避 孕 藥 的 正 確 使 用 與 溝 通 技 巧

Transcription

1 避 孕 藥 的 正 確 使 用 與 溝 通 技 巧 三 軍 總 醫 院 臨 床 藥 學 部 張 絜 雯 藥 師 2009/7/ /7/26 1

2 內 容 大 綱 避 孕 的 方 式 避 孕 藥 的 作 用 機 轉 避 孕 藥 的 種 類 避 孕 藥 的 副 作 用 避 孕 藥 的 交 互 作 用 使 用 禁 忌 Q and A 2009/7/26 2

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4 Contraceptive Methods Barrier methods condoms contraceptive sponge cervical caps Hormonal methods Oral contraceptives Contraceptive patch and vaginal rings Injectable contraceptives Other methods fertility awarenessbased methods spermicides lactational amenorrhea method 2009/7/26 4

5 GENERAL Combination oral contraceptives inhibit ovulation via a negative feedback mechanism on the hypothalamus: alters the normal pattern of gonadotropin secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by the anterior pituitary. The follicular phase FSH and midcycle surge of gonadotropins are inhibited. In addition, oral contraceptives produce alterations in the genital tract, including changes in the cervical mucus, rendering it unfavorable for sperm penetration even if ovulation occurs. Changes in the endometrium may also occur, producing an unfavorable environment for nidation. Mechanism of Action Oral contraceptive drugs may alter the tubal transport of the ova through the fallopian tubes. Progestational agents may also alter sperm fertility. 2009/7/26 5

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7 Oral contraceptives Monophasic oral contraceptives Multiphasic oral contraceptives Progestin only oral contraceptives Emergency Contraceptive 2009/7/26 7

8 Monophasic oral contraceptives 1 tablet PO once daily, most available in packs of 21 or 28 pills ethinyl estradiol 50 mcg formulations ethinyl estradiol 35 mcg formulations ethynodiol diacetate norethindrone norgestrel mestranol 50 mcg and norethindrone 1 mg (mestranol 50 mcg may be similar to ethinyl estradiol mcg) 2009/7/26 8

9 ethinyl estradiol 30 mcg formulations with desogestrel 0.15 mg with drospirenone 3 mg (Yasmin 28) with levonorgestrel 0.15 mg with norethindrone acetate 1.5 mg ethinyl estradiol 20 mcg formulations with levonorgestrel 0.1 mg with levonorgestrel 90 mcg for continuous use with norethindrone acetate 1 mg 2009/7/26 9

10 Multiphasic oral contraceptives ethinyl estradiol 30 or 40 mcg plus levonorgestrel 0.05 or or mg ethinyl estradiol 20 or 30 or 35 mcg plus norethindrone acetate 1 mg ethinyl estradiol 35 mcg plus norgestimate 0.18 or or 0.25 mg 2009/7/26 10

11 Progestin only oral contraceptives Micronor (norethindrone 0.35 mg) 1 tablet PO once daily, also available as Nor-QD, may still be available as generic Ovrette (norgestrel mg) 1 tablet PO once daily progestin-only pills ("minipills") associated with more breakthrough bleeding, daily compliance more critical in preventing pregnancy, generally used only for breastfeeding women or women who can't take estrogen 2009/7/26 11

12 第 一 代 避 孕 藥 : 動 情 激 素 ( 雌 激 素 ; 炔 雌 醇 ; Ethinylestradiol;EE) 含 量 是 高 於 50 微 克 (50ug; 0.05mg) 第 二 代 避 孕 藥 : 黃 體 素 是 norethindrone 類 的 成 份, 例 如 levonorgestrel,norgestimate 等 等 第 三 代 避 孕 藥 : 黃 體 素 使 用 的 是 desogestrel 或 是 gestodene 等 副 作 用 更 小 的 種 類 ( 如 不 容 易 水 腫 ) 2009/7/26 12

13 台 灣 常 見 避 孕 藥 避 孕 藥 成 分 主 成 份 : A.Levonorgestrel B.Ethinyl estradiol ( 雌 激 素 ) C.Desogestrel D.Gestodene E.Cyproterone acetate F.Drospirenone(DRSP) G.Norelogestromine H.Ethynodiol Acetate J.Etonogestrel 2009/7/26 13

14 台 灣 常 見 避 孕 藥 母 扶 樂 21:C 0.15mg +B 0.03mg 美 適 儂 21:C 0.15mg +B 0.02mg 息 妊 佳 21:C 0.15 mg+b 0.02 mg 克 妊 滿 Conova 30 :H 2000mcg(estrogenic) +B 0.03mg 樂 定 偶 21:A 0.25mg +B 0.05mg 欣 無 妊 21:A 0.25mg +B 0.05mg ( 衛 署 家 計 三 號 ) 娜 迪 21:A 0.15mg +B 0.03mg 碧 韻 21:A 0.125mg +B 0.03mg 樂 婷 錠 28:( 前 21 顆 ) A 100ug + B 20ug 黛 麗 安 21:E 2mg +B 0.035mg( 這 類 適 合 容 易 長 痘 痘 及 多 毛 症 患 者 ) 妮 娜 21:E 2mg +B 0.035mg 諾 婷 21:E 2mg +B 0.035mg 先 靈 悅 己 膜 衣 錠 21:F 3mg +B 0.03mg( 最 不 容 易 水 腫 ) 悅 姿 Yaz 錠 28 :F 3mg +B 0.02mg /24 顆, 另 外 4 顆 安 慰 劑 ( 核 准 可 抗 經 前 憂 鬱 症 ) 祈 麗 安 21:D 0.075mg +B 0.03mg 玫 麗 安 21:D mg+b 0.02 mg 新 定 偶 膜 衣 錠 28:D 0.06mg +B 0.015mg 敏 定 偶 膜 衣 錠 28:D 0.07mg +B 0.030mg 溫 不 妊 28( 衛 署 家 計 二 號 ): 前 6 顆 :A 0.05mg +B 0.03mg 中 5 顆 :A 0.075mg +B 0.04mg 後 10 顆 :A 0.125mg +B 0.03mg 以 芙 EVRA 貼 片 :G 150ug + B 20 ( 實 際 測 得 約 32)ug /24hr ( 唯 一 用 貼 的 ) 舞 悠 陰 道 避 孕 環 :J 11.7mg +B 2.7m ( 每 日 釋 放 J 0.120mg +B 0.015mg) 2009/7/26 14

15 Comparisons of Drug Classes Low-dose estrogens low-dose estrogens may cause less bloating and breast tenderness but more breakthrough bleeding low-dose estrogen combination oral contraceptives associated with higher rates of abnormal bleeding patterns addition of ethinyl estradiol 10 mcg to combination oral contraceptives with ethinyl estradiol 20 mcg (levonorgestrel 100 mcg or norethindrone acetate 1 mg) not associated with improved bleeding patterns i in 4-way randomized trial with 139 women, but conclusions limited by 45% dropout rate. 2009/7/26 15

16 Multiphasic vs. monophasic oral contraceptives: no evidence to show benefit of multiphasic oral contraceptives over monophasic oral contraceptives insufficient evidence to support clear benefit of triphasic over monophasic oral contraceptives biphasic oral contraceptives do not appear to offer any significant advantages over monophasic oral contraceptives insufficient evidence to support benefit of triphasic over biphasic oral contraceptives, levonorgestrel may be associated with better cycle control than norethindrone) 2009/7/26 16

17 Other comparisons: third- and second-generation progestagens more acceptable than first-generation progestagens in combination contraceptives 2009/7/26 17

18 Contraindications BLACK BOX WARNING Cigarette smoking increases the risk of serious cardiovascular side effects from hormonal contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use hormonal contraceptives should be strongly advised not to smoke. 2009/7/26 18

19 Contraindications smoking, heavy (greater than 15 cigarettes per day) and over age 35 abnormal genital bleeding, undiagnosed adrenal insufficiency; risk of hyperkalemia carcinoma of breast, known or suspected or personal history of breast cancer carcinoma endometrial, or other known or suspected estrogen-dependent neoplasia cerebral vascular or coronary artery disease, current or history cholestatic jaundice of pregnancy or jaundice with prior hormonal contraceptive use deep vein thrombophlebitis or thromboembolic disorders, past history diabetes with vascular disease headaches with focal neurological symptoms hepatic adenomas or carcinomas 2009/7/26 19

20 Contraindications hepatocellular disease with abnormal liver function, acute or chronic hepatic dysfunction with use of drospirenone; risk of hyperkalemia hypertension, severe or uncontrolled hypersensitivity to any component of the product major surgery with prolonged immobilization pregnancy, known or suspected renal insufficiency with use of drospirenone; risk of hyperkalemia thrombogenic rhythm disorders thrombophilias, hereditary or acquired thrombophlebitis or thromboembolic disease valvular heart disease with complications 2009/7/26 20

21 Side effects type of oral contraceptive appears to have little effect on tolerance estrogens - nausea, breast tenderness, breast enlargement progestins - higher LDL and lower HDL cholesterol levels weight gain and depression not clearly related to estrogen or progestin components increased risk of cardiovascular disease with combination oral contraceptives in women > 35 who smoke weight gain or weight loss not clearly established as side effects combination contraceptives do not appear to have large effect on weight low-dose oral contraceptives not associated with substantial change in weight over 13 cycles in randomized trial comparing 2 different contraceptives in 2,894 women 2009/7/26 21

22 Side effects insufficient evidence to determine effect of hormonal contraceptives on carbohydrate metabolism oral contraceptives do not appear to have clinically important effect on headache activity in most women combined oral contraceptives, but not progestin-only or nonhormonal contraceptives, appear to be associated with increased blood pressure 2009/7/26 22

23 Venous thromboembolism small increased risk for venous thromboembolism third generation oral contraceptives associated with increased risk for venous thrombosis compared to second generation oral contraceptives increased risk of venous thromboembolism with third generation contraceptives appears real but small increased thromboembolism risk with ethinyl estradiol/dropirenone appears similar to risk with other oral contraceptives avoidance of oral contraceptives in patients at "high risk" of thromboembolism may be warranted, but no good screening test for "high risk" patients; 2009/7/26 23

24 Breast cancer risk small increased risk of having breast cancer diagnosed while taking combined oral contraceptives and up to 10 years after stopping oral contraceptive use associated with increased risk of premenopausal breast cancer history of oral contraceptive use associated with increased risk for breast cancer among firstdegree relatives of breast cancer patients 2009/7/26 24

25 Cervical cancer risk long-term use of hormonal contraceptives associated with cervical cancer 2009/7/26 25

26 Cardiovascular disease systematic reviews have differing conclusions regarding low-dose oral contraceptives and risk of stroke depending on how data is combined low-dose oral contraceptives have no clear association with stroke current oral contraceptive use associated with small increased risk for ischemic stroke progestogin-only contraceptives may not be associated with increased risk for stroke oral contraceptives not associated with increased risk of myocardial infarction combination oral contraceptives associated with small increase in risk for stroke and myocardial infarction in women with hypertension 2009/7/26 26

27 Effect on lactation insufficient evidence regarding effect of hormonal contraceptives during lactation combination oral contraceptives and breastfeeding insufficient evidence to determine harms or lack of harms combination oral contraceptives may reduce breast milk volume ACOG, WHO, La Leche League Internation and Physician's Desk Reference all recommend against using combination oral contraceptives in breastfeeding women 2009/7/26 27

28 Bone health (risk unclear) use of oral contraceptives may be associated with lower bone density no randomized trials found reporting effect of hormonal contraceptives on fracture risk FDA added BLACK BOX WARNING label that prolonged use of Depo-Provera may result in loss of bone density depot medroxyprogesterone acetate may lower bone mineral density but clinical significance unknown 2009/7/26 28

29 Drug-drug Interactions Antibiotics rifampin is only antibiotic with evidence of reducing effectiveness of oral contraceptives, but current studies cannot rule out possibility that some women are more vulnerable to contraceptive failure when taking antibiotics review of effect of antibiotics on oral contraceptives rifampin and griseofulvin are highly likely to reduce efficacy of oral contraceptives other oral antibiotics (particularly tetracyclines and penicillins) may reduce oral contraceptive efficacy in a minority of susceptible women, but no practical way to predict who is susceptible consider using back-up contraceptive method if taking oral antibiotics 2009/7/26 29

30 Drug-drug Interactions drugs which may decrease oral contraceptive levels antibiotics - erythromycin, dirithromycin, penicillins, rifampin, tetracycline anticonvulsants - barbiturates, carbamazepine, ethosuximide, felbamate, lamotrigine, oxcarbazepine, phenytoin, primidone, topiramate antifungals - fluconazole, griseofulvin, itraconazole, ketoconazole antivirals - atazanavir, lopinavir, nelfinavir, nevirapine, ritonavir garlic modafinil (Provigil) St. John's wort 2009/7/26 30

31 Drug-drug Interactions drugs which may increase oral contraceptive levels atorvastatin (Lipitor) fosamprenavir (Lexiva) non-nucleoside reverse transcriptase inhibitors - delavirdine, efavirenz 2009/7/26 31

32 Drug-drug Interactions oral contraceptives may decrease some drug levels (or drug effects) amprenavir (Agenerase), fosamprenavir (Lexiva) aspirin benzodiazepines metabolized by glucuronidation - lorazepam, oxazepam, temazepam lamotrigine (Lamictal) morphine 2009/7/26 32

33 Drug-drug Interactions oral contraceptives may increase some drug levels (or drug effects) antipsychotics - chlorpromazine, clozapine benzodiazepines metabolized by oxidation - alprazolam, chlordiazepoxide, clonazepam, diazepam, flurazepam, midazolam, prazepam, quazepam, triazolam corticosteroids cyclosporine mephenytoin (Mesantoin) selegiline (Eldepryl) theophylline tricyclic antidepressants - amitriptyline, desipramine, doxepin, imipramine, nortriptyline 2009/7/26 33

34 Drug-drug Interactions drugs which may increase potassium levels with drospirenone/ethinyl estradiol (Yasmin) ACE inhibitors aldosterone antagonists - eplerenon, spironolactone angiotensin receptor blockers NSAIDs 2009/7/26 34

35 Drug-herb interactions St. John's wort St. John's wort may reduce efficacy of oral contraceptives by inducing cytochrome P450 3A4 metabolism of ethinyl estradiol chasteberry may reduce effectiveness of oral contraceptives, based on theoretical effect on progesterone 2009/7/26 35

36 Drug-Food Combinations Caffeine Interaction Effect: enhanced CNS stimulation Summary: Concomitant use of combination contraceptives and caffeine ingestion increases the half-life of caffeine by 45% to 90% and decreases the clearance of caffeine by 40% to 65%. In some patients, caffeine ingestion may need to be reduced due to excessive CNS stimulation. Severity: moderate Onset: rapid Substantiation: probable Clinical Management: Advise patients that consumption of caffeinated beverages or medications containing caffeine may result in increased CNS stimulation and possibly difficulty sleeping at night. Advise patients to decrease caffeine intake while taking combination contraceptives. Probable Mechanism: inhibition by combination contraceptives of caffeine metabolism 2009/7/26 36

37 Drug-Food Combinations Grapefruit Juice Interaction Effect: increased plasma concentrations of estrogens Summary: Inhibitors of cytochrome P450 3A4, such as grapefruit juice, may increase plasma concentrations of estrogens and may result in side effects of estrogen. Concomitant grapefruit juice intake with ethinyl estradiol increased serum concentrations of estrone and ethinyl estradiol. However, the clinical significance of this interaction is unclear. Severity: moderate Onset: rapid Substantiation: probable Clinical Management: Monitor for signs and symptoms of increased estrogen plasma concentrations such as hypertension, depression, headache, thromboembolism, fluid retention, abdominal cramps, bloating, and weight gain. Probable Mechanism: inhibition of cytochrome P450 3A4- mediated estrogen metabolism of grapefruit juice 2009/7/26 37

38 Drug-Tobacco Combinations Tobacco Interaction Effect: an increased risk of cardiovascular disease Summary: The use of combination contraceptives with tobacco smoking (more than 15 cigarettes daily) may increase the risk of cardiovascular adverse effects in persons older than 35 years. The use of combination contraceptives and tobacco smoking may significantly increase the risk of myocardial infarction, subarachnoid hemorrhage, venous thromboembolism, and other strokes. Severity: minor Onset: delayed Substantiation: theoretical Clinical Management: Combination contraceptive users should be cautioned regarding the dangers of tobacco smoking and should be advised to discontinue smoking. Probable Mechanism: unknown 2009/7/26 38

39 Contraceptive Patch (Ortho Evra) Dosing: 1 patch applied weekly to abdomen, buttock, upper outer arm or upper torso (not breasts) for 3 weeks then 1 patch-free week 1 patch provides norelgestromin 150 mcg/day and ethinyl estradiol 20 mcg/day if patch left off for > 24 hours, restarting cycle and using back-up contraception for 7 days recommended 2009/7/26 39

40 Contraceptive Patch ~Contraindications~ pregnancy breastfeeding thromboembolism hepatic disease estrogen-dependent neoplasm 2009/7/26 40

41 Contraceptive Patch~Cautions~ Ortho Evra labeling updated to include epidemiologic study finding higher risk of venous thromboembolism in users of birth control patch than birth control pills Transdermal contraceptive may be associated with increased risk of venous thromboembolism compared to oral contraceptive Ortho Evra labeling updated to warn that it exposes women to higher estrogen levels than most birth control pills 2009/7/26 41

42 Contraceptive Patch~Adverse effects~ Common Dermatologic: Application site reaction Gastrointestinal: Abdominal pain, Nausea Neurologic: Headache Psychiatric: Mood swings Reproductive: Breast finding, Dysmenorrhea Serious Cardiovascular: Arterial thromboembolism, Hypertension, Myocardial infarction, Thrombophlebitis, Venous thrombosis Gastrointestinal: Disorder of gallbladder Hepatic: Benign neoplasm of liver, Neoplasm of liver Neurologic: Cerebral hemorrhage, Cerebral thrombosis Respiratory: Pulmonary embolism 2009/7/26 42

43 Emergency contraception also called morning-after contraception no treatment - 8% chance of conception best regimens based on efficacy and side effects levonorgestrel 0.75 mg orally twice 12 hours apart, available in United States as Plan B levonorgestrel 1.5 mg orally once mifepristone (RU-486) mg - not available in United States FDA approves over-the-counter access for Plan B for women 17 years and older, prescription still required for women < 17 years old 2009/7/26 43

44 Levonorgestrel (Plan B) Plan B is first progestin-only emergency contraceptive, consists of two levonorgestrel 0.75 mg tablets, used within 72 hours of intercourse as 1 tablet with second tablet repeated 12 hours later 2009/7/26 44

45 Mifepristone (RU486) mifepristone (RU486) 600 mg given 72 hours after intercourse found to be 100% effective in 2 randomized trials of total 600 women. 2009/7/26 45

46 Yuzpe method (ethinyl estradiol/levonorgestrel) 2 tablets of 50 mcg ethinyl estradiol and 250 mcg levonorgestrel with antiemetic (e.g. 50 mg dimenhydrinate) followed by second identical dose 12 hours later. 2009/7/26 46

47 Q & A 如 何 正 確 服 用 口 服 避 孕 藥? 2009/7/26 47

48 Q & A 若 忘 了 服 藥, 該 怎 麼 辦? 2009/7/26 48

49 Q & A 服 用 口 服 避 孕 藥 時, 應 注 意 甚 麼? 2009/7/26 49

50 Q & A 口 服 避 孕 藥 有 副 作 用 嗎? 出 現 副 作 用 時 該 如 何 處 理? 2009/7/26 50

51 Reference DynaMed. Available from ebscohost.com/. Accessed June 26, 2009 Micromedex Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc. Updated periodically. 2009/7/26 51

52 Thanks for your attention!! 2009/7/26 52