Bol Inf Far 2013;7(2)
BIF
(National Drug Information Center)
Boletín Informativo Farmacéutico (Drug Information Bulletin) Volume 7 -‐ No. 2. MAY-‐ AUGUST 2013
How hormonal contraceptives are used appropriately?
Dr. Alfonso Pereira Céspedes
Sr. David Garro Zamora
CIMED© Pharmacist
CIMED© Assistant
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INTRODUCTION Hormonal contraception (HC) is based on exogenous ovarian hormones that play a key role in the menstrual cycle. Therefore, hormonal contraceptives consist of a combination of estrogen and progestogens or progestogens only (6,8). This bulletin will focus on combined hormonal contraceptives. Better known studies about adverse effects refer to first Currently, hormonal generation contraceptives using high doses of estrogen and contraceptives have progestogens. Moreover, those with antiandrogenic effects have decreased the incidence of serious complications (6,7). evolved towards formulations with much Most frequent adverse reactions, even though less severe, that usually disappear after the first three months of lower doses of estrogen treatment are: •
•
•
• • •
and progestogens lacking androgenic effects or with antiandrogenic effects, so it has reduced the incidence of severe complications
Nausea that may become vomiting, especially with HC containing high doses of estrogens. This symptom gets better after the first 2-‐3 months of using the treatment. It may be recommended a change in the treatment schedule (6,7). Transitional mastalgia that if persist should be recommended referral to a gynecologist to modify the HC at a lower dose preparation or another progestogen (6,7). Weight gain and fluid retention that can be explained by the increase of plasmatic cortisol and decreased excretion of 17-‐OH and 17-‐ketosteroids, also aldosterone which produces estrogen (6,7). Headaches triggered by the effect of estrogen on aldosterone (6). Dizziness or lightheadedness (6,7). Irregular Spotted (Spotting): If spotting appear at the start of the treatment must yield spontaneously after the first few months. However, if bleeding continues after months or years of use, must be ruled out: an underlying infection, pregnancy or cervical pathology (6,7).
A review of the actual contraindications of these preparations has concluded that the most important aspects influencing the safety of these patients are risk factors for arterial cardiovascular disease (such as age ≥ 40 years, smoking, diabetes and hypertension), so most health interventions will be aimed at early detection of these problems and prevent their use as deemed that women who request them, or use them, do not meet the required security standards (6,7). In addition, other risk factors of hormonal contraceptives usage are: deep vein thrombosis, migraine headache and breast cancer (6,7). Tables 1, 2 and 3 summarize the main considerations for the use of HC as well as trademarks and composition available in the private market of Costa Rica.
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Table 1. Major considerations of oral combined hormonal contraceptives. Composition (2,3)
Cyproterone 2.0 mg + Ethinylestradiol 0.035 mg
Trademarks and Presentation (2,3) CORRECTIA® DANIELE® DIANE 35 ® DIXI 35 ® 21 coated tablets
Chlormadinone acetate 2 mg + Ethinylestradiol 0.03 mg
BELARA® DALHIA® 21 tablets
Desogestrel 0.075 mg
CERAZETTE® MICROTAB 28® 28 tablets
Treatment scheme (cycle start day) (2,4,5)
Other Use in lactation indications (2,4) (1,2,4)
Treatment starts the first day of Treatment of the menstrual cycle by taking one androgen-‐ dependent tablet daily. diseases like acne If the presentation is 21 tablets: accompanied by take 1 tablet daily for 21 seborrhea, consecutive days followed by 7 androgenic days without medication. alopecia and mild of Immediately after the break (the forms hirsutism. 8th day) cycle restarts the same way. Treatment starts the first day of Contraceptive in the menstrual cycle by taking one women with tablet daily. androgenic If the presentation is 21 tablets: diseases. Take 1 tablet daily for 21 Dysmenorrhea consecutive days followed by 7 Dysfunctional days without medication. uterine bleeding Immediately after the break (the 8th day) cycle restarts the same way. Start treatment on the first day of Dysmenorrhea menstruation continuously, Dysfunctional regardless of the occurrence of uterine bleeding bleeding.
Not recommended
Not recommended
Compatible
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Desogestrel 0.15 mg + Ethinylestradiol 0.02 mg
DAL 28® 28 tablets MERCILON® 21 tablets MIDALET ® 21 tablets
Dienogest + Estradiol 2 dark yellow tablets. Each containing 3 mg of estradiol valerate. 5 intermediate red tablets. Each tablet contains 2 mg of estradiol valerate and 2 mg of dienogest. 17 light yellow tablets. Each tablet contains 2 mg of estradiol valerate and 3 mg dienogest. 2 dark red tablets. Each tablet contains 1 mg estradiol valerate. Drospirenone 3.00 mg + Ethinylestradiol 0.03 mg
QLAIRA® 28 tablets
FEMIPLUS CD® MIA® PRIMABELA ® YASMIN®
Treatment starts the first day of the menstrual cycle by taking one tablet daily. If the presentation is 21 tablets: Take 1 tablet daily for 21 consecutive days followed by a 7 day break without medication. The cycle restarts the same way immediately after the break (the 8th day). If the presentation is 28 tablets: start the treatment the first day of the menstrual cycle and continue for 28 consecutive days. Start a new package once you have finished the previous one. Take 1 tablet the first day of the menstrual cycle, and continue for 28 consecutive days. Start a new package once you have finished the previous one.
Dismenorrea Hemorragias uterinas disfuncionales Hipermenorrea Dysmenorrhea Dysfunctional uterine bleeding Hypermenorrhea
Treatment starts the first day of the menstrual cycle taking 1 tablet daily. If the presentation is 21 tablets: Take 1 tablet daily for 21
Dysmenorrhea Dysfunctional uterine bleeding Premenstrual dysphoric
Not recommended
Pain associated Not with recommended endometriosis Dysmenorrhea Dysfunctional uterine bleeding Treatment of hypermenorrhea
Not recommended
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SUSY® 21 coated tablets
Drospirenone 3.00 mg + Ethinylestradiol 0.02 mg
Gestodene 0.075 mg + Ethinylestradiol 0.030 mg
Gestodene 0.075 mg. + Ethinylestradiol 0.020 mg
Gestodene 0.060 mg. + Ethinylestradiol 0.015 mg
Norgestrel 0.5 mg + Ethinylestradiol 0.05 mg
consecutive days followed by a by 7 day break without medication. The cycle restarts the same way immediately after the break (the 8th day). FEMIPLUS ® Take one tablet the day 1 of the MIA 20 ® menstrual cycle and continue for SUSY 20® 28 consecutive days. Start a new YAZ® package once you have finished 28 coated the previous one. tablets CICLOTAB® Treatment starts the first day of GYNOVIN® the menstrual cycle taking 1 tablet 21 dragees daily. If the presentation is 21 tablets: Take 1 tablet daily for 21 consecutive days followed by a 7 day break without medication. The cycle restarts the same way immediately after the break (the 8th day). CICLOTAB Treatment starts the first day of 20® the menstrual cycle and continues FEMIANE® for 21 consecutive days followed 21 dragees by a 7 day break without medication. The cycle restarts the HORMOFEN® same way immediately after the 21 coated break (the 8th day). tablets CAREZA® Take 1 tablet the first day of the CICLOTAB menstrual cycle, and continue for 15® 28 consecutive days. Start a new 28 dragees package once you have finished MIRELLE® the previous one. coated tablets NORGYL® Treatment starts the fifth day of 21 tablets the menstrual cycle taking 1 tablet daily. If the presentation is 21 tablets: Take 1 tablet daily for 21 consecutive days followed by a 7 day break without medication. The cycle restarts the same way immediately after the break (the 8th day).
syndrome Acne
Dysmenorrhea Dysfunctional uterine bleeding
Not recommended
Dysmenorrhea Dysfunctional uterine bleeding Ovarian rest
Not recommended
Dysmenorrhea Dysfunctional uterine bleeding Ovarian rest
Not recommended
Dysmenorrhea Dysfunctional uterine bleeding
Not recommended
Dysmenorrhea Dysfunctional uterine bleeding Endometriosis
Not recommended
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Levonorgestrel 0.100 mg + Ethinylestradiol 0.02 mg
Levonorgestrel 0.15 mg + Ethinylestradiol 0.03 mg
Levonorgestrel 0.25 mg + Ethinylestradiol 0.05 mg
Lynestrenol 0.5 mg
CECIL®
Treatment starts the first day of the menstrual cycle taking 1 tablet daily.If the presentation is 21 tablets: Take 1 tablet daily for 21 consecutive days followed by a 7 day break without medication. The cycle restarts the same way immediately after the break (the 8th day). If the presentation is 28 tablets: Take 1 tablet the 1st of the menstrual cycle and continue for 28 consecutive days. Start a new package once you have finished the previous one. ANULETTE ® Take 1 tablet daily from the first MICROGYNO day of the menstrual cycle until N® finish the last tablet (21 days), then NORGYLEN® rest for 7 consecutive days without NORDET® medication. The cycle restarts the PRIMAFEN® same way immediately after the 21 tablets break (the 8th day). If the presentation is 28 tablets: Take 1 tablet the first day of the menstrual cycle and continue for 28 consecutive days. Start a new package once you have finished the previous one. For ® NORGYLEN the start day is the 5th day of the cycle. NEOGYNON® Take 1 tablet daily from the first 21 dragees day of the menstrual cycle until ending with the last tablet (21 days), then rest for 7 consecutive days without medication. The cycle restarts the same way immediately after the break (the 8th day). PRIMOR® Treatment starts the first day of 28 dragees the menstrual cycle taking 1 tablet daily. If the presentation is 28 tablets: Take 1 tablet the first day of the menstrual cycle, and continue for 28 consecutive days. Start a new package once you have finished the previous one.
Dysmenorrhea Dysfunctional uterine bleeding
Not recommended
Dysmenorrhea Endometriosis treatment Dysfunctional uterine bleeding
Not recommended
Endometriosis treatment Dysfunctional uterine bleeding
Not recommended
Dysmenorrhea Dysfunctional uterine bleeding
Compatible
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Norgestimate 0.25 mg + Ethinylestradiol 0.035 mg
CILEST® 21 tablets
Take 1 tablet daily from the 5th Dysmenorrhea day of the menstrual cycle until Dysfunctional finished the last tablet (21 days), uterine bleeding then rest for 7 consecutive days without medication. The cycle restarts the same way immediately after the break (the 8th day).
Not recommended
Table 2. Key considerations of the combined contraceptive patch formulation and intrauterine device (IUD). Composition and Performance (2,3) PATCH Norelgestramina 6 mg + Ethinylestradiol 0.6 mg
Treatment scheme Other indications (cycle start day) (2,4) (2,4,5) EVRA® The first time applied must Not reported be the first day of menstruation cycle. Apply 1 patch each week for three continuous weeks (21 days) then rest for a week or 7 days (without application). Start again the same day of the week that had started for the first time. Intrauterine Device MIRENA® Initial release rate: 20 Not reported levonorgestrel 52 µg/day, reducing to 11 mg µg/day after 5 years. Intrauterine Device NUVARING ® Each ring lasts only 1 cycle. Not reported Etonogestrel 11.7 Insert at the bottom of the mg +Ethinylestradiol vagina on days 1 to 5 of the 2.7 mg cycle. Use a barrier (Intravaginal ring) method for the first 7 days of the first cycle. Remove the ring in 3 weeks and reinsert 1 ring after 1 week off.
Trademark (2,3)
Use in lactation (1,2,4) Contraindicated
Not recommended Not recommended
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Table 3. General considerations of injectable hormonal contraceptives. Composition (2,3)
Trademark (2,3)
Treatment scheme (cycle start day) (2,4,5)
Other indications (2,4,5)
Norethisterone 50 MESYGEST ® mg +Estradiol 5mg MESYGINA® FEMGYL®
Not recommended
Dihydroxyprogeste rone (Algestone) + Estradiol
Not recommended
Medroxyprogester one 150 mg/mL
1 ampoule IM within the Not reported first days of the menstrual cycle and then repeat it every 27-‐33 days. PROTER® (150 1 ampoule IM between the Not reported mg+10 mg 7th and 9th day from the /mL) start of menstruation, TOPASEL® then continue applying 1 (150 mg+10 ampoule IM the 8th day of mg /mL) the menstrual cycle. YECTAMES® (75 mg+5mg/mL) DEPO-‐ 150 mg IM within the first Not reported PROV 5 days of the menstrual ERA® cycle every 3 months.
Use in lactation (1,2,4)
Compatible
CONCLUSIONS As can be seen in the Costa Rica´s market, there are several trademarks of HC. These combinations have special considerations (indications, therapeutic regimens, safety profiles, among others) to be taken into account when prescribing, recommending and administering these medications. This information can assess the need, effectiveness and safety of these treatments enriching the overall vision of study of the patient pharmacotherapy.
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REFERENCES 1. Briggs G, Freeman R, Yaffe S. Drugs in Pregnancy and Lactation. 8th ed. USA: Lippincott William & Wilkins; 2008. 2. Dana WJ, Fuller MA, Golembiewski JA, Gonzales JP, Fisher J, Snoke J. Drug Information Handbook International. 2012-‐2013. 21st ed. Canada: Lexi-‐Comp. 3. Registro de medicamentos aprobados en Costa Rica. Ministerio de Salud. Updated 6-‐5-‐13. 4. Consejo General de Colegios Oficiales de Farmacéuticos de España. Base de Datos del Conocimiento Sanitario. CD-‐Rom version; 2012. 5. Villa F. Medimecum, Guía de Terapia Farmacológica. 14th ed. España: Adis; 2009. 6. García P, Martínez F, Pintor A, Caelles Neus, Ibañez J. Guía de utilización de medicamentos anticonceptivos hormonales. Granada, España: GIAF-‐UGR; no date. 7. Molinero AM, De Diego C, Esteso P, García P, González A, Méndez P, et al. Características de la utilización de anticonceptivos hormonales orales a través del servicio de dispensación en la farmacia comunitaria. FARMACÉUTICOS COMUNITARIOS 2010; 2(2): 56-‐61.
8. González R. Anticonceptivos orales y uso concomitante de antibióticos ¿existe una interacción? Revista Médica de Costa Rica y Centroamérica. 2004;(566): 23-‐31.
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The Boletín Informativo Farmacéutico (Drug Information Bulletin) is a quarterly electronic publication distributed free of charge to professional pharmacists with the purpose of informing, updating and contributing to the promotion of the rational use of prescription drugs. Editorial Board: Dr. Victoria Hall Ramírez, Director CIMED® / Dr. María Soledad Quesada Morúa, CIMED® Pharmacist / Dr. Milania Rocha Palma, CIMED® Pharmacist / Dr. Wendy Montoya Vargas, CIMED® Pharmacist/ Dr. Angie Ortiz Ureña, CIMED® Pharmacist / Dr. Catalina Lizano Barrantes, CIMED® Pharmacist / Dr. Karla Bedoya Arroyo, CIMED® Pharmacist / Dr. Luis Esteban Hernández, CIMED® Pharmacist / Dr. Angie León Salas, CIMED® Pharmacist Editor in chief : Dr. Alfonso Pereira Céspedes, CIMED® Pharmacist
Produced by: CIMED®-‐National Drug Information Center – 30 years of service. INIFAR, Facultad de Farmacia – Universidad de Costa Rica. Tel: (506) 2511 8313 – 2511 8327 – 2511 8328 – 2511 8311. Fax: (506) 2511 5700. Email: cimed.inifar@ucr.ac.cr
Centro Nacional de Información de Medicamentos (CIMED®). INIFAR, Facultad de Farmacia, Universidad de Costa Rica. teléfonos: 2511-‐8311/2511-‐8313/ 2511 8327/ 2511-‐8328, y Fax 2511-‐5700. Email: cimed.inifar@ucr.ac.cr
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