Comparison of Oral Contraceptives and Non-Oral Alternatives

PL Detail-Document #290305 −This PL Detail-Document gives subscribers

additional insight related to the Recommendations published in− PHARMACIST’S LETTER / PRESCRIBER’S LETTER March 2013

Comparison of Oral Contraceptives and Non-Oral Alternatives —More information about the use of contraceptives is available in our PL Detail-Document, Hormonal Contraception—

Productsa Manufacturerb Estrogen Progestin LOW-DOSE MONOPHASIC PILLS Aviane-28 Teva EE 20 mcg Levonorgestrel 0.1 mg Falmina Novast Lessina Teva Lutera Actavis Orsythia Qualitest Sronyx Actavis

Gildess Fe 1/20 Qualitest EE 20 mcg Norethindrone acetate Junel 1/20 Teva 1 mg Junel Fe 1/20 Teva Loestrin-21 1/20 Warner Chilcott/Teva Loestrin Fe 1/20 Warner Chilcott/Teva Microgestin 1/20 Actavis Microgestin Fe 1/20 Actavis

Generess Fe chewable Actavis EE 25 mcg Norethindrone 0.8 mg

Altavera Sandoz EE 30 mcg Levonorgestrel 0.15 mg Kurvelo Lupin Levora Actavis Marlissa Glenmark Nordette-28 Duramed/Teva Portia-28 Teva

Cryselle-28 Teva EE 30 mcg Norgestrel 0.3 mg Elinest Novast Low-Ogestrel-21 Actavis Low-Ogestrel-28 Actavis Lo/Ovral-28 Wyeth

Gildess Fe 1.5/30 Qualitest EE 30 mcg Norethindrone acetate Junel 1.5/30 Teva 1.5 mg Junel Fe 1.5/30 Teva Loestrin 1.5/30-21 Warner Chilcott/Teva Loestrin Fe 1.5/30 Warner Chilcott/Teva Microgestin 1.5/30 Actavis Microgestin Fe 1.5/30 Actavis

More. . . Copyright © 2013 by Therapeutic Research Center 3120 W. March Lane, Stockton, CA 95219 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.PharmacistsLetter.com ~ www.PrescribersLetter.com ~ www.PharmacyTechniciansLetter.com (PL Detail-Document #290305: Page 2 of 7)

Productsa Manufacturerb Estrogen Progestin LOW-DOSE MONOPHASIC PILLS (cont.) Apri Teva EE 30 mcg Desogestrel 0.15 mg Desogen Organon Emoquette Qualitest Ortho-Cept Ortho Reclipsen Actavis Solia Prasco levonorgestrel/ethinyl Lupin EE 30 mcg Drospirenone 3 mg estradiol Ocella Teva Safyralc Bayer Syeda Sandoz Zarah Actavis Yasmin Bayer

Kelnor 1/35 Teva EE 35 mcg Ethynodiol diacetate Zovia 1/35 Actavis 1 mg

Estarylla Sandoz EE 35 mcg Norgestimate 0.25 mg Mono-Linyah Novast MonoNessa Actavis Norgestimate/ethinyl Glenmark estradiol Ortho-Cyclen-28 Ortho Previfem Qualitest Sprintec Teva

Necon 1/50 Actavis Mestranol 50 mcg Norethindrone 1 mg Norinyl 1+50 Actavis

Balziva Teva EE 35 mcg Norethindrone 0.4 mg; Briellyn Glenmark total of 8.4 mg/cycle.1 Femcon Fe chewable Warner Chilcott Gildagia Qualitest Ovcon-35 Warner Chilcott Philith Novast Vyfemla Lupin Zenchent Actavis Zeosa chewable Teva Brevicon-28 Actavis EE 35 mcg Norethindrone 0.5 mg; Modicon-28 Ortho total of 10.5 mg/cycle. Necon 0.5/35 Actavis Nortrel 0.5/35 Teva Wera Novast

Alyacen 1/35 Glenmark EE 35 mcg Norethindrone 1 mg; Cyclafem 1/35 Qualitest total of 21 mg/cycle.1 Dasetta 1/35 Novast Necon 1/35-28 Actavis Norinyl 1+35-28 Actavis Nortrel 1/35-28 Teva Ortho-Novum 1/35-28 Ortho

(PL Detail-Document #290305: Page 3 of 7)

Productsa Manufacturerb Estrogen Progestin HIGH-DOSE MONOPHASIC PILLS Ovcon-50 Warner Chilcott EE 50 mcg Norethindrone 1 mg

Ogestrel 0.5/50-28 Actavis EE 50 mcg Norgestrel 0.5 mg

Zovia 1/50-28 Actavis EE 50 mcg Ethynodiol diacetate 1 mg

BIPHASIC PILLS Azurette Actavis EE 20 mcg x 21 days, Desogestrel Kariva Teva placebo x 2 days, 10 mcg 0.15 mg x 21 days Mircette Teva x 5 days. Viorele Glenmark

Necon 10/11 Actavis EE 35 mcg Norethindrone 0.5 mg x 10 days, 1 mg x 11 days. TRIPHASIC PILLS Estrostep Fe Warner Chilcott EE 20 mcg x 5 days, Norethindrone acetate Tilia Actavis 30 mcg x 7 days, 35 mcg 1 mg x 21 days Tilia Fe Actavis x 9 days Tri-Legest Fe Teva Norgestimate/ethinyl Lupin EE 25 mcg x 21 days Norgestimate estradiol 0.18 mg x 7 days, Ortho Tri-Cyclen Lo Ortho 0.215 mg x 7 days, Tri Lo Sprintec Actavis 0.25 mg x 7 days.

Caziant Actavis EE 25 mcg x 21 days Desogestrel Cesia Prasco 0.1 mg x 7 days, Cyclessa Schering-Plough 0.125 mg x 7 days, Velivet Teva 0.15 mg x 7 days.

Enpresse Teva EE 30 mcg x 6 days, Levonorgestrel Levonest Novast 40 mcg x 5 days, 30 mcg 0.05 mg x 6 days, Myzilra Qualitest x 10 days. 0.075 mg x 5 days, Trivora Actavis 0.125 mg x 10 days. Total of 1.925 mg/cycle.1 Ortho Tri-Cyclen Ortho EE 35 mcg x 21 days Norgestimate Tri-Estarylla Sandoz 0.18 mg x 7 days, Tri-Linyah Novast 0.215 mg x 7 days, TriNessa Actavis 0.25 mg x 7 days. Tri-Previfem Qualitest Tri-Sprintec Teva

Aranelle Teva EE 35 mcg x 21 days Norethindrone Leena Actavis 0.5 mg x 7 days, Tri-Norinyl Actavis 1 mg x 9 days, 0.5 mg x 5 days. Total of 15 mg/cycle.1 Alyacen 7/7/7 Glenmark EE 35 mcg x 21 days Norethindrone Cyclafem 7/7/7 Qualitest 0.5 mg x 7 days, Dasetta 7/7/7 Novast 0.75 mg x 7 days, Nortrel 7/7/7 Teva 1 mg x 7 days. Necon 7/7/7 Actavis Total of 15.75 mg/cycle.1 Ortho-Novum 7/7/7 Ortho More. . . Copyright © 2013 by Therapeutic Research Center 3120 W. March Lane, Stockton, CA 95219 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.PharmacistsLetter.com ~ www.PrescribersLetter.com ~ www.PharmacyTechniciansLetter.com

(PL Detail-Document #290305: Page 4 of 7)

Productsa Manufacturerb Estrogen Progestin FOUR-PHASIC Natazia Bayer Estradiol valerate 3 mg x Dienogest 2 days, then 2 mg x 22 none x 2 days, then days, then 1 mg x 2 days, 2 mg x 5 days, then then 2-day pill-free 3 mg x 17 days, then interval. none x 4 days

EXTENDED-CYCLE PILLS Lo Loestrin Fe Warner Chilcott EE 10 mcg x 26 days Norethindrone acetate Lo Minastrin Fe chewable Warner Chilcott 1 mg x 24 days

Loestrin 24 Fe discontinued Warner Chilcott EE 20 mcg x 24 days Norethindrone acetate Minastrin 24 Fe chewable Warner Chilcott 1 mg x 24 days

Amethia Lo Actavis EE 20 mcg x 84 days, Levonorgestrel Ethinyl Lupin 10 mcg x 7 days. 0.1 mg x 84 days estradiol/levonorgestrel LoSeasonique Teva

Introvale Sandoz EE 30 mcg x 84 days Levonorgestrel Jolessa Teva 0.15 mg x 84 days Levonorgestrel/ethinyl Lupin estradiol Quasense Actavis Seasonale Teva

Amethia Actavis EE 30 mcg x 84 days, Levonorgestrel Seasonique Teva 10 mcg x 7 days. 0.15 mg x 84 days

Quartette Teva EE 20 mcg x 42 days, Levonorgestrel 25 mcg x 21 days, 0.15 mg x 84 days 30 mcg x 21 days, then 10 mcg x 7 days Beyazc Bayer EE 20 mcg x 24 days Drospirenone Gianvi Teva 3 mg x 24 days Loryna Sandoz Vestura Actavis Yaz Bayer

CONTINUOUS-CYCLE PILLS Amethyst Actavis EE 20 mcg Levonorgestrel 90 mcg (No pill-free interval) PROGESTIN-ONLY PILLSd - “Mini-pill” Camila Teva Not applicable Norethindrone 0.35 mg Errin Teva Heather Glenmark Jolivette Actavis Micronor Ortho Nor-QD Actavis Nora-BE Actavis

(PL Detail-Document #290305: Page 5 of 7)

Productsa Manufacturerb Estrogen Progestin EMERGENCY CONTRACEPTION Ella Actavis Not applicable Ulipristal 30 mg tablet (progesterone receptor modulator) Levonorgestrel Perrigo R and D Not applicable Levonorgestrel Next Choice Actavis 0.75 mg tablets x 2 Plan B Teva (separated by 12 hours)

Next Choice One Dose Actavis Not applicable Levonorgestrel Plan B One-Step Teva 1.5 mg tablet x 1

Abbreviations: EE = ethinyl estradiol; IUS = intrauterine system

HORMONAL ALTERNATIVES TO ORAL CONTRACEPTION Brand Name Manufacturer Estrogen Progestin Dose/Route Depo-Provera CI Pfizer None Medroxyprogesterone Medroxyprogesterone Sicor acetate 150 mg Acetate Injection3,d

Intramuscular (IM) injection in the gluteal or deltoid muscle once every 3 months (13 weeks) Depo-subQ Provera 1044,d,e 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)

Mirena6,d,g Bayer None Levonorgestrel 20 mcg/day (IUS) for up to 5 years Nexplanon5,d,f Schering-Plough None Etonogestrel (release rate varies over Implanted subdermally just time) for up to 3 years under the skin at the inner side of the non-dominant arm NuvaRing7 Schering-Plough Ethinyl estradiol Etonogestrel (active form 15 mcg/day of desogestrel) Vaginal ring inserted and left 0.12 mg/day in for 3 weeks and removed for 1 week Ortho Evra9,h,i Ortho Ethinyl estradiol Norelgestromin (active 35 mcg/day form of norgestimate) Transdermal patch applied 200 mcg/day weekly (for 3 weeks, then week 4 is patch-free) Skyla8,d Bayer None Levonorgestrel 14 mcg/day (IUS) (after first 24 days of insertion) for up to 3 years

(PL Detail-Document #290305: Page 6 of 7)

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 (http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm). b. On January 24, 2013 the name of Watson Pharmaceuticals was changed to Actavis, Inc. c. Beyaz and Safyral also contain levomefolate (0.451 mg) in each tablet. d. Progestin-only contraceptives considered to be safer than combined oral contraceptives for women with: migraine headache [Level B]; smoker over 35 years old [Level A]; history of thromboembolic disease [Level A]; less than two weeks postpartum; hypertension with vascular disease or over 35 years of age; diabetes with vascular disease or over 35 years of age; systemic lupus erythematosus with vascular disease, nephritis, or antiphospholipid antibodies [Level B]; hypertriglyceridemia.2 Combined oral contraceptives are contraindicated in coronary artery disease, congestive heart failure, and cerebrovascular disease; a progestin-only contraceptive may be an appropriate alternative for women with these conditions [Level C]. Combined oral contraceptives may be considered for women with migraine who do not have focal neurologic signs, do not smoke, are otherwise healthy, and are younger than 35 years old [Level B]. Progestin-only contraceptives can be started immediately postpartum. They are the preferred form of hormonal contraception in women who are breast-feeding; combined oral contraceptives can be considered when milk flow is well established [Level A].1,2 e. FDA approved for use as a contraceptive and for management of pain associated with endometriosis.4 f. Effectiveness rate in very overweight women unknown.1 g. FDA-approved for use as a contraceptive and to treat heavy menstrual bleeding in women who use IUS for contraception.6 h. 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 i. Release rate extrapolated from Canadian product monograph which shows identical pharmacokinetic data for Evra [Canada] and Ortho Evra [U.S.].11

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.

(PL Detail-Document #290305: Page 7 of 7)

Levels of Evidence 2. CDC. U.S. Medical Eligibility Criteria for In accordance with the trend towards Evidence-Based Contraceptive Use, 2010. MMWR 2010;59:1-86. Medicine, we are citing the LEVEL OF EVIDENCE http://www.cdc.gov/mmwr/pdf/rr/rr59e0528.pdf. (Accessed February 4, 2013). for the statements we publish. 3. Product information for Depo-Provera CI. Pfizer Level Definition Inc. New York, NY 10017. April 2012. A High-quality randomized controlled trial (RCT) 4. Product information for Depo-subQ Provera 104. High-quality meta-analysis (quantitative Pfizer Inc. New York, NY 10017. November 2010. systematic review) 5. Product information for Nexplanon. Merck & Co., B Nonrandomized clinical trial Inc. Whitehouse Station, NJ 08889. May 2012. Nonquantitative systematic review 6. Product information for Mirena. Bayer HealthCare Lower quality RCT Pharmaceuticals Inc. Wayne, NJ 07470. October Clinical cohort study 2009. Case-control study 7. Product information for NuvaRing. Merck & Co., Historical control Inc. Whitehouse Station, NJ 08889. May 2012. Epidemiologic study 8. Product information for Skyla. Bayer HealthCare C Consensus Pharmaceuticals Inc. Wayne, NJ 07470. January Expert opinion 2013. D Anecdotal evidence 9. Product information for Ortho Evra. Ortho-McNeil. In vitro or animal study Raritan, NJ 08869. August 2012. Adapted from Siwek J, et al. How to write an evidence-based 10. Stewart FH, Kaunitz AM, Laguardia KD, et al. clinical review article. Am Fam Physician 2002;65:251-8. Extended use of transdermal norelgestromin/ethinyl estradiol: a randomized trial. Project Leader in preparation of this PL Detail- Obstet Gynecol 2005;105:1389-96. Document: Neeta Bahal O’Mara, Pharm.D., 11. Product monograph for Evra. Janssen Inc. Toronto, ON M3C 1L9. December 2012. BCPS, Drug Information Consultant

References 1. Hatcher RA, Trussell J, Stewart F, et al. Contraceptive Technology: 20th Revised Edition. New York, NY: Ardent Media, Inc., 2011.

Cite this document as follows: PL Detail-Document, Comparison of Oral Contraceptives and Non-Oral Alternatives. Pharmacist’s Letter/Prescriber’s Letter. March 2013.

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