Choosing a Hormonal Contraceptive

Transcription

1 PL Detail-Document # This PL Detail-Document gives subscribers additional insight related to the Recommendations published in PHARMACIST S LETTER / PRESCRIBER S LETTER October 2015 Choosing a Hormonal Contraceptive Hormonal contraception is a safe and effective way to prevent unwanted pregnancy. However, with over 70 different formulations and products, choosing the one that is safest and most effective for an individual patient can be challenging. 1 Make sure your patient does not have a contraindication to estrogen-containing hormonal contraceptives (e.g., thromboembolic disorder, severe hypertension, breast cancer). Take the patient s medical history, measure their blood pressure, ensure they are not currently pregnant, and ask about other medications they may be taking. If hormonal contraception is right for your patient, use the chart below to help you make your selection. Note that the chart below does not offer complete information on long-acting contraceptives like IUDs and implants, some of which do contain hormones. For more on these and additional information, see some of our other PL resources on this topic: PL Charts, Comparison of Oral Contraceptives and Non-Oral Alternatives (U.S. subscribers; Canadian subscribers), Contraception for Women with Chronic Medical Conditions, Missed Doses of Hormonal Contraceptives: A Less Complicated Approach; PL Voices, Choosing Hormonal Contraceptives, Role of Long-Acting Contraceptives; and PL CE, Choosing Wisely: Contraception Check for: Absence of risk factors A CYP3A4 inducer (phenytoin, carbamazepine, some HIV drugs, topiramate, rifampin, St. John s wort, etc) INITIAL SCREENING Considerations for Choosing Contraceptive For long-term, high efficacy, consider an IUD or an implant. For short-term, suggest starting with a combined oral contraceptive (COC) containing 20 mcg ethinyl estradiol plus an older progestin such as levonorgestrel or norethindrone, for a good balance of safety and efficacy. 1 These meds induce the metabolism of estrogen, potentially decreasing efficacy. Oral progestin-only contraceptives and etonogestrel implant may also be affected. 5 Injectable medroxyprogesterone preferred, or an IUD. 5 Consider a higher estrogen content COC ( 30 mcg ethinyl estradiol). 1 See our PL Chart, Cytochrome P450 Drug Interactions, for additional information. Your Notes/Interventions Copyright 2015 by Therapeutic Research Center ~ ~

2 (PL Detail-Document #311001: Page 2 of 6) INITIAL SCREENING Check for: Considerations for Choosing Contraceptive Obesity Controversial efficacy and safety of hormonal contraceptives due to potential for slightly higher failure rates with oral contraceptives and higher risk of venous thromboembolism. 5 Consider formulations with up to 35 mcg ethinyl estradiol. 2,3 Consider an extended-cycle pill to decrease the hormone-free interval to try to improve efficacy. 1 If also over age 35, consider a non-estrogen containing contraceptive to minimize risk of thrombosis. Patch may not be as effective if >198 pounds (90 kg). 4 See our PL Detail-Document, Use of Hormonal Contraceptives in Obese Women. Your Notes/Interventions Risk of nonadherence Consider IUD, implant, depot medroxyprogesterone, weekly patch, or monthly vaginal ring. Avoid progestin-only pills as varying daily administration time by more than three hours can decrease efficacy. 5 Breastfeeding Avoid estrogen-containing COC, patch, and vaginal ring. Consider a progestin-only pill as this won t decrease milk production. 5 Smoker If 35 years old: avoid COCs due to increased risk of cardiovascular disease; but, if alternatives are limited, can consider COC if the patient smokes less than 15 cigarettes/day. 6 If <35 years old: suggest COCs IF no other risk factors for thrombosis. 6 Hypertension Adequately controlled hypertension, or if SBP 140 to 159 mmhg or DBP 90 to 99 mmhg: avoid estrogen-containing contraceptives; suggest progestin-only pill, depot medroxyprogesterone, implant, or levonorgestrel-releasing IUD. 5 If SBP 160 mmhg or DBP 100 mmhg: non-hormonal contraception preferred, but can consider progestin-only pill, implant, or levonorgestrel-releasing IUD. 5 Copyright 2015 by Therapeutic Research Center ~ ~

3 (PL Detail-Document #311001: Page 3 of 6) Check for: Increased risk of thrombosis: history of clots, age 35 or older, smokers, severe hypertension, diabetes, high cholesterol, etc INITIAL SCREENING Considerations for Choosing Contraceptive Controversial issue although risk of venous thrombosis with hormonal contraceptives still lower than risk with pregnancy. Consider a progestin-only contraceptive. 5 Can consider a COC with 20 mcg ethinyl estradiol plus an older progestin (levonorgestrel, etc). 5 Avoid the vaginal ring, as higher levels of sex hormone binding globulin (as seen with NuvaRing) may increase risk of thrombosis. 1 Avoid desogestrel and drospirenone as risk may be higher with these than other progestins. 1 Avoid hormonal patches (which have a warning to not use if patient has a high risk of thrombosis) due to increased estrogen exposure vs oral contraceptives. 8,9 Listen to our PL Voices, Risk of Blood Clots with Hormonal Contraceptives. See our PL Detail-Document, Hormonal Contraceptives and Thrombosis Risk. Your Notes/Interventions Migraines Use of COCs is controversial due to potential increased risk of stroke. Increased risk with older, higher-dose estrogen-containing contraceptives. Consider a progestin-only contraceptive. 2 If patient does not have an aura, can consider a low-dose estrogen COC ( 20 mcg ethinyl estradiol) IF <35 years old, non-smoker, normal BP. 5 If patient does have an aura, avoid estrogen-containing contraceptives. 5 If menstrual migraines: suggest extended-cycle COCs to help alleviate by avoiding drops in estrogen. 1 Listen to our PL Voices, Combined Oral Contraceptives in Women with Migraines. See our PL Detail-Document, Oral Contraceptives and Migraines. Osteoporosis Avoid injectable medroxyprogesterone due to decreases in bone mineral density. 10 Copyright 2015 by Therapeutic Research Center ~ ~

4 (PL Detail-Document #311001: Page 4 of 6) INITIAL SCREENING Check for: Considerations for Choosing Contraceptive Other conditions For information on the use of hormonal contraceptives in other conditions such as breast cancer, liver disease, lupus, rheumatoid arthritis, blood disorders, recent or planned surgery, etc, see our PL Chart, Contraception for Women with Chronic Medical Conditions or CDC s U.S. Medical Eligibility Criteria for Contraceptive Use at Your Notes/Interventions Managing COMPLAINTS/SIDE EFFECTS Side Effect: Considerations for switching contraceptive Breakthrough Common with all forms of COC especially in the first three months bleeding of use. 6 Ensure patient is adherent, no drug interactions, etc. 6 If early or mid-cycle: Possibly too little estrogen. 6 If late cycle: Possibly too little progestin. 1 Low dose, 1st generation progestins tend to have higher risk of unscheduled spotting and bleeding. 1 If on <30 mcg of ethinyl estradiol, consider changing to a higher estrogen dose. 1 If already on 30 mcg of ethinyl estradiol, consider changing the progestin to one with higher progestin activity (levonorgestrel, desogestrel) or increase progestin dose if on progestin-only pill or multiphasic COC. 1 Migraines If migraines develop in a patient or worsen, stop estrogen-containing contraceptives. 3 Vasomotor symptoms If symptoms during hormone-free days, try a continuous- or of perimenopause extended-cycle low-dose estrogen COC. 1 Acne COCs in general improve acne. 1 Some are FDA- or Health Canadalabeled for acne: Estrostep (U.S.), Ortho Tri-Cyclen (U.S.), Tri- Cyclen (Canada), Yaz, Yasmin (Canada), and Alesse (Canada). Consider switching to a COC with a 3rd generation progestin as they have less androgenic activity. 1 Consider switching to a higher estrogen dose product or move to an extended- or continuous-cycle regimen. 7 Copyright 2015 by Therapeutic Research Center ~ ~ Your notes/interventions

5 (PL Detail-Document #311001: Page 5 of 6) Side Effect: Headache, breast tenderness, fatigue, changes in mood Increased appetite, weight gain, acne, oily skin, hirsutism, dyslipidemia Nausea, breast tenderness, increased BP, melasma, headache, bloating Menstruation-related problems (anemia menorrhagia, bloating, dysmenorrhea, endometriosis, menstrual headache) Endometriosis-related menstrual pain Managing COMPLAINTS/SIDE EFFECTS Considerations for switching contraceptive Too much progestin, consider switching to a progestin with less progestin activity, such as drospirenone. 1 Too much androgen. 1 If using a 2 nd generation progestin (which have the most androgenic activity), consider switching to an anti-androgenic progestin (e.g., drospirenone) or a first- or third-generation progestin (norethindrone, desogestrel, etc). Too much estrogen, consider switching to a lower-dose estrogen formulation. 1 Avoid the patch which gives the highest estrogen exposure. 6 Consider the vaginal ring which has the lowest estrogen exposure. 11 Formulation with the progestin, drospirenone may help with bloating as it has weak potassium-sparing diuretic effects. 1 Consider a continuous- or extended-cycle regimen. 6 Pain not adequately relieved by a traditional cycle COC. Consider a continuous regimen. 6 Your notes/interventions 1 st generation progestins: norethindrone, norethindrone acetate, ethynodiol diacetate 2 nd generation progestins: levonorgestrel, norgestrel 3 rd generation progestins: norgestimate, desogestrel 4 th generation progestins: drospirenone, dienogest Low-estrogen COC = 20 mcg ethinyl estradiol Copyright 2015 by Therapeutic Research Center ~ ~

6 (PL Detail-Document #311001: Page 6 of 6) Users of this PL Detail-Document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and internet links in this article were current as of the date of publication. Project Leader in preparation of this PL Detail- Document: Annette Murray, BScPharm References 1. Hatcher RA, Trussell J, Nelson AL, et al. Contraceptive Technology: 20 th Revised Edition. New York, NY: Ardent Media, Inc., Black A, Francoeur D, Rowe T, et al. Society of Obstetricians and Gynaecologists of Canada; Canadian contraception consensus. J Obstet Gynaecol Can 2004;26: WHO. Medical eligibility criteria for contraceptive use. 4th ed. Geneva: WHO; _eng.pdf. (Accessed September 11, 2015). 4. Shrader SP, Dickerson LM. Extended- and continuous-cycle oral contraceptives. Pharmacotherapy 2008;28: CDC. U.S. Medical Eligibility Criteria for Contraceptive Use, MMWR Recomm Rep 2010;59: Martin KA, Douglas PS. Risks and side effects associated with estrogen-progestin contraceptives. June 17, Up To Date. (Accessed September 11, 2015). 7. Faculty of Sexual and Reproductive Healthcare Clinical Guidance. Contraceptive choices for young people, clinical effectiveness unit. March pdf. (Accessed September 10, 2015). 8. Product monograph for Evra. Janssen. Toronto, ON M3C 1L9. May Product information for Ortho Evra. Janssen. Titusville, NJ September Product information for Depo-Provera. Pfizer. New York, NY January Product information for NuvaRing. Merck. Whitehouse Station, NJ November Cite this document as follows: PL Detail-Document, Choosing a Hormonal Contraceptive. Pharmacist s Letter/Prescriber s Letter. October Evidence and Recommendations You Can Trust 3120 West March Lane, Stockton, CA ~ TEL (209) ~ FAX (209) Copyright 2015 by Therapeutic Research Center Subscribers to the Letter can get PL Detail-Documents, like this one, on any topic covered in any issue by going to or

7 This Clinical Resource gives subscribers additional insight related to the Recommendations published in June 2017 ~ Resource # Comparison of Oral Contraceptives and Non-Oral Alternatives Abbreviations: EE = ethinyl estradiol; Fe = iron. Products a Manufacturer Estrogen Progestin LOW-DOSE MONOPHASIC PILLS Aubra Aviane Falmina Larissia Lessina levonorgestrel/ee levonorgestrel/ee Lutera Orsythia Sronyx Afaxys Amneal Mylan Par Actavis EE 20 mcg Levonorgestrel 0.1 mg Junel 1/20 Junel Fe 1/20 Loestrin-21 1/20 Loestrin Fe 1/20 norethindrone/ee norethindrone/ee/fe Microgestin 1/20 Microgestin Fe 1/20 Tarina Fe 1/20 branded branded Mylan Afaxys EE 20 mcg Norethindrone acetate 1 mg Generess Fe chewable Layolis Fe Allergan EE 25 mcg Norethindrone 0.8 mg Altavera Chateal Kurvelo levonorgestrel/ee Marlissa Portia-28 Sandoz Afaxys Mylan EE 30 mcg Levonorgestrel 0.15 mg Cryselle-28 Elinest Low-Ogestrel-28 Lo/Ovral-28 Pfizer EE 30 mcg Norgestrel 0.3 mg Junel 1.5/30 Junel Fe 1.5/30 Larin 1.5/30 Larin Fe 1.5/30 Loestrin 1.5/30-21 Loestrin Fe 1.5/30 Microgestin 1.5/30 Microgestin Fe 1.5/30 branded branded EE 30 mcg Norethindrone acetate 1.5 mg Copyright 2017 by Therapeutic Research Center

8 (Clinical Resource #330609: Page 2 of 8) Products a Manufacturer Estrogen Progestin LOW-DOSE MONOPHASIC PILLS (cont.) Apri Desogen desogestrel/ee Emoquette Enskyce Juleber Reclipsen Cyred Merck Par Afaxys EE 30 mcg Desogestrel 0.15 mg drospirenone/ee drospirenone/ee Ocella Safyral c Syeda Zarah Yasmin Bayer Sandoz Bayer EE 30 mcg Drospirenone 3 mg Kelnor 1/35 Zovia 1/35 EE 35 mcg Ethynodiol diacetate 1 mg Estarylla Femynor Mono-Linyah MonoNessa norgestimate/ee norgestimate/ee Ortho-Cyclen Previfem Sprintec Sandoz Amneal Janssen Par EE 35 mcg Norgestimate 0.25 mg Necon 1/50 Mestranol 50 mcg Norethindrone 1 mg Balziva Briellyn Femcon Fe chewable Gildagia Ovcon 35 Philith Vyfemla Wymzya Fe chewable Zenchent Zenchent Fe chewable Allergan Par Allergan Amneal EE 35 mcg Norethindrone 0.4 mg Brevicon-28 Modicon Necon 0.5/35 Nortrel 0.5/35 Wera Allergan Janssen EE 35 mcg Norethindrone 0.5 mg Copyright 2017 by Therapeutic Research Center

9 (Clinical Resource #330609: Page 3 of 8) Products a Manufacturer Estrogen Progestin LOW-DOSE MONOPHASIC PILLS (cont.) Alyacen 1/35 Cyclafem 1/35 Dasetta 1/35 Nortrel 1/35-21 Nortrel 1/35-28 Ortho-Novum 1/35 Pirmella 1/35 Par Janssen EE 35 mcg Norethindrone 1 mg HIGH-DOSE MONOPHASIC PILLS Ogestrel 0.5/50-28 EE 50 mcg Norgestrel 0.5 mg Zovia 1/50-28 EE 50 mcg Ethynodiol diacetate 1 mg BIPHASIC PILLS Azurette desogestrel/ee Kariva Mircette Pimtrea Viorele Mylan branded EE 20 mcg x 21 days, placebo x 2 days, 10 mcg x 5 days Desogestrel 0.15 mg x 21 days TRIPHASIC PILLS Estrostep Fe Tilia Fe Tri-Legest Fe-28 Allergan EE 20 mcg x 5 days, 30 mcg x 7 days, 35 mcg x 9 days Norethindrone acetate 1 mg x 21 days norgestimate/ee Ortho Tri-Cyclen Lo Tri-Lo-Estarylla Tri-Lo-Marzia Tri-Lo-Sprintec TriNessa Lo Janssen Sandoz EE 25 mcg x 21 days Norgestimate 0.18 mg x 7 days, mg x 7 days, 0.25 mg x 7 days Caziant Cyclessa Velivet Merck EE 25 mcg x 21 days Desogestrel 0.1 mg x 7 days, mg x 7 days, 0.15 mg x 7 days Enpresse-28 Levonest levonorgestrel/ee Myzilra Trivora Par EE 30 mcg x 6 days, 40 mcg x 5 days, 30 mcg x 10 days Levonorgestrel 0.05 mg x 6 days, mg x 5 days, mg x 10 days norgestimate/ee norgestimate/ee Ortho Tri-Cyclen Tri-Estarylla Tri-Linyah TriNessa Tri-Previfem Tri-Sprintec Sandoz Janssen Par EE 35 mcg x 21 days Norgestimate 0.18 mg x 7 days, mg x 7 days, 0.25 mg x 7 days Copyright 2017 by Therapeutic Research Center

10 (Clinical Resource #330609: Page 4 of 8) Products a Manufacturer Estrogen Progestin TRIPHASIC PILLS (cont.) Aranelle Leena EE 35 mcg x 21 days Norethindrone 0.5 mg x 7 days, 1 mg x 9 days, 0.5 mg x 5 days Alyacen 7/7/7 Cyclafem 7/7/7 Dasetta 7/7/7 Necon 7/7/7 Nortrel 7/7/7 Ortho-Novum 7/7/7 Pirmella 7/7/7 Par Janssen EE 35 mcg x 21 days Norethindrone 0.5 mg x 7 days, 0.75 mg x 7 days, 1 mg x 7 days FOUR-PHASIC Natazia Bayer Estradiol valerate 3 mg x 2 days, then 2 mg x 22 days, then 1 mg x 2 days, then 2-day pill-free interval Dienogest none x 2 days, then 2 mg x 5 days, then 3 mg x 17 days, then none x 4 days EXTENDED-CYCLE PILLS Lo Loestrin Fe Allergan EE 10 mcg x 26 days Norethindrone acetate 1 mg x 24 days Junel Fe 24 Larin 1/20 Larin Fe 1/20 Larin 24 Fe Loestrin 24 Fe Lomedia 24 Fe Minastrin 24 Fe chewable Microgestin 24 Fe norethindrone acetate/ee/fe Taytulla i Amneal Allergan Mylan Allergan EE 20 mcg x 24 days Norethindrone acetate 1 mg x 24 days Amethia Lo Camrese Lo levonorgestrel/ee LoSeasonique branded EE 20 mcg x 84 days, 10 mcg x 7 days Levonorgestrel 0.1 mg x 84 days Introvale Jolessa levonorgestrel/ee levonorgestrel/ee Quasense Setlakin Sandoz EE 30 mcg x 84 days Levonorgestrel 0.15 mg x 84 days Amethia Ashlyna Daysee levonorgestrel/ee Seasonique Camrese Mylan branded EE 30 mcg x 84 days, 10 mcg x 7 days Levonorgestrel 0.15 mg x 84 days Copyright 2017 by Therapeutic Research Center

11 (Clinical Resource #330609: Page 5 of 8) Products a Manufacturer Estrogen Progestin EXTENDED-CYCLE PILLS (cont.) Beyaz c drospirenone/ee Gianvi Loryna Nikki Rajani c Vestura Yaz Bayer Sandoz Bayer EE 20 mcg x 24 days Drospirenone 3 mg x 24 days CONTINUOUS-CYCLE PILLS Amethyst levonorgestrel/ee (No pill-free interval) PROGESTIN-ONLY PILLS d - Mini-pill Camila Errin Heather Jencycla Jolivette Lyza Afaxys Nora-BE Actavis norethindrone 0.35 mg norethindrone 0.35 mg Mylan norethindrone 0.35 mg Ortho Micronor Janssen Sharobel EE 20 mcg Not applicable Levonorgestrel 90 mcg Norethindrone 0.35 mg EMERGENCY CONTRACEPTION Ella Afaxys Not applicable Ulipristal 30 mg tablet (progesterone receptor modulator) After Pill EContra EZ Fallback Solo My Way Next Choice One Dose Opticon One Step Plan B One-Step others Syzygy Afaxys Gavis Sun Pharma branded Not applicable Levonorgestrel 1.5 mg tablet x 1 HORMONAL ALTERNATIVES TO ORAL CONTRACEPTION Brand Name Dose/Route/Cost Manufacturer Estrogen Progestin Depo-Provera CI 3,d WAC $174 Pfizer None Medroxyprogesterone acetate 150 mg Intramuscular (IM) injection in the gluteal or deltoid muscle once every 3 months (13 weeks) Copyright 2017 by Therapeutic Research Center

12 (Clinical Resource #330609: Page 6 of 8) Brand Name Dose/Route/Cost Depo-subQ Provera 104 4,d,e WAC $195 Manufacturer Estrogen Progestin Pfizer None Medroxyprogesterone acetate 104 mg 0.65 ml (104 mg) subcutaneous (SC) injection into the anterior thigh or abdomen, once every 3 months (12-14 weeks) Kyleena 2 (IUD) WAC $858 Bayer None Levonorgestrel 17.5 mcg/day (after first 24 days of insertion) for up to 5 years Liletta 12 (IUD) WAC $684 Allergan USA, Inc. None Levonorgestrel 18.6 mcg/day initially then approximately 16.3 mcg/day at 1 year, 14.3 mcg/day at 2 years, and 12.6 mcg/day at 3 years. Must be removed by the end of the third year Mirena 6,d,g (IUD) Bayer None Levonorgestrel 20 mcg/day for up to 5 years WAC $858 Nexplanon 5,d,f,h WAC $772 Implanted subdermally just under the skin at the inner side of the non-dominant arm. Merck None Etonogestrel (release rate varies over time) for up to 3 years NuvaRing 7 WAC $136 Merck Ethinyl estradiol 15 mcg/day Etonogestrel (active form of desogestrel) 0.12 mg/day Vaginal ring inserted and left in for 3 weeks and removed for 1 week Xulane 9,b WAC $24 Mylan Ethinyl estradiol 35 mcg/day Norelgestromin (active form of norgestimate) 150 mcg/day Transdermal patch applied weekly (for 3 weeks, then week 4 is patch-free) ParaGard T380A (IUD) WAC $739 Non-hormonal, copper IUD Copyright 2017 by Therapeutic Research Center

13 (Clinical Resource #330609: Page 7 of 8) Brand Name Dose/Route/Cost Skyla 8,d (IUD) WAC $715 Manufacturer Estrogen Progestin Bayer None Levonorgestrel 14 mcg/day (after first 24 days of insertion) for up to 3 years a. This grouping is not an indication of therapeutic equivalence for purposes of substitution as defined by the FDA s Orange Book. For therapeutic equivalence, consult the Orange Book ( b. Cycle control poor in 20% of women in first cycle. More breast discomfort in first 2 cycles than with combined oral contraceptive. Body weight >90 kg may increase risk of unintended pregnancy. 1 Has been used continuously with 12 active patches in a row followed by 7-day patch-free interval. 10 c. Beyaz, Rajani, and Safyral also contain levomefolate (0.451 mg) in each tablet. d. For information on which oral hormonal contraceptive to use, see our charts, Choosing a Hormonal Contraceptive and Contraception for Women with Chronic Medical Conditions. e. FDA approved for use as a contraceptive and for management of pain associated with endometriosis. 4 f. Effectiveness rate in very overweight women (e.g., >130% of ideal body weight) unknown. 5,11 g. FDA approved for use as a contraceptive and to treat heavy menstrual bleeding in women who use IUD for contraception. 6 h. Implanon was previously available in the U.S. Implanon and Nexplanon differ in insertion applicator and radio-opacity. i. Available as a softgel capsule. The four non-hormonal capsules each contain ferrous fumarate 75 mg. 11 Users of this resource are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and internet links in this article were current as of the date of publication. Project Leader in preparation of this clinical resource (330609): Beth Bryant, Pharm.D., BCPS, Assistant Editor References 1. Hatcher RA, Trussell J, Stewart F, et al. Contraceptive Technology: 20th Revised Edition. New York, NY: Ardent Media, Inc., Product information for Kyleena. Bayer HealthCare Pharmaceuticals, Inc. Whippany, NJ September Product information for Depo-Provera CI. Pfizer. New York, NY January Product information for Depo-subQ Provera 104. Pfizer, Inc. New York, NY December Product information for Nexplanon. Merck & Co., Inc. Whitehouse Station, NJ December Product information for Mirena. Bayer HealthCare Pharmaceuticals, Inc. Whippany, NJ December Product information for NuvaRing. Merck & Co., Inc. Whitehouse Station, NJ September Product information for Skyla. Bayer HealthCare Pharmaceuticals, Inc. Whippany, NJ December Product information for Xulane. Mylan Pharmaceuticals, Inc. Morgantown, WV March Stewart FH, Kaunitz AM, Laguardia KD, et al. Extended use of transdermal norelgestromin/ethinyl estradiol: a randomized trial. Obstet Gynecol 2005;105: Product information for Taytulla. Allergan USA, Inc. Irvine, CA August Product information for Liletta. Allergan USA, Inc. Irvine, CA May Cite this document as follows: Clinical Resource, Comparison of Oral Contraceptives and Non-Oral Alternatives. Pharmacist s Letter/Prescriber s Letter. June Copyright 2017 by Therapeutic Research Center

14 (Clinical Resource #330609: Page 8 of 8) Evidence and Recommendations You Can Trust 3120 West March Lane, Stockton, CA ~ TEL (209) ~ FAX (209) Copyright 2017 by Therapeutic Research Center Subscribers to the Letter can get clinical resources, like this one, on any topic covered in any issue by going to PharmacistsLetter.com, PrescribersLetter.com, PharmacyTechniciansLetter.com, or NursesLetter.com

15 This Professional Resource gives subscribers additional insight related to the Recommendations published in PHARMACIST S LETTER / PRESCRIBER S LETTER September 2016 ~ Resource # Contraception for Women With Chronic Medical Conditions In healthy women, hormonal contraception is a safe and effective way to prevent unwanted pregnancy. However, for women with coexisting medical conditions, some forms of contraception may be harmful or have reduced efficacy. For example, women with high blood pressure, diabetes, and migraines may be at increased risk of adverse effects with hormonal contraceptive use. In some situations, the risk of pregnancy will need to be weighed against the risks of hormonal contraceptive use. The chart below provides guidance to aid healthcare professionals in providing safe and effective contraception options for patients. This chart was developed using a variety of resources (e.g., Centers for Disease Control and Prevention, 1 World Health Organization, 2 American College of Obstetrics and Gynecology, 3 Society of Obstetricians and Gynecologists of Canada, 4,16,17 others) and does not represent any one organization s opinions. For a listing of available hormonal contraceptives, see our chart, Comparison of Oral Contraceptives and Non-Oral Alternatives (U.S. subscribers); (Canadian subscribers). Abbreviations: BMI = body mass index; BP = blood pressure; COC = combined estrogen/progestin oral contraceptive; CV = cardiovascular; DBP = diastolic blood pressure; DM = diabetes mellitus; IUD = intrauterine device; MI = myocardial infarction; SBP = systolic blood pressure. NOTE: Progestin-only pill efficacy is highly dependent on strict adherence; it is critical pill is taken at the same time (within 3 hours) every day. 24 Condition a Bariatric Surgery Concerns/ Considerations Reduced oral absorption of contraceptives with malabsorptive procedures (e.g., Roux-en-Y bypass). 1 Preferred Method of Contraception b Malabsorptive procedures (e.g., Roux-en-Y bypass): Give preference to non-oral contraceptive (e.g., patch, vaginal ring, implants, IUD). 1 Avoid oral contraceptives. 1 Restrictive procedures (e.g., banding, sleeve): All forms of contraception are acceptable. 1 Comments Complications such as vomiting following bariatric surgery may also contribute to reduced effectiveness of oral contraceptives. 1 Breast Cancer Benign breast disease/family history of breast cancer: Possible increased breast cancer risk. 1,3 Breast cancer (current/personal history): Worsening or recurrence of disease. 1,2 Family history of breast cancer or benign breast disease: All forms of contraception are acceptable. 1,2 Current or past history of breast cancer: Copper IUD preferred. 1,2 Theoretical and proven risks with all other types of contraception are unacceptable. 1,2 Copyright 2016 by Therapeutic Research Center Disease progression may be less with levonorgestrel-releasing IUDs compared to COCs or higher-dose progestin-only contraceptives because breast cancer is a hormonally sensitive tumor. 1

16 (Professional Resource #320901: Page 2 of 10) Condition a Breastfeeding Concerns/ Considerations Estrogen-containing contraceptives may reduce milk production, especially concerning when milk production is being established. 1,3 Women at risk for breastfeeding problems (e.g., poor lactation, preterm delivery) may be more prone to progestins reducing milk supply. 17 Preferred Method of Contraception b Progestin-only contraceptives can be used (e.g., oral, depot medroxyprogesterone, implants, and levonorgestrel-releasing IUD) immediately. 1,2,19 Estrogen-containing contraceptives are an acceptable alternative >6 weeks 1 (per WHO >6 months 2 ) postpartum. (See postpartum section for when to restart estrogen-containing contraceptives in women with thromboembolism risk factors and contraceptive use in non-breastfeeding women). Comments Postpartum insertion of a copper or levonorgestrel-containing IUD immediately after vaginal delivery or during Cesarean section procedure is associated with lower expulsion rate than delayed insertion (up to 48 hours 16 or 72 hours 1 after delivery). Depression Depression may be adversely affected by progestins. 7 All types of contraceptives can be used, even in patients taking a selective serotonin reuptake inhibitor. 1,2 History of depression is not a contraindication to long-acting progestins (e.g., depot medroxyprogesterone, levonorgestrel-releasing IUD). Though, they are more difficult to discontinue if use exacerbates depression. 7 Diabetes Possible impaired glucose control and carbohydrate metabolism. 2 Possible negative effect of progesterone on lipid metabolism. 1,3 *Examples of vascular disease may include nephropathy, neuropathy, or retinopathy. Women with DM and no vascular disease: Copper IUD is preferred. 1,3 Most experts would consider all types of contraceptives appropriate, depending on the patient s other cardiovascular risks. 1,3 DM with vascular disease* or DM for >20 years: Copper IUD is preferred. 1 Oral progestins, implants, and levonorgestrelreleasing IUD acceptable alternatives. 1 Avoid estrogen-containing contraceptives and depot medroxyprogesterone. 1,10 In women with no vascular complications, COC use had only a limited effect on daily insulin dose, A1C, or lipids. 1 Concern about the negative effect of progesterone on lipid metabolism, possibly affecting progression of nephropathy, retinopathy, or other vascular disease. 10 Copyright 2016 by Therapeutic Research Center

17 (Professional Resource #320901: Page 3 of 10) Condition a Epilepsy Concerns/ Considerations Some antiepileptic medications (not lamotrigine) induce hepatic enzymes and reduce serum concentrations, and therefore the efficacy, of estrogen, progestin, or both. 1,3 Preferred Method of Contraception b If taking lamotrigine: 1 Estrogen reduces lamotrigine levels ~50%. 14,15 o Avoid estrogen-containing contraceptives. All other contraceptives are acceptable. If taking phenytoin, carbamazepine, barbiturates, primidone, topiramate, or oxcarbazepine: 1 Depot medroxyprogesterone and IUDs are preferred. Implants are an acceptable alternative. Avoid estrogen-containing contraceptives and oral progestin-only contraceptives. Comments Contraceptive estrogen and/or progestin levels are not affected by ethosuximide, gabapentin, levetiracetam, tiagabine, valproic acid, and zonisamide. 3 Headache/ Migraine Estrogen-containing contraceptives may increase the risk of stroke in women with migraine headaches with aura. 3 Non-migraine headaches: All contraceptives are acceptable. 1,2 Migraine without aura: All contraceptives are acceptable. 1,2 If migraines are exacerbated by estrogencontaining contraceptives, discontinue. 1,2 Menstrual migraine: o All contraceptives are acceptable. 1 o If using a COC, prefer continuous or extended cycle to minimize the hormonefree interval. 11 Regardless of age, women who develop migraine headaches, with or without aura, or whose migraines worsen while using estrogencontaining contraceptives, should discontinue estrogen use. 2 Other risk factors for stroke (e.g., age [>35 years old], 2 hypertension, smoking) may impact choice of contraceptives. Migraines with aura: Give preference to progestin-only or nonhormonal contraceptives. 1 If possible, avoid estrogen-containing contraceptives as the risk of stroke is higher in women with migraine with aura, compared to women without migraines. 1 Copyright 2016 by Therapeutic Research Center

18 (Professional Resource #320901: Page 4 of 10) Condition a Hypercoagulable conditions (e.g., history of deep vein thrombosis, pulmonary embolism) Concerns/ Considerations Possible increased coagulability and risk of thromboembolism due to estrogen content. 1,3 Possible increased coagulability and risk of thromboembolism due to newer progestins (e.g., desogestrel, norgestimate, drospirenone) Preferred Method of Contraception b Family history of DVT or PE: All forms of contraception are acceptable. 1 History of DVT or PE (not taking anticoagulant therapy or taking less than three months): Copper IUD preferred. 1 Progestin-only contraceptives can be used (e.g., oral, depot medroxyprogesterone, implants, and levonorgestrel-releasing IUD). 1 Avoid estrogen-containing contraceptives. 1,3 Comments Data with the contraceptive patch indicates there is a greater exposure to estrogen compared with COCs, and an associated higher rate of thromboembolism. 12,25 History of DVT or PE (taking anticoagulant therapy for at least three months): Avoid estrogen-containing contraceptives. 1 All other forms of contraception are acceptable. 1 Hyperlipidemia Oral estrogen may increase triglyceride levels and progestins may increase LDL levels. 2 Copper IUD is preferred. 2 All other forms of contraception are acceptable alternatives. 2 Routine screening of lipid levels is not necessary because of contraceptive use. 2 COC use has shown inconsistent impact on lipids. 2 If lipids are a concern, give preference to COC with a less androgenic progestin. 3 See our CE courses, The Art of Selecting and Prescribing Hormonal Contraception and Choosing Wisely: Contraception. Copyright 2016 by Therapeutic Research Center

19 (Professional Resource #320901: Page 5 of 10) Condition a Hypertension Concerns/ Considerations Estrogen may increase BP and risk of CV events in women with hypertension. 1,3 Preferred Method of Contraception b Adequately controlled BP, or SBP = 140 to 159 mmhg or DBP = 90 to 99 mmhg: 1-3 Avoid estrogen-containing contraceptives, if not adequately controlled. Consider progestin-only or non-hormonal contraceptives. Feel comfortable using low-dose (e.g., 20 mcg estrogen) COCs if BP is controlled and no other risk factors. Monitor BP. SBP >160 mmhg or DBP >100 mmhg: 1,10 Copper IUD is preferred. Next, consider progestin-only options (e.g., levonorgestrel-releasing IUD, implants, progestin-only pill). Other non-hormonal (e.g., condoms) forms of contraception are acceptable alternatives. Avoid depot medroxyprogesterone or combined hormonal contraceptives. Comments Risk for CV events may significantly increase with coexisting conditions (e.g., hyperlipidemia, obesity). 1 Weigh risk of CV events against risk of adverse pregnancy outcomes. 3 If possible, control BP prior to initiating hormonal contraceptives. 3 Monitor BP after starting estrogencontaining contraceptives. 3 Depot medroxyprogesterone might negatively impact lipid metabolism, and increase potential progression of nephropathy, retinopathy, or other vascular disease. 10 Obesity Continued Obesity is an independent risk factor for venous thromboembolism. Obese women who use COCs may have an even greater risk of venous thromboembolism. In addition, conflicting reports of failure rates of estrogen-containing contraceptives. 1 All forms of contraception are acceptable in women with a BMI >30 kg/m 2. 1,2 o Use caution, due to potential for reduced efficacy, with the contraceptive patch in women >90 kg. 1,3,12,13 o Use an extended cycle COC (e.g., Seasonique) with 20 to 35 mcg of estrogen for otherwise healthy women preferring a COC. Risk of thromboembolism increases in women with risk factors for thromboembolism other than obesity (e.g., smoking, age >35 years). In this case, a progestin-only or nonhormonal Copyright 2016 by Therapeutic Research Center Evidence suggests that with consistent use, ovulation suppression is similar in normal-weight and obese women. 6 The role of obesity and contraceptive failure is unclear. 5 Some experts suggest high-dose estrogen COC in obese women. 18 Others suggest decreasing (or eliminating) the pill-free interval for heavier women. 18

20 (Professional Resource #320901: Page 6 of 10) Condition a Obesity, continued Concerns/ Considerations Preferred Method of Contraception b method may be preferred. 1,2 Emergency contraceptive pills may be less effective in women with a BMI >30 kg/m 2 compared to women with a BMI <25 kg/m 2. 1,2 o Lean toward ulipristal instead of levonorgestrel, due to slightly improved prevention rates. Copper IUD is an effective alternative. 23 Comments Postpartum Women remain in a hypercoagulable state for many weeks after childbirth. Estrogen may increase the risk of thromboembolism. 3 Non-breastfeeding women <21 days postpartum: o Avoid estrogen-containing contraceptives. 1,2 o All other contraceptives are acceptable. 1,2 >21 days postpartum: o Estrogen-containing contraceptives are generally acceptable without risk factors for thromboembolism (e.g., age >35 years, BMI >30 kg/m 2, smoking, preeclampsia). 1,2 >42 days postpartum: o Estrogen-containing contraceptives are acceptable, even with risk factors for thromboembolism. 1,2 Postpartum insertion of a copper or levonorgestrel-containing IUD immediately after vaginal delivery or during Cesarean section procedure is associated with lower expulsion rate than delayed insertion (up to 48 hours 16 or 72 hours 1 after delivery). Breastfeeding women with risk factors: <21 days postpartum: o Copper or levonorgestrel-releasing IUDs are preferred. 1 o Progestin-only contraceptives (e.g., implants, depot medroxyprogesterone, progestin-only pills) are acceptable alternatives. 1 Continued Copyright 2016 by Therapeutic Research Center

21 (Professional Resource #320901: Page 7 of 10) Condition a Postpartum, continued Concerns/ Considerations Preferred Method of Contraception b 21 to <30 days postpartum: o Copper or levonorgestrel-releasing IUDs are preferred. 1 o Progestin-only contraceptives (e.g., implants, depot medroxyprogesterone, progestin-only pills) are generally acceptable alternatives to 42 days postpartum: o Try to avoid estrogen-containing contraceptives. 1 o All other contraceptives are acceptable. 1 >42 days postpartum: o Estrogen-containing contraceptives are generally acceptable. 1 o All other contraceptives are acceptable. 1 Comments (See breastfeeding section for contraception use in breastfeeding women without risk factors.) Smoking Older studies of COCs with >50 mcg of estrogen demonstrated increased risk of MI, especially in women in their mid-30s or older. 3 All forms of contraception, including estrogencontaining, are acceptable in women <35 years old. 1-4 Avoid estrogen-containing contraceptives in women >35 years, especially if smoking >15 cigarettes/day. 1-4 All other contraceptives are acceptable in women >35 years old. 1-4 U.S. studies found COCs with <50 mcg of estrogen did not increase risk of MI in smokers compared to non-smokers, regardless of age. 3 Dutch studies found COC use may increase risk of MI in smokers compared with non-use in smokers (age of study group 18 to 49 years). 3 Stroke Hormonal contraception can increase the risk of hypercoagulability and stroke. 1,8 Copper IUD is preferred. 1,2 Levonorgestrel-releasing IUD is an acceptable alternative. 1,2 Avoid all other types of contraception. 1,2 COCs with <30 mcg of estrogen have the lowest risk of thromboembolism. 9 Early studies of oral contraceptives and stroke used 50 mcg of estrogen. 9 Copyright 2016 by Therapeutic Research Center

22 (Professional Resource #320901: Page 8 of 10) Condition a Systemic lupus erythematosus (SLE) Concerns/ Considerations Increased risk of ischemic heart disease, stroke, and venous thromboembolism, especially in women with antiphospholipid antibodies. 1 Preferred Method of Contraception b Positive or unknown antiphospholipid antibody test: 1,2 Copper IUD is preferred. Avoid all other contraceptives. Receiving immunosuppressive therapy (and antiphospholipid antibody negative): 1,2 Copper IUD is preferred. All other contraceptives are acceptable alternatives. Comments Limited data on use of IUDs in women with lupus. However, they are an effective reasonable alternative in this population. 3 Severe thrombocytopenia: Levonorgestrel-releasing IUD may be preferred to treat menorrhagia. 2 All other contraceptives are acceptable. 2 a. Common medical conditions are listed in this chart. Other medical conditions (not listed) may need to be considered when selecting contraceptive methods. b. The suggested methods of contraception are for the purpose of contraception only, and do not take into consideration use for other reasons (e.g., treatment of certain conditions, prevention of sexually transmitted diseases). In addition, there will be times when conditions overlap (i.e., patients with multiple conditions) or a patient s individual circumstances need to be considered. In these cases, choice of contraceptive should be based on the clinician s best judgment and evaluation of contributing factors. Users of this resource are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and internet links in this article were current as of the date of publication. Copyright 2016 by Therapeutic Research Center

23 (Professional Resource #320901: Page 9 of 10) Project Leader in preparation of this professional resource: Beth Bryant, Pharm.D., BCPS, Assistant Editor References 1. CDC. U.S. Medical Eligibility Criteria for Contraceptive Use, MMWR 2016;65: m. (Accessed August 2, 2016). 2. WHO. Medical eligibility criteria for contraceptive use. 5th ed. Geneva: WHO; _eng.pdf?ua=1. (Accessed August 2, 2016). 3. ACOG Committee on Practice Bulletins-Gynecology. ACOG practice bulletin. No. 73: Use of hormonal contraception in women with coexisting medical conditions. Obstet Gynecol 2006;107: [Reaffirmed 2013]. 4. Reid R, Leyland N, Wolfman W, et al. SOGC clinical practice guidelines: oral contraceptives and the risk of venous thromboembolism: an update: no. 252, December Int J Gynaecol Obstet 2011;112: Brunner Huber LR, Toth JL. Obesity and oral contraceptive failure: findings from the 2002 National Survey on Family Growth. Am J Epidemiol 2007;166: Westhoff CL, Torgal AH, Mayeda ER, et al. Ovarian suppression in normal-weight and obese women during oral contraceptive use: a randomized controlled trial. Obstet Gynecol 2010;116(2 part 1): Nelson AL. Combined oral contraceptives. In: Hatcher RA, Trussel J, Nelson AL, et al, Eds. Contraceptive Technology, 19th ed. Baltimore, MD: Ardent Medica, 2007: Manchikanti A, Grimes DA, Lopez LM, Schulz KF. Steroid hormones for contraception in women with sickle cell disease. Cochrane Database Syst Rev 2007;(2):CD Roach RE, Helmerhorst FM, Lijfering WM, et al. Combined oral contraceptives: the risk of myocardial infarction and ischemic stroke. Cochrane Database Syst Rev 2015(8):CD Zieman M, Hatcher RA. Managing Contraception. 11 th ed. Tiger, Georgia: Bridging the Gap Foundation, Guilbert E, Boroditsky R, Black A, et al. Canadian consensus guideline on continuous and extended hormonal contraception, J Obstet Gynaecol Can 2007;29(7 Suppl 2):S Product information for Xulane. Mylan. Morgantown, WV March Product monograph for Evra. Janssen Inc. Toronto, ON M3C 1L9. November Product information for Lamictal. GlaxoSmithKline. Research Triangle Park, NC May Product monograph for Lamictal. GlaxoSmithKline. Mississauga, Ontario L5N 6L4. March Black A, Guilbert E, Costescu D, Dunn S, et al. Canadian contraception consensus (Part 3 of 4): chapter 7 intrauterine contraception. J Obstet Gynaecol Can 2016;38: Black A, Guilbert E, Costescu D, Dunn S, et al. Canadian contraception consensus (Part 3 of 4): chapter 8 progestin-only contraception. J Obstet Gynaecol Can 2016;38: Daly MC, Edelman A. Obese women need higher or continuous dose for oral contraceptive success. January podcast-obesity-contraception.aspx. (Accessed August 3, 2016). 19. Committee on obstetric practice. American Congress of Obstetricians and Gynecologists. Committee opinion. August Publications/Committee-Opinions/Committee-on- Obstetric-Practice/Immediate-Postpartum-Long- Acting-Reversible-Contraception. (Accessed August 12, 2016). 20. Pearce HM, Layton D, Wilton LV, Shakir SA. Deep vein thrombosis and pulmonary embolism reported in the Prescription Event Monitoring Study of Yasmin. Br J Clin Pharmacol 2005;60: van Vliet HA, Frolich M, Christella M, et al. Association between sex hormone-binding globulin levels and activated protein C resistance in explaining the risk of thrombosis in users of oral contraceptives containing different progestogens. Hum Reprod 2005;20: Hatcher RA, Trussel J, Nelson AL, et al (eds). Contraceptive Technology. 20th ed. Ardent Media: New York, NY Glasier A, Cameron ST, Blithe D, et al. Can we identify women at risk of pregnancy despite using emergency contraception? Data from randomized trials of ulipristal acetate and levonorgestrel. Contraception 2011;84: Association of Reproductive Health Professionals. Choosing a birth control method: progestin-only oral contraceptives. and-resources/quick-reference-guide-for- Clinicians/choosing/Progestin-Only-OCs. (Accessed August 17, 2016). 25. FDA. Combined hormonal contraceptives (CHCs) and the risk of cardiovascular disease endpoints. October 22, M pdf. (Accessed August 18, 2016). Cite this document as follows: Contraception for Women With Chronic Medical Conditions. Pharmacist s Letter/Prescriber s Letter. September Copyright 2016 by Therapeutic Research Center

24 (Professional Resource #320901: Page 10 of 10) Evidence and Recommendations You Can Trust 3120 West March Lane, Stockton, CA ~ TEL (209) ~ FAX (209) Copyright 2016 by Therapeutic Research Center Subscribers to the Letter can get professional resources, like this one, on any topic covered in any issue by going to PharmacistsLetter.com, PrescribersLetter.com, PharmacyTechniciansLetter.com, or NursesLetter.com