rather than relying on individual pharmacist/physician agreements. The training is provided by qualified organizations including the Department of Health, Planned Parenthood, or an ACPE-approved body. The education must cover specified topics including current standards of drug therapy, counseling and referral, and pharmacists must complete 2 hours of live continuing education on emergency contraception drug therapy yearly.

New York was on track to become another state to offer OTC ECs. On June 22, 2005 the state Senate followed the lead of the Assembly and passed a bill, “The Unintended Pregnancy Prevention Act”, which would allow females to purchase emergency contraception at any pharmacy without need for prescription or parental consent. The bill was vetoed by the governor but was reintroduced in February 2006. Massachusetts Governor Romney vetoed an expanded emergency contraception bill which would have permitted pharmacists to provide the product without a prescription and require emergency room physicians to offer ECs to rape victims, although the legislature overrode the veto.

Advocates for expanding access to ECs OTC via pharmacies cite a number of potential benefits.³⁸ In addition to reducing the number of unwanted pregnancies and abortions, ECs could reduce health care costs (potential savings to New York state is estimated at $400 million/year), provide women with more timely access to the health care system and professional consultation (eg, women in California accessing ECs through a pharmacist reportedly had a better understanding of the need to take ECs sooner than women receiving a prescription for them). Data also suggest that there is no increase in risky sexual behavior or STDs in emergency contraception users.³⁹

Interestingly, the results of a survey in Minnesota suggest that pharmacists are less enthusiastic about the prospect of OTC ECs.⁴⁰ Among three possible means to increase access to the products–prescription by mid-level medical practitioners, prescription by pharmacists via collaborative practice arrangements, or OTC availability–the OTC option was the least favored (84% of pharmacists opposed this approach). Approximately 40% of pharmacists did not support collaborative practice/“behind-the-counter” strategies. Among the most frequently cited reasons for reluctance about collaborative practice drug therapy agreements were concerns about liability or safety, inadequacy of pharmacist education, and interference with the doctor-patient relationship.

EC advocates have also used other means to increase access to ECs. In North Carolina, a collaborative effort among several family planning agencies including Planned Parenthood developed a project called DIAL EC.⁴¹ A woman who wants ECs calls a statewide toll free number and is screened over the phone by a trained emergency contraception specialist. Following the call, the specialist prints a medical record sheet that includes all information provided by and to the caller. Within usually 1 hour, the specialist contacts a Planned Parenthood clinician, who reviews the information. If the clinician determines that the caller met the single criterion for receiving ECs (absence of evidence of current pregnancy) the clinician approves the prescription, and the specialist faxes a computer-printed prescription form to the chosen pharmacy or Planned Parenthood health center. In the first year and a half of the program, almost 10,000 prescriptions were provided; about 40% of the callers were teenagers (19 or younger).

EXPERIENCE IN OTHER COUNTRIES

ECs are available without prescription in at least 25 countries worldwide, in some cases behind the counter and in others truly over the counter.⁴² ECs became available without a prescription in Canada in 2000 and a recent study evaluated the impact of the policy change on their use in that country.⁴³ Provision of products by pharmacists increased the number of emergency contraceptive prescriptions, especially for Plan B. The total number of prescriptions more than doubled in 2002 compared with pre-OTC years with the highest frequency in women 20-24 years of age. Only 2% of women received ECs three or more times a year. When providing ECs, pharmacists used the opportunity to give referrals on birth control and STD screening.

Another study reported on the experiences of women in four European countries where ECs are available.⁴² The study found substantial differences in knowledge about their proper use. Women in Sweden were far more knowledgeable about the correct therapeutic window for ECs than their counterparts in France, Portugal, or Norway. Overwhelmingly, participants believed that nonprescription delivery increases accessibility to ECs by eliminating time and cost barriers. Their views on the role of the pharmacist also differed.⁴² Women in France felt that pharmacists play a "fundamental" role in the OTC provision of ECs and as such, they should ask basic questions and provide counseling on administration, efficacy, and side effects. On the other hand, women in Norway preferred not to discuss ECs with pharmacists. Some women preferred to rely on the package insert for information rather than discuss this with the pharmacist. Their interactions with pharmacists were often positive with women mentioning their trust in pharmacists, although some women complained that pharmacists were judgmental, moralistic, or uncooperative. Many women also felt that a pharmacy did not afford sufficient privacy to discuss such a personal matter. Some women opted to send a male partner to purchase the product in the pharmacy. Pharmacists in the United States who wish to counsel patients receiving ECs need to be certain that adequate privacy is available.

PERSONAL BELIEFS AND PROFESSIONAL OBLIGATIONS

Superimposed on the highly charged debate over the status of ECs is the equally divisive issue of pharmacists’personal beliefs and their effects on practice. Pharmacists in several states have refused to fill prescriptions for ECs (and, in some cases, oral contraceptives), citing that to do so is contrary to their moral or religious beliefs. Some pharmacists have gone so far as to refuse to return prescriptions for ECs to the patient.

Practitioner organizations have long recognized that a pharmacist’s personal beliefs may be at odds with the needs of the patient. The APhA and several state organizations have adopted a “conscience clause” that recognizes a pharmacist’s right to refuse a valid prescription while also acknowledging a patient’s right to therapy. (APhA recognizes the individual pharmacist's right to exercise conscientious refusal and supports the establishment of systems to ensure patient access to legally prescribed therapy without compromising the pharmacist's right of conscientious refusal. [It should also be noted that the APhA supports OTC status for ECs.]) Pharmacists relying on a conscience clause may be afforded some protection when refusing to dispense ECs, however the pharmacist may be required to refer the patient to another pharmacy.

Employers have offered mixed responses to the issue of dispensing of ECs. Wal-Mart does offer oral contraceptive products but its stores do not stock the ECs for "business reasons." Wal-Mart, Walgreens, and other chains do not require their pharmacists to fill prescriptions that violate personal religious or moral beliefs. In such cases, however, pharmacists still must follow through with the patient, either by referral to another store pharmacist to fill the prescription or by referring the patient to a nearby pharmacy that can fill it. Pharmacists who may object to dispensing ECs on moral grounds need to be aware of their employer’s policies. It should be noted that Eckerd disciplined a pharmacist who refused to fill a prescription for an emergency contraceptive for a rape victim.

The controversy has prompted conflicting legislative responses in several states. The governor of Illinois issued an emergency rule on April 1, 2005 requiring pharmacists to dispense contraceptives to a patient “without delay.” The order was apparently in response to a complaint filed with the Illinois Department of Professional Regulation alleging that a pharmacist refused to fill a prescription for an emergency contraceptive. The order was to remain in effect for 150 days while the Governor sought a permanent rule. In August, 2005, a legislative rules committee voted to make the order permanent. Several pharmacists have sued the governor over the rule. Three other states (Missouri, New Jersey and West Virginia) have introduced similar legislation.

On the other hand, four states (Arkansas, Georgia, Mississippi, and South Dakota) passed legislation that permits a pharmacist to refuse to dispense ECs and similar legislation is under consideration in at least 13 other states.⁴⁴ Regulations of the California Board of Pharmacy permit pharmacists to refuse to dispense ECs if they are exercising their conscience, but they must refer the patient to another provider of ECs.³⁶

Pharmacists need to be aware of ongoing legislative and administrative changes and rulings in their state of practice. In Wisconsin, the Pharmacy Examining Board sanctioned a pharmacist who refused to fill a contraceptive prescription and refused to transfer the prescription to another pharmacy. Pharmacists also need to be aware that if they refuse to fill a prescription for ECs and do not offer to find an alternative source, they are potentially liable for damages due to wrongful conception.⁴⁵ Moreover, at a recent meeting, the AMA House of Delegates voted in favor of a resolution calling for revised state laws that would permit physicians to dispense medications when there is no willing pharmacist within a 30-mile radius.

At the present time, there is no Federal response to this controversy. However, a bill entitled the “Access to Legal Pharmaceuticals Act," was introduced in Congress in 2005.⁴⁶ The law, if passed, would establish certain duties for pharmacies whose pharmacists refuse to fill a valid prescription on the basis of “personal beliefs” or other reasons. Under the provisions of the act, if a pharmacist refuses to fill a valid prescription, the pharmacy must ensure that it is filled by another pharmacist “without delay.” If the product is not in stock, the pharmacy must order the product immediately unless the pharmacy does not keep any product for that “condition” in stock. The bill does not specifically apply to ECs, but supporters indicated that this was behind the introduction of the bill, which came one day after pharmacists sued the Illinois governor. Failure to comply with the act could subject the pharmacy to a penalty of $5000/day and the aggrieved patient could bring a suit against the pharmacy.⁴⁶ Pharmacists need to track the progress of this legislation.

SUMMARY AND CONCLUSIONS

The future status of emergency contraception remains obscure, but the potential broadening of its therapeutic use and the relative lack of sophistication of consumers marks this as an area ripe for pharmacist intervention and application of pharmacy care. In particular, the extended hours of a pharmacy are an attraction for a woman seeking help following contraceptive failure or non-consensual sex. The interested pharmacist needs to be ready to correct misconceptions about emergency contraception use. The pharmacist also needs to stay abreast of legislative activity in his or her state which can affect access to ECs. Collaborative practice agreements, if available in the pharmacist’s state, may be an ideal solution to many of the pitfalls inherent in providing emergency contraception services.

In August, 2006, the FDA approved over-the-counter sales of Plan B to women 18 and older. Sales will be restricted to health clinics and pharmacies and proof of age will be required for OTC purchase. Anyone under 18 will still need a prescription; men may buy the product for their partner. The FDA will rely on the manufacturer to enforce the rules. New packaging is expected to be available by the end of the year.