Emergency Contraception a practitioner s guide

Updated April 2014 Emergency Contraception a practitioner s guide TOPICS Emergency Contraception 1 EC Products 1 Mechanism of Action 2 Efficacy 2 BMI and EC 2 Side Effects of EC 3 Access to EC 4 Follow-Up Care 5 Table 1. OCPs as EC 6 Table 2. EC Decision Tree 7 Additional Resources 8 References 9 Emergency contraception (EC) is a safe and effective way to prevent pregnancy after unprotected intercourse, sexual assault, or contraceptive failure, such as a torn condom or missed birth control pills. Available methods of EC in the United States include emergency contraceptive pills (ECP) and the copper intrauterine device (Cu-IUD). FDA approved ECP products include progestin-only (levonorgestrel or LNG) pills and progesterone modulators (ulipristal acetate or UPA). 1-5 Currently available LNG pills include Plan B One-Step and the generic versions, Next Choice One Dose and My Way and the two-pill levonorgestrel tablets. The UPA ECP available in the United States is ella. Another approach to EC is the Yuzpe method, which consists of taking several combination oral contraceptive pills at once that contain the hormones estrogen and progestin. 6 The Cu-IUD as EC has several advantages: it is the most effective form of EC, it has few contraindications, and it can be used by nulliparous, adolescent, and overweight women. It can be continued as a regular form of birth control for up to 10 years (evidence suggests up to 12 years) and may be removed anytime for rapid return to fertility. 1-3 EC Products Product brand Method Dose Window of efficacy Restrictions Plan B One-Step Next Choice One Dose My Way Levonorgestrel tablets Levonorgestrel 1.5 mg (one pill).75 mg (two pills) 0-120 hours (Less effective between 72 and 120 hours 13 and may be less effective for women with BMI>30kg/m 2 ) 15,16 OTC for men and women of all ages OTC for people 17 years and older; prescription required for minors (disclaimer below) Not OTC; prescription required for patients 16 years and younger ella Ulipristal acetate 30 mg 0-120 hours Prescription only for all ages ParaGard Cu-IUD Hormone-free 0-120 hours Available for all ages but requires insertion by clinician Yuzpe method See Table 1. Marketed combination oral contraceptive pills that can be used as EC in the U.S. 0-72 hours Prescription only; see link for information by state: ec.princeton.edu/ countryquery.asp Notes: OTC=Over-the-counter; more information on Prescribing EC, Efficacy, and BMI and Its Effect on EC below. Disclaimer: While the generic brands Next Choice One Dose and My Way have received FDA-approval to go OTC, it is not clear when the product manufacturers will be able to bring the products to the shelf; for now they remain behind the pharmacy counter. 30

2 Emergency Contraception a practitioner s guide ECP are NOT abortifacients and will not disrupt an existing pregnancy, nor will they have adverse effects on the fetus. Mechanism of Action Oral methods of EC disrupt normal follicular development by delaying or inhibiting ovulation; they do not prevent fertilization or implantation. 8, 9, 11 Once fertilization has occurred, ECP are not effective. The Cu-IUD releases copper that induces an inflammatory response and can inhibit fertilization or 4, 14 implantation of a fertilized egg. Mifepristone is a powerful progesterone antagonist (RU-486) marketed under the brand name Mifeprex. This medication is used to terminate an established pregnancy by inducing a medication abortion. 10 EC should not be confused with mifepristone: ECP are not abortifacients and will not 7, 11 disrupt an existing pregnancy, nor will they have adverse effects on the fetus. Efficacy Although it is possible to quantify how many pregnancies occur in a given population after EC use, it is much harder to assess how many pregnancies were prevented. Therefore, absolute efficacy rates of EC are difficult to determine. Estimating efficacy rates for ECP are complex because specific formulations, doses in the regimen, time between unprotected intercourse, risk of conception, and further unprotected intercourse all impact pregnancy rates. 8 The Cu-IUD is the most effective (~99%) method of EC, without a change in efficacy when inserted up to five days after unprotected intercourse 14, but it is a lot less convenient to administer than ECP and some women may not desire this method. UPA ECP are more effective than LNG ECP and well-tolerated. 1,3,4 A meta-analysis by Glasier et al. 2010 found that women treated with UPA ECP had a significant reduction in their risk for pregnancy compared to those who received LNG pills. 12 Unlike LNG pills, which are effective only until the onset of the luteinizing hormone surge, UPA pills continue to be effective closer to ovulation. 7 ECP are somewhat effective for up to 120 hours, but LNG EC decreases in efficacy as time progresses and is most effective when taken within 72 hours. 13 Although the Yuzpe method is least effective, it may be a convenient option when dedicated ECP products are not available. See Table 1. BMI and Its Effect on EC A body mass index (BMI) greater than 30 kg/m 2 is not a contraindication to ECP; however, evidence from Glasier et al. 2011 indicates a decrease in efficacy with increasing BMI for LNG ECP. 15 UPA ECP (ella ) or the Cu-IUD would be the most effective EC methods for women with a BMI >30 kg/m 2 as its efficacy is not dependent on weight. 8,16 Trussell et al. 2013 recommends the Cu-IUD for obese women when clinically appropriate. 25 Research to date has not addressed the effect of weight on the efficacy of the Yuzpe method.

Emergency Contraception a practitioner s guide 3 Side Effects and Contraindications of EC Plan B One-Step / Other LNG EC pills ella Paragard T380A IUD Possible Side Effects Absolute Contraindications Menstrual changes Headache Abdominal pain Nausea Fatigue Dizziness Pregnancy (will not harm an existing pregnancy and medication will be ineffective) Menstrual changes Headache Abdominal pain Nausea Fatigue Dizziness Dysmenorrhea Pregnancy (will not harm an existing pregnancy and medication will be ineffective) Irregular bleeding Cramps Pain Heavier menses Pregnancy Mucopurulent cervicitis Active pelvic infection Postpartum/ postabortal endometritis (in past 3 months) Abnormalities of the uterus (distortion of uterine cavity incompatible with insertion) Copper allergy Wilson s disease Notes: Side effects usually do not occur for more than a few days after treatment and usually diminish within 24 hours; see advice below on Nausea/Vomiting. Information retrieved from FDA product labeling. 31-33 Nausea/Vomiting Some women experience symptoms of nausea and vomiting after taking ECP. These symptoms are more common with the Yuzpe method, which contains estrogen, and is not common with LNG or UPA ECP. If vomiting does occur within two hours after a patient has taken ECP, some clinicians may advise taking an antiemetic. 19 In cases when vomiting makes oral administration impossible, a repeat antiemetic dose may be administered vaginally (inserted high in the vagina). Breastfeeding LNG ECP are not contraindicated during lactation. Until more data is available, it is recommended that women who take UPA ECP express and discard their breast milk for 36 hours post UPA intake or use LNG ECP instead. 20 Pregnancy ECP do not affect an existing pregnancy. ECP are not recommended for women with known or suspected pregnancy because it will be ineffective. EC medications are safe and can be considered even for women who have medical conditions that make them poor candidates for combined oral contraceptives, as ECP do not contain estrogen. This is especially important when pregnancy is unsafe for some women.

4 Emergency Contraception a practitioner s guide Access to EC Over-the-Counter (OTC) Availability Plan B One-step is available OTC for men and women of any age. While the generic brands Next Choice One Dose and My Way have received FDA-approval to go OTC, it is not clear when the product manufacturers will be able to bring the products to the shelf; for now they remain behind the pharmacy counter. 30 planbonestep.com mywaypill.com mynextchoiceonedose.com levo4u.com Prescribing EC Health care providers play an important role in educating all patients about EC and improving access to the medication. The UPA ECP ella are available for patients of all ages with a prescription. Some states allow people 16 years and younger to obtain Next Choice One Dose and My Way without a prescription, these states include: Alaska, California, Hawaii, Maine, Massachusetts, New Hampshire, New Mexico, Vermont, and Washington State. (See ec.princeton.edu/questions/statepharmacy-access-list.html to find up-to-date information on pharmacy access.) Any physician, physician assistant, nurse practitioner, or nurse midwife with prescribing privileges can prescribe EC just like any other prescription medication. Some insurance plans may not cover LNG ECP if patients purchase it without a prescription; therefore, we recommend providing patients with written prescriptions for insurance purposes. Prescriptions may also be helpful for patients seeking reimbursement from health savings accounts or similar sources. Patients should check with their insurance provider about coverage for EC. Prescriptions also make it easier for patients to obtain LNG ECP if they do not have a government issued ID available, are embarrassed to request EC from the pharmacist at the counter without a doctor s prescription, or want to avoid additional questions from pharmacists about their intended use of LNG ECP. In many states, Medicaid only covers EC for enrolled women with a prescription. Advance Prescription We support prescribing ECP with refills in advance during routine gynecologic/primary care visits because of the time-sensitive nature of EC. Evidence shows that women are more likely to take ECP 21 and take it sooner 22 after an episode of unprotected intercourse if they receive the medication in advance. 23 Advance prescription is especially important for rural women, for whom long travel distances may preclude timely access to EC through pharmacies. The American Medical Association 24, American Congress of Obstetricians and Gynecologists 25, American Academy of Pediatrics 21, Society for Adolescent Health and Medicine 22, and the American Academy of Family Physicians 23 all support advance prescription of EC. ella-rx.com Stock Not all pharmacies stock ella, Plan B One-Step, Next Choice, levonorgestrel tablets, or other ECP. Since ECP are only effective for a limited time and some products are more effective the sooner they are taken, providers should keep a list of local pharmacies that stock EC products and encourage others to begin stocking them. This is another reason to provide advance prescription of EC. Clinicians may also stock EC at their practices. Additionally, some ECP may be available to order or available by prescription online. (For more information, see www.kwikmed.com/ella.asp and shop.fphs.org/plan-b-one-step-1)

Emergency Contraception a practitioner s guide 5 Follow-Up Care and Quick Start Supportive, nonjudgmental approaches are best for providing information and encouraging patients to voice concerns and ask questions. Providers should give instructions and information on effectiveness and potential side effects to patients who choose to take EC. Training all staff, including receptionists, in EC protocols will facilitate access to the medications. An office visit for a pelvic exam or pregnancy test is not necessary for ECP; health care professionals can safely prescribe ECP over the phone. When prescribing by phone, clinicians should review the patient s menstrual history and determine when unprotected acts of intercourse occurred, in order to assess the likelihood that the patient is already pregnant, in which case an OTC pregnancy test can be recommended. Crisis Management Health care providers should be aware of the possibility that a woman requesting EC may be a victim of sexual assault; should screen patients, as appropriate; and should know how to provide counseling and referrals and compassionate and sensitive care. Survivors of sexual assault who are seen in an emergency setting should be offered EC for pregnancy prevention. Quick Start The CDC s 2013 update for Selected Practice Recommendations for Contraceptive Use (http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6205a1.htm) recommends that women start any method of regular contraception immediately after taking LNG ECP or use a barrier method until her next period. While still theoretical, some experts suggest that the UPA ECP may decrease the efficacy of hormonal contraception due to its anti-progestin properties; alternatively, the efficacy of UPA ECP may be decreased if a hormonal contraceptive method is immediately started. 17 Evidence on when a woman can initiate regular hormonal birth control is limited to expert opinion and product labeling. 18 Providers can advise patients to abstain from sexual intercourse or use a barrier method with their usual hormonal method for a least two weeks after ella intake. A pregnancy test is recommended if menses or withdrawal bleeding does not start within three weeks of taking ECP. 17 Repeat Use There are no studies on the safety of ECP with frequent use 26 ; studies have not found any unique risks with repeated use of LNG ECP when taken within the same menstrual cycle. 27 The label for ella states that Repeated use of ella within the same menstrual cycle is not recommended, as safety and efficacy of repeat use within the same cycle has not been evaluated. 28

6 Emergency Contraception a practitioner s guide Table 1. Regular oral contraceptives that can be used for emergency contraception in the U.S. Brand Pills per dose Ethinyl Estradiol per dose (µg) Lenonorgestrel per dose (mg) Combined progestin and estrogen pills: Take two 12 hours apart Altavera ; Amethia ; Camrese ; Cryselle ; Introvale ; Jolessa ; Levora ; Lo/Ovral ; Low- Ogestrel ; Nordette ; Portia ; Quasense ; Seasonale ; Seasonique 4 pills 120 0.60 Amethia Lo ; Aviane ; CamreseLo ; Lessina ; LoSeasonique ; Lutera ; Ogestrel ; Stronyx 5 pills 100 0.50 Amethyst ; Lybrel 5 pills 120 0.54 Source: not-2-late.com Enpresse ; Trivora 4 pills 120 0.50 The FDA has declared the above combined oral contraceptive pills as safe and effective for use as EC, although they are not marketed as EC products. 29 This method is not preferred and it is uncommon that providers will counsel their patients to utilize the Yuzpe method for EC. We have provided information on this method solely to acknowledge it as an option under the circumstance that a woman is unable to access an FDA-approved ECP.

Emergency Contraception a practitioner s guide 7 Table 2. EC decision tree Unprotected Sex Up to 72 hours ago (3 days) When? 72 to 120 hours ago (3 to 5 days) Most effective Most effective BMI? Cu-T380A IUD 30 >30 Unable to have a Cu-IUD inserted? Preferred ella Plan B ella ella ella not available? ella not available? Plan B Plan B Created by Anne R. Davis, MD, MPH

8 Emergency Contraception a practitioner s guide Resources for Providers and Patients: 55 West 39 th Street Suite 1001 New York, NY 10018 Phone: 646-366-1890 Fax: 646-366-1897 Email: info@prh.org www.not-2-late.com: Provides a list of local providers and answers to the most common questions about EC www.backupyourbirthcontrol.org: Offers basic facts about EC; mainly intended for the general public with a section for providers National Sexual Assault Hotline, 1-800-656-HOPE: Provides victims of sexual assault with free, confidential, around-the-clock services www.rhtp.org: The Reproductive Health Technologies Project website offers detailed information on the approval and regulation process for emergency contraceptives and other existing and emerging reproductive health technologies www.cecinfo.org: The International Consortium on Emergency Contraception produces research and info on EC ec.princeton.edu: A site with credible research sources aimed at patients 2014 Physicians for Reproductive Health Physicians for Reproductive Health is a doctor-led national advocacy organization. We use evidence-based medicine to promote sound reproductive health policies. We believe in reproductive choice for everyone. Our network unites the medical community and concerned supporters. Together we work to improve access to comprehensive reproductive health care, including contraception and abortion, and especially for economically disadvantaged patients. Physicians does not accept contributions or sponsorships from corporations and does not engage in the endorsement or promotion of any specific emergency contraceptive or oral contraceptive product. For more information about Physicians, visit www.prh.org. To learn more about our network of pro-choice physicians and supporters or make a financial contribution, please call 646-366-1890, or email info@prh.org.

References 9 1. Fine, P., Mathé, H., Ginde, S., Cullins, V., Morfesis, J., & Gainer, E. (February 2010). Ulipristal acetate taken 48 120 hours after intercourse for emergency contraception The American College of Obstetricians and Gynecologists, 115(2 (1)), 257-263. 2. Gemzell-Danielsson, K., Rabe, T., & Cheng, L. (2013). Emergency contraception. Gynecological Endocrinology: The Official Journal of the International Society of Gynecological Endocrinology, 29 Suppl 1, 1-14. 3. Glasier, A. (2013). Emergency contraception: Clinical outcomes. Contraception, 87(3), 309-313. 4. Koyama, A., Hagopian, L., & Linden, J. (2013). Emerging options for emergency contraception. Clinical Medicine Insights: Reproductive Health, 7(3547-), 23-35. 5. Lalitkumar, P. G. L., Berger, C., & Gemzell-Danielsson, K. (2013). Emergency contraception. Best Practice & Research Clinical Endocrinology & Metabolism, 27(1), 91-101. 6. Ellertson, C., Evans, M., Ferden, S., Leadbetter, C., Spears, A., Johnstone, K., et al. (2003). Extending the time limit for starting the yuzpe regimen of emergency contraception to 120 hours. Obstetrics and Gynecology, 101(6), 1168-1171. 7. Brache, V., Cochon, L., Jesam, C., Maldonado, R., Salvatierra A.M., Levy, D. P., et al. (2009). Immediate preovulatory administraion of 30 mg ulipristal acetate significantly delays follicular rupture. Human Reproduction, 25(9), 2256-2263. 8. Gemzell-Danielsson, K., Berger, C., & P.G.L., L. (2013). Emergency contraception mechanisms of action. Contraception, 87(3), 300-308. 9. Marions, L., Hultenby, K., Lindell, I., Sun, X., Ståbi, B., & Gemzell Danielsson, K. (2002). Emergency contraception with mifepristone and levonorgestrel: Mechanism of action. Obstetrics & Gynecology, 100(1), 65-71. 10. Mozzanega, B., Cosmi, E., & Nardelli, G. B. (2013). Ulipristal acetate in emergency contraception: Mechanism of action. Trends in Pharmacological Sciences, 34(4), 195-196 11. Trussell, J., & Jordan, B. (2006). Mechanism of action of emergency contraceptive pills. Contraception, 74(2), 87-89. 12. Glasier, A. F., Cameron, S. T., Fine, P. M., Logan, S. J., Casale, W., Van Horn, J., et al. (2010). Ulipristal acetate versus levonorgestrel for emergency contraception: A randomised non-inferiority trial and meta-analysis. The Lancet, 375(9714), 555-562. 13. Raymond, E., Taylor, D., Trussell, J., & Steiner, M. J. (2004). Minimum effectiveness of the levonorgestrel regimen of emergency contraception. Contraception, 69(1), 79-81. 14. International Consortium for Emergency Contraception. (2012). The Intrauterine Device (IUD) for Emergency Contraception. 15. Glasier, A., Cameron, S. T., Blithe, D., Scherrer, B., Mathe, H., Levy, D., et al. (2011). Can we identify women at risk of pregnancy despite using emergency contraception? data from randomized trials of ulipristal acetate and levonorgestrel. Contraception, 84(4), 363-367. 16. Reproductive Health Technologies Project. (2013). Frequently Asked Questions: The Impact of Weight on Efficacy of Emergency Contraception. 17. Centers for Disease Control and Prevention. U.S. Selected Practice Recommendations for Contraceptive Use, 2013: Adapted from the World Health Organization selected Practice Recommendations for Contraceptive Use, 2 nd Edition. Morbidity and Mortality Weekly Report: June 21, 2013. Recommendations and Reports.2013: 62; 5 18. Salcedo, J., Rodriguez, M. I., Curtis, K. M., & Kapp, N. (2013). When can a woman resume or initiate contraception after taking emergency contraceptive pills? A systematic review. Contraception, 87(5), 602-604. 19. Raymond, E. G., Creinin, M. D., Barnhart, K. T., Lovvorn, A. E., Rountree, R. W., & Trussell, J. (2000). Meclizine for prevention of nausea associated with use of emergency contraceptive pills: A randomized trial. Obstetrics & Gynecology, 95(2), 271-277.

10 References 20. International Consortium for Emergency Contraception. (2012). Emergency Contraceptive Pills: Medical and Service Delivery Guidelines, third edition. 21. American Academy of Pediatrics, Committee on Adolescence. Emergency contraception. Pediatrics 2005;116:1026-1035. 22. Gold MA, Sucato GS, Conard LA, Hillard PJ, Society for Adolescent Medicine. Provision of emergency contraception to adolescents: position paper of the Society for Adolescent Medicine. J Adolesc Health. 2004;35:67-70. 23. Weismiller DG. Emergency contraception. Am Fam Physician. 2004;70:707-714. 24. American Medical Association. Access to emergency contraception. Policy of the House of Delegates, H- 75.985; 2002 https://ssl3.ama-assn.org/apps/ecomm/policyfinderform.pl?site=www.amaassn.org&uri=%2fresources%2fhtml%2fpolicyfinder%2fpolicyfiles%2fhne%2fh-75.985.htm. Accessed March 19, 2014 25. American College of Obstetricians and Gynecologists. Emergency Contraception. ACOG Practice Bulletin, Number 69. Washington, DC: The American College of Obstetrics and Gynecologists, December 2005. Obstet Gynecol. 2005;106:1443-1451. 26. Trussell, J., Raymond E.G., Cleland, K. Emergency Contraception: A last chance to prevent unintended pregnancy. Office of the Population Research & Association of Reproductive Health Professionals. http://ec.princeton.edu/emergency-contraception.html. Accessed March 19, 2014 27. Efficacy and side effects of immediate postcoital levonorgestrel used repeatedly for contraception. (2000). Contraception, 61(5), 303-308. 28. Food and Drug Administration. FDA approved Drugs. U.S. Department of Health and Human Services. Accessed March 20, 2014: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=search.drugdetails 29. Food and Drug Administration. Prescription drug products: certain combined oral contraceptives for use as postcoital emergency contraception. Federal Register 1997; 62: 8610-2. 30. Food and Drug Administration. Letter Reference ID 346025. Accessed April 10, 2014: http://www.hpm.com/pdf/blog/plan%20b%20-%20fda%20exclusivity%20&%20carve- Out%20Determination.pdf 31. U.S. Food and Drug Administration, Center for Drug Evaluation and Research. Plan B One-Step NDA 21998/S- 003. Retrieved April 2, 2014, from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021998lbl.pdf 32. U.S. Food and Drug Administration, Center for Drug Evaluation and Research. Ella NDA 22474/S-002. Retrieved April 2, 2014, from : http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022474s000lbl.pdf 33. U.S. Food and Drug Administration, Center for Drug Evaluation and Research. Paragard T380A NDA 18680/S- 066. Retrieved April 2, 2014, from