The Family Practice Newsletter The Ohio University College of Osteopathic Medicine The Ohio Northern University Raabe College of Pharmacy Doctors Hospital Family Practice Volume 5, Issue 5 January, 2006 Guidelines for the Selection of Hormonal Contraceptives Laura Oinonen, Ohio State University Doctor of Pharmacy Candidate With such a large selection of hormonal contraceptive (HC) options available for women today, it is important to have some guidelines when selecting one for a given patient. Unless otherwise contraindicated or intolerable, most women find success using a combined contraceptive product, which contains ethinyl estradiol(EE) and a progestin. Depending on tolerance, many women can safely and effectively be started on 35 micrograms or less of EE6. If an ample trial period has been given and the patient is experiencing early or mid-cycle breakthrough bleeding (BTB), spotting, or hypomenorrhea, the estrogen component strength selected may be too low 6. If nausea, bloating, breast tenderness, increased BP or headache is experienced, the estrogen component strength may be too high6. Choosing the progestin portion of the formulation, however, can prove to be a bit more challenging. The available progestins used in HCs vary according to potency, as well as estrogenic, anti-estrogenic, and androgenic activity. Select one based on the patient’s characteristics and adjust, if needed. Too much progestin may lead to breast tenderness, headache, fatigue, or changes in mood, while too little may lead to late BTB6. If the progestin component selected has too much androgenic activity, some side effects observed may be characteristic of those seen in an androgenic excess patient, including acne, oily skin, increased appetite, weight gain, hirsuitism, decreased libido, increased breast size and/or tenderness, and changes in lipid profiles6. Hormonal Contraceptive Progestin-Only Pills (POPs) Ex: Camila, Micronor, NorQD Combined Oral Contraceptives -progestin and an estrogen in various strengths in mono, bi or tri-phasic formulations Extended cycle pills: Seasonale (3 cycles taken continuously without sugar pill may lead to sometimes desirable 4 periods per year 6) Other combined contraceptives: Vaginal ring Ex: NuvaRing Transdermal patch Ex: OrthoEvra IUDs implanted with hormones Ex: Mirena (progestin only) The patient it IS GOOD for -Women who desire HC while breastfeeding -Those who cannot take COCs due to estrogen component -Majority of women since they are available in various strength formulations -Good form if woman desires HC for cycle regulation or contraception -Pregnancy can be achieved normally after discontinuation of product if desired. The patient it is NOT GOOD for -Those who cannot take the pill consistently on time each day (6) -Women who desire a non-oral option dosed once a month (those who may not adhere to once daily dosing of oral method) -Releases a steady stream of hormones over a 3 week period, reducing fluctuations and possibly AEs -Women who desire a non-oral method of HC applied weekly for 3 weeks, then off, to the skin -Women who have had at least one child, who are in a monogamous relationship, breast-feeding mothers, those who desire effective contraception for up to five years -Those with very low adherence potential who do not desire sterilization and do not desire injection therapy (below) -Woman must be comfortable keeping ring inside vagina for 3 weeks -Some women feel the ring in place during intercourse or have trouble with expulsion due to body shape -Any women who has contraindications to use of COCs -Those who are breastfeeding -Women who are over 90kg (less effective)4 -Women who may not want a visible/irritating patch on skin -Device is placed in the uterus for up to five years, have to go to physician for implantation and removal, may cause cramping initially -Those who desire an estrogen component to their HC IM, SQ medroxyprogesterone injection, implants Ex: DepoProvera IM, SQ, Norplant -Women who are breastfeeding -Women who want an option that lasts 3 months with no estrogen and no internal device -Women who are concerned about weight gain should be warned of this possible AE -Those who desire an estrogen component to their HC Above table adapted from reference 6 One of the newer COCs available is Yasmin (EE 0.03mg/ drospirenone 3mg). Drospirenone is a spironolactone-like moiety which may add a mild diuretic-like effect during its use. This ingredient, unlike other progestins, has anti-androgenic and anti-mineralocorticoid activity5. This may be especially useful in women with androgen-excess induced acne or hirsuitism (such as women with PCOS).3,7 Other Issuses with hormonal contraception Two COCs have been FDA approved for the treatment of acne, Ortho Tri-Cyclen and Estrostep5. Trials have shown that improvements in acne or hirsuitism requires several months of use of the product. Due to its unique structure, Yasmin can exhibit some potassium-sparing properties6. Serum potassium levels should be checked after the 1 st cycle, especially in high risk patients. Concomitant use of Yasmin with ACEi, ARBs, and spironolactone may also potentiate hyperkalemia, which should be closely monitored over time if these medications are used together. Due to its lack of androgenic activity, its progestin component may also minimize any progestin-induced weight gain. HCs are metabolized via many similar CYP450 enzymes as other medications and may compete for or depleate there activity (ie, cause a drug-drug interaction). The following table lists some drugs that increase enzyme activity and therefore may decrease COC levels in the body, thereby making them less effective. If these medications are selected to be used with COCs, the patient should be advised of the increased risk of failure 8. Drug Class Anticonvulsants Generic (Trade) Barbiturates (phenobarbitol) Carbamazepine (Tegretol) Phenytoin (Dilantin) Topiramate (Topamax) Recommendation Use alternative contraception, use higher dose OC if appropriate -Could use Valproate (Depakene), levetriacetam (Keppra), and gabapentin (Neurontin) (These do not decrease effectiveness of OCs) Anti-Infectives Rifampin (Rifabutin) Griseofulvin (Grisactin) Erythromycin (E-Mycin) Penicillins, Tetracyclines Use back up method during treatment -Rifampin use requires back-up method one month after d/c of drug -Advise patient it may be wise to use back-up method during and for a week after treatment -Conflicting information exists regarding this interaction. GI bacteria are decreased with antibiotic use, which may interfere with enterohepatic circulation, thereby reducing effectiveness of OC. D/V caused by some antibiotic use may also be responsible for decreased gut absorption of OCs -Advise patient to disclose all herbal, supplement, OTC use to physician and pharmacist -Reports of unintended pregnancy or break-through bleeding with use5 -Advised back-up birth control use if desire to take these products Broad Spectrum Antibiotics OTC Herbals, Supplements St. John’s Wort Garlic preps that contain allicin Above table adapted from table found in reference 8. The following medications may increase hormone levels of HC’s, causing side effects, such as: Fluconazole (Diflucan), ketoconazole (Nizoral), Itraconazole (Sporonox), and atorvastatin (Lipitor-moderate increase reported)8. Some common interactions where HCs may increase effectiveness of other medication levels include: Chlorpromazine (Thorazine), clozapine (Clozaril), various benzodiazepines metabolized by oxidation, such as diazepam (Valium), alprazolam (Xanax), and caffeine8. Other medications may have reduced effectiveness when taken with COCs including: Lamotrigine (Lamictal) and various benzodiazepines metabolized by glucuronidation such as lorazepam (Ativan) and temazepam (Restoril) 8. When any of the above listed medications are used simultaneously with HC therapy, close monitoring of drug effects should be implemented. In conclusion, selecting an appropriate HC in women can be challenging. But by asking the correct questions related to adherence, lifestyle, and other health conditions, the selection process is much easier and can assist in treatment success. References 1. Body Mass Index, Weight, and Oral Contraceptive Failure Risk. Holt; VL, Scholes, D; Wicklund, KG et al. Obstetrics and Gynecology. 2005; 105: 4652. 2. Contraceptive Use by Diabetic and Obese Women. Chuang, CH et al. Women’s Health Issues 15(2005); 167-173. 3. Drospirenone for the Treatment of Hirsute Women with Polycystic Ovary Syndrome: A Clinical, Endocrinological, Metabolic Pilot Study. Guido, M et al. Journal of Clinical Endocrinology & Metabolism. 2004 89(6): 2817-2823. 4. Efficacy of Oral Contraceptives in Overweight Women. Pharmacist’s Letter/Prescriber’s Letter 2005;21(2): 210212. 5. Herb-Drug Interactions: An Overview of the Clinical Evidence. Izzo, AA. Fundamental & Clinical Pharmacology. 2004(19): 1-16. 6. Hormonal Contraception. Pharmacist’s Letter/Prescriber’s Letter 2003; 19(10): 191010. 7. Pharmacologic Treatment of Polycystic Ovary Syndrome. Pharmacist’s Letter/Prescriber’s Letterr 2004; 20(10): 201006. 8. Oral contraceptive (OC) drug interactions. Pharmacist’s Letter/Prescriber’s Letter 2005; 21(9): 210903.