The Evolving Role of Pharmacists in Providing Contraception: A Practical Guide to Contraceptive Prod

The Evolving Role of Pharmacists in Providing Contraception: A Practical Guide to Contraceptive Products Authors: Kari Allan, Pharm.D. Candidate and Erin Raney, Pharm.D., BCPS, BC-ADM; Midwestern University College of Pharmacy – Glendale

Objectives: At the completion of the CPE activity, participants should be able to: 1. Discuss recent changes in legislation that affect provision of contraceptives by pharmacists.

2. Identify current hormone-based products for contraception.

3. Choose safe products for women seeking contraception based on their individual medical history.

4. Include information about proper use of emergency contraception while counseling on contraceptive use.

Introduction: In light of recent legislation in various states allowing pharmacists to prescribe contraception, it is vital that those working in patient care environments optimize their working knowledge of available options. This review discusses commonly-used contraceptive products, concentrating on the hormonal contraception options for which pharmacist prescribing has become permissible in some states. This discussion also includes precautions and contraindications to consider when selecting contraceptive products, the current role of longacting reversible contraception, and emergency contraception.

Background: Unplanned pregnancies in the United States remain high – up to 50% of all pregnancies.1 Improving access to effective birth control is a key component of reducing this statistic. In a recent national survey, 30% of women reported some level of difficulty with accessing contraception prescriptions or refills at some point.2 Removing the requirement for a physician’s order for contraception through legislation at the state level is a recent movement that aims to break down barriers between patients and direct access to birth control by allowing pharmacists to prescribe these medications. 1,3-4 Obtaining hormonal contraception directly from pharmacies facilitates improved access for women due to the high accessibility of pharmacists, and because pharmacies are typically numerous and central within communities.1 Since 2013, several states have introduced legislation allowing for pharmacists to prescribe contraception. As of June 2017, Oregon, California, Colorado, and New Mexico have passed and/or enacted laws, and several more including Maryland, Hawaii, Illinois, Minnesota, Missouri, and New Hampshire have proposed legislation pending approval.5 While these permissions are similar across states, they do vary in the types of products pharmacists can prescribe, the age of the patient to which they can be prescribed without a physician’s order, and the requirements for evidence of recent women’s health exams.1 The majority of existing legislation includes procedures to ensure that pharmacists obtain sufficient patient information to safely forgo a visit to a physician prior to obtaining contraception. Pharmacists must complete a training program and obtain a medical and medication history (typically by questionnaire) for each patient, as well as perform a blood pressure screening.3 Pharmacists with prescribing privileges take on the responsibility of screening patients for contraindications to contraception use and counseling on alternative forms of contraception that are not available through the provision of a pharmacist.

Resources for Contraception Provision: Two clinical practice guidelines assist with the selection and provision of contraception. The U.S. Medical Eligibility Criteria for Contraceptive Use (US MEC) lists classes of available contraceptives and contraindications associated with each, thereby providing guidance for safe, patient-specific contraceptive selection. This document was most recently updated in 2016 and lists recommendations first by class of contraception, then by concurrent medical conditions, and then by classifications that indicate the relative risk associated with their use. These classifications range from 1 (the benefit of the contraceptive outweighs any risks associated with the medical condition) to 4 (unacceptable risk associated with use of the contraceptive).6

The 2016 U.S. Selected Practice Recommendations for Contraceptive Use (US SPR) are intended to be used in conjunction with the US MEC and provide guidance for contraceptive selection, patient education, and monitoring parameters. Information includes appropriate timing of initiation/placement of the contraceptive products and need for backup methods, among other guidance points. Both the US MEC and US SPR documents are foundational for any pharmacist involved in recommending contraception options and counseling on best use. Table 1 outlines electronic access points to these resources.6-7 Oral Hormonal Contraception: Oral hormonal contraception remains one of the most popular forms of birth control among women in the United States, and stands to greatly increase in use as pharmacist provision of contraception expands. In a survey of women currently not using any contraception, 41% stated that they would begin to use a hormonal contraceptive if it were to become available without physician prescription.2 There are both progestin-only and combination (estrogen plus progestin) products within this category – each have benefits and risks to different patient populations. Patient screening is necessary to conduct prior to provision of these products, to include an evaluation of current pregnancy status, current and past medical history, current medications (including herbal supplements and over-the-counter medications), and a blood pressure assessment.3 The National Association of State Pharmacy Associations along with state boards of pharmacy provide links to the state-specific screening procedures recommended in approved and pending legislation.2 Combination Oral Contraception (COC) Combination products include estrogen, most commonly as ethinyl estradiol, in conjunction with a progestin such as levonorgestrel, norethindrone acetate, desogestrel, drospirenone, and norgestrel. There are many different available products that vary in the dose of ethinyl estradiol, the dose and type of progestin, and the cycle pattern. Increasingly more of these products become available each year, and the sheer number can make it challenging to select an agent to use. Product selection varies depending on characteristics of the individual patient.

COCs are typically packaged as a 21-day pack containing 3 weeks of active pills only, or as a 28-day pack that includes 21 or 24 days of active hormone pills followed by 4-7 days of placebo or supplements (such as iron or folic acid). If the active pills contain the same amount of estrogen and progestin each day, the product is considered “monophasic.” If the amounts of active ingredients vary throughout the active portion of the cycle, it is considered “multiphasic.” The design of a single-cycle COC pack provides hormone for 3 weeks followed by a hormone-free period (usually 4-7 days) during which a withdrawal bleed occurs. However, there are multiple options that provide several months of estrogen and progestin continuously, which allow for fewer withdrawal bleed periods per year (typically between 1-4). These are “continuous cycle” products.7 Patient screening processes for contraception provision focus on potential contraindications for use of estrogen and/or progestin.3 Table 2 displays select examples of common precautions and/or contraindications to the use of COCs.7 Interestingly, a recent study found that up to 23% of women using COCs prescribed by a physician were doing so despite a high-risk condition.2 Therefore, pharmacist-initiated screening for these highrisk conditions will be an important strategy to improve this finding moving forward. While studies have shown that self-screening by patients tends to be generally effective, aided screening by a health care professional results in the most accurate determination of genuine contraindications.8 While perfect use of COCs results in a pregnancy prevention rate of 99%, typical use of these medications has a lower efficacy rate of 91%. A crucial factor in their effectiveness lies in the proper timing of the doses, with consistent daily use required for maximum effectiveness. These pills must be taken at the same time every day, and while one missed dose can be made up by taking it as soon as possible, 2 or more consecutive missed doses necessitates use of a backup method (BUM) or abstinence for at least 7 days of consistent COC use. Depending on where the missed dose falls within the pill pack, emergency contraception (EC), other than ulipristal acetate, should also be considered. Detailed instructions regarding missed pills are provided in the product package insert as well as the US SPR.2,6 Also important to the efficacy of COCs is the appropriate use of a BUM, such as male or female condoms, during the initiation period. For example, if a woman begins a COC less than 5 days from the beginning of her menstrual bleed, no BUM is needed. If, however, a COC is initiated more than 5 days after

menstruation begins, a BUM is needed for the first 7 days of COC use if a woman does not wish to abstain from sexual activity during that time. This 7-day cross-over period also applies if a woman has amenorrhea (no evidence of a menstrual bleed), is more than 21 days postpartum, or when switching from one oral product to another.6 Typical side effects of COCs can include weight gain, mood changes, headache, nausea, and abnormal menstrual bleeding patterns. While most of these symptoms are mild, occasionally an alternative product is required. For weight gain, mood changes, headache, and nausea, the type of progestin or the amount of estrogen in the product can be responsible. A common approach is to change to a product that contains a different dose of estrogen or form of progestin. On the other hand, if breakthrough bleeding (bleeding that occurs outside the expected withdrawal bleed interval) occurs and does not resolve within approximately 3 months of use, the dose of estrogen or progestin contained in the product may be too low. Changing to a product that contains a higher dose of hormone may help alleviate this issue.6,9 Progestin-Only Pills (POP) Among oral contraception users in the U.S., only about 4% use POPs.2 Also known as the “mini pill,” they are equally efficacious in pregnancy prevention under conditions of ideal use, although this is notably more difficult to achieve than with COCs. These options are an alternative for women who have contraindications to the estrogen component of COCs but who still desire a hormone-based oral option.

The progestin component of POPs has a shorter duration of action than the COC products, and therefore correctly timed doses is even more crucial. A dose of a POP is considered “missed” if it is taken more than 3 hours after it is due, and it is recommended to take a missed dose as soon as possible to allow the woman to quickly resume their normal schedule. This applies even if it is necessary to take 2 pills within the same day in order to take the next regularly-scheduled dose. When a dose is missed, a BUM is recommended until at least 2 consecutive doses have been taken properly to reduce the risk of unintended pregnancy.6 Additional Hormonal Contraceptives: Multiple routes of administration are available for hormonal contraceptive products. In some states, pharmacists can prescribe transdermal patches, intravaginal rings, and/or intramuscular injections in addition to COCs and POPs. The transdermal patch contains estrogen and progestin and is applied to the skin (rotating placement) once weekly for 3 weeks, and then removed for 1 week to allow for the withdrawal bleed, similar to the placebo period in COCs. Alternatively, the vaginal ring is a combination product that is inserted by the patient once per month for 3 weeks, and then removed for one week to allow for the withdrawal bleed. These combined hormone products have the same contraindications and precautions listed in Table 2. The depo medroxyprogesterone acetate intramuscular injection is administered once every 3 months, and can be an option for women with contraindications to the estrogen component of combined products.

For women seeking a contraceptive option that is less dependent on the user for efficacy, long-acting reversible contraceptives (LARCs) are an excellent option. These products include copper and levonorgestrel intrauterine devices (IUDs) and the etonogestrel implant. Many experts recommend LARCs as first-line contraceptive options because they do not depend on patient adherence to a dosing regimen and are therefore less likely to fail under “typical” use.6 Because of these benefits, pharmacists should include information on LARCs when counseling women on individualized contraceptive choices.2 Emergency Contraception (EC): EC is intended to prevent a pregnancy in the event of unprotected sexual intercourse or failed contraception if administered within a short time afterwards. It is recommended to discuss EC with all women who are provided hormonal contraception, especially since missed doses are a common occurrence and greatly impact efficacy. There are multiple forms of EC. The copper IUD, if placed within 5 days (120 hours) of unprotected intercourse, has been shown to be a highly effective form of EC (especially for obese women for whom other options may not be as effective) but requires an appointment with a healthcare provider for insertion.6 Additionally, two oral products are available for EC: levonorgestrel and ulipristal acetate. Ulipristal is currently only available via prescription, and can be utilized up to 5 days from unprotected intercourse.

Levonorgestrel is available without a prescription and has maximum efficacy if taken within 72 hours of unprotected intercourse. These two products have largely replaced the traditional Yuzpe method (taking 2 doses of multiple COC pills, totaling 100 mcg of ethinyl estradiol and 0.5-1 mg of levonorgestrel, given 12 hours apart) due to the high risk of nausea and vomiting associated with its use. It is important to counsel women that EC is most effective the sooner it is used after unprotected intercourse, and is never a guarantee of pregnancy prevention.10 There are no medical contraindications to the use of oral EC products due to their short duration of use.7 However, if ulipristal is used by a woman who is breastfeeding, breast milk should be discarded for 24 hours after its use due to the potential for infant exposure.6 It is appropriate to counsel frequent users of EC to consider a LARC for routine contraception. If a levonorgestrel product is used for EC, women can resume their hormonal contraception immediately following its use. If ulipristal acetate is used, it is recommended that a hormonal form of contraception should be resumed or initiated after a delay of at least 5 days to avoid interference between the two products.6 The copper IUD, if placed for the purposes of EC, provides contraception for up to 10 years.10 Conclusion: The recent expansion of pharmacist scopes of practice to allow for hormonal contraceptive provision in several states translates into a responsibility on the part of pharmacists practicing in patient care settings to effectively screen patients for safe and appropriate use of these methods. Hormonal contraception, especially combination estrogen/progestin products, is a relatively convenient and cost-effective method of contraception.

Pharmacists must be familiar with contraindications to hormonal methods, and recommend individualized options based on a woman’s medical history and lifestyle preferences. Finally, counseling on emergency contraception and backup contraceptive methods is an essential component of contraception provision to maximize efficacy and further reduce unintended pregnancies. The 2016 US MEC and US SPR are essential references for pharmacists providing patient counseling or selection and monitoring of contraceptive methods.

Table 1. Select recommended contraceptive resources Centers for Disease Control and Prevention US Medical Eligibility Criteria (US MEC) for Contraceptive Use, 2016

Full print version and a summary chart can be downloaded directly from the site

https://www.cdc.gov/re productivehealth/contra ception/mmwr/mec/sum mary.html

US Selected Practice Recommendations (US SPR) for Contraceptive Use, 2016

Full print version and a summary chart can be downloaded directly from the site

https://www.cdc.gov/re productivehealth/contra ception/mmwr/spr/sum mary.html

2016 US MEC and US SPR app

Providing Quality Family Planning Services

Mobile app available for Android and iOS; combines information from the both of the CDC guidelines listed above Full print version can be downloaded directly from the site

Available at either of the two links listed above

https://www.cdc.gov/re productivehealth/contra ception/qfp.htm

Family Planning National Training Center The Quality Family Planning Services (QFP) Mobile App

Free mobile app on Android and iOS

https://fpntc.org/training -and-resources/qualityfamily-planningservices-mobile-app

Table 2. Select precautions and contraindications to the use of combination hormonal contraceptives Condition Concerns/Comments Category <21 days postpartum

4

21-42 days postpartum with other VTE risk factors

VTE risk factors = age ≥ 35, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI ≥ 30, postpartum hemorrhage, Csection, preeclampsia, smoking

21-30 days postpartum and breastfeeding without other VTE risk factors Age ≥ 35 years smoking less than 15 cigarettes per day Age ≥ 35 years smoking more than 15 cigarettes per day Multiple risk factors for ASVCD

3 3 4 ASCVD risk factors = older age, smoking, diabetes, hypertension, low HDL, high LDL, high triglycerides

Hypertension adequately controlled Elevated blood pressure Elevated blood pressure

3 or 4

3 Systolic 140-159 mm Hg or diastolic 90-99 mm Hg Systolic ≥ 160 mm Hg OR diastolic ≥ 100 mg Hg

Vascular disease Acute DVT/PE or history of DVT/PE with higher risk for recurrence (has risk factors)

3

3 4 4

DVT/PE risk factors = history of estrogen-dependent, pregnancyassociated, or idiopathic DVT/PE, known thrombophilia, active cancer, recurrent DVT/PE

History of DVT/PE with lower risk for recurrence (no risk factors) Major surgery with prolonged immobilization

4

3 4

Current/history of ischemic heart disease

Includes stroke or complicated valvular heart disease

4

Systemic lupus erythematosus

Positive or unknown antiphospholipid antibodies

4

Migraine with aura

4

Current breast cancer

4

Past breast cancer in remission for at least 5 years Diabetes with nephropathy, retinopathy, neuropathy, other vascular disease, or > 20 years' duration Concurrent use with certain anticonvulsants, rifampin, or rifabutin

3 Specific classification depends on severity of disease

3 or 4

Anticonvulsants include phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine, lamotrigine

3

Severe (decompensated) cirrhosis, hepatocellular adenoma, or malignant hepatoma

4

3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method.

4 = A condition that represents an unacceptable health risk if the contraceptive method is used.7

References: 1. The PEW Charitable Trusts. States start to let pharmacists prescribe birth control (2016). http://www.pewtrusts.org/en/research-and-analysis/blogs/stateline/2016/02/18/states-start-to-let-pharmacists-prescribebirth-control-pills (accessed 2017 May 27).

2. Grossman D. Over-the-counter access to oral contraceptives. Obstet Gynecol Clin North Am 2015;42(4):619-629.

3. Vivian JC. Pharmacists prescribing birth control. US Pharm 2016;41(2):48-50.

4. Pharmacy Times. Colorado is third state allowing pharmacists to prescribe birth control (2017). http://www.pharmacytimes.com/contributor/sally-rafie-pharmd/2017/02/colorado-is-third-state-allowing-pharmacists-toprescribe-birth-control (accessed 2017 May 27).

5. National Alliance of State Pharmacy Associations. Pharmacists authorized to prescribe birth control in more states (2017). https://naspa.us/2017/05/pharmacists-authorized-prescribe-birth-control-states/ (accessed 2017 July 11).

6. Centers for Disease Control. U.S. Selected Practice Recommendations for Contraceptive Use, 2016. http://www.cdc.gov.mwu.idm.oclc.org/mmwr/preview/mmwrhtml/rr6205a1.htm. (accessed 2017 May 27).

7. Curtis KM, Tepper NK, Jatlaoui TC, et al. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep 2016; 65:1.

8. Grossman D, Fernandez L, Hopkins K et al. Accuracy of self-screening for contraindications to combined oral contraceptive use. Obstet Gynecol 2008;112(3):572-8.

9. Lexicomp Online [online database]. Hudson, OH: Lexi-Comp (accessed 2017 May 27).

10. Batur P, Kransdorf LN, Casey PM. Emergency contraception. Mayo Clin Proc 2016; 91(6):802-7.