Boxed Warning
Cigarette smoke and serious cardiovascular events:
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, combination oral contraceptives should not be used in women who are over 35 years and smoke.
Endometrial cancer:
There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be taken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal genital bleeding.
Cardiovascular disease:
Estrogen-alone therapy should not be used for the prevention of cardiovascular disease. The Women's Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens 0.625 mg alone, relative to placebo.
Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease. The WHI estrogen plus progestin substudy reported increased risks of DVT, pulmonary embolism (PE), stroke, and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg), relative to placebo.
Breast cancer:
The WHI estrogen-plus-progestin substudy demonstrated an increased risk of invasive breast cancer.
Dementia:
Estrogen-alone therapy should not be used for the prevention of dementia. The WHI Memory Study (WHIMS) estrogen-alone ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily conjugated estrogens (0.625 mg) alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.
Estrogen plus progestin therapy should not be used for the prevention of dementia. The WHIMS estrogen plus progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.
Risk vs benefit:
In the absence of comparable data, these risks should be assumed to be similar for other doses of conjugated estrogens (with or without medroxyprogesterone acetate) and other dosage forms of estrogens (with or without progestins). Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Taytulla: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [24 capsules] and ferrous fumarate 75 mg [4 capsules] [contains brilliant blue fcf (fd&c blue #1), fd&c red #40, sesame oil, soybean oil]
Tablet, Oral:
Alyacen 1/35: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #2 (indigotine), fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]
Alyacen 7/7/7: Day 1-7: Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [7 tablets]; Day 8-14: Ethinyl estradiol 0.035 mg and norethindrone 0.75 mg [7 tablets]; Day 15-21: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [7 tablets]; Day 22-28: 7 inactive tablets [contains fd&c blue #2 (indigotine), fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]
Aranelle: Day 1-7: Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [7 tablets]; Day 8-16: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [9 tablets]; Day 17-21: Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [5 tablets]; Day 22-28: 7 inactive tablets [contains fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake]
Aurovela 1.5/30: Ethinyl estradiol 0.03 mg and norethindrone acetate 1.5 mg
Aurovela 1/20: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [contains fd&c yellow #10 aluminum lake]
Aurovela 24 FE: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [24 tablets] and ferrous fumarate 75 mg [4 tablets] [contains fd&c yellow #10 aluminum lake]
Aurovela Fe 1.5/30: Ethinyl estradiol 0.03 mg and norethindrone acetate 1.5 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets]
Aurovela FE 1/20: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets] [contains fd&c yellow #10 aluminum lake]
Balziva: Ethinyl estradiol 0.035 mg and norethindrone 0.4 mg [21 tablets and 7 inactive tablets] [contains corn starch, fd&c yellow #6 aluminum lake]
Blisovi 24 Fe: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [24 tablets] and ferrous fumarate 75 mg [4 tablets] [contains corn starch]
Blisovi Fe 1.5/30: Ethinyl estradiol 0.03 mg and norethindrone acetate 1.5 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets] [contains corn starch, fd&c red #40]
Blisovi FE 1/20: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets] [contains corn starch, fd&c yellow #10 aluminum lake]
Brevicon (28): Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [21 tablets and 7 inactive tablets] [DSC]
Briellyn: Ethinyl estradiol 0.035 mg and norethindrone 0.4 mg [21 tablets and 7 inactive tablets] [contains fd&c yellow #6 aluminum lake]
Cyclafem 1/35: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #2 (indigotine), fd&c red #40 aluminum lake]
Cyclafem 7/7/7: Day 1-7: Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [7 tablets]; Day 8-14: Ethinyl estradiol 0.035 mg and norethindrone 0.75 mg [7 tablets]; Day 15-21: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [7 tablets]; Day 22-28: 7 inactive tablets [contains fd&c blue #2 (indigotine), fd&c red #40 aluminum lake]
Dasetta 1/35: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #2 aluminum lake, fd&c red #40 aluminum lake, fd&c yellow #5 aluminum lake, fd&c yellow #6 aluminum lake, soybean lecithin]
Dasetta 7/7/7: Day 1-7: Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [7 tablets]; Day 8-14: Ethinyl estradiol 0.035 mg and norethindrone 0.75 mg [7 tablets]; Day 15-21: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [7 tablets]; Day 22-28: 7 inactive tablets [contains fd&c blue #2 aluminum lake, fd&c red #40 aluminum lake, fd&c yellow #5 aluminum lake, fd&c yellow #6 aluminum lake, soybean lecithin]
Estrostep Fe: Day 1-5: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [5 tablets]; Day 6-12: Ethinyl estradiol 0.03 mg and norethindrone acetate 1 mg [7 tablets]; Day 13-21: Ethinyl estradiol 0.035 mg and norethindrone acetate 1 mg [9 tablets]; Day 22-28: Ferrous fumarate 75 mg [7 tablets]
Femhrt Low Dose: Ethinyl estradiol 0.0025 mg and norethindrone acetate 0.5 mg
Fyavolv: Ethinyl estradiol 0.0025 mg and norethindrone acetate 0.5 mg
Fyavolv: Ethinyl estradiol 0.005 mg and norethindrone acetate 1 mg [contains fd&c blue #2 (indigotine)]
Gildagia: Ethinyl estradiol 0.035 mg and norethindrone 0.4 mg [21 tablets and 7 inactive tablets] [DSC] [contains fd&c blue #2 (indigotine), fd&c yellow #6 aluminum lake]
Gildess 1/20: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [DSC]
Gildess 1.5/30: Ethinyl estradiol 0.03 mg and norethindrone acetate 1.5 mg [DSC] [contains fd&c blue #1 aluminum lake, fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake]
Gildess 24 FE: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [24 tablets] and ferrous fumarate 75 mg [4 tablets] [DSC]
Gildess FE 1/20: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets] [DSC]
Gildess FE 1.5/30: Ethinyl estradiol 0.03 mg and norethindrone acetate 1.5 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets] [DSC] [contains fd&c blue #1 aluminum lake, fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake]
Hailey 1.5/30: Ethinyl estradiol 0.03 mg and norethindrone acetate 1.5 mg [contains brilliant blue fcf (fd&c blue #1), corn starch, fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]
Hailey 24 Fe: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [24 tablets] and ferrous fumarate 75 mg [4 tablets] [contains corn starch]
Jevantique Lo: Ethinyl estradiol 0.0025 mg and norethindrone acetate 0.5 mg [DSC]
Jinteli: Ethinyl estradiol 0.005 mg and norethindrone acetate 1 mg
Junel 1.5/30: Ethinyl estradiol 0.03 mg and norethindrone acetate 1.5 mg [contains fd&c red #40 aluminum lake]
Junel 1/20: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [contains fd&c yellow #10 aluminum lake]
Junel FE 1.5/30: Ethinyl estradiol 0.03 mg and norethindrone acetate 1.5 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets] [contains fd&c red #40 aluminum lake]
Junel Fe 24: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [24 tablets] and ferrous fumarate 75 mg [4 tablets] [contains fd&c yellow #10 aluminum lake]
Junel FE 1/20: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets] [contains fd&c yellow #10 aluminum lake]
Larin 1/20: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [contains fd&c blue #2 aluminum lake, fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake, soybean lecithin]
Larin 1.5/30: Ethinyl estradiol 0.03 mg and norethindrone acetate 1.5 mg [contains fd&c blue #2 aluminum lake, fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake, soybean lecithin]
Larin 24 FE: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [24 tablets] and ferrous fumarate 75 mg [4 tablets] [contains fd&c blue #2 aluminum lake, fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake, soybean lecithin]
Larin Fe 1/20: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets] [contains fd&c blue #2 aluminum lake, fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake, soybean lecithin]
Larin Fe 1.5/30: Ethinyl estradiol 0.03 mg and norethindrone acetate 1.5 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets] [contains fd&c blue #2 aluminum lake, fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake, soybean lecithin]
Leena: Day 1-7: Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [7 tablets]; Day 8-16: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [9 tablets]; Day 17-21: Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [5 tablets]; Day 22-28: 7 inactive tablets [contains brilliant blue fcf (fd&c blue #1), corn starch, fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]
Lo Loestrin Fe: Day 1-24: Ethinyl estradiol 0.01 mg and norethindrone acetate 1 mg [24 tablets]; Day 25-26: Ethinyl estradiol 0.01 mg [2 tablets]; Day 27-28: Ferrous fumarate 75 mg [2 tablets] [contains fd&c blue #1 aluminum lake]
Loestrin 1.5/30 (21): Ethinyl estradiol 0.03 mg and norethindrone acetate 1.5 mg [contains fd&c red #40 aluminum lake]
Loestrin 1/20 (21): Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [contains fd&c yellow #10 aluminum lake]
Loestrin Fe 1.5/30: Ethinyl estradiol 0.03 mg and norethindrone acetate 1.5 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets] [contains fd&c red #40 aluminum lake]
Loestrin Fe 1/20: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets] [contains fd&c yellow #10 aluminum lake]
Lomedia 24 FE: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [24 tablets] and ferrous fumarate 75 mg [4 tablets] [DSC]
Microgestin 1.5/30: Ethinyl estradiol 0.03 mg and norethindrone acetate 1.5 mg [contains brilliant blue fcf (fd&c blue #1), corn starch, fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]
Microgestin 1/20: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]
Microgestin 1.5/30: Ethinyl estradiol 0.03 mg and norethindrone acetate 1.5 mg [DSC] [contains fd&c blue #1 aluminum lake, fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake]
Microgestin 24 Fe: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [24 tablets] and ferrous fumarate 75 mg [4 tablets] [DSC]
Microgestin FE 1/20: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets]
Microgestin FE 1/20: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets] [DSC] [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]
Microgestin FE 1.5/30: Ethinyl estradiol 0.03 mg and norethindrone acetate 1.5 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets] [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]
Modicon (28): Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [21 tablets and 7 inactive tablets] [DSC] [contains fd&c blue #2 aluminum lake, fd&c yellow #10 aluminum lake]
Necon 7/7/7: Day 1-7: Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [7 tablets]; Day 8-14: Ethinyl estradiol 0.035 mg and norethindrone 0.75 mg [7 tablets]; Day 15-21: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [7 tablets]; Day 22-28: 7 inactive tablets [DSC] [contains fd&c blue #2 aluminum lake, fd&c yellow #10 aluminum lake, fd&c yellow #6 (sunset yellow)]
Necon 0.5/35 (28): Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [21 tablets and 7 inactive tablets] [DSC]
Necon 0.5/35 (28): Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [21 tablets and 7 inactive tablets] [contains corn starch, fd&c yellow #10 aluminum lake]
Necon 1/35 (28): Ethinyl estradiol 0.035 mg and norethindrone 1 mg [21 tablets and 7 inactive tablets] [DSC]
Necon 10/11 (28): Day 1-10: Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [10 tablets]; Day 11-21: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [11 tablets]; Day 22-28: 7 inactive tablets [DSC]
Norinyl 1+35 (28): Ethinyl estradiol 0.035 mg and norethindrone 1 mg [21 tablets and 7 inactive tablets] [DSC]
Nortrel 7/7/7: Day 1-7: Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [7 tablets]; Day 8-14: Ethinyl estradiol 0.035 mg and norethindrone 0.75 mg [7 tablets]; Day 15-21: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [7 tablets]; Day 22-28: 7 inactive tablets [contains corn starch, fd&c blue #1 aluminum lake, fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake]
Nortrel 0.5/35 (28): Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [21 tablets and 7 inactive tablets]
Nortrel 1/35 (21): Ethinyl estradiol 0.035 mg and norethindrone 1 mg [21 tablets and 7 inactive tablets]
Nortrel 1/35 (28): Ethinyl estradiol 0.035 mg and norethindrone 1 mg [21 tablets and 7 inactive tablets]
Ortho-Novum 1/35 (28): Ethinyl estradiol 0.035 mg and norethindrone 1 mg [21 tablets and 7 inactive tablets] [contains corn starch, fd&c blue #2 aluminum lake, fd&c yellow #10 aluminum lake, fd&c yellow #6 (sunset yellow)]
Ortho-Novum 7/7/7 (28): Day 1-7: Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [7 tablets]; Day 8-14: Ethinyl estradiol 0.035 mg and norethindrone 0.75 mg [7 tablets]; Day 15-21: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [7 tablets]; Day 22-28: 7 inactive tablets [contains corn starch, fd&c blue #2 aluminum lake, fd&c yellow #10 aluminum lake, fd&c yellow #6 (sunset yellow)]
Ovcon-35 (28): Ethinyl estradiol 0.035 mg and norethindrone 0.4 mg [21 tablets and 7 inactive tablets] [DSC] [contains fd&c yellow #6 aluminum lake]
Philith: Ethinyl estradiol 0.035 mg and norethindrone 0.4 mg [21 tablets and 7 inactive tablets] [contains soybean lecithin]
Pirmella 1/35: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #2 (indigotine), fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]
Pirmella 7/7/7: Day 1-7: Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [7 tablets]; Day 8-14: Ethinyl estradiol 0.035 mg and norethindrone 0.75 mg [7 tablets]; Day 15-21: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [7 tablets]; Day 22-28: 7 inactive tablets [contains fd&c blue #2 (indigotine), fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]
Tarina 24 Fe: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [24 tablets] and ferrous fumarate 75 mg [4 tablets] [contains fd&c yellow #10 aluminum lake]
Tarina FE 1/20: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets]
Tarina FE 1/20 EQ: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets] [contains fd&c yellow #10 aluminum lake]
Tilia Fe: Day 1-5: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [5 tablets]; Day 6-12: Ethinyl estradiol 0.03 mg and norethindrone acetate 1 mg [7 tablets]; Day 13-21: Ethinyl estradiol 0.035 mg and norethindrone acetate 1 mg [9 tablets]; Day 22-28: Ferrous fumarate 75 mg [7 tablets] [DSC]
Tilia Fe: Day 1-5: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [5 tablets]; Day 6-12: Ethinyl estradiol 0.03 mg and norethindrone acetate 1 mg [7 tablets]; Day 13-21: Ethinyl estradiol 0.035 mg and norethindrone acetate 1 mg [9 tablets]; Day 22-28: Ferrous fumarate 75 mg [7 tablets] [contains corn starch]
Tri-Legest Fe: Day 1-5: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [5 tablets]; Day 6-12: Ethinyl estradiol 0.03 mg and norethindrone acetate 1 mg [7 tablets]; Day 13-21: Ethinyl estradiol 0.035 mg and norethindrone acetate 1 mg [9 tablets]; Day 22-28: Ferrous fumarate 75 mg [7 tablets] [contains fd&c blue #2 aluminum lake, fd&c red #40 aluminum lake, fd&c yellow #10 aluminum lake]
Tri-Norinyl (28): Day 1-7: Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [7 tablets]; Day 8-16: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [9 tablets]; Day 17-21: Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [5 tablets]; Day 22-28: 7 inactive tablets [DSC] [contains brilliant blue fcf (fd&c blue #1), corn starch, fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]
Tri-Norinyl (28): Day 1-7: Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [7 tablets]; Day 8-16: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [9 tablets]; Day 17-21: Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [5 tablets]; Day 22-28: 7 inactive tablets [DSC] [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]
Vyfemla: Ethinyl estradiol 0.035 mg and norethindrone 0.4 mg [21 tablets and 7 inactive tablets] [contains fd&c yellow #6 aluminum lake]
Wera: Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [21 tablets and 7 inactive tablets]
Zenchent: Ethinyl estradiol 0.035 mg and norethindrone 0.4 mg [21 tablets and 7 inactive tablets] [DSC] [contains corn starch, fd&c yellow #6 aluminum lake]
Zenchent: Ethinyl estradiol 0.035 mg and norethindrone 0.4 mg [21 tablets and 7 inactive tablets] [DSC] [contains fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake]
Generic: Ethinyl estradiol 0.0025 mg and norethindrone acetate 0.5 mg, Ethinyl estradiol 0.005 mg and norethindrone acetate 1 mg, Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg, Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets], Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [24 tablets] and ferrous fumarate 75 mg [4 tablets], Ethinyl estradiol 0.03 mg and norethindrone acetate 1.5 mg, Ethinyl estradiol 0.03 mg and norethindrone acetate 1.5 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets]
Tablet Chewable, Oral:
Femcon Fe: Ethinyl estradiol 0.035 mg and norethindrone 0.4 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets] [DSC]
Generess FE: Ethinyl estradiol 0.025 mg and norethindrone 0.8 mg [24 tablets] and ferrous fumarate 75 mg [4 tablets] [contains fd&c blue #1 aluminum lake, fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake]
Kaitlib Fe: Ethinyl estradiol 0.025 mg and norethindrone 0.8 mg [24 tablets] and ferrous fumarate 75 mg [4 tablets] [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow)]
Layolis FE: Ethinyl estradiol 0.025 mg and norethindrone 0.8 mg [24 tablets] and ferrous fumarate 75 mg [4 tablets] [contains fd&c blue #1 aluminum lake, fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake]
Melodetta 24 Fe: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [24 tablets] and ferrous fumarate 75 mg [4 tablets]
Mibelas 24 Fe: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [24 tablets] and ferrous fumarate 75 mg [4 tablets] [contains corn starch]
Minastrin 24 Fe: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [24 tablets] and ferrous fumarate 75 mg [4 tablets] [fresh mint flavor]
Wymzya Fe: Ethinyl estradiol 0.035 mg and norethindrone 0.4 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets]
Wymzya Fe: Ethinyl estradiol 0.035 mg and norethindrone 0.4 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets] [DSC] [scored; spearmint flavor]
Zenchent FE: Ethinyl estradiol 0.035 mg and norethindrone 0.4 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets] [DSC] [contains fd&c yellow #10 (quinoline yellow)]
Generic: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [24 tablets] and ferrous fumarate 75 mg [4 tablets], Ethinyl estradiol 0.025 mg and norethindrone 0.8 mg [24 tablets] and ferrous fumarate 75 mg [4 tablets], Ethinyl estradiol 0.035 mg and norethindrone 0.4 mg [21 tablets] and ferrous fumarate 75 mg [7 tablets]
Pharmacology
Mechanism of Action
Combination oral contraceptives inhibit ovulation via a negative feedback mechanism on the hypothalamus, which alters the normal pattern of gonadotropin secretion of a follicle-stimulating hormone (FSH) and luteinizing hormone by the anterior pituitary. The follicular phase FSH and midcycle surge of gonadotropins are inhibited. In addition, combination hormonal 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. Combination hormonal contraceptive drugs may alter the tubal transport of the ova through the fallopian tubes. Progestational agents may also alter sperm fertility.
In postmenopausal women, exogenous estrogen is used to replace decreased endogenous production. The addition of progestin reduces the incidence of endometrial hyperplasia and risk of endometrial cancer in women with an intact uterus.
Pharmacokinetics/Pharmacodynamics
Absorption
Ethinyl estradiol: Rapid
Distribution
Ethinyl estradiol: Vd: 2 to 4 L/kg
Metabolism
Ethinyl estradiol: Hepatic via oxidation and conjugation in GI tract; hydroxylated via CYP3A4 to metabolites; first-pass effect; enterohepatic recirculation; reversibly converted to estrone and estriol
Excretion
Ethinyl estradiol: Urine (as estradiol, estrone, and estriol); feces
Half-Life Elimination
Ethinyl estradiol: 19 to 24 hours
Protein Binding
Ethinyl estradiol: >95% to albumin
Use: Labeled Indications
Acne vulgaris (Estrostep Fe, Tilia Fe, Tri-Legest Fe): Treatment of moderate acne vulgaris in females at least 15 years.
Limitations of use: When used for acne, use only in females ≥15 years who have achieved menarche, who also desire combination hormonal contraceptive therapy, are unresponsive to topical treatments, have no contraindications to combination hormonal contraceptive use, and plan to stay on therapy for ≥6 months.
Contraception: Prevention of pregnancy.
Limitations of use: The efficacy of some products has not been established in women with a BMI >35 kg/m2.
Osteoporosis prevention (female) (femhrt, Jevantique Lo, Jinteli): Prevention of postmenopausal osteoporosis.
Limitations of use: For use only in women at significant risk of postmenopausal osteoporosis; consider use of nonestrogen medications.
Vasomotor symptoms associated with menopause (femhrt, Jevantique Lo, Jinteli): Treatment of moderate to severe vasomotor symptoms associated with menopause.
Use: Off Label
Abnormal uterine bleeding (acute)byes
Data from a randomized, open-label clinical study support the use of ethinyl estradiol/norethindrone in the treatment of acute uterine bleeding in nonpregnant, hemodynamically stable premenopausal women requiring emergent medical intervention Munro 2006.
Based on the American College of Obstetricians and Gynecologists (ACOG) committee opinion on the management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women, ethinyl estradiol/norethindrone (among other oral contraceptive combinations) is effective and recommended for the management of acute abnormal uterine bleeding in patients who are clinically stable ACOG 557 2013.
Dysmenorrheayes
Based on the ACOG Practice Bulletin on Noncontraceptive Uses of Hormonal Contraceptives, ethinyl estradiol and norethindrone (among other oral contraceptive combinations) is effective and recommended for the management of dysmenorrhea ACOG 2010.
Hirsutismyes
Based on the Endocrine Society Clinical Practice Guideline for the Evaluation and Treatment of Hirsutism in Premenopausal Women, ethinyl estradiol and norethindrone is effective and recommended (among other oral estrogen-progestin contraceptive combinations) for the treatment of adult women with hirsutism (including idiopathic hirsutism and hirsutism in women with polycystic ovary syndrome [PCOS] or nonclassical congenital adrenal hyperplasia). Oral contraceptive therapy is recommended for initial therapy in most women of reproductive potential who are not seeking fertility Endocrine Society [Martin 2018].
Menstrual bleeding (menorrhagia)yes
Based on the ACOG Practice Bulletin on Noncontraceptive Uses of Hormonal Contraceptives, ethinyl estradiol and norethindrone (among other oral contraceptive combinations) is effective and recommended for the management of menstrual bleeding (menorrhagia) ACOG 2010.
Polycystic ovary syndrome (PCOS) in women with menstrual irregularities and hirsutism/acneyes
Based on the Endocrine Society Clinical Practice Guideline for the Diagnosis and Treatment of Polycystic Ovary Syndrome, ethinyl estradiol and norethindrone (among other oral contraceptive combinations) is effective and recommended for the treatment of menstrual irregularities and hirsutism/acne in women with PCOS ES [Legro 2013].
Contraindications
Combination hormonal contraceptives: Hypersensitivity to ethinyl estradiol, norethindrone, or any component of the formulation; breast cancer, or other estrogen- or progestin-sensitive cancer (current or a history of); hepatic tumors (benign or malignant) or hepatic disease; pregnancy; undiagnosed abnormal uterine bleeding; concomitant use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir
Use is also contraindicated in women at high risk of arterial or venous thrombotic diseases for example, women with: Cerebrovascular disease; coronary artery disease; diabetes mellitus with vascular disease; DVT or PE (current or history of); hypertension (uncontrolled); headaches with focal neurological symptoms; migraine headaches with aura or migraine headaches if >35 years; women >35 years who smoke; hypercoagulopathies (inherited or acquired); thrombogenic valvular or thrombogenic rhythm diseases of the heart (eg, subacute bacterial endocarditis with valvular disease, atrial fibrillation)
Canadian labeling: Additional contraindications (not in US labeling): Angina pectoris or myocardial infarction (current or history of); steroid-dependent jaundice or cholestatic jaundice; any ocular lesion arising from ophthalmic vascular disease (such as partial or complete loss of vision or visual field defect); migraine with focal aura (current or history of); pancreatitis associated with severe hypertriglyceridemia (current or history of); severe dyslipoproteinemia; persistent blood pressure ≥160 mm Hg systolic or ≥100 mm Hg diastolic; women with hereditary or acquired predisposition for arterial or venous thrombosis, for example: factor V Leiden mutation, activated protein C (APC-) resistance, antithrombin-III-deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia (eg, due to MTHFR C677T, A1298 mutations), prothrombin mutation G20210A, and antiphospholipid-antibodies (anticardiolipin antibodies, lupus anticoagulant); coadministration with paritaprevir, ritonavir, ombitasvir (with or without dasabuvir)
Products used for postmenopausal indications: Angioedema, anaphylactic reaction, or hypersensitivity to any component of the formulation; undiagnosed abnormal genital bleeding; DVT or PE (current or history of); active or history of arterial thromboembolic disease (eg, stroke, MI); breast cancer (known, suspected or history of); estrogen-dependent tumor (known or suspected); hepatic impairment or disease; known protein C, protein S, antithrombin deficiency or other known thrombophilic disorders; pregnancy
Canadian labeling: Additional contraindications (not in US labeling): endometrial hyperplasia, classical migraine, lactation
Documentation of allergenic cross-reactivity for estrogens and progestins is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Dosage and Administration
Dosing: Adult
Abnormal uterine bleeding, acute (off-label use): Oral: Ethinyl estradiol 0.035 mg/norethindrone 1 mg three times a day for 7 days (ACOG 557 2013; Munro 2006)
Acne: Adolescents ≥15 years of age and Adults: Females: Oral (Estrostep Fe, Tilia Fe, Tri-Legest Fe): Refer to dosing for contraception
Contraception: Females: One tablet once daily
Schedule 1 (Sunday starter): Dose begins on first Sunday after onset of menstruation; if the menstrual period starts on Sunday, take first tablet that very same day. (This schedule is not preferred for all products [eg, Generess Fe, Lo Loestrin Fe]). With a Sunday start, an additional method of contraception should be used until after the first 7 days of consecutive administration (all products).
Schedule 2 (Day 1 starter): Dose starts on first day of menstrual cycle taking 1 tablet daily.
Additional contraceptive dosing considerations:
Switching from a different contraceptive:
Oral contraceptive: Start on the same day that a new pack of the previous oral contraceptive would have been taken.
Transdermal patch, vaginal ring, injection: Start on the day the next dose would have been due.
IUD or implant: Start on the day of removal. A backup method of contraception should be used for the first 7 days if IUD is not removed on the first day of the menstrual cycle.
Use after first trimester abortion or miscarriage: Therapy may be started immediately. If not started within 5 days, a back-up method of contraception should be used for the first 7 days.
Use after childbirth (in women who are not breastfeeding) or after second trimester abortion or miscarriage: Therapy may be started ≥4 weeks postpartum. Pregnancy should be ruled out prior to treatment if menstrual periods have not restarted. An additional method of contraception (nonhormonal) should be used until after the first 7 days of consecutive administration.
Also refer to prescribing information for product specific information (or Curtis 2016a) for general guidance.
Missed or late doses (Curtis 2016a):
If one dose is late (<24 hours since dose should have been taken) or if one dose is missed (24 to <48 hours since dose should have been taken): Take dose as soon as possible. Continue remaining doses at the usual time (even if that means 2 doses on the same day).
If ≥2 consecutive doses are missed (≥48 hours since dose should have been taken): Take the most recently missed dose as soon as possible, discard any other missed doses. Continue remaining doses at the usual time (even if that means taking 2 doses on the same day); use back-up contraception until hormonal pills have been taken for 7 consecutive days. If doses were missed during the last week of hormonal (active) tablets (eg, days 15 to 21 of a 28 day pack), omit the hormone free interval by finishing the current pack and starting a new pack. If unable to start a new pack immediately, back up contraception is needed until hormonal pills from a new pack have been taken for 7 consecutive days. Consider use of emergency contraception in some situations (refer to guidelines for details).
Also refer to prescribing information for product specific information.
Postmenopausal indications: General dosing guidelines: When treating symptoms of menopause, hormone therapy should be evaluated routinely for appropriate dose, duration, and route of administration for each individual patient based on treatment goals, risk factors, and overall health (NAMS 2017). Combined estrogen/progestin therapy is indicated for postmenopausal persons with a uterus to decrease the risk of endometrial cancer. Individuals who have had a hysterectomy generally do not need a progestin; however, one may be needed if there is a history of endometriosis. Adjust dose based on patient response.
Osteoporosis prevention: Females: Oral (femhrt, Jevantique Lo, Jinteli): One tablet daily
Vasomotor symptoms associated with menopause: Females: Oral (femhrt, Jevantique Lo, Jinteli): Initial: One tablet daily.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Acne: Adolescent females ≥15 years: Oral (Estrostep Fe, Tilia Fe, Tri-Legest Fe): Refer to adult dosing for contraception; not to be used prior to menarche
Contraception: Females: Oral: Refer to adult dosing; not to be used prior to menarche.
Administration
Combination hormonal contraceptives:
Administer at the same time each day at intervals not >24 hours; without regard to meals. The Femcon Fe tablet may be chewed or swallowed whole; if chewed, immediately drink a full glass of liquid (240 mL) after swallowing.
For some products (eg, Femcon Fe, Generess Fe, Lo Loestrin Fe), if vomiting or diarrhea occurs within 3 to 4 hours of a dose, consider the dose to be missed. Additional guidelines are also available (Curtis 2016a).
For the 21-tablet package, one dose is taken for 21 consecutive days, followed by 7 days off of the medication; a new course begins on the 8th day after the last tablet is taken.
For the 28-tablet package, one dose is taken daily without interruption.
Combined hormonal contraceptives may be initiated at any time during the menstrual cycle if it is reasonably sure the woman is not pregnant. Back-up contraception should be used for 7 days unless contraception is initiated within the first 5 days of menstrual bleeding or the woman abstains from sexual intercourse. Combined hormonal contraceptives may be started immediately following or within 7 days of a first or second trimester abortion; backup contraception is needed for 7 days unless contraception is started at the time of surgical abortion (Curtis 2016a).
Postmenopausal indications: Administer at the same time each day.
Dietary Considerations
Ensure adequate calcium and vitamin D intake when used for the prevention of osteoporosis.
Storage
Store at controlled room temperature.
Estrostep Fe, Femcon Fe: Protect from light.
Ethinyl Estradiol and Norethindrone Images
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ethinyl estradiol/norethindrone ethinyl estradiol 50 mcg / norethindrone acetate 2.5 mg -
ethinyl estradiol/norethindrone ethinyl estradiol 50 mcg / norethindrone acetate 1 mg -
ethinyl estradiol/norethindrone ethinyl estradiol 0.02 mg / norethindrone acetate 1 mg -
ethinyl estradiol/norethindrone ethinyl estradiol 0.02 mg / norethindrone acetate 1 mg -
ethinyl estradiol/norethindrone ethinyl estradiol 0.02 mg / norethindrone acetate 1 mg -
ethinyl estradiol/norethindrone 0.0025 mg / 0.5 mg
Drug Interactions
Acitretin: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Given the potential for progestin-only preparations to fail to prevent pregnancy during acitretin therapy, such products should not be relied upon. Alternative, nonhormonal forms of contraception must be employed during acitretin therapy. Consider therapy modification
Ajmaline: Estrogen Derivatives may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Monitor therapy
Anastrozole: Estrogen Derivatives may diminish the therapeutic effect of Anastrozole. Avoid combination
Anthrax Immune Globulin (Human): Estrogen Derivatives may enhance the thrombogenic effect of Anthrax Immune Globulin (Human). Monitor therapy
Anticoagulants: Estrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of estrogens against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Consider therapy modification
Anticoagulants: Progestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of progestins against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Consider therapy modification
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Antihepaciviral Combination Products: Ethinyl Estradiol may enhance the hepatotoxic effect of Antihepaciviral Combination Products. Management: Use of ethinyl estradiol must be discontinued prior to use of this combination; ethinyl estradiol can be restarted 2 weeks after cessation of the antihepaciviral combination product. Avoid combination
Aprepitant: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Use of a non-hormone-based contraceptive is recommended. Consider therapy modification
Aprepitant: May decrease the serum concentration of Progestins (Contraceptive). Management: Alternative or additional methods of contraception should be used both during treatment with aprepitant or fosaprepitant and for at least one month following the last aprepitant/fosaprepitant dose. Consider therapy modification
Armodafinil: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Use alternative or concomitant methods of contraception in patients taking armodafinil and for one month after armodafinil discontinuation. Consider therapy modification
Artemether: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Consider the use of an alternative (i.e., non-hormonal) means of contraception in all women of childbearing potential who are using artemether. Consider therapy modification
Artemether: May decrease the serum concentration of Progestins (Contraceptive). Management: Consider the use of an alternative (i.e., non-hormonal) means of contraception in all women of childbearing potential who are using artemether. Consider therapy modification
Ascorbic Acid: May increase the serum concentration of Estrogen Derivatives. Monitor therapy
Asunaprevir: May decrease the serum concentration of Ethinyl Estradiol. Management: For patients using hormone-based contraception, a high-dose oral contraceptive containing at least 30 mcg of ethinyl estradiol combined with norethindrone acetate/norethindrone is recommended during treatment with asunaprevir. Consider therapy modification
Atazanavir: May increase the serum concentration of Progestins (Contraceptive). However, atazanavir may lead to decreased ethinyl estradiol concentrations and decreased effectiveness of oral contraceptive products. Management: Consider an alternative or additional method of contraception, particularly with combined estrogen/progestin products. Depot medroxyprogesterone acetate may be used without a need for additional contraception. Consider therapy modification
Barbiturates: May diminish the therapeutic effect of Estrogen Derivatives (Contraceptive). Contraceptive failure is possible. Management: Use of a non-hormonal contraceptive is recommended. Consider therapy modification
Barbiturates: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Consider therapy modification
Bexarotene (Systemic): May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Women of childbearing potential receiving bexarotene should use two reliable forms of contraception (including at least one nonhormonal form). Consider therapy modification
Bexarotene (Systemic): May decrease the serum concentration of Progestins (Contraceptive). Management: Women of childbearing potential receiving bexarotene should use two reliable forms of contraception (including at least one nonhormonal form). Consider therapy modification
Bile Acid Sequestrants: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Administer estrogen-based oral contraceptives at least 1 to 4 hours prior to or 4 to 6 hours after administration of a bile acid sequestrant. Consider therapy modification
Bile Acid Sequestrants: May decrease the serum concentration of Progestins (Contraceptive). Management: Administer oral progestin-containing contraceptives at least 1 to 4 hours prior to or 4 to 6 hours after administration of a bile acid sequestrant. Consider therapy modification
Bosentan: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Use an alternative (i.e., non-hormonal) means of contraception for all women of childbearing potential who are using bosentan, and do not rely on hormonal contraceptives alone. Consider therapy modification
Bosentan: May decrease the serum concentration of Progestins (Contraceptive). Management: Use an alternative (i.e., non-hormonal) means of contraception for all women of childbearing potential who are using bosentan, and do not rely on hormonal contraceptives alone. Consider therapy modification
Brigatinib: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Females of childbearing potential should use an alternative, non-hormonal contraceptive during brigatinib therapy and for at least 4 months after the final brigatinib dose. Consider therapy modification
Brigatinib: May decrease the serum concentration of Progestins (Contraceptive). Management: Females of childbearing potential should use an alternative, non-hormonal contraceptive during brigatinib therapy and for at least 4 months after the final brigatinib dose. Consider therapy modification
C1 inhibitors: Estrogen Derivatives may enhance the thrombogenic effect of C1 inhibitors. Monitor therapy
C1 inhibitors: Progestins may enhance the thrombogenic effect of C1 inhibitors. Monitor therapy
CarBAMazepine: May diminish the therapeutic effect of Estrogen Derivatives (Contraceptive). Contraceptive failure is possible. Management: Use of a nonhormonal contraceptive is recommended. Consider therapy modification
CarBAMazepine: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Consider therapy modification
Carfilzomib: May enhance the thrombogenic effect of Estrogen Derivatives (Contraceptive). Management: Consider alternative, non-hormonal methods of contraception in patients requiring therapy with carfilzomib. Consider therapy modification
Carfilzomib: May enhance the thrombogenic effect of Progestins (Contraceptive). Management: Consider alternative, non-hormonal methods of contraception in patients requiring therapy with carfilzomib. Consider therapy modification
Cenobamate: May decrease the serum concentration of Hormonal Contraceptives. Management: Women should use additional or alternative non-hormonal birth control while taking cenobamate. Consider therapy modification
Chenodiol: Estrogen Derivatives may diminish the therapeutic effect of Chenodiol. Management: Monitor clinical response to chenodiol closely when used together with any estrogen derivative. Monitor therapy
Cladribine: May diminish the therapeutic effect of Hormonal Contraceptives. Management: Women using systemically acting hormonal contraceptives should add a barrier method during cladribine dosing and for at least 4 weeks after the last dose in each treatment course. Consider therapy modification
CloBAZam: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Consider therapy modification
CloBAZam: May decrease the serum concentration of Progestins (Contraceptive). Consider therapy modification
CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy
Cobicistat: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Consider an alternative, nonhormone-based contraceptive in patients receiving cobicistat-containing products. Consider therapy modification
Cobicistat: May increase the serum concentration of Progestins (Contraceptive). Management: Consider an alternative, nonhormone-based contraceptive in patients receiving cobicistat-containing products. Drospirenone is specifically contraindicated with atazanavir and cobicistat. Consider therapy modification
Colesevelam: May decrease the serum concentration of Ethinyl Estradiol. Management: Oral contraceptives containing ethinyl estradiol and norethindrone should be administered at least 4 hours before colesevelam. Consider therapy modification
Colesevelam: May decrease the serum concentration of Norethindrone. Management: Oral contraceptives containing ethinyl estradiol and norethindrone should be administered at least 4 hours before colesevelam. Consider therapy modification
Corticosteroids (Systemic): Estrogen Derivatives may increase the serum concentration of Corticosteroids (Systemic). Monitor therapy
Cosyntropin: Estrogen Derivatives may diminish the diagnostic effect of Cosyntropin. Management: Discontinue estrogen containing drugs 4 to 6 weeks prior to cosyntropin (ACTH) testing. Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Estrogen Derivatives. Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Estrogen Derivatives. Monitor therapy
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dabrafenib: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Females of reproductive potential should use an alternative, highly effective, non-hormonal means of contraception during and at least 2 weeks (dabrafenib alone) or 4 months (dabrafenib + trametinib) after discontinuation of dabrafenib treatment. Consider therapy modification
Dabrafenib: May decrease the serum concentration of Progestins (Contraceptive). Management: Females of reproductive potential should use an alternative, highly effective, non-hormonal means of contraception during and at least 2 weeks (dabrafenib alone) or 4 months (dabrafenib + trametinib) after discontinuation of dabrafenib treatment. Consider therapy modification
Dantrolene: Estrogen Derivatives may enhance the hepatotoxic effect of Dantrolene. Monitor therapy
Darunavir: May decrease the serum concentration of Norethindrone. Consider therapy modification
Dasabuvir: Ethinyl Estradiol may enhance the hepatotoxic effect of Dasabuvir. Avoid combination
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Dehydroepiandrosterone: May enhance the adverse/toxic effect of Estrogen Derivatives. Avoid combination
Efavirenz: May decrease the serum concentration of Progestins (Contraceptive). Management: Use an alternative or additional method of contraception due to possibly decreased contraceptive effectiveness. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. Consider therapy modification
Elagolix: Estrogen Derivatives (Contraceptive) may diminish the therapeutic effect of Elagolix. Management: Use an alternative, non-hormonal contraceptive during treatment with elagolix and for at least 1 week following discontinuation of elagolix treatment. Consider therapy modification
Elexacaftor, Tezacaftor, and Ivacaftor: Hormonal Contraceptives may enhance the adverse/toxic effect of Elexacaftor, Tezacaftor, and Ivacaftor. Specifically, the risk for rash may be increased. Monitor therapy
Elvitegravir: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Consider the use of an alternative, non-hormone-based contraceptive, in patients who are being treated with elvitegravir-containing products. Consider therapy modification
Encorafenib: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Avoid combination
Encorafenib: May decrease the serum concentration of Progestins (Contraceptive). Avoid combination
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Eslicarbazepine: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Alternative non-hormonal means of birth control should be considered for women of child-bearing potential. Consider therapy modification
Eslicarbazepine: May decrease the serum concentration of Progestins (Contraceptive). Management: Alternative, non-hormonal means of birth control should be considered for women of child-bearing potential. Consider therapy modification
Exemestane: Estrogen Derivatives may diminish the therapeutic effect of Exemestane. Avoid combination
Exenatide: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Administer oral contraceptives at least one hour prior to exenatide. Consider therapy modification
Exenatide: May decrease the serum concentration of Progestins (Oral Contraceptive). Management: Administer oral contraceptives at least one hour prior to exenatide. Consider therapy modification
Felbamate: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Contraceptive failure is possible. Management: Use of a nonhormonal contraceptive is recommended. Consider therapy modification
Felbamate: May decrease the serum concentration of Progestins (Contraceptive). Management: Contraceptive failure is possible. Use of an alternative, nonhormonal method of contraception is recommended. Consider therapy modification
Flibanserin: Estrogen Derivatives (Contraceptive) may increase the serum concentration of Flibanserin. Monitor therapy
Flibanserin: Progestins (Contraceptive) may increase the serum concentration of Flibanserin. Monitor therapy
Fosamprenavir: Progestins (Contraceptive) may decrease serum concentrations of the active metabolite(s) of Fosamprenavir. Fosamprenavir may decrease the serum concentration of Progestins (Contraceptive). Management: Consider using an alternative or additional means of contraception. Injected depot medroxyprogesterone acetate may be used without a need for additional contraception. Consider therapy modification
Fosaprepitant: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). The active metabolite aprepitant is likely responsible for this effect. Management: Alternative or additional methods of contraception should be used both during treatment with fosaprepitant or aprepitant and for at least one month following the last fosaprepitant/aprepitant dose. Consider therapy modification
Fosaprepitant: May decrease the serum concentration of Progestins (Contraceptive). The active metabolite aprepitant is likely responsible for this effect. Management: Alternative or additional methods of contraception should be used both during treatment with aprepitant or fosaprepitant and for at least one month following the last aprepitant/fosaprepitant dose. Consider therapy modification
Fosphenytoin: May diminish the therapeutic effect of Estrogen Derivatives (Contraceptive). Contraceptive failure is possible. Management: Use of an alternative, nonhormonal means of contraception is recommended. Consider therapy modification
Fosphenytoin: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification
Glecaprevir and Pibrentasvir: Ethinyl Estradiol may enhance the adverse/toxic effect of Glecaprevir and Pibrentasvir. Specifically, the risk for ALT elevation may be increased with this combination. Avoid combination
Griseofulvin: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Avoid combination
Guanethidine: Estrogen Derivatives (Contraceptive) may diminish the therapeutic effect of Guanethidine. Monitor therapy
Hemin: Estrogen Derivatives may diminish the therapeutic effect of Hemin. Avoid combination
Herbs (Estrogenic Properties): May enhance the adverse/toxic effect of Estrogen Derivatives. Monitor therapy
Herbs (Progestogenic Properties) (eg, Bloodroot, Yucca): May enhance the adverse/toxic effect of Progestins. Monitor therapy
Hyaluronidase: Estrogen Derivatives may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving estrogens (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Consider therapy modification
Immune Globulin: Estrogen Derivatives may enhance the thrombogenic effect of Immune Globulin. Monitor therapy
Indium 111 Capromab Pendetide: Estrogen Derivatives may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Avoid combination
Ivosidenib: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Consider alternative methods of contraception (ie, non-hormonal) in patients receiving ivosidenib. Consider therapy modification
Ivosidenib: May decrease the serum concentration of Progestins (Contraceptive). Management: Consider alternative methods of contraception (ie, non-hormonal) in patients receiving ivosidenib. Consider therapy modification
Ixazomib: May decrease the serum concentration of Progestins (Contraceptive). More specifically, use of ixazomib with dexamethasone may decrease the serum concentrations of contraceptive progestins. Management: Patients of childbearing potential should use a nonhormonal barrier contraceptive during and 90 days following ixazomib treatment. Avoid combination
LamoTRIgine: Estrogen Derivatives (Contraceptive) may decrease the serum concentration of LamoTRIgine. Management: Most patients taking estrogen-containing contraceptives will require lamotrigine dose increases up to 2-fold over the recommended target lamotrigine dose. Increase lamotrigine doses by 50 to 100 mg/day every week based on clinical response. Consider therapy modification
Lenalidomide: Estrogen Derivatives may enhance the thrombogenic effect of Lenalidomide. Monitor therapy
Lesinurad: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Use of an additional, nonhormonal contraceptive is recommended in patients being treated with lesinurad who desire effective contraception. Consider therapy modification
Lesinurad: May decrease the serum concentration of Progestins (Contraceptive). Management: Use of an additional, nonhormonal contraceptive is recommended in patients being treated with lesinurad who desire effective contraception. Consider therapy modification
Lixisenatide: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Administer oral contraceptives 1 hour before or at least 11 hours after administration of lixisenatide. Consider therapy modification
Lixisenatide: May decrease the serum concentration of Progestins (Contraceptive). Management: Administer oral contraceptives 1 hour before or at least 11 hours after administration of lixisenatide. Consider therapy modification
Lomitapide: Ethinyl Estradiol may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 40 mg/day. Consider therapy modification
Lopinavir: May decrease the serum concentration of Progestins (Contraceptive). Lopinavir may increase the serum concentration of Progestins (Contraceptive). Management: Consider using an alternative or additional means of contraception. Injected depot medroxyprogesterone acetate and etonogestrel implants may be used without a need for additional contraception. Consider therapy modification
Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification
Lumacaftor and Ivacaftor: May decrease the serum concentration of Hormonal Contraceptives. Management: Do not rely on hormone-based contraceptives with concurrent use of lumacaftor/ivacaftor; an alternative, non-hormonal, method of contraception should be used if this combination is required. Consider therapy modification
Metreleptin: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Metreleptin may increase the serum concentration of Estrogen Derivatives (Contraceptive). Monitor therapy
Metreleptin: May decrease the serum concentration of Progestins (Contraceptive). Metreleptin may increase the serum concentration of Progestins (Contraceptive). Monitor therapy
MiFEPRIStone: May diminish the therapeutic effect of Progestins (Contraceptive). MiFEPRIStone may increase the serum concentration of Progestins (Contraceptive). Management: Women of childbearing potential should use an effective, nonhormonal means of contraception during and 4 weeks following mifepristone treatment. Consider therapy modification
MiFEPRIStone: May diminish the therapeutic effect of Estrogen Derivatives (Contraceptive). MiFEPRIStone may increase the serum concentration of Estrogen Derivatives (Contraceptive). Management: Women of childbearing potential should use an effective, nonhormonal means of contraception during and 4 weeks following mifepristone treatment. Consider therapy modification
Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification
Mivacurium: Estrogen Derivatives may increase the serum concentration of Mivacurium. Monitor therapy
Modafinil: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Use alternative or concomitant methods of contraception in patients taking modafinil and for one month after modafinil discontinuation. Consider therapy modification
Mycophenolate: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Average AUC values were unchanged, but there was evidence of substantial patient-to-patient variability in response to this combination. Management: Women of childbearing potential who are receiving mycophenolate mofetil should consider using an alternative and/or additional form of contraception. Consider therapy modification
Mycophenolate: May decrease the serum concentration of Progestins (Contraceptive). Management: Use of an additional or alternative (nonhormonal) method of contraception should be considered. Consider therapy modification
Nafcillin: May increase the metabolism of Estrogen Derivatives (Contraceptive). Management: Use of an alternative, nonhormonal form of contraception during nafcillin therapy is recommended. Consider therapy modification
Nelfinavir: May decrease the serum concentration of Progestins (Contraceptive). Management: Use an alternative or additional method of contraception due to possibly decreased contraceptive effectiveness. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May enhance the thrombogenic effect of Estrogen Derivatives. Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may increase the serum concentration of Estrogen Derivatives. Monitor therapy
Ospemifene: Estrogen Derivatives may enhance the adverse/toxic effect of Ospemifene. Estrogen Derivatives may diminish the therapeutic effect of Ospemifene. Avoid combination
OXcarbazepine: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Contraceptive failure is possible. Management: Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification
OXcarbazepine: May decrease the serum concentration of Progestins (Contraceptive). Management: Contraceptive failure is possible. Use of an additional or alternative, nonhormonal method of contraception is recommended. Consider therapy modification
Perampanel: May decrease the serum concentration of Progestins (Contraceptive). Management: Patients should use an alternative, nonhormonal-based form of contraception both during the concurrent use of perampanel and for 1 month after discontinuing perampanel. Consider therapy modification
Phenytoin: May diminish the therapeutic effect of Estrogen Derivatives (Contraceptive). Contraceptive failure is possible. Management: Use of an alternative, nonhormonal means of contraception is recommended. Consider therapy modification
Phenytoin: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification
Pitolisant: May decrease the serum concentration of Hormonal Contraceptives. Management: Patients using hormonal contraception should be advised to use an alternative non-hormonal contraceptive method during treatment with pitolisant and for at least 21 days after discontinuation of pitolisant treatment. Consider therapy modification
Pomalidomide: May enhance the thrombogenic effect of Estrogen Derivatives. Management: Canadian pomalidomide labeling recommends caution with use of hormone replacement therapy and states that hormonal contraceptives are not recommended. US pomalidomide labeling does not contain these specific recommendations. Consider therapy modification
Pomalidomide: Progestins may enhance the thrombogenic effect of Pomalidomide. Management: Canadian pomalidomide labeling recommends caution with use of hormone replacement therapy and states that hormonal contraceptives are not recommended. US pomalidomide labeling does not contain these specific recommendations. Consider therapy modification
Primidone: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Consider therapy modification
Proguanil: Ethinyl Estradiol may diminish the therapeutic effect of Proguanil. Monitor therapy
Protease Inhibitors: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Use oral contraceptives containing at least 35mcg ethinyl estradiol with atazanavir/ritonavir, or no more than 30mcg in patients receiving atazanavir alone. Use of an alternative, non-hormonal contraceptive is recommended with other protease inhibitors. Exceptions: Indinavir. Consider therapy modification
Retinoic Acid Derivatives: May diminish the therapeutic effect of Progestins (Contraceptive). Retinoic Acid Derivatives may decrease the serum concentration of Progestins (Contraceptive). Management: Two forms of effective contraception should be used in patients receiving retinoic acid derivatives. Microdosed progesterone-only preparations (ie, minipills that do not contain estrogen) are considered an inadequate method of contraception. Exceptions: Adapalene; Alitretinoin (Topical); Bexarotene (Topical); Tretinoin (Topical). Consider therapy modification
Rifamycin Derivatives: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Contraceptive failure is possible. Management: Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification
Rifamycin Derivatives: May decrease the serum concentration of Progestins (Contraceptive). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification
ROPINIRole: Estrogen Derivatives may increase the serum concentration of ROPINIRole. Monitor therapy
Rufinamide: May decrease the serum concentration of Ethinyl Estradiol. Consider therapy modification
Rufinamide: May decrease the serum concentration of Norethindrone. Consider therapy modification
Saquinavir: May decrease the serum concentration of Progestins (Contraceptive). Management: Use an alternative or additional method of contraception due to possibly decreased contraceptive effectiveness. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. Consider therapy modification
Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Selegiline: Estrogen Derivatives (Contraceptive) may increase the serum concentration of Selegiline. Monitor therapy
Selegiline: Progestins (Contraceptive) may increase the serum concentration of Selegiline. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
St John's Wort: May diminish the therapeutic effect of Estrogen Derivatives (Contraceptive). Contraceptive failure is possible. Management: Consider an alternative to St John's wort if possible. If this combination is used, an alternative, nonhormonal contraceptive is recommended. Consider therapy modification
St John's Wort: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Consider using a product other than St John's wort. Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification
Succinylcholine: Estrogen Derivatives may increase the serum concentration of Succinylcholine. Monitor therapy
Sugammadex: May decrease the serum concentration of Progestins (Contraceptive). Management: Patients receiving any hormonal contraceptive (oral or non-oral) should use an additional, nonhormonal contraceptive method during and for 7 days following sugammadex treatment. Consider therapy modification
Sugammadex: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Patients receiving any hormonal contraceptive (oral or non-oral) should use an additional, nonhormonal contraceptive method during and for 7 days following sugammadex treatment. Consider therapy modification
Tazemetostat: May decrease the serum concentration of Hormonal Contraceptives. Management: Women of reproductive potential should use a non-hormonal contraceptive method during treatment with tazemetostat and for 6 months after. Men with female partners should use contraception during treatment and for 3 months after. Consider therapy modification
Tetrahydrocannabinol and Cannabidiol: May decrease the serum concentration of Hormonal Contraceptives. Management: Women using hormonal contraceptives should consider adding a barrier contraceptive due to the potential for tetrahydrocannabinol and cannabidiol to decrease concentrations and effectiveness of hormonal contraceptives. Consider therapy modification
Thalidomide: Estrogen Derivatives (Contraceptive) may enhance the thrombogenic effect of Thalidomide. Monitor therapy
Thalidomide: Progestins (Contraceptive) may enhance the thrombogenic effect of Thalidomide. Monitor therapy
Thalidomide: Estrogen Derivatives may enhance the thrombogenic effect of Thalidomide. Monitor therapy
Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy
Thyroid Products: Estrogen Derivatives may diminish the therapeutic effect of Thyroid Products. Monitor therapy
Tipranavir: Estrogen Derivatives may enhance the dermatologic adverse effect of Tipranavir. The combination of tipranavir/ritonavir and ethinyl estradiol/norethindrone was associated with a high incidence of skin rash. Tipranavir may decrease the serum concentration of Estrogen Derivatives. Management: Women using hormonal contraceptives should consider alternative, non-hormonal forms of contraception. Consider therapy modification
Tipranavir: May increase the serum concentration of Progestins (Contraceptive). Management: Use an alternative or additional method of contraception due to possibly decreased contraceptive effectiveness. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. Consider therapy modification
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification
Tobacco (Smoked): May enhance the adverse/toxic effect of Estrogen Derivatives (Contraceptive). Specifically, the risk of serious cardiovascular events (eg, stroke, venous thromboembolism, myocardial infarction) may be increased. Management: Avoid cigarette smoking in patients who use estrogen containing contraceptives whenever possible. If combined, monitor for signs and symptoms of serious cardiovascular events (eg, stroke, venous thromboembolism, myocardial infarction). Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Topiramate: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Contraceptive failure is possible. Management: Risk appears greatest for higher topiramate doses (200 mg/day or greater). Some have recommended using at least 50 mcg/day of ethinyl estradiol, but the effectiveness of this is unclear. Consider a nonhormonal form of contraception. Consider therapy modification
Topiramate: May decrease the serum concentration of Progestins (Contraceptive). Management: Caution patients that this combination may be associated with reduced contraceptive effectiveness. Consider adding an additional (non-hormonal) contraceptive method. Consider therapy modification
Tranexamic Acid: Progestins (Contraceptive) may enhance the thrombogenic effect of Tranexamic Acid. Avoid combination
Tranexamic Acid: Estrogen Derivatives (Contraceptive) may enhance the thrombogenic effect of Tranexamic Acid. Avoid combination
Triazolam: Hormonal Contraceptives may increase the serum concentration of Triazolam. Monitor therapy
Ulipristal: Progestins may diminish the therapeutic effect of Ulipristal. Ulipristal may diminish the therapeutic effect of Progestins. Management: Ulipristal for uterine fibroids (Canadian indication): avoid progestins within 12 days of stopping ulipristal; as emergency contraceptive (U.S. indication): avoid progestins within 5 days of stopping ulipristal. Avoid combination
Ursodiol: Estrogen Derivatives may diminish the therapeutic effect of Ursodiol. Monitor therapy
Valproate Products: Estrogen Derivatives (Contraceptive) may decrease the serum concentration of Valproate Products. Monitor therapy
Vitamin K Antagonists (eg, warfarin): Estrogen Derivatives (Contraceptive) may diminish the anticoagulant effect of Vitamin K Antagonists. In contrast, enhanced anticoagulant effects have also been noted with some products. Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Progestins (Contraceptive) may diminish the anticoagulant effect of Vitamin K Antagonists. In contrast, enhanced anticoagulant effects have also been noted with some products. Management: When possible, concomitant hormonal contraceptives and coumarin derivatives should be avoided in order to eliminate the risk of thromboembolic disorders. Consider using an alternative, nonhormonal contraceptive. Consider therapy modification
Voriconazole: May decrease the metabolism of Estrogen Derivatives (Contraceptive). Estrogen Derivatives (Contraceptive) may increase the serum concentration of Voriconazole. Monitor therapy
Voriconazole: May increase the serum concentration of Progestins (Contraceptive). Progestins (Contraceptive) may increase the serum concentration of Voriconazole. Monitor therapy
Adverse Reactions
Menopausal vasomotor symptoms and osteoporosis prevention:
>10%: Endocrine & metabolic: Increased sex hormone binding globulin (22%)
1% to 10%:
Cardiovascular: Edema (5%)
Central nervous system: Headache (6%)
Gastrointestinal: Abdominal pain (5% to 7%)
Genitourinary: Mastalgia (8% to 9%), endometrial hyperplasia (≤1%)
Contraception and Acne:
>10%:
Endocrine & metabolic: Change in menstrual flow (including absence of withdrawal bleeding: 31% to 41%), amenorrhea (8% to 36%)
Genitourinary: Breakthrough bleeding (≤86%), spotting (≤86%)
1% to 10%:
Central nervous system: Headache (≤8%), migraine (≤8%), depression (≤4%), mood changes (≤4%), mood disorder (≤3%), anxiety (≤2%)
Dermatologic: Acne vulgaris (3%)
Endocrine & metabolic: Heavy menstrual bleeding (≤5%), weight changes (4%), weight gain (2%)
Gastrointestinal: Nausea (≤9%), vomiting (≤9%), abdominal pain (3%)
Genitourinary: Vulvovaginal candidiasis (6%), abnormal uterine bleeding (≤5%), irregular menses (≤5%), vaginal hemorrhage (≤5%), dysmenorrhea (4%), uterine cramps (4%), abnormal cervical or vaginal Papanicolaou smear (3%), bacterial vaginosis (3%), breast tenderness (≤3%), mastalgia (≤2%)
Frequency not defined:
Cardiovascular: Hypertension
Endocrine & metabolic: Decreased libido
<1%, postmarketing, and/or case reports: Abdominal cramps, abnormal sensory symptoms, allergic skin rash, alopecia, altered serum glucose, anaphylaxis, anemia, angina pectoris, angioedema, arthralgia, back pain, benign breast nodule, bipolar mood disorder, bloating, blurred vision, breast changes, breast disease, breast hypertrophy, breast secretion, burning sensation of skin, cerebral embolism, cerebral thrombosis, cerebrovascular accident, change in appetite, change in cervical ectropion, change in cervical secretions, change in corneal curvature (steepening), change in libido, chest pain, chloasma, cholecystitis, cholelithiasis, cholestatic jaundice, chorea, constipation, contact lens intolerance, corneal thinning, coronary thrombosis, cystitis-like syndrome, deep vein thrombosis, dementia, diabetes mellitus, dissociative reaction, dizziness, drowsiness, dyspnea, dysuria, embolism, endometrial carcinoma, erythema, erythema multiforme, erythema nodosum, exacerbation of asthma, exacerbation of epilepsy, exacerbation of hepatic hemangioma, exacerbation of porphyria, facial swelling, fatigue, fibrocystic breast changes, fungal infection, galactorrhea not associated with childbirth, gallbladder disease, hemangioma (hepatic), hemiparesis, hemorrhagic eruption, hepatic adenoma, hirsutism, homicidal ideation, hot flash, hyperesthesia, hypersensitivity reaction, hyperthyroidism, hypocalcemia, hypoesthesia, hypoglycemia, hypothyroidism, impaired glucose tolerance/prediabetes, increased blood pressure, increased serum triglycerides, insomnia, irregular pulse, irritability, ischemic stroke, localized edema (pelvic), loss of consciousness, loss of scalp hair, lower limb cramp, malaise, malignant neoplasm of breast, malignant neoplasm of ovary, malignant neoplasm of uterus, myalgia, myocardial infarction, nervousness, night sweats, nipple discharge, nipple pain, nonimmune anaphylaxis, ovarian cyst, palpitations, pancreatitis, panic attack, paresthesia, pelvic pain, peripheral edema, pollakiuria, premenstrual syndrome, pruritus, pulmonary embolism, retinal thrombosis, rupture of ovarian cyst, skin discoloration, skin rash, suicidal ideation, superficial venous thrombosis, swelling of lips, tachycardia, thrombophlebitis, thrombosis (including ovarian), transient blindness, transient ischemic attacks, urticaria, uterine fibroid enlargement, uterine hypertrophy, vaginal infection, vaginitis, visual impairment, weight loss
Warnings/Precautions
Concerns related to adverse effects:
- Breast cancer: [US Boxed Warning]: Based on data from the Women’s Health Initiative (WHI) studies, an increased risk of invasive breast cancer was observed in postmenopausal women using conjugated estrogens (CE) in combination with medroxyprogesterone acetate (MPA). Observational studies noted this risk declines once therapy is discontinued. The WHI study did not observe an increased risk of invasive breast cancer in women with a hysterectomy using CE alone. The risk of breast cancer in postmenopausal patients on hormone therapy may depend upon type of estrogen and/or progestin, dose, timing of therapy initiation, duration of therapy, route of administration, and individual patient characteristics (AACE/ACE [Cobin 2017]; NAMS 2017). Hormone therapy may be associated with increased breast density (NAMS 2017); an increase in abnormal mammogram findings requiring further evaluation has been reported with estrogen alone or in combination with progestin therapy. Estrogen use may lead to severe hypercalcemia in patients with breast cancer and bone metastases; discontinue estrogen if hypercalcemia occurs. In women at risk for breast cancer due to family history or susceptibility genes (BRCA1, BRCA2), the use of combination hormonal contraceptives has not been shown to modify the risk for breast cancer. However, breast cancer is a hormonal sensitive tumor and the prognosis for women with a current or recent history of breast cancer may be worse with combination hormonal contraceptive use (Curtis 2016b). Use is contraindicated in patients with (or history of) breast cancer.
- Cervical cancer: The use of combination hormonal contraceptives has been associated with a slight increased risk of cervical cancer; however, studies are not consistent and may be related to additional risk factors (Gierisch 2013). Theoretically, use may affect prognosis of existing disease. Women awaiting treatment for cervical cancer may use combination hormonal contraceptives (Curtis 2016b).
- Chloasma: Combination hormonal contraceptives, hormone replacement therapy, as well as sun exposure and pregnancy, are triggers for chloasma. Women with a susceptibility to chloasma or additional risk factors should avoid exposure to sun or ultraviolet radiation during therapy (Handel 2014).
- Cholestasis: Risk of cholestasis may be increased with previous cholestasis of pregnancy or cholestasis with prior oral contraceptive use.
- Dementia: [US Boxed Warning]: Estrogens with or without progestin should not be used to prevent dementia. In the Women’s Health Initiative Memory Study (WHIMS), an increased incidence of probable dementia was observed in women ≥65 years of age taking CE alone or in combination with MPA. Because the WHI memory studies were conducted in women ≥ 65 years of age, it is unknown if these findings apply to younger postmenopausal women. However, hormone therapy is not recommended at any age to prevent or treat cognitive decline or dementia (AACE [Goodman 2011]; NAMS 2017).
- Endometrial cancer: [US Boxed Warning]: The use of unopposed estrogen in women with an intact uterus is associated with an increased risk of endometrial cancer. The addition of a progestin to estrogen therapy may decrease the risk of endometrial hyperplasia, a precursor to endometrial cancer. Adequate diagnostic measures, including endometrial sampling if indicated, should be performed to rule out malignancy in postmenopausal women with undiagnosed abnormal vaginal bleeding. There is no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens at equivalent estrogen doses. The risk of endometrial cancer appears to be dose and duration dependent, greatest with use ≥5 years, and may persist following discontinuation of therapy. The use of a progestin is not generally required when low doses of estrogen are used locally for vaginal atrophy, although long term data (>1 year) supporting this recommendation are lacking (NAMS 2013; NAMS 2017). The risk of endometrial cancer is decreased in women using combination hormonal contraceptives. Women awaiting treatment for endometrial cancer may use combination hormonal contraceptives (Curtis 2016b).
- Endometriosis: Estrogens may exacerbate endometriosis. Malignant transformation of residual endometrial implants has been reported posthysterectomy with unopposed estrogen therapy. Consider adding a progestin in women with residual endometriosis posthysterectomy.
- Lipid effects: Combination hormonal contraceptives may adversely affect lipid levels, including serum triglycerides. Women with hypertriglyceridemia or a family history of hypertriglyceridemia may be at increased risk of pancreatitis when using combination hormonal contraceptives. Consider alternative contraception for women with uncontrolled dyslipidemia.
- Ovarian cancer: Available information related to the use of menopausal estrogen or estrogen/progestin therapy and risk of ovarian cancer is inconsistent. If an association is present, the absolute risk is likely rare and may be influenced by duration of therapy (AACE [Goodman 2011]; ES [Stuenkel 2015]; NAMS 2017). The risk of ovarian cancer is decreased in women using combination hormonal contraceptives (Curtis 2016b; Walker 2015). Oral contraceptives may be used to reduce the risk of ovarian cancer including those women with BRCA1 and BRCA2 mutations (Walker 2015). Women awaiting treatment for ovarian cancer may use combination hormonal contraceptives (Curtis 2016b).
- Retinal vascular thrombosis: Discontinue if unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions occur and immediately evaluate for retinal vein thrombosis.
- Thromboembolic disorders: Discontinue use of combination hormonal contraceptives if an arterial or venous thrombotic event occurs. Oral contraceptives may increase the risk of venous thromboembolism (risk is greatest during first year of use and less than the risk associated with pregnancy); some studies suggest this risk may be higher in preparations with third- or fourth-generation progestins and/or high dose ethinyl estradiol. Women with inherited thrombophilias (eg, protein C or S deficiency, factor V Leiden mutation, prothrombin mutation, antithrombin deficiency) may have increased risk of venous thromboembolism. Age >35 years of age, hypertension, obesity, and tobacco use also increase the risk of thrombotic events in women taking combination hormonal contraceptives (ASRM 2017; Curtis 2016b; DeSancho 2010; van Vlijmen 2011). Combination hormonal contraceptives may also increase the risk of arterial thrombosis (eg, MI, stroke) and should not be used in women with a history of stroke or ischemic heart disease (Curtis 2016b). Use of combination hormonal contraceptives is contraindicated in women with a high risk of arterial or venous thrombotic disease.
- Vaginal bleeding: Breakthrough or intracyclic bleeding and spotting may occur, especially during the first 3 months of therapy. In addition, occasional missed periods may occur. Presentation of irregular, unresolving vaginal bleeding warrants further evaluation to rule out malignancy or pregnancy. Amenorrhea or oligomenorrhea may occur after discontinuing combination hormonal contraceptives, especially when such a condition was preexistent.
Disease-related concerns:
- Abnormal uterine bleeding: When considering specific treatment for acute or chronic abnormal uterine bleeding (AUB) due to ovulatory dysfunction (not structural causes), consideration should be given to medical contraindications to available therapies as well as if simultaneous contraception is needed or pregnancy is desired (ACOG 136 2013; ACOG 557 2013).
- Bariatric surgery:
– Altered absorption: Consider nonoral contraceptive options in patients who had specific bariatric procedures (Roux-en-Y, biliopancreatic diversion); malabsorptive procedures can potentially decrease absorption of oral contraceptives (Kominiarek 2017; Mechanick 2013; Schlatter 2017). It is difficult to recommend against the use of oral contraceptives in restrictive procedures (sleeve gastrectomy, gastric banding) as the evidence is limited (Merki-Feld 2015).
– Venous thromboembolism risk: Consider discontinuation of estrogen-containing medications 30 days prior to bariatric surgery to reduce risk of venous thromboembolism; however, practice may vary based upon institutional protocols (Mechanick 2013).
- Cardiovascular disease: [US Boxed Warning]: Estrogens with or without progestin should not be used to prevent cardiovascular disease. Using data from the Women’s Health Initiative (WHI) studies, an increased risk of deep vein thrombosis (DVT) and stroke has been reported with CE and an increased risk of DVT, stroke, pulmonary emboli (PE) and myocardial infarction (MI) has been reported with CE with MPA in postmenopausal women 50 to 79 years of age. Additional risk factors include diabetes mellitus, hypercholesterolemia, hypertension, SLE, obesity, tobacco use, and/or history of venous thromboembolism (VTE). Risk factors should be managed appropriately; discontinue use immediately if adverse cardiovascular events occur or are suspected. Due to possible lower risk of thrombotic events, transdermal administration may be preferred for treating vasomotor symptoms of menopause in patients with risk factors for cardiovascular disease (AACE/ACE [Cobin 2017]; ACOG 556 2013; ES [Stuenkel 2015]). Use is contraindicated in women with active DVT, PE, arterial thromboembolic disease (stroke and MI), or a history of these conditions. Use combination hormonal contraceptives with caution in patients with risk factors for cardiovascular disease (eg, hypertension, low HDL, high LDL, high triglycerides, older age, diabetes, women who smoke); use of combination hormonal contraceptives may increase the risk of cardiovascular disease (Curtis 2016b). Prior to therapy for menopausal symptoms, consider age, cardiovascular and metabolic risk factors in patients previously diagnosed with diabetes (AACE/ACE [Cobin 2017]). Use of combination hormonal contraceptives may be contraindicated in women at high risk of arterial or venous thrombotic diseases.
- Depression: Use with caution in patients with a history of depression; discontinue if serious depression recurs.
- Diabetes: May impair glucose tolerance; use caution in women with diabetes or prediabetes. In general, use of combination oral contraceptives has limited effects on daily insulin needs and no long-term effects on diabetes control in women with nonvascular disease. However, use in women with concomitant nephropathy, neuropathy, retinopathy, other vascular disease, or diabetes >20 years' duration should be evaluated for contraceptive use based on the severity of the condition (Curtis 2016b). Prior to therapy for menopausal symptoms, consider age, cardiovascular, and metabolic risk factors in patients previously diagnosed with diabetes (AACE/ACE [Cobin 2017]). Use is of combination hormonal contraceptives is contraindicated in women with diabetes mellitus and vascular disease.
- Diseases exacerbated by fluid retention: Use with caution in patients with diseases which may be exacerbated by fluid retention, including cardiac or renal dysfunction.
- Epilepsy: Use caution with epilepsy; may exacerbate disease.
- Gallbladder disease: Combination hormonal contraceptives may have a small increased risk of gallbladder disease or may worsen existing gallbladder disease (Curtis 2016b). Use of postmenopausal estrogen may be associated with an increased risk of gallbladder disease requiring surgery.
- Hepatic adenomas or carcinomas: Use of combination hormonal contraceptives is associated with hepatic adenomas (rare); rupture may cause fatal intra-abdominal hemorrhage. Long term use may be associated with an increased risk of hepatocellular carcinoma (rare). Use is contraindicated with preexisting hepatic tumors.
- Hepatic impairment: Estrogens may be poorly metabolized in women with hepatic impairment. Discontinue if jaundice develops during therapy or if liver function becomes abnormal. Use is contraindicated with preexisting hepatic disease. Use of combination hormonal contraceptives may be considered in women with mild (compensated) cirrhosis but should not be used in women with severe (decompensated) cirrhosis (Curtis 2016b).
- Hepatitis: Initiation of combination hormonal contraceptives is not recommended in women with acute viral hepatitis or during a flare. Continuation of use in women with chronic hepatitis has not been shown to increase the rate or severity of cirrhotic fibrosis or hepatocellular carcinoma. Continuation of use in women who are carriers has not been shown to trigger liver failure or severe hepatic dysfunction (Curtis 2016b).
- Hepatic hemangiomas: Use with caution in patients with hepatic hemangiomas; may exacerbate disease.
- Hereditary angioedema: Exogenous estrogens may exacerbate angioedema symptoms in women with hereditary angioedema (Geng 2013; Zuraw 2013).
- Hypertension: The risk of hypertension may be increased with age, dose, and duration of use. Combination hormonal contraceptives should not be used in women with hypertension and vascular disease, or persistent blood pressure values ≥160 mm Hg systolic or ≥100 mm Hg diastolic. The risks of use may not outweigh the benefits of treatment in women with less severe hypertension (140 to 159 mm Hg systolic or 90 to 99 mm Hg diastolic) or those with hypertension that is adequately controlled (Curtis 2016a). Other risk factors for cardiovascular disease (eg, older age, smoking, diabetes) should be considered when prescribing contraceptives (Curtis 2016b). The manufacturer contraindicates use in women with uncontrolled hypertension and recommends monitoring women with well-controlled hypertension; discontinue therapy if blood pressure rises significantly.
- Hypoparathyroidism: Use caution in patients with hypoparathyroidism; estrogen-induced hypocalcemia may occur.
- Migraine: Evaluate new, recurrent, severe, or persistent headaches. Use of combination hormonal contraceptives may be considered in women who have migraines without aura (including menstrual migraines) (Curtis 2016b). Use in women with headaches with focal neurological symptoms, or migraine headaches with or without aura if >35 years is contraindicated.
- Otosclerosis: Use caution in patients with otosclerosis.
- Porphyria: Use with caution in patients with porphyria; may exacerbate disease.
- Solid organ transplant: Although data is limited, serious medical complications have been reported in women with complicated organ transplants (eg, graft failure, rejection, cardiac allograft vasculopathy); use of combination hormonal contraceptives is not recommended in women with complicated organ transplants (Curtis 2016b).
- Systemic lupus erythematosus: Use with caution in patients with systemic lupus erythematosus (SLE); may exacerbate disease. Women with SLE are at an increased risk for heart disease, stroke, and VTE. Combination hormonal contraceptives should not be used in women with SLE who have positive (or unknown) antiphospholipid antibodies, due to an increased risk of arterial and venous thrombosis (Curtis 2016b).
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist with hormonal contraceptives, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
- Thyroid replacement therapy: Estrogens may increase thyroid-binding globulin (TBG) levels leading to increased circulating total thyroid hormone levels. Women on thyroid replacement therapy may require higher doses of thyroid hormone while receiving estrogens.
Special populations:
- Contact lens wearers: Any changes with lens tolerance or vision should be evaluated by an ophthalmologist.
- Obese: The efficacy of some products (generally those containing lower concentrations of ethinyl estradiol [eg, Generess Fe, Lo Estrin 24 Fe, Lo Loestrin Fe; Minastrin 24 Fe]) have not been established in women with a BMI >35 kg/m2. Available evidence suggests efficacy of combination hormonal contraceptives may be decreased in women with a BMI ≥30 kg/m2; however, reductions in effectiveness are considered minimal and information is conflicting. The risk of VTE may be increased in obese women using combination hormonal contraceptives. In general, the benefits of combination hormonal contraceptives may outweigh the risks in obese women who otherwise are eligible for this method (Curtis 2016b). Consult product labeling.
- Pediatric: Not for use prior to menarche.
- Smokers: [US Boxed Warning]: Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives use. This risk increases with age, particularly in women >35 years of age, and with the number of cigarettes smoked. For this reason, combination oral contraceptives should not be used by women who are >35 years of age and smoke. Use of combination hormonal contraceptives is contraindicated in patients >35 years who smoke.
- Surgical patients: Whenever possible, discontinue at least 4 weeks prior to and for 2 weeks following major surgery or other surgeries known to have an increased risk of thromboembolism or during periods of prolonged immobilization.
Dosage form specific issues:
- Lactose: Tablets may contain lactose; avoid use in patients with lactase deficiency, galactose intolerance or glucose-galactose malabsorption.
- Tartrazine: Some products may contain tartrazine, which may cause allergic reactions in certain individuals.
Other warnings/precautions:
- Appropriate use: When initiating a combination oral contraceptive, consider initiating with a monthly bleeding monophasic formulation containing ethinyl estradiol 30 to 35 mcg plus a progestin, and adjusting based on adverse events and patient preference (Ott 2014).
- Duration of use: Extended use of menopausal hormone therapy may be considered for persistent vasomotor symptoms, issues related to quality of life, or for osteoporosis prevention in women at increased risk of fracture. Menopausal hormonal therapy does not need to be routinely discontinued in women >60 years of age and may continue in women >65 years of age after clinical evaluation and discussion of benefits and risks of treatment. Annual exams should be performed with a review of comorbidities; possible adjustments to safer lower-dose and/or route of administration should be discussed (ACOG 565 2013; NAMS 2017).
- HIV infection protection: Combination hormonal contraceptives do not protect against HIV infection or other sexually transmitted diseases (Curtis 2016a; Curtis 2016b).
- Laboratory changes: The use of estrogens and/or progestins may change the results of some laboratory tests (eg, coagulation factors, lipids, glucose tolerance, binding proteins).
- Osteoporosis: In women with premature menopause, hormone therapy to prevent bone loss may be used unless otherwise contraindicated; therapy should be reassessed when the average age of menopause is reached. It is also an appropriate bone-active therapy for women with vasomotor symptoms who are <60 years of age or within 10 years of menopause onset. Use may be considered for women at high risk of fractures who are not candidates for other osteoporosis therapies (NAMS 2017).
- Risks vs benefits: When used for the relief of menopausal symptoms or increased risk of bone fracture/loss, the benefit-risk of hormone therapy is most favorable if started in patients who have no contraindications to therapy, are <60 years of age, within 10 years of menopause onset, have a favorable lipid profile, and do not have the factor V Leiden genotype or metabolic syndrome. Risk factors for cardiovascular disease should also be considered when evaluating therapy and route of administration (AACE/ACE [Cobin 2017]; NAMS 2017). [US Boxed Warning]: Estrogens with or without progestin should be used for the shortest duration possible at the lowest effective dose consistent with treatment goals and risks for the individual woman. Patients should be reevaluated as clinically appropriate to determine if treatment is still necessary. Available data related to treatment risks are from Women’s Health Initiative (WHI) studies, which evaluated oral CE 0.625 mg with or without MPA 2.5 mg relative to placebo in postmenopausal women. Other combinations and dosage forms of estrogens and progestins were not studied. Outcomes reported from clinical trials using CE with or without MPA should be assumed to be similar for other doses and other dosage forms of estrogens and progestins until comparable data becomes available.
Monitoring Parameters
Hormonal contraceptives: Assessment of pregnancy status (prior to therapy); blood pressure (prior to therapy and yearly); weight (optional; BMI at baseline may be helpful to monitor changes during therapy); assess potential health status changes at routine visits (Curtis 2016a).
If all doses have not been taken on schedule and one menstrual period is missed, the possibility of pregnancy should be considered. If 2 consecutive menstrual periods are missed, access pregnancy status before a new dosing cycle is started.
Monitor patient for vision changes; blood pressure; signs and symptoms of thromboembolic disorders; signs or symptoms of depression; glycemic control in patients with diabetes; lipid profiles in patients being treated for hyperlipidemias. Adequate diagnostic measures should be performed to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding.
Postmenopausal indications:
Prior to therapy, baseline risk for breast cancer and CVD. During therapy, age appropriate breast and pelvic exams; blood pressure; unscheduled bleeding lasting >6 months for endometrial pathology (sooner in patients who are obese, diabetic, or have a history of endometrial cancer); serum triglycerides (2 weeks after starting therapy in patients with baseline level >200 mg/dL); TSH (6 to 12 weeks after starting oral therapy in patients taking thyroid replacement) (ES [Stuenkel 2015]).
Menopausal symptoms: Efficacy beginning 1 to 3 months after starting therapy, then every 6 to 12 months as appropriate. Duration of treatment should be evaluated at least annually (ES [Stuenkel 2015]).
Note: Monitoring of FSH and serum estradiol is not useful when managing vasomotor symptoms of menopause
Prevention of osteoporosis: Bone density measurement
Pregnancy
Pregnancy Risk Factor
X
Pregnancy Considerations
Use is contraindicated in pregnant women. Combination hormonal contraceptives are used to prevent pregnancy; treatment should be discontinued if pregnancy occurs. In general, the use of combination hormonal contraceptives, when inadvertently used early in pregnancy, have not been associated adverse fetal or maternal effects (Curtis 2016b).
The manufacturer states that combination hormonal contraceptives should not be started until ≥4 weeks after delivery in women who choose not to breastfeed. Due to the increased risk of venous thromboembolism (VTE) postpartum, combination hormonal contraceptives should not be started in any woman <21 days following delivery. The risk decreases to baseline by postpartum day 42. Use of combination hormonal contraceptives in women between 21 and 42 days after delivery should take into consideration the individual woman's risk factors for VTE (eg, age ≥35 years, previous VTE, thrombophilia, immobility, preeclampsia, transfusion at delivery, cesarean delivery, peripartum cardiomyopathy, BMI ≥30 kg/m2, postpartum hemorrhage, smoking) (Curtis 2016b).
Patient Education
What is this drug used for?
- It is used to prevent pregnancy.
- It is used to put off soft, brittle bones (osteoporosis) in women after change of life.
- It is used to prevent or lower the signs of the change of life (menopause).
- It is used to treat pimples (acne).
- It may be given to you for other reasons. Talk with the doctor.
Frequently reported side effects of this drug
- Nausea
- Vomiting
- Lack of appetite
- Increased hunger
- Weight gain
- Weight loss
- Cramps
- Bloating
- Enlarged breasts
- Tender breasts
- Menstrual changes
- Diarrhea
- Dark patches on face
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Severe cerebrovascular disease like change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes
- Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.
- Gallstones like pain in the upper right abdominal area, right shoulder area, or between the shoulder blades; yellow skin; or fever with chills
- Blood clots like numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood.
- Edema
- Severe dizziness
- Passing out
- Severe headache
- Depression
- Mood changes
- Lump in breast
- Breast soreness or pain
- Nipple discharge
- Abnormal or persistent vaginal bleeding
- Vaginal pain, itching, and discharge
- Vision changes
- Bulging eyes
- Blindness
- Contact lens discomfort
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
