Hormonal contraception: NHS Tayside Formulary, pharmacological content and other characteristics

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Hormonal contraception: NHS Tayside Formulary, pharmacological content and other characteristics Advice from the Tayside Sexual & Reproductive Health Service (TSRHS) (Last update: 10/2017)

Combined hormonal contraception (CHC): pharmacological content (NHS Tayside Formulary contraceptives are in green, first choice COC is in dark green with white font, current most cost-effective brands are in bold font, a non-formulary brand is in red, a COC not licensed for contraception is in yellow) Oestrogen Ethinylestradiol (EE) First Norethisterone (NE) Second Levonorgestrel (LNG) Gestodene (GSD) Progestogen Third Norgestimate¹ (NGM)/ Norelgestromin² (NGMN) Desogestrel (DSG)/ Etonorgestrel³ (ENG) Fourth Drospirenone (DRSP)/ Dienogest (DNG)/ Nomegestrol (NOM) 17 OH⁴ Cyproterone acetate (CPA) 15 mcg NuvaRing (120 mcg ENG/24h) 20 mcg Loestrin 20 (NE 1mg) Femodette (GSD 75 mcg) ~ Millinette 20/75 ~ Sunya Mercilon (DSG 150 mcg) ~ Gedarel 20/150 ~ Munalea 20/150 ~ Bimizza Eloine (3 mg) (DRSP 3 mg) ~ Daylette 30 mcg Loestrin 30 (NE 1.5 mg) Microgynon 30 Microgynon 30 ED⁵ (LNG 150 mcg) ~ Levest ~ Rigevidon ~ Ovranette Femodene / Femodene ED⁵ (GSD 75 mcg) ~ Millinette 30/75 ~ Katya Marvelon (DSG 150 mcg) ~ Gedarel 30/150 ~ Munalea 30/150 Yasmin (DRSP 3 mg) ~ Lucette ~ Yacella Logynon Logynon ED⁵ (LNG 50/75/125 mcg) (triphasic) 35 mcg Bevinor (NE 0.5 mg) ~Ovysmen Norimin (NE1 mg) BiNovum (biphasic) (NE 0.5mg/1mg) Synphase (triphasic) (NE 0.5/1/0.5 mcg) TriNovum (triphasic) (NE 0.5/0.75/1 mg) Triadene (GSD 50/70/100 mcg, EE 30/40/30 mcg) (triphasic) Cilest (250 mcg NGM) ~ Cilique ~ Lizinna Evra (patch) (33.9 mcg EE/ 203 mcg NGMN/24h) Dianette ⁶ (CPA 2mg) ~ Co-cyprindiol 2

Combined hormonal contraception (CHC): pharmacological content (cont.) (NHS Tayside Formulary: non-formulary brands are in red) Oestrogen Mestranol First Norethisterone (NE) Second Levonorgestrel (LNG) Gestodene (GSD) Progestogen Third Norgestimate¹ (NGM)/ Norelgestromin² (NGMN) Desogestrel (DSG)/ Etonorgestrel³ (ENG) Fourth Drospirenone (DRSP)/ Dienogest (DNG)/ Nomegestrol (NOM) 17 OHP⁴ Cyproterone acetate (CPA) 50 mcg Norinyl-1 (NE 1 mg) Estradiol Valerate (EV) 1-3 mg Qlaira (DNG 0-3 mg, EV 0-3 mg) (26d/2d) (quadriphasic) Estradiol Hemihydrate (EH) 2.5 mg Zoely (NOM 2.5 mg/ EH 1.5 mg) (24d/4d) (monophasic) ¹ Norgestimate: metabolized mostly to levonorgestrel and its metabolites ² Norelgestromin: metabolite of Norgestimate ³ Etonogestrel: active metabolite of the inactive prodrug desogestrel ⁴ 17 OHP: 17 hydroxyprogesterone ⁵ ED: every day (28-day) preparation that can be considered for women with compliance issues ⁶ Cyproterone acetate products are not licensed for oral contraception but for hormone treatment of acne Check BNF and MIMS for other brands and the availability of non-proprietary tablets. 3

Venous Thromboembolism risk (VTE) with combined hormonal contraception (CHC) Situation VTE risk per 10,000 healthy women per year Non contraceptive user, not pregnant 2 Pregnant women 29 Postpartum period 300-400 CHC containing norethisterone, levonorgestrel or norgestimate 5-7 CHC containing etonorgestrel (ring) or norelgestromin (patch) 6-12 CHC containing gestodene, desogestrel, drospirenone or cyproterone acetate 9-12 Newer synthetic estrogens and progestogens such as estradiol valerate/dienogest (Qlaira ) and estradiol hemihydrate/nomegestrol acetate (Zoely ) are being incorporated into combined oral contraception (COC) products. Long-term safety data for these new formulations are not yet available. Therefore, the risks and benefits of use must be assumed to be as for other combine hormonal contraception (CHC). Reference: FSRH- Venous Thromboembolism (VTE) and Hormonal Contraception 2014 4

Progestogen-only contraception: pharmacological content (excluding emergency contraception) (NHS Tayside Formulary contraceptives are in green, first choice IUS and contraceptive injection are in in dark green with white font, the current most cost-effective POP is in bold font) Progestogen Via Oral First Second Etynodiol diacetate (ED) Norethisterone (NE)¹ Levonorgestrel (LNG) Femulen (500 mcg) (withdrawn) Micronor (NE 350 mcg) ~ Noriday Norgeston (LNG 30 mcg) Third Desogestrel (DSG)/ Etonorgestrel² (ENG) DSG 75 mcg (generic brand) ~ Cerazette ~ Cerelle 17 OHP³ Medroxyprogesterone acetate (MDPA) Intrauterine Mirena IUS (52 mcg- 20 mcg/24h in the first year, 5 years licence) Levosert IUS (52 mcg- 20 mcg/24h in the first year, currently 3 years licence) Jaydess IUS (13.5 mcg- 14 mcg/24h in the first year, 3 years licence) Subdermal Nexplanon 3 (68 mg Etonogestrel², 70-25 mcg/d) Intramuscular DepoProvera (DMPA 150 mg) (every 13 weeks) Subcutaneous SayanaPress (DMPA 104 mg) (every 13 weeks) ¹ Norethisterone: metabolite of etynodiol diacetate ² Etonogestrel: : active metabolite of the inactive prodrug desogestrel ³ 17 OHP: 17 hydroxyprogesterone 5

Non-contraceptive benefits of hormonal contraceptive methods Method Ovulation suppression Menstrual suppression or reduction Menstrual predictability Estrogenic benefits & risks CHC- cyclical use + + ++ + CHC- continuous use (off license) ++ ++ ++ ++ DepoProvera or SayanaPress ++ ++ - - - IUS (Mirena ) - or +/- ++ - - IUS (Jaydess ) - + - - POP (second : NE, LNG) +/- +/- - - POP (third : DSG) ++ + - - SDI (Nexplanon ) ++ +/- - - CHC: combined hormonal contraception (combined pill, patch or vaginal ring) DSG: desogestrel IUS: intrauterine system (hormone coil ) NE: norethisterone LNG: levonorgestrel POP: progestogen-only pill SDI: subdermal contraceptive implant Scale: : negative effect : no effect +/- : variable effect + : good effect ++ : very good effect 6

Possible side effects of hormonal contraceptive methods: classification according to hormone class Side effect Estrogenic Progestogenic Acne +/- seborrhoea - + Anxiety - + Bloating + + Breast swelling + - Breast tenderness + +/- Decreased sex drive + +/- (assoc. with depression) Depression - + Growth of uterine fibroids + - Headaches + + Hirsutism - + Irregular bleeding +/- + Mood swings +/- + Nausea/vomiting + - Raised BP + - Weight gain +/- (water retention: cyclical gain) +/- (increased appetite: sustained gain- mainly DMPA) 7

Clinical problem Acne/ hirsutism Bloating Breast tenderness (bilateral) Headache Heavy withdrawal bleeding in pill-free interval Loss of sex drive Mood changes (depression, anxiety +/- irritability) Nausea Unscheduled bleeding Water retention Weight gain Possible side effects on combined hormonal contraception (CHC): advice and treatment options Suggestions Take history and exclude pathology. Consider checking FAI levels. Give lifestyle, skin care and diet advice. Treat condition(s). Encourage perseverance for 3/12. Change progestogen to less androgenic third progestogen. Omit pill-free interval (unlicensed). Increase estrogen content* unless higher VTE risk. Change to an EE/cyproterone acetate COC (Dianette / Co-Cyprindiol ) (licensed only for acne treatment). Change to non-hormonal method. Take history, give lifestyle and diet advice. Exclude GI and ovarian pathology. Encourage perseverance for 3/12. Change progestogen. Change to progestogen-only or nonhormonal method. Reduce estrogen content** if due to water retention. Exclude pathology. Improve bra support. Encourage perseverance for 3/12. Add evening primrose oil. Reduce estrogen content**. Change to progestogen-only or non-hormonal method. General advice: take a history and exclude other pathology. Check BP. Give lifestyle advice and suggest more suitable analgesia. Complicated migraine: stop CHC immediately and start progestogen-only or non-hormonal method. Classical migraine: encourage perseverance for 3/12. Omit pill-free interval (unlicensed). Reduce estrogen content**. Start progestogen-only or non-hormonal method. Other headaches: encourage perseverance for 3/12. Omit pill-free interval (unlicensed). Reduce estrogen content*. Change to progestogen-only or non-hormonal method. Take history, screen for STIs. Exclude pregnancy. Do pelvic exam +/- arrange pelvic USS. Consider FBC, TFT and haemophilia screen. Add mefenamic +/- tranexamic acid. Encourage perseverance for 3/12. Omit pill-free interval (unlicensed). Change progestogen. Change to estradiol/dienogest COC (Qlaira ) (not recommended by the SMC). Change to a progestogen-only (especially recommended: Mirena IUS) or non-hormonal method. Encourage perseverance for 3/12. Take medical and psychosexual history, explore relationship issues including GBV. Consider referral to Sexual Problems Clinic. Change progestogen to a more androgenic second progestogen (norethisterone/ levonorgestrel). Reduce estrogen content** or change to combined transdermal contraception (which has less effect on SHBG). Change to a progestogen-only or non-hormonal method. Take a history (previous sensitivity to progestogens?, history of PMS or postnatal depression?). Exclude suicidal ideation. Explore and treat other causes or signpost to other agencies (advice about benefitsetc.). Encourage perseverance for 3/12. Omit pill-free interval (unlicensed). Change progestogen (consider use of drospirenone). Do not use biphasic or triphasic COCs. Might try progestogen-only method (but avoid DepoProvera /SayanaPress ) with close monitoring of mood or non-hormonal method. Consider PMS treatment according to RCOG guideline (if applicable). Take a history and exclude other causes. Do a pregnancy test. Encourage perseverance for 3/12. Take tablet at night. Take tablet with food. Reduce estrogen content**. Change to a progestogen-only or non-hormonal method. Check history (before and after starting CHC), compliance and drug interactions (including OTC drugs like St John s Wort). Exclude pregnancy. Screen for STIs. Check compliance with cervical screening program. Inspect cervix. Add Mefenamic acid. Encourage perseverance for 3/12. Change progestogen. Increase estrogen content* or change to vaginal ring (more expensive option). Change to Mirena IUS, DepoProvera /SayanaPress or non-hormonal method. See FSRH CEU Guideline Unscheduled bleeding on hormonal contraception for more info. Take history, exclude other pathology, give lifestyle and diet advice. Encourage perseverance for 3/12. If evidence of water retention: reduce estrogen content** or change to EE/drospirenone COC (Yasmin / Lucette / Daylette ) with anti-mineralcorticoid activity (not recommended by the SMC). Change to a progestogen-only or non-hormonal method. Take history, give lifestyle and diet advice. Conisder checking TFT. Encourage perseverance for 3/12. If proven weight gain: change to an IUS or non-hormonal method. Might try different progestogen or progestogen-only method. Avoid DepoProvera and SayanaPress. *Increase estrogen content: change to 35 mcg EE combined oral contraceptive pill like Cilest /Cilique (non-formulary) or to the combined transdermal patch (Evra ) which leads to approximately 34 mcg/24 hours systemic EE levels. **Reduce estrogen content: change to a 20 mcg EE combined oral contraceptive pill or to the combined vaginal ring (NuvaRing ) which leads to approximately 15 mcg/24 hours systemic EE levels (but has a much higher cost). Suggestions modified from: FSRH guidance and Mansour D, Searle S, Smith D at al: Rational Prescribing of Oral Contraceptives. CH-OCS-0005-01/2016. 8

Heike Gleser, Consultant Sexual & Reproductive Health, Tayside Sexual & Reproductive Health Service. Contact: heikegleser@nhs.net. Last update: 10/2017 9