Release Date: November 1, 2009
Emergency contraception (EC), sometimes referred to as the “morning-after pill,” is a safe and effective method of preventing pregnancy after intercourse. Levonorgestrel, a hormone found in many birth control pills, is the active ingredient in most emergency contraceptive products used in the U.S. The Food and Drug Administration (FDA) approved the first levonorgestrel-only emergency contraceptive, Plan B (levonorgestrel 0.75 mg oral tablets), in 1999 for prescription use. In 2006, the FDA widened access to EC by approving over-the-counter (OTC) sale to consumers 18 years of age or older.1,2 At the time, Plan B was the first product to be approved in the U.S. with dual status (a single product approved for OTC sale or prescription only access to consumers based on age). More recently, the FDA further increased access to EC by reducing the age for OTC access to anyone 17 years and older, continuing access to girls under age 17 by prescription only. Two new EC products recently became available in the U.S. In July 2009, the FDA approved a one-dose emergency contraceptive, Plan B One-Step (levonorgestrel 1.5 mg tablet) for OTC sale to consumers age 17 and older and by prescription to girls under age 17.3 Next Choice (levonorgestrel 0.75 mg tablets) was also approved in 2009 and is a generic formulation of the original Plan B. Although three lev- onorgestrel EC products may be currently available—Plan B, Plan B One- Step, and Next Choice— the distribution of Plan B will cease as Plan B One- Step launches into the marketplace. All EC products are approved to prevent pregnancy when a contraceptive method has failed or was not used during intercourse.
Unintended pregnancies are associated with many personal and public health related consequences. In the U.S., approximately half of all pregnancies occurring each year are unintended and as many as half of the unintended pregnancies are terminated by elective abortion.4 When taken within 72 hours of unprotected intercourse, levonorgestrel-only EC reduces the risk of pregnancy by as much as 89%.2,3 Studies to date have not been able to show that having EC available without a prescription has reduced the rates of unintended pregnancy in the U.S. as was originally anticipated.5,6 The reason for the lower-than-anticipated impact on unintended pregnancy rates may be related to the persistence of barriers to EC access, including misunderstanding by consumers about when to use EC.
Pharmacists and other health care professionals can help to reduce barriers that limit the use of EC by improving patient access and being available to answer questions about the use of EC. Pharmacists, as the “most accessible” health care provider, are in a unique position and play a crucial role in providing timely access to and information about EC to consumers. OTC availability in the pharmacy to consumers age 17 and over improves access to EC by reducing the delays that were associated with obtaining a prescription in the limited time frame needed for efficacy of the product.
Background and Clinical History of EC
Levonorgestrel has been extensively studied as an emergency contraceptive worldwide since the 1970s. After almost 40 years of EC use, the high degree of efficacy in preventing pregnancy (up to 89% reduction) and the low rate of adverse effects have been well documented.5,7-10 A 2009 update to a Cochrane review of EC interventions included more than 88 studies and concluded that levonorgestrel is both safe and effective in preventing pregnancy after intercourse.7
The first products approved by the FDA for EC were Preven (ethinyl estradiol 0.25 mg/levonorgestrel 0.5 mg tablets) in 1998 and Plan B (levonorgestrel 0.75 mg tablets) one year later. Both products were approved for use by prescription and to be taken in a two-dose regimen initiated within 72 hours of unprotected intercourse. Despite FDA approval, an increase in the utilization of EC by women was hampered by a number of barriers (TABLE 1).
To improve access, a request was made to move Plan B to OTC status. Plan B appeared to satisfy FDA requirements for conversion from prescription to OTC status, which include a minimum of two years of prescription use with a high degree of safety and studies establishing that consumers can interpret labeled instructions correctly. Although an FDA Advisory Committee voted in 2003 in support of the request for nonprescription status, the FDA approved a change for Plan B in 2006 to “dual status” instead.11 Under dual status, Plan B was made available without prescription to consumers at or above a certain age (originally 18 years but now 17) and remained available by prescription to younger women. Packaging for the product was approved to meet the requirements for both prescription and nonprescription products. Since then, Next Choice and Plan B One- Step have also been approved for dual status distribution in pharmacies and clinics (TABLE 2).
Before the approval of dedicated products for EC, commercially available oral contraceptives containing ethinyl estradiol with either norgestrel or levonorgestrel (often referred to as the “Yuzpe regimen”) were used for EC. More recent studies have shown these combinations to be less effective (ranging from 49% to 75%) than levonorgestrel-only regimens.7,9 Furthermore, the Yuzpe regimen has more side effects, especially nausea and vomiting, which often require the addition of an antiemetic medication. Production of Preven, a commercially available equivalent to the Yuzpe regimen, was stopped in 2004. Because of its lower efficacy and increased frequency of side effects, use of the Yuzpe type combination regimens has declined but remains an option when levonorgestrel is not available.
Several other methods have been evaluated for EC, including combinations of estrogen with norethindrone, combining levonorgestrel with the COX-2 inhibitor meloxicam, Yuzpe or levonorgestrel regimens using different time intervals or doses, insertion of a copper IUD, an investigational progesterone modulator ulipristal (available as ellaOne in Europe) and low doses of mifepristone.7,12
Combination regimens using norethindrone appear to be less effective than levonorgestrel regimens.13 Regimens using mifepristone in doses ranging from 10 mg to 50 mg appear to be effective; however, these doses are not available in the U.S.7 Insertion of a copper IUD up to 10 days after intercourse appears to have a low failure rate (0.01% to 0.02%), but IUD insertion requires a clinician visit and may not be suitable for some women.8The investigational progesterone receptor modulator recently approved in Europe, ulipristal, may be as effective with similar side effects as levonorgestrel.14 Studies evaluating the use of levonorgestrel as a single dose (1.5 mg) did not find a significant difference in efficacy compared with 0.75 mg two-dose regimens.7 The newly approved Plan B One-Step (1.5 mg) is a single-dose regimen that may be more convenient and easier to use.
Mechanism of Action
Levonorgestrel, the only active ingredient in Plan B, Plan B One-Step, and Next Choice, is a synthetic progestin also available in hormonal contraceptives. The mechanisms by which levonorgestrel prevent pregnancy are likely similar to those of other hormonal contraceptives. All currently available hormonal methods of contraception have been shown to act by one or more of the following mechanisms: altering the endometrial lining, altering cervical mucus, interfering with fertilization or transport of an egg, or preventing implantation. There is good evidence that levonorgestrel prevents or delays ovulation as its primary mechanism of action; however, it is possible that additional mechanisms may be involved.15-20 There are no data supporting the view that levonorgestrel can impair the development of the embryo or prevent implantation.20
A number of publications have shed light on the mechanisms of action for levonorgestrel-only EC.15-20 Levonorgestrel-only EC has been shown to inhibit the preovulatory surge of luteinizing hormone (LH), thereby inhibiting follicular development and/or the release of the egg. A properly timed and sufficient surge of LH is required for the release of an ovum or ovulation. Ovulation must take place for fertilization to be possible. Research has demonstrated that EC inhibits the midcycle surge of LH from the pituitary and, if taken at least two days before ovulation, ovulation is delayed or prevented. Ovulation may occur if the administration of levonorgestrel is delayed until ovulation is imminent.20
If levonorgestrel is taken later in the cycle, the effect on the LH surge may be equal to that of a placebo and pregnancy may occur. These time-sensitive events may explain why taking EC as soon as possible after unprotected intercourse is critical for maximizing its effectiveness.
Studies of levonorgestrel and its potential effects on endometrial function have not shown changes that would prevent the implantation of a fertilized ovum.17 Women who have used Plan B to prevent a pregnancy early in their menstrual cycle remain at risk for pregnancy later in the same cycle if contraception is not resumed or fails again. This indicates that the endometrium is still intact and capable of implanting a fertilized ovum.19
It has been speculated that levonorgestrel may alter the movement of a fertilized egg, which would be expected to increase the risk of an ectopic pregnancy. Studies have not supported this assumption. The risk of an ectopic pregnancy after levonorgestrel use may be slightly lower than national ectopic pregnancy rates.21 The Cochrane review found only five cases of ectopic pregnancy reported in more than 45,000 uses of EC and concluded that ectopic pregnancy was not associated with any specific type of EC or a likely consequence from using EC.7
The International Consortium for Emergency Contraception (ICEC), in a 2008 Policy Statement on mechanism of action, reported that levonorgestrel-only EC pills inhibit, delay, or interfere with ovulation and may possibly prevent the sperm and egg from meeting by affecting cervical mucus or the ability of sperm to bind to the egg.22 The ICEC also stated that there are no direct clinical data to support mechanisms other than the inhibition, delay, or alteration of ovulation.22 Levonorgestrel only EC does not cause abortion or interfere with an established pregnancy and, if inadvertently taken by a woman who is pregnant, the pregnancy will not be harmed. The ICEC noted that EC might actually prevent abortions by reducing unplanned pregnancies.22
Indications and Contraindications
EC is the use of a contraceptive method to prevent pregnancy after intercourse. Levonorgestrel products are approved for use within 72 hours after intercourse. There is evidence that taking EC as soon as possible may maximize its effectiveness and that use up to 120 hours may be effective. Consumers who are unsure of when to use EC or whether EC is needed may ask the pharmacist about its appropriateness. Circumstances where EC is indicated are listed in TABLE 3.
Pharmacists can reassure women that EC is safe and effective and can be used when needed to prevent pregnancy after unprotected intercourse. A myth that may present a barrier to access to EC is belief that it can only be used once in a lifetime, once per year, or only once during a menstrual cycle. Pharmacists should not restrict the purchase of EC based on prior use or out of concern that repeated use of EC is not safe.12
There is no evidence that repeat use of EC poses increased risk to patients.23 Because EC is less effective as birth control than ongoing methods of contraception (such as condoms or birth control pills), it is recommended only as a backup method and not as a substitute for ongoing, more effective methods. EC can be purchased in advance and kept at home in case the need arises, as this avoids the delay of going to the pharmacy.
There are few contraindications to the use of EC. The WHO Medical Criteria for Contraceptive Use 2005 stated that there are “no conditions where the risks of EC outweigh the benefits.”23 Product labeling lists the contraindications as an established pregnancy or known allergy to the ingredients in EC. There are no studies of EC use by women with migraine headaches, smokers over age 35, or other precautions applicable to the regular use of combination oral contraceptives. However, these conditions should not limit the use of EC.
Timing of the EC Dose
Levonorgestrel is thought to be more effective the sooner it is taken, therefore pharmacists should encourage women take EC as soon as possible after unprotected intercourse.24 The FDA-approved dosing recommends initiating therapy within 72 hours of unprotected intercourse. For levonorgestrel 0.75 mg tablets, a second dose is required 12 hours after the initial dose.5,8 Although there is evidence of efficacy as late as 120 hours after intercourse, women should be encouraged to seek treatment as soon as possible, preferably within the 72-hour timeframe.21,25-28 Since the time required from intercourse or ovulation to implantation is approximately 6 to 7 days, use of hormonal EC beyond 120 hours is not likely to be effective.13
Studies evaluating single-dose levonorgestrel (1.5 mg) have concluded that the single dose is not less effective than the two-dose regimen.21,28,29 Plan B One-Step has been approved for use as a single 1.5 mg dose for EC. The single dose formula may improve compliance by simplifying the EC regimen and will replace the Plan B 0.75 mg levonorgestrel preparation.
Concerns have been raised that providing EC to women in advance of need to keep on hand “just in case” of a contraceptive failure might lead to an increase in unprotected intercourse or encourage women to discontinue the use of their usual method of contraception. However, studies evaluating the outcomes of providing EC in advance of need have not found that women engage in more unprotected intercourse or abandon their usual method.6,7,30,31 These studies have reported that women are more likely to use EC after unprotected intercourse if it is provided in advance of need. Based upon the findings of the studies, providing EC in advance of need can be recommended to improve timely access to the product.
Dual Status: EC in the Pharmacy
The dual status of levonorgestrel-only EC necessitates that products be kept within the pharmacy or behind the counter. In the pharmacy a consumer has access to the pharmacist, a knowledgeable health care provider, to answer questions regarding the use of EC. EC products must only be sold in pharmacies or licensed clinics and are not available at other types of retail establishments. Keeping EC hidden behind the pharmacy counter may pose a barrier to some consumers because they may expect to find the products on pharmacy shelves or within sight behind the pharmacy counter. Pharmacists are encouraged to provide shelf tags or display EC products in a conspicuous location to facilitate access by consumers who may be reluctant to ask if they do not easily see the product in the pharmacy.
“CARE” Program: Convenient Access, Responsible Education
The terms of the FDA approval of Plan B for OTC access by consumers age 17 and older included requirements restricting the distribution of EC, meeting labeling requirements for both OTC and prescription use, and for the manufacturer to provide support and education about the use of the product to health care providers and consumers and to continue ongoing monitoring. The dual-labeled, behind-the-counter labeling launched with the approval of Plan B was the first time the FDA had approved the same product package for both OTC and prescription-only use. The approved packaging includes room for a prescription label (to be used when the product is dispensed by prescription), as well as the required Drug Facts box for OTC sales.
The CARE program specifies that EC is to be sold only from behind the counter in the pharmacy and not be available through nonpharmacy retail outlets. The FDA approval allows EC to be sold without a prescription to women or men 17 or over as long as they can show proof of age.2 Pharmacies must have a pharmacist on duty and available for consumer consultation in order to sell EC. Although the pharmacist must be available, it is not required that the pharmacist be the person who sells the product, or for the consumer to consult with the pharmacist. Any member of the pharmacy staff working behind the pharmacy counter may sell the products to eligible consumers as long as a pharmacist is on duty and available for consultation if requested by the purchaser.
Medical clinics may also sell EC if there is a licensed health care provider on the premises for consumer consultation at the time of sale. Retail outlets with pharmacies where the retail store has longer hours of business than the pharmacy are not able to sell EC when the pharmacy is closed.
There is no limit to the number of packages that may be sold to an eligible consumer. A consumer may purchase one or more packages of the product in a single transaction. In addition, there is no requirement that this OTC product must be used by the purchaser, and men may purchase it as long as they are at least 17 years of age. There is no requirement for purchasers of EC to sign a registry in the pharmacy or to provide photo identification for purchases.
Providing an environment where consumers can feel comfortable asking questions can greatly improve access to EC. Because all members of the pharmacy staff can provide EC to consumers, they should be aware of where it is stocked in the pharmacy, how consumers might ask for EC (e.g., the “morning-after pill”), and to respect the confidential nature of and need for privacy that may accompany the request. Pharmacy staff may offer but should not require consultation with the pharmacist to consumers asking about EC. Pharmacists may want to inform the entire staff that some consumers may present an “EC request card” (available online at www.PlanBOne-Step.com/how-to-get plan-b.asp or www.pharmacyaccess.org/ ECPromotionalOpps.htm) to avoid being overheard or because they are embarrassed to ask for EC at the pharmacy counter. Keeping EC in an area where consumers can easily see that the products are available in the pharmacy may also be helpful to consumers.
Although consultation with the pharmacist is not required for the OTC purchase of EC, many consumers will have questions for the pharmacist. Common questions about EC include its effectiveness, possible side effects, and how to know if the product was effective. When consumers ask the pharmacist about what to expect after taking EC, the pharmacist should include information about possible side effects, when to expect her next menstrual period, how to resume routine birth control methods (e.g., oral contraceptives), and when follow-up care is indicated (FAQ).
Most women who take EC will not experience side effects. The most commonly experienced side effects (nausea, dizziness, fatigue, headache, and breast tenderness) are mild (TABLE 4).3 The side effects resolve quickly after the regimen is completed and do not require treatment. Most women will have their next menses within one week of the originally expected date. However, other menstrual changes can occur, including spotting or changes to the menstrual flow volume during the next cycle. Pharmacists may reassure women that changes in menses, while common, are self-limiting. Women can be advised to obtain follow-up care if menses does not occur within seven days of the expected onset date or, for women with irregular menses, within three weeks after using EC.
Emergency contraceptives are less effective and are more costly than routine methods of contraception and thus should not be relied upon as an ongoing method of contraception. Contraceptive use is needed for future acts of intercourse if pregnancy is not desired. Women may resume the use of barrier or oral contraceptives right away after taking EC.
The pharmacist should be aware that using EC reduces the risk of pregnancy but does not provide protection from sexually transmitted infections (STIs). When requested, the pharmacist should be prepared to make referral to clinics or health care providers that provide testing and treatment for STIs. The use of condoms for protection from STIs should be encouraged, when applicable.
Pharmacists may advise consumers to keep EC products at home and available in case of a contraceptive failure. Keeping EC at home may be more convenient and better facilitate timely administration. Although EC is indicated for use after unprotected intercourse, consumers do not need to wait to purchase it until after they have experienced a contraceptive emergency.
Pharmacists who are available to consumers with questions about EC will have an opportunity to make referrals to community resources. Pharmacists are in an excellent position to serve as a resource for consumers and provide information about other methods of contraception that, when used before or during intercourse, are more effective than EC in preventing unintended pregnancies. Pharmacists should have available the name, address, and phone number for local referral services when the consumer’s contraceptive needs cannot be met in the pharmacy. This may include consumers lacking proof of age needed to purchase EC without a prescription, girls under the age of 17, consumers unable to pay for EC, or those who want to be examined for STIs. In the event that the pharmacy does not have EC in stock, the pharmacy staff should be prepared to provide consumers with contact information for a nearby pharmacy, after verifying the product is in stock, to avoid delays in starting therapy.
Pharmacists should be aware that some women seeking EC may be victims of sexual assault. If a woman discloses violence to the pharmacist, whether in the context of purchasing EC or first aid supplies such as bandages, offering access to a private phone and referral information for support services is indicated. Every pharmacist should also have national and local domestic and sexual violence service agency contact information readily available for consumers.
Pharmacy Access Programs
In states with pharmacy access programs, women seek- ing EC who are unable to show proof of age or who need a prescription for insurance purposes may be able to have a prescription for EC initiated by a pharmacist. Direct access from a pharmacist is currently permitted in nine states: Alaska, California, Hawaii, Maine, Massachusetts, New Mexico, New Hampshire, Vermont, and Washington.31 States permitting pharmacists to initiate prescriptions have specific requirements for pharmacist participation that may include training and/or collaborative protocol arrangements. In some states with pharmacy access it may be permitted to provide other prescription oral contraceptive products for use as EC under certain circumstances, such as when levonorgestrel-only products are unavailable (TABLE 5).
Pharmacy access programs are not available to males under age 17 seeking EC because only the person taking the medication can receive a prescription from the pharmacist. If EC products are out of stock or otherwise unavailable, there are alternative regimens such as oral contraceptive combinations that can be provided by the pharmacist under some access programs. These regimens have more side effects and may be less effective; however, if there are no other options (such as referral to a nearby pharmacy or clinic) they may serve as a backup option.8,25,32
Summary and Conclusions
Levonorgestrel-only EC is safe and effective for preventing unintended pregnancy after intercourse. The OTC sale to consumers at least 17 years of age is a major step toward improving access and removing barriers to the use of EC in the U.S. The time sensitive nature of EC means that ready access to women is an essential component of successful use. Pharmacists serve a critical role in expanding access to EC and are relied upon for up-to-date information regarding the safety and efficacy of EC. The role of the pharmacist includes: providing information and counseling to consumers seeking EC, maintaining an adequate supply of EC at all times, and in states where collaborative practice allows pharmacists to provide EC directly to those under age 17, becoming an EC direct provider. By understanding the appropriate use and distribution of EC products, pharmacists can significantly reduce barriers preventing consumers from using these products.
FAQ (Frequently Asked Questions) About Emergency Contraception A Reference for Pharmacists
Who can use levonorgestrel for emergency contraception (EC)?
Levonorgestrel can be used by women after unprotected intercourse to prevent pregnancy. Women who are already pregnant or who have experienced an allergic reaction to a levonorgestrel containing product in the past should not use this form of EC. Women with a history of migraine headaches, smokers over age 35, or other contraindications to the use of combination oral contraceptives may use EC. EC should not be used by women who are already pregnant because it is not effective. If EC is taken by a woman who is already pregnant or becomes pregnant after taking EC, it will not harm the fetus or disrupt the pregnancy. Women who are pregnant should consult a healthcare provider.
How effective is levonorgestrel for (EC)?
Plan B and Plan B One-Step have been shown to reduce the risk of pregnancy by up to 89% when taken within three days (72 hours) of a contraceptive failure or unprotected intercourse. If taken within the first 24 hours after unprotected sex, EC may be more effective. One way to explain the effectiveness of EC is: if 100 women had unprotected intercourse during week two or three of their menstrual cycle and no contraception was used, eight women would be expected to become pregnant. If all 100 women used EC, only one woman would be pregnant, thus there is an 89% reduction in the pregnancy rate (one instead of 8 women become pregnant). The effectiveness of EC for an individual may vary depending on the timing of intercourse, delay in taking EC, and the inherent fertility of the couple.
How long should I wait to take (EC)?
For best results, emergency contraception should be taken as soon as possible after unprotected intercourse or contraceptive failure. For Plan B and Next Choice the first tablet (0.75 mg levonorgestrel) should be taken within 72 hours of unprotected intercourse followed by a second tablet 12 hours later. For Plan B One-Step, a single tablet (1.5 mg levonorgestrel) should be taken within 72 hours of unprotected intercourse. Taking EC as soon as possible is highly recommended.
What if it has been more than 72 hours since intercourse?
Although EC has only been approved for use up to 72 hours after unprotected intercourse, the available research indicates that levonorgestrel retains significant activity in reducing the risk of pregnancy for at least 120 hours after unprotected intercourse.6 While EC is more effective when taken earlier, using it up to 120 hours after intercourse may still prevent pregnancy. (Please note that the use of levonorgestrel only EC products after 72 hours for EC has not been approved by the FDA.) Users of EC should be aware that the product may be less effective when taken later than 72 hours after unprotected intercourse.
What can I expect after using EC?
Most women do not experience side effects from taking EC. Some mild side effects that may occur include: nausea, headache, fatigue mild abdominal discomfort or a change in the timing/bleeding of the next menstrual cycle. These are self-limited and do not require treatment. Most women should expect to have their period within about one week of when it would be expected. If a woman does not menstruate within three weeks of using EC, she should consult her healthcare provider and/or use a home pregnancy test.
Is EC also known as the “abortion pill”?
No, the “abortion pill,” Mifiprex® or RU486, is completely different from emergency contraception. Levonorgestrel (the hormone in emergency contraception) does not cause an abortion and will not be effective if taken by a woman who is already pregnant. Similar to oral contraceptives, EC has been shown to work by preventing ovulation. Once implantation of an embryo begins, EC is not effective.
What if I have taken EC more than once?
Women may use EC once or more than once depending on their regular birth control method and their personal circumstances. Levonorgestrel for emergency contraception is safe and may be used when needed to prevent pregnancy. Emergency contraception is not as effective as other methods of contraception (such as condoms, oral contraceptives) and therefore the routine use of EC is not recommended. Emergency contraception is intended to be a backup method of contraception.