Ethinyl Estradiol and Norethindrone (Lexi-Drugs)

ALERT: US Boxed Warning
   Cigarette smoke and serious cardiovascular events:
  Endometrial cancer:
  Cardiovascular disease:
  Breast cancer:
  Dementia:
  Risk vs benefit:
Pronunciation

(ETH in il es tra DYE ole & nor eth IN drone)

Brand Names: US

Alyacen 1/35; Alyacen 7/7/7; Aranelle; Balziva; Blisovi 24 Fe; Blisovi Fe 1.5/30; Blisovi FE 1/20; Brevicon (28) [DSC]; Briellyn; Cyclafem 1/35; Cyclafem 7/7/7; Dasetta 1/35; Dasetta 7/7/7; Estrostep Fe; Femcon Fe [DSC]; Femhrt Low Dose; Fyavolv; Generess FE; Gildagia [DSC]; Gildess 1.5/30 [DSC]; Gildess 1/20 [DSC]; Gildess 24 FE [DSC]; Gildess FE 1.5/30 [DSC]; Gildess FE 1/20 [DSC]; Hailey 24 Fe; Jevantique Lo [DSC]; Jinteli; Junel 1.5/30; Junel 1/20; Junel FE 1.5/30; Junel FE 1/20; Junel Fe 24; Kaitlib Fe; Larin 1.5/30; Larin 1/20; Larin 24 FE; Larin Fe 1.5/30; Larin Fe 1/20; Layolis FE; Leena; Lo Loestrin Fe; Loestrin 1.5/30 (21); Loestrin 1/20 (21); Loestrin Fe 1.5/30; Loestrin Fe 1/20; Lomedia 24 FE [DSC]; Melodetta 24 Fe; Mibelas 24 Fe; Microgestin 1.5/30; Microgestin 1/20; Microgestin 24 Fe [DSC]; Microgestin FE 1.5/30; Microgestin FE 1/20; Minastrin 24 Fe; Modicon (28) [DSC]; Necon 0.5/35 (28); Necon 1/35 (28) [DSC]; Necon 10/11 (28) [DSC]; Necon 7/7/7 [DSC]; Norinyl 1+35 (28) [DSC]; Nortrel 0.5/35 (28); Nortrel 1/35 (21); Nortrel 1/35 (28); Nortrel 7/7/7; Ortho-Novum 1/35 (28); Ortho-Novum 7/7/7 (28); Ovcon-35 (28) [DSC]; Philith; Pirmella 1/35; Pirmella 7/7/7; Tarina 24 Fe; Tarina FE 1/20; Tarina FE 1/20 EQ; Taytulla; Tilia Fe; Tri-Legest Fe; Tri-Norinyl (28); Vyfemla; Wera; Wymzya Fe; Zenchent FE [DSC]; Zenchent [DSC]

Brand Names: Canada

Brevicon 0.5/35; Brevicon 1/35; FemHRT [DSC]; Loestrin 1.5/30; Lolo; Minestrin 1/20; Ortho 0.5/35 [DSC]; Ortho 1/35 [DSC]; Ortho 7/7/7 [DSC]; Select 1/35; Synphasic

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: Renal Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). Use with caution and monitor blood pressure closely.

Dosing: Hepatic Impairment: Adult

Use is contraindicated in patients with hepatic impairment.

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.

Dosing: Renal Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). Use with caution and monitor blood pressure closely.

Dosing: Hepatic Impairment: Pediatric

Use is contraindicated in patients with hepatic impairment.

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: Adult

  Abnormal uterine bleeding (acute)Level of Evidence [B, G]

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 Ref.

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 Ref.

  DysmenorrheaLevel of Evidence [G]

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 Ref.

  HirsutismLevel of Evidence [G]

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 Ref.

  Menstrual bleeding (menorrhagia)Level of Evidence [G]

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) Ref.

  Polycystic ovary syndrome (PCOS) in women with menstrual irregularities and hirsutism/acneLevel of Evidence [G]

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 Ref.

Level of Evidence Definitions
  Level of Evidence Scale
Clinical Practice Guidelines

Acne:

American Academy of Dermatology, “Guidelines of care for the management of acne vulgaris,” May 2016

Contraception:

CDC, “US Medical Eligibility Criteria for Contraceptive Use, 2016” MMWRJuly 2016

CDC, “US Selected Practice Recommendations for Contraceptive Use, 2016” MMWRJuly 2016

Hirsutism:

Endocrine Society, “Evaluation and Treatment of Hirsutism in Premenopausal Women,” April 2018

Menopausal Hormone Therapy:

American Association of Clinical Endocrinologists (AACE), Diagnosis and treatment of menopause, 2011

Endocrine Society (ES), Treatment of Symptoms of the Menopause, 2015

North American Menopause Society (NAMS), Hormone Therapy, 2017

US Preventive Services Task Force (USPSTF), Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women, 2017

Osteoporosis:

American Association of Clinical Endocrinologists and American College of Endocrinology, “Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis,” 2016

American College of Physicians, “Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update from the American College of Physicians,” 2017

National Osteoporosis Foundation, “Clinician’s Guide to Prevention and Treatment of Osteoporosis,” 2014

Administration: Oral

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.

Administration: Pediatric

Oral:

Contraception: Females of reproductive potential: Administer at the same time each day at intervals not >24 hours; without regard to meals.

Femcon Fe, Minastrin 24 Fe: Tablet may be chewed or swallowed whole; if chewed, immediately drink a full glass of liquid (240 mL) after swallowing.

Generess Fe: Chew and swallow tablet without water.

Lo Minastrin Fe: Blue tablets should be chewed and swallowed; immediately drink a full glass of water (240 mL) after swallowing. White and brown tablets are swallowed. It is important to take tablets in the order indicated on the blister pack.

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; back-up contraception is needed for 7 days unless contraception is started at the time of surgical abortion (Curtis 2016a).

According to the manufacturer, if diarrhea or vomiting occur, back-up contraceptive measures may be needed. Additional guidelines are 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

Acne: Estrostep Fe, Tilia Fe, Tri-Legest Fe: Females ≥15 years: Follow administration for contraception.

Dietary Considerations

Ensure adequate calcium and vitamin D intake when used for the prevention of osteoporosis.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 2]).

Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends single gloving for administration of intact tablets or capsules (NIOSH 2016).

Storage/Stability

Store at controlled room temperature.

Estrostep Fe, Femcon Fe: Protect from light.

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, lack of appetite, increased hunger, weight gain, cramps, bloating, enlarged breasts, hair loss, decreased libido, menstrual changes, diarrhea, or dark patches on face. Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of gallstones (pain in the upper right abdominal area, right shoulder area, or between the shoulder blades; jaundice; or fever with chills), signs of blood clots (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; angina; shortness of breath; tachycardia; or coughing up blood), edema, severe dizziness, passing out, severe headache, depression, severe loss of strength and energy, urinary retention, change in amount of urine passed, lump in breast, breast soreness or pain, nipple discharge, vaginal bleeding, vaginitis, vision changes, bulging eyes, blindness, or contact lens discomfort (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
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.

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).

• 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.

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).

Breast-Feeding Considerations

Contraceptive steroids may be present in breast milk. Adverse health outcomes, or consistent effects on infant growth or illness due to exogenous estrogens have not been reported following maternal use of combination hormonal contraceptives in breastfeeding women (Curtis 2016b). Because estrogen containing contraceptives may reduce milk production, the manufacturer recommends use of other forms of contraception until the child is weaned.

Due to the increased risk of venous thromboembolism (VTE) postpartum, combination hormonal contraceptives should not be started in breastfeeding 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). The risks, benefits, and alternatives to combination hormonal contraception should be evaluated when initiating treatment in breastfeeding women (Curtis 2016b).

Briggs’ Drugs in Pregnancy & Lactation
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

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

Refer to individual components.

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.Risk D: Consider therapy modification

Ajmaline: Estrogen Derivatives may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy

Anastrozole: Estrogen Derivatives may diminish the therapeutic effect of Anastrozole. Risk X: Avoid combination

Anthrax Immune Globulin (Human): Estrogen Derivatives may enhance the thrombogenic effect of Anthrax Immune Globulin (Human). Risk C: 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. Risk D: 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. Risk D: Consider therapy modification

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: 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. Risk X: Avoid combination

Aprepitant: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Use of a non-hormone-based contraceptive is recommended. Risk D: 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. Risk D: Consider therapy modification

Armodafinil: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: The manufacturer recommends that patients use nonhormonal contraceptives, in addition to or in place of hormonal contraceptives, during and for one month following treatment with armodafinil. Risk D: 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. Risk D: 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. Risk D: Consider therapy modification

Ascorbic Acid: May increase the serum concentration of Estrogen Derivatives. Risk C: 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. Risk D: 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. Risk D: 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. Risk D: Consider therapy modification

Barbiturates: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Risk D: 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). Risk D: 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). Risk D: 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. Risk D: 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. Risk D: 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. Risk D: 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. Risk D: 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. Risk D: 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. Risk D: Consider therapy modification

C1 inhibitors: Estrogen Derivatives may enhance the thrombogenic effect of C1 inhibitors. Risk C: Monitor therapy

C1 inhibitors: Progestins may enhance the thrombogenic effect of C1 inhibitors. Risk C: Monitor therapy

CarBAMazepine: May diminish the therapeutic effect of Estrogen Derivatives (Contraceptive). Contraceptive failure is possible. Management: Use of a nonhormonal contraceptive is recommended. Risk D: Consider therapy modification

CarBAMazepine: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Risk D: 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. Risk D: 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. Risk D: 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. Risk C: Monitor therapy

CloBAZam: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Risk D: Consider therapy modification

CloBAZam: May decrease the serum concentration of Progestins (Contraceptive). Risk D: 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. Risk C: 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. Risk D: 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. Risk D: 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. Risk D: 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. Risk D: Consider therapy modification

Corticosteroids (Systemic): Estrogen Derivatives may increase the serum concentration of Corticosteroids (Systemic). Risk C: 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. Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: 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. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Estrogen Derivatives. Risk C: 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). Risk D: 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. Risk D: 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. Risk D: Consider therapy modification

Dantrolene: Estrogen Derivatives may enhance the hepatotoxic effect of Dantrolene. Risk C: Monitor therapy

Darunavir: May decrease the serum concentration of Norethindrone. Risk D: Consider therapy modification

Dasabuvir: Ethinyl Estradiol may enhance the hepatotoxic effect of Dasabuvir. Risk X: Avoid combination

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Dehydroepiandrosterone: May enhance the adverse/toxic effect of Estrogen Derivatives. Risk X: 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. Risk D: 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. Risk D: Consider therapy modification

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. Risk D: Consider therapy modification

Encorafenib: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Risk X: Avoid combination

Encorafenib: May decrease the serum concentration of Progestins (Contraceptive). Risk X: 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. Risk D: Consider therapy modification

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. Risk D: 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. Risk D: Consider therapy modification

Exemestane: Estrogen Derivatives may diminish the therapeutic effect of Exemestane. Risk X: Avoid combination

Exenatide: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Administer oral contraceptives at least one hour prior to exenatide. Risk D: Consider therapy modification

Exenatide: May decrease the serum concentration of Progestins (Oral Contraceptive). Management: Administer oral contraceptives at least one hour prior to exenatide. Risk D: 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. Risk D: 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. Risk D: Consider therapy modification

Flibanserin: Estrogen Derivatives (Contraceptive) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy

Flibanserin: Progestins (Contraceptive) may increase the serum concentration of Flibanserin. Risk C: 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. Risk D: 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. Risk D: 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. Risk D: 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. Risk D: 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. Risk D: 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. Risk X: Avoid combination

Griseofulvin: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Risk X: Avoid combination

Guanethidine: Estrogen Derivatives (Contraceptive) may diminish the therapeutic effect of Guanethidine. Risk C: Monitor therapy

Hemin: Estrogen Derivatives may diminish the therapeutic effect of Hemin. Risk X: Avoid combination

Herbs (Estrogenic Properties): May enhance the adverse/toxic effect of Estrogen Derivatives. Risk C: Monitor therapy

Herbs (Progestogenic Properties) (eg, Bloodroot, Yucca): May enhance the adverse/toxic effect of Progestins. Risk C: 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. Risk D: Consider therapy modification

Immune Globulin: Estrogen Derivatives may enhance the thrombogenic effect of Immune Globulin. Risk C: Monitor therapy

Indium 111 Capromab Pendetide: Estrogen Derivatives may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Risk X: 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. Risk D: 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. Risk D: 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. Risk X: Avoid combination

LamoTRIgine: Estrogen Derivatives (Contraceptive) may decrease the serum concentration of LamoTRIgine. Management: Monitor for increased serum concentrations/effects of lamotrigine in patients in whom a hormonal contraceptive is discontinued/dose decreased (this includes during a pill-free week). A reduced dosage of lamotrigine may be needed.Risk D: Consider therapy modification

Lenalidomide: Estrogen Derivatives may enhance the thrombogenic effect of Lenalidomide. Risk C: 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. Risk D: 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. Risk D: 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. Risk D: 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. Risk D: 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. Risk D: 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. Risk D: 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. Risk D: Consider therapy modification

Lumacaftor: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). 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. Risk D: Consider therapy modification

Lumacaftor: May decrease the serum concentration of Progestins (Contraceptive). 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. Risk D: Consider therapy modification

Metreleptin: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Metreleptin may increase the serum concentration of Estrogen Derivatives (Contraceptive).Risk C: Monitor therapy

Metreleptin: May decrease the serum concentration of Progestins (Contraceptive). Metreleptin may increase the serum concentration of Progestins (Contraceptive). Risk C: 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. Risk D: 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.Risk D: 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. Risk D: Consider therapy modification

Mivacurium: Estrogen Derivatives may increase the serum concentration of Mivacurium. Risk C: Monitor therapy

Modafinil: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: The manufacturer recommends that patients use nonhormonal contraceptives, in addition to or in place of hormonal contraceptives, during and for one month following treatment with modafinil. Risk D: 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. Risk D: 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. Risk D: 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. Risk D: 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. Risk D: Consider therapy modification

Nevirapine: May decrease the serum concentration of Estrogen Derivatives (Contraceptive). Risk D: Consider therapy modification

Nevirapine: May decrease the serum concentration of Progestins (Contraceptive). Management: Instruct patients receiving nevirapine to use an alternative or additional nonhormonal contraceptive. Nevirapine product labeling however suggests that depo-medroxyprogesterone acetate may be used as a sole method of contraception. Risk D: 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. Risk C: Monitor therapy

Ospemifene: Estrogen Derivatives may enhance the adverse/toxic effect of Ospemifene. Estrogen Derivatives may diminish the therapeutic effect of Ospemifene. Risk X: 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. Risk D: 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. Risk D: 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. Risk D: 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. Risk D: 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. Risk D: Consider therapy modification

Pitolisant: May diminish the therapeutic effect of Estrogen Derivatives (Contraceptive). Management: The combination of hormonal contraceptives with pitolisant should be avoided, and an alternate means of contraception should be used. Risk D: Consider therapy modification

Pitolisant: May diminish the therapeutic effect of Progestins (Contraceptive). Management: The combination of hormonal contraceptives with pitolisant should be avoided, and an alternate means of contraception should be used. Risk D: Consider therapy modification

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Risk D: 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. Risk D: 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. Risk D: Consider therapy modification

Primidone: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Risk D: Consider therapy modification

Proguanil: Ethinyl Estradiol may diminish the therapeutic effect of Proguanil. Risk C: 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. Risk D: 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. Particularly, microdosed progesterone-only preparations may be inadequately effective. Exceptions: Adapalene; Bexarotene (Topical); Tretinoin (Topical). Risk D: 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. Risk D: 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. Risk D: Consider therapy modification

ROPINIRole: Estrogen Derivatives may increase the serum concentration of ROPINIRole. Risk C: Monitor therapy

Rufinamide: May decrease the serum concentration of Ethinyl Estradiol. Risk D: Consider therapy modification

Rufinamide: May decrease the serum concentration of Norethindrone. Risk D: 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. Risk D: Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Selegiline: Estrogen Derivatives (Contraceptive) may increase the serum concentration of Selegiline. Risk C: Monitor therapy

Selegiline: Progestins (Contraceptive) may increase the serum concentration of Selegiline. Risk C: Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: 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. Risk D: 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. Risk D: Consider therapy modification

St John’s Wort: May decrease the serum concentration 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. Risk D: Consider therapy modification

Succinylcholine: Estrogen Derivatives may increase the serum concentration of Succinylcholine. Risk C: 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. Risk D: 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. Risk D: Consider therapy modification

Thalidomide: Estrogen Derivatives (Contraceptive) may enhance the thrombogenic effect of Thalidomide. Risk C: Monitor therapy

Thalidomide: Progestins (Contraceptive) may enhance the thrombogenic effect of Thalidomide. Risk C: Monitor therapy

Thalidomide: Estrogen Derivatives may enhance the thrombogenic effect of Thalidomide. Risk C: Monitor therapy

Theophylline Derivatives: Estrogen Derivatives may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Risk C: Monitor therapy

Thyroid Products: Estrogen Derivatives may diminish the therapeutic effect of Thyroid Products. Risk C: 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. Risk D: 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. Risk D: 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.Risk D: 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). Risk D: Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: 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. Risk D: 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. Risk D: Consider therapy modification

Tranexamic Acid: Progestins (Contraceptive) may enhance the thrombogenic effect of Tranexamic Acid. Risk X: Avoid combination

Tranexamic Acid: Estrogen Derivatives (Contraceptive) may enhance the thrombogenic effect of Tranexamic Acid. Risk X: Avoid combination

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. Risk X: Avoid combination

Ursodiol: Estrogen Derivatives may diminish the therapeutic effect of Ursodiol. Risk C: Monitor therapy

Valproate Products: Estrogen Derivatives (Contraceptive) may decrease the serum concentration of Valproate Products. Risk C: 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. Risk D: 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. Risk D: Consider therapy modification

Voriconazole: May decrease the metabolism of Estrogen Derivatives (Contraceptive). Estrogen Derivatives (Contraceptive) may increase the serum concentration of Voriconazole. Risk C: Monitor therapy

Voriconazole: May increase the serum concentration of Progestins (Contraceptive). Progestins (Contraceptive) may increase the serum concentration of Voriconazole. Risk C: Monitor therapy

Food Interactions

Routine use of ethanol increases estrogen level and risk of breast cancer. Management: Avoid ethanol.

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

Advanced Practitioners Physical Assessment/Monitoring

See individual agents.

Nursing Physical Assessment/Monitoring

See individual agents.

Dosage Forms: US

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]

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]

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 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 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 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 [DSC] [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]

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 [DSC]

Loestrin 1/20 (21): Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg [contains fd&c yellow #10 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] [DSC]

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] [DSC] [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]

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]

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 [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]

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] [DSC]

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]

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Brevicon 1/35: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [21 tablets and 7 inactive tablets]

Brevicon 0.5/35: Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [21 tablets and 7 inactive tablets]

Brevicon 0.5/35: Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [21 tablets and 7 inactive tablets] [contains FD&C YELLOW #6 ALUMINUM LAKE]

FemHRT: Ethinyl estradiol 0.005 mg and norethindrone acetate 1 mg [DSC]

Loestrin 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)]

Minestrin 1/20: Ethinyl estradiol 0.02 mg and norethindrone acetate 1 mg

Ortho 1/35: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [21 tablets and 7 inactive tablets] [DSC]

Ortho 0.5/35: Ethinyl estradiol 0.035 mg and norethindrone 0.5 mg [21 tablets and 7 inactive tablets] [DSC]

Ortho 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]

Ortho 1/35: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [21 tablets and 7 inactive tablets] [DSC] [contains FD&C BLUE #2 ALUMINUM LAKE, FD&C YELLOW #10 ALUMINUM LAKE]

Ortho 0.5/35: 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]

Select 1/35: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [21 tablets and 7 inactive tablets]

Select 1/35: Ethinyl estradiol 0.035 mg and norethindrone 1 mg [21 tablets and 7 inactive tablets] [contains FD&C YELLOW #6 ALUMINUM LAKE]

Synphasic: 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 [contains FD&C BLUE #2 (INDIGOTINE)]

Synphasic: 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 [contains FD&C BLUE #2 (INDIGOTINE), FD&C YELLOW #6 ALUMINUM LAKE]

Tablet Therapy Pack, Oral:

Lolo: 1-0.01 / 0.01 MG (28ea) [contains BRILLIANT BLUE FCF (FD&C BLUE #1), FD&C BLUE #1 ALUMINUM LAKE, FD&C RED #40]

Generic Available (US)

May be product dependent

Pricing: US

Capsules (Taytulla Oral)

1-20 mg-mcg (24) (per each): $8.01

Chewable (Generess FE Oral)

0.8-25 mg-mcg (per each): $7.01

Chewable (Kaitlib Fe Oral)

0.8-25 mg-mcg (per each): $4.36

Chewable (Layolis FE Oral)

0.8-25 mg-mcg (per each): $4.36

Chewable (Melodetta 24 Fe Oral)

1-20 mg-mcg (24) (per each): $5.96

Chewable (Mibelas 24 Fe Oral)

1-20 mg-mcg (24) (per each): $5.96

Chewable (Minastrin 24 Fe Oral)

1-20 mg-mcg (24) (per each): $7.61

Chewable (Norethin Ace-Eth Estrad-FE Oral)

1-20 mg-mcg (24) (per each): $5.96

Chewable (Norethin-Eth Estradiol-Fe Oral)

0.4-35 mg-mcg (per each): $3.20

0.8-25 mg-mcg (per each): $4.36

Chewable (Wymzya Fe Oral)

0.4-35 mg-mcg (per each): $2.61

Tablets (Aranelle Oral)

0.5/1/0.5-35 mg-mcg (per each): $1.41

Tablets (Balziva Oral)

0.4-35 mg-mcg (per each): $1.60

Tablets (Blisovi 24 Fe Oral)

1-20 mg-mcg (24) (per each): $3.20

Tablets (Blisovi Fe 1.5/30 Oral)

1.5-30 mg-mcg (per each): $1.03

Tablets (Blisovi FE 1/20 Oral)

1-20 mg-mcg (per each): $1.02

Tablets (Cyclafem 1/35 Oral)

1-35 mg-mcg (per each): $1.05

Tablets (Cyclafem 7/7/7 Oral)

0.5/0.75/1-35 mg-mcg (per each): $1.15

Tablets (Dasetta 1/35 Oral)

1-35 mg-mcg (per each): $1.05

Tablets (Dasetta 7/7/7 Oral)

0.5/0.75/1-35 mg-mcg (per each): $1.15

Tablets (Estrostep Fe Oral)

1-20/1-30/1-35 mg-mcg (per each): $8.07

Tablets (Femhrt Low Dose Oral)

0.5-2.5 mg-mcg (per each): $6.72

Tablets (Fyavolv Oral)

0.5-2.5 mg-mcg (per each): $4.22

1-5 mg-mcg (per each): $3.14

Tablets (Hailey 24 Fe Oral)

1-20 mg-mcg (24) (per each): $3.20

Tablets (Jinteli Oral)

1-5 mg-mcg (per each): $2.93

Tablets (Junel 1.5/30 Oral)

1.5-30 mg-mcg (per each): $1.38

Tablets (Junel 1/20 Oral)

1-20 mg-mcg (per each): $1.36

Tablets (Junel FE 1.5/30 Oral)

1.5-30 mg-mcg (per each): $1.03

Tablets (Junel FE 1/20 Oral)

1-20 mg-mcg (per each): $1.02

Tablets (Junel Fe 24 Oral)

1-20 mg-mcg (24) (per each): $3.20

Tablets (Larin 1.5/30 Oral)

1.5-30 mg-mcg (per each): $1.38

Tablets (Larin 1/20 Oral)

1-20 mg-mcg (per each): $1.36

Tablets (Larin 24 FE Oral)

1-20 mg-mcg (24) (per each): $3.20

Tablets (Larin Fe 1.5/30 Oral)

1.5-30 mg-mcg (per each): $1.02

Tablets (Larin Fe 1/20 Oral)

1-20 mg-mcg (per each): $1.02

Tablets (Leena Oral)

0.5/1/0.5-35 mg-mcg (per each): $2.61

Tablets (Lo Loestrin Fe Oral)

1 MG-10 MCG / 10 mcg (per each): $6.03

Tablets (Loestrin 1.5/30 (21) Oral)

1.5-30 mg-mcg (per each): $7.56

Tablets (Loestrin 1/20 (21) Oral)

1-20 mg-mcg (per each): $7.56

Tablets (Loestrin Fe 1.5/30 Oral)

1.5-30 mg-mcg (per each): $5.67

Tablets (Loestrin Fe 1/20 Oral)

1-20 mg-mcg (per each): $5.67

Tablets (Microgestin 1.5/30 Oral)

1.5-30 mg-mcg (per each): $1.23

Tablets (Microgestin 1/20 Oral)

1-20 mg-mcg (per each): $1.36

Tablets (Microgestin FE 1.5/30 Oral)

1.5-30 mg-mcg (per each): $1.03

Tablets (Microgestin FE 1/20 Oral)

1-20 mg-mcg (per each): $1.02

Tablets (Necon 0.5/35 (28) Oral)

0.5-35 mg-mcg (per each): $1.15

Tablets (Norethin Ace-Eth Estrad-FE Oral)

1-20 mg-mcg (per each): $1.02

1-20 mg-mcg (24) (per each): $3.20

Tablets (Norethindrone Acet-Ethinyl Est Oral)

1-20 mg-mcg (per each): $1.36

Tablets (Norethindrone-Eth Estradiol Oral)

0.5-2.5 mg-mcg (per each): $3.75 – $3.90

1-5 mg-mcg (per each): $2.39 – $2.93

Tablets (Nortrel 0.5/35 (28) Oral)

0.5-35 mg-mcg (per each): $1.15

Tablets (Nortrel 1/35 (21) Oral)

1-35 mg-mcg (per each): $1.40

Tablets (Nortrel 1/35 (28) Oral)

1-35 mg-mcg (per each): $1.05

Tablets (Nortrel 7/7/7 Oral)

0.5/0.75/1-35 mg-mcg (per each): $1.15

Tablets (Ortho-Novum 1/35 (28) Oral)

1-35 mg-mcg (per each): $3.04

Tablets (Ortho-Novum 7/7/7 (28) Oral)

0.5/0.75/1-35 mg-mcg (per each): $1.64

Tablets (Philith Oral)

0.4-35 mg-mcg (per each): $1.60

Tablets (Pirmella 1/35 Oral)

1-35 mg-mcg (per each): $1.05

Tablets (Pirmella 7/7/7 Oral)

0.5/0.75/1-35 mg-mcg (per each): $1.15

Tablets (Tarina 24 Fe Oral)

1-20 mg-mcg (24) (per each): $3.84

Tablets (Tarina FE 1/20 EQ Oral)

1-20 mg-mcg (per each): $1.23

Tablets (Tarina FE 1/20 Oral)

1-20 mg-mcg (per each): $1.02

Tablets (Tilia Fe Oral)

1-20/1-30/1-35 mg-mcg (per each): $7.26

Tablets (Tri-Legest Fe Oral)

1-20/1-30/1-35 mg-mcg (per each): $2.04

Tablets (Tri-Norinyl (28) Oral)

0.5/1/0.5-35 mg-mcg (per each): $3.19

Tablets (Vyfemla Oral)

0.4-35 mg-mcg (per each): $1.60

Tablets (Wera Oral)

0.5-35 mg-mcg (per each): $1.15

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

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.

Pharmacodynamics/Kinetics

Norethindrone: See individual monograph.

Ethinyl estradiol:

Absorption: Rapid

Bioavailability: 43% to 55%

Distribution: Vd: 2 to 4 L/kg

Protein binding: >95% to albumin

Metabolism: Hepatic via oxidation and conjugation in GI tract; hydroxylated via CYP3A4 to metabolites; first-pass effect; enterohepatic recirculation; reversibly converted to estrone and estriol

Half-life elimination: 19 to 24 hours

Excretion: Urine (as estradiol, estrone, and estriol); feces

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Dental Health Professional Considerations

Current hormone contraceptives should not be considered a risk factor for gingival or periodontal disease (Preshaw 2013).

Effects on Dental Treatment

When prescribing antibiotics, patient must be warned to use additional methods of birth control if on oral contraceptives.

Effects on Bleeding

No information available to require special precautions

Index Terms

Estrostep 21; Eth Estradiol/Norethindr/Iron; Ethinyl Estradiol/Norethindr; Norethind Ac/Ethinyl Estradiol; Norethindrone Acetate and Ethinyl Estradiol; Ortho Novum; Ovcon-50

References

American College of Obstetricians and Gynecologists. ACOG committee opinion no. 557: Management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women. Obstet Gynecol. 2013;121(4):891-896.[PubMed 23635706]

American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 565: Hormone therapy and heart disease. Obstet Gynecol. 2013;121(6):1407-1410. doi: 10.1097/01.AOG.0000431053.33593.2d.[PubMed 23812486]

American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins—Gynecology. Practice bulletin no. 136: management of abnormal uterine bleeding associated with ovulatory dysfunction. Obstet Gynecol. 2013;122(1):176-185. doi: 10.1097/01.AOG.0000431815.52679.bb.[PubMed 23787936]

American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 110: Noncontraceptive Uses of Hormonal Contraceptives. Obstet Gynecol, 2010;115(1):206-18.[PubMed 20027071]

American College of Obstetricians and Gynecologists. ACOG committee opinion no. 556: Postmenopausal estrogen therapy: route of administration and risk of venous thromboembolism. Obstet Gynecol. 2013;121(4):887-890.[PubMed 23635705]

Anderson GL, Limacher M, Assaf AR, et al, “Effects of Conjugated Equine Estrogen In Postmenopausal Women With Hysterectomy: The Women’s Health Initiative Randomized Controlled Trial.” JAMA, 2004, 291(14):1701-12.[PubMed 15082697]

Arnaelle (norethindrone and ethinyl estradiol) [prescribing information]. North Wales, PA: Teva Pharmaceuticals; September 2015.

Brevicon (norethindrone and ethinyl estradiol) [product monograph]. Kirkland, Quebec, Canada: Pfizer Canada Inc; June 2018.

Burkman R, Schlesselman JJ, and Zieman M, “Safety Concerns and Health Benefits Associated With Oral Contraception,” Am J Obstet Gynecol, 2004, 190(4 Suppl):5-22.

Cobin RH, Goodman NF; AACE Reproductive Endocrinology Scientific Committee. American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) position statement on menopause-2017 update. Endocr Pract. 2017;23(7):869-880. doi: 10.4158/EP171828.PS.[PubMed 28703650]

Crandall CJ, Hovey KM, Andrews CA, et al. Breast cancer, endometrial cancer, and cardiovascular events in participants who used vaginal estrogen in the Women’s Health Initiative Observational Study. Menopause. 2018;25(1):11-20. doi: 10.1097/GME.0000000000000956.[PubMed 28816933]

Curtis KM, Jatlaoui TC, Tepper NK, et al. US selected practice recommendations for contraceptive use, 2016. MMWR Recomm Rep. 2016a;65(4):1‐66. doi: 10.15585/mmwr.rr6504a1.[PubMed 27467319]

Curtis KM, Tepper NK, Jatlaoui TC, et al. US medical eligibility criteria for contraceptive use, 2016. MMWR Recomm Rep. 2016b;65(3):1‐103. doi: 10.15585/mmwr.rr6503a1.[PubMed 27467196]

DeSancho MT, Dorff T, and Rand JH, “Thrombophilia and the Risk of Thromboembolic Events In Women on Oral Contraceptives and Hormone Replacement Therapy,” Blood Coagul Fibrinolysis, 2010, 21(6):534-8.[PubMed 20581664]

Estrostep Fe (ethinyl estradiol and norethindrone acetate) [prescribing information]. Irvine, CA; Allergan USA, Inc: August 2017.

Femcon Fe (norethindrone and ethinyl estradiol) [prescribing information]. Irvine, CA: Allergan USA, Inc; August 2017.

Femhrt (norethindrone and ethinyl estradiol) [prescribing information]. Irvine, CA: Allergan USA, Inc; November 2017.

Fraser IS, Critchley HO, Broder M, et al. The FIGO recommendations on terminologies and definitions for normal and abnormal uterine bleeding. Semin Reprod Med. 2011;29(5):383-90. doi: 10.1055/s-0031-1287662.[PubMed 22065325]

Generess Fe (norethindrone and ethinyl estradiol) [prescribing information]. Irvine, CA: Allergan USA, Inc; August 2017.

Geng B, Riedl MA. HAE update: special considerations in the female patient with hereditary angioedema. Allergy Asthma Proc. 2013;34(1):13-18.[PubMed 23406930]

Gierisch JM, Coeytaux RR, Urrutia RP, et al. Oral contraceptive use and risk of breast, cervical, colorectal, and endometrial cancers: a systematic review. Cancer Epidemiol Biomarkers Prev. 2013;22(11):1931-43. doi:10.1158/1055-9965.EPI-13-0298.[PubMed 24014598]

Goodman NF, Cobin RH, Ginzburg SB, et al; American Association of Clinical Endocrinologists (AACE). American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of menopause. Endocr Pract. 2011;17(suppl 6):1-25.[PubMed 22193047]

Handel AC, Miot LD, Miot HA. Melasma: a clinical and epidemiological review. An Bras Dermatol. 2014;89(5):771-782.[PubMed 25184917]

Hsia J, Langer RD, Manson JE, et al, “Conjugated Equine Estrogens and Coronary Heart Disease: The Women’s Health Initiative,” Arch Intern Med, 2006, 166(3):357-65.[PubMed 16476878]

Holt VL, Scholes D, Wicklund KG, et al, “Body Mass Index, Weight, and Oral Contraceptive Failure Risk,” Obstet Gynecol, 2005, 105(1):46-52.[PubMed 15625141]

Junel (ethinyl estradiol and norethindrone) [prescribing information]. Sellersville, PA: Teva Pharmaceuticals; July 2014.

Junel Fe (ethinyl estradiol and norethindrone) [prescribing information]. Sellersville, PA: Teva Pharmaceuticals; November 2014.

Larin 24 Fe (norethindrone acetate, ethinyl estradiol, and ferrous fumarate) [prescribing information]. Memphis, TN: Northstar Rx LLC; November 2016.

Layolis Fe (norethindrone and ethinyl estradiol) [prescribing information]. Parsippany, NJ: Actavis Pharma; March 2012.

Legro RS, Arslanian SA, Ehrmann DA, et al. Diagnosis and treatment of polycystic ovary syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(12):4565-4592.[PubMed 24151290]

Loestrin (ethinyl estradiol and norethindrone) [prescribing information]. Rockaway, NJ: Warner Chilcott; August 2016.

Loestrin 24 Fe (ethinyl estradiol and norethindrone) [prescribing information]. Rockaway, NJ: Warner Chilcott; August 2016.

Lo Lestrin Fe (ethinyl estradiol and norethindrone acetate) [prescribing information]. Irvine, CA; Allergan USA, Inc: August 2017.

Lomedia 24 FE (ethinyl estradiol and norethindrone) [prescribing information]. Corona, CA: Watson Laboratories Inc; October 2013.

Martin KA, Anderson RR, Chang RJ, et al. Evaluation and treatment of hirsutism in premenopausal women: an Endocrine Society clinical practice guideline [published online March 7, 2018]. J Clin Endocrinol Metab. doi: 10.1210/jc.2018-00241.[PubMed 29522147]

Minastrin 24 Fe (norethindrone acetate, ethinyl estradiol, and ferrous fumarate) [prescribing information]. Irvine, CA: Allergan USA, Inc.; December 2016.

Minestrin 1/20 (norethindrone acetate and ethinyl estradiol) [product monograph]. Markham, Ontario, Canada: Allergan Inc; February 2019.

Modicon (ethinyl estradiol and norethindrone) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals; November 2017.

Munro MG, Mainor N, Basu R, Brisinger M, Barreda L. Oral medroxyprogesterone acetate and combination oral contraceptives for acute uterine bleeding: a randomized controlled trial. Obstet Gynecol. 2006;108(4):924-929. doi: 10.1097/01.AOG.0000238343.62063.22.[PubMed 17012455]

North American Menopause Society (NAMS). The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017;24(7):728-753. doi: 10.1097/GME.0000000000000921.[PubMed 28650869]

Nortrel 7/7/7 (ethinyl estradiol and norethindrone) [prescribing information]. North Wales, PA: Teva Pharmaceuticals; September 2016.

Orme ML, Back DJ, and Breckenridge AM, “Clinical Pharmacokinetics of Oral Contraceptive Steroids,” Clin Pharmacokinet, 1983, 8(2):95-136.[PubMed 6342899]

Ortho 0.5/35 (ethinyl estradiol and norethindrone) [product monograph]. Toronto, Ontario, Canada: Janssen Inc; March 2017.

Ortho 1/35 (ethinyl estradiol and norethindrone) [product monograph]. Toronto, Ontario, Canada: Janssen Inc; March 2017.

Ortho 7/7/7 (ethinyl estradiol and norethindrone) [product monograph]. Toronto, Ontario, Canada: Janssen Inc; March 2017.

Ortho-Novum (ethinyl estradiol and norethindrone) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals; November 2017.

Ott MA, Sucato GS; Committee on Adolescence. Contraception for adolescents. Pediatrics. 2014;134(4):e1257-81. doi: 10.1542/peds.2014-2300.[PubMed 25266435]

Practice Committee of the American Society for Reproductive Medicine (ASRM).Combined hormonal contraception and the risk of venous thromboembolism: a guideline. Fertil Steril. 2017;107(1):43-51. doi: 10.1016/j.fertnstert.2016.09.027.[PubMed 27793376]

Preshaw PM. Oral contraceptives and the periodontium. Peridontol 2000. 2013;61(1):125-159.[PubMed 23240947]

Rossouw JE, Anderson GL, Prentice RL, et al, “Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principle Results From the Women’s Health Initiative Randomized Controlled Trial,”JAMA, 2002, 288(3):321-33.[PubMed 12117397]

Shenfield GM and Griffin JM, “Clinical Pharmacokinetics of Contraceptive Steroids. An Update,” Clin Pharmacokinet, 1991, 20(1):15-37.[PubMed 2029800]

Shumaker SA, Legault C, Rapp SR, et al, “Estrogen Plus Progestin and the Incidence of Dementia and Mild Cognitive Impairment in Postmenopausal Women: The Women’s Health Initiative Memory Study: A Randomized Controlled Trial,” JAMA, 2003, 289(20):2651-62.[PubMed 12771112]

Sitruk-Ware R and Nath A, “Metabolic Effects of Contraceptive Steroids,” Rev Endocr Metab Disord, 2011, 12(2):63-75.[PubMed 21538049]

Stuenkel CA, Davis SR, Gompel A, et al. Treatment of symptoms of the menopause: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015;100(11):3975-4011. doi: 10.1210/jc.2015-2236.[PubMed 26444994]

Tarina Fe 1/20 (norethdrine acetate/ethinyl estradiol) [prescribing information]. Charleston, SC: Afaxys; August 2015.

Tilia Fe (ethinyl estradiol/norethindrone/iron) [prescribing information]. Greenville, NC: Mayne Pharma; January 2016.

The North American Menopause Society [NAMS] Statement on Continuing Use of Systemic Hormone Therapy After Age 65. Menopause. 2015;22(7):693. doi: 10.1097/GME.0000000000000492.[PubMed 26035150]

Tri-norinyl (ethinyl estradiol/norethindrone/iron) [prescribing information]. Greenville, NC: Mayne Pharma; January 2016.

US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. http://www.cdc.gov/niosh/topics/antineoplastic/pdf/hazardous-drugs-list_2016-161.pdf. Updated September 2016. Accessed October 5, 2016.

van Vlijmen EF, Veeger NJ, Middeldorp S, et al, “Thrombotic Risk During Oral Contraceptive Use and Pregnancy in Women With Factor V Leiden or Prothrombin Mutation: A Rational Approach to Contraception,” Blood, 2011, 118(8):2055-61.[PubMed 21659542]

Vyfemla (norethindrone and ethinyl estradiol) [prescribing information]. Baltimore, MD: Lupin Pharmaceuticals, Inc; October 2013.

Walker JL, Powell CB, Chen LM, et al. Society of Gynecologic Oncology recommendations for the prevention of ovarian cancer [published online ahead of prin March 27, 2015]. Cancer. 2015. doi: 10.1002/cncr.29321.[PubMed 25820366]

Wymzya Fe (ethinyl estradiol/norethindrone/iron) [prescribing information]. Baltimore, MD: Lupin Pharmaceuticals; June 2016.

Zuraw BL, Bernstein JA, Lang DM, et al; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology. A focused parameter update: hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema. J Allergy Clin Immunol. 2013;131(6):1491-1493.[PubMed 23726531]

Brand Names: International

Brevinor (AU, BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, NZ, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW); Covina (TW); Estracomb (IL); Estragest TTS (IL); Eveclin Half (KR); Eveprem (KR); Eviclin (KR); Evorel Cont (IL); Evorel Conti (AR); Evorel Sequi (IL); Evorelconti (MX); Lunabell (JP); Micropil (PH); Norimin (AE, AU, BF, BH, BJ, CI, CY, EG, ET, GB, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, NZ, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZM, ZW); Ortho 7 7 7 (BB, BM, BS, BZ, GY, JM, NL, PR, SR, TT); Ortho-Novum 1 35 (CO, FR); Ortho-Novum 1/35 (FR); Ovysmen (AE, BF, BH, BJ, CI, CY, EG, ET, GB, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZM, ZW); Ovysmen 0.5 35 (AT, DE); Ovysmen 1 35 (AT, CH, DE); Synphase-2 (AE); Synphasic 28 (AU, NZ); Tri-Sequens (KR, SG); Triella (FR); Trinovum (AT, BE, BF, BJ, CH, CI, CO, CZ, DE, DK, ET, GB, GH, GM, GN, HR, IE, IS, IT, KE, LR, LU, MA, ML, MR, MU, MW, NE, NG, PL, RU, SC, SD, SI, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Trisekvens (SE); Trisequens (BR, PE, PY, UY); Trisequens Forte (IL)

Ethinyl Estradiol and Norethindrone (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(ETH in il es tra DYE ole & nor eth IN drone)

Brand Names: US

Alyacen 1/35; Alyacen 7/7/7; Aranelle; Balziva; Blisovi 24 Fe; Blisovi Fe 1.5/30; Blisovi FE 1/20; Brevicon (28) [DSC]; Briellyn; Cyclafem 1/35; Cyclafem 7/7/7; Dasetta 1/35; Dasetta 7/7/7; Estrostep Fe; Femcon Fe [DSC]; Femhrt Low Dose; Fyavolv; Generess FE; Gildagia [DSC]; Gildess 1.5/30 [DSC]; Gildess 1/20 [DSC]; Gildess 24 FE [DSC]; Gildess FE 1.5/30 [DSC]; Gildess FE 1/20 [DSC]; Hailey 24 Fe; Jevantique Lo [DSC]; Jinteli; Junel 1.5/30; Junel 1/20; Junel FE 1.5/30; Junel FE 1/20; Junel Fe 24; Kaitlib Fe; Larin 1.5/30; Larin 1/20; Larin 24 FE; Larin Fe 1.5/30; Larin Fe 1/20; Layolis FE; Leena; Lo Loestrin Fe; Loestrin 1.5/30 (21); Loestrin 1/20 (21); Loestrin Fe 1.5/30; Loestrin Fe 1/20; Lomedia 24 FE [DSC]; Melodetta 24 Fe; Mibelas 24 Fe; Microgestin 1.5/30; Microgestin 1/20; Microgestin 24 Fe [DSC]; Microgestin FE 1.5/30; Microgestin FE 1/20; Minastrin 24 Fe; Modicon (28) [DSC]; Necon 0.5/35 (28); Necon 1/35 (28) [DSC]; Necon 10/11 (28) [DSC]; Necon 7/7/7 [DSC]; Norinyl 1+35 (28) [DSC]; Nortrel 0.5/35 (28); Nortrel 1/35 (21); Nortrel 1/35 (28); Nortrel 7/7/7; Ortho-Novum 1/35 (28); Ortho-Novum 7/7/7 (28); Ovcon-35 (28) [DSC]; Philith; Pirmella 1/35; Pirmella 7/7/7; Tarina 24 Fe; Tarina FE 1/20; Tarina FE 1/20 EQ; Taytulla; Tilia Fe; Tri-Legest Fe; Tri-Norinyl (28); Vyfemla; Wera; Wymzya Fe; Zenchent FE [DSC]; Zenchent [DSC]

Brand Names: Canada

Brevicon 0.5/35; Brevicon 1/35; FemHRT; Loestrin 1.5/30; Lolo; Minestrin 1/20; Ortho 0.5/35; Ortho 1/35; Ortho 7/7/7; Select 1/35; Synphasic

Warning
  • Birth control:
  • Smoking cigarettes while using this drug raises the chance of very bad heart and blood-related side effects. This chance is raised with age (mainly in women older than 35 years of age). It is also raised with the number of cigarettes smoked. It is strongly advised not to smoke. Do not use this drug if you smoke and are older than 35 years of age.
  • Hormone replacement therapy (HRT):
  • Estrogens may raise the chance of uterine cancer. Progestins may lower this chance. A warning sign for cancer of the uterus is vaginal bleeding. Report any vaginal bleeding to the doctor.
  • Do not use estrogens to prevent heart disease or dementia. Using estrogens may raise the chances of having a heart attack, a stroke, breast cancer, ovarian cancer, a blood clot, or dementia.
  • Use estrogens with or without progestin for the shortest time needed at the lowest useful dose.
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.
What do I need to tell my doctor BEFORE I take this drug?
  • For all patients taking this drug:
  • If you have an allergy to ethinyl estradiol, norethindrone, or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have had any of these health problems: Blood clots, blood clotting problem, breast cancer or other cancer where hormones make it grow, diseased blood vessels in the brain or heart, disease of a heart valve with problems, heart disease, chest pain caused by angina, heart attack, stroke, high blood pressure, liver disease, liver tumor, very bad headache or migraine, or diabetes that affects blood flow.
  • If you have had any of these health problems: Endometrial cancer, cancer of the cervix or vagina, or vaginal bleeding where the cause is not known.
  • If you have surgery and need bedrest.
  • If you are pregnant or may be pregnant. Do not take this drug if you are pregnant.
  • If you are breast-feeding or plan to breast-feed.
  • If you are taking ombitasvir, paritaprevir, and ritonavir (with or without dasabuvir).
  • Birth control:
  • If you turned yellow during pregnancy or with estrogen-based or hormone contraceptive use.
  • Children:
  • If your child has not had her first period.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • All products:
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists. This drug may need to be stopped before certain types of surgery as your doctor has told you. If this drug is stopped, your doctor will tell you when to start taking this drug again after your surgery or procedure.
  • This drug may raise the chance of blood clots, a stroke, or a heart attack. Talk with the doctor.
  • Talk with your doctor if you will need to be still for long periods of time like long trips, bedrest after surgery, or illness. Not moving for long periods may raise your chance of blood clots.
  • Some studies have shown the risk of breast cancer is raised in women taking birth control pills, especially at a younger age. This includes birth control pills that have drugs like this one in them. The risk was also linked to how long the birth control pills were taken. One study showed the risk of breast cancer was also raised in women who took birth control pills within the past 10 years. Talk with the doctor.
  • If you have high blood sugar (diabetes), talk with your doctor. This drug may raise blood sugar.
  • Check your blood sugar as you have been told by your doctor.
  • High blood pressure has happened with drugs like this one. Have your blood pressure checked as you have been told by your doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Be sure to have regular breast exams and gynecology check-ups. Your doctor will tell you how often to have these. You will also need to do breast self-exams as your doctor has told you. Talk with your doctor.
  • If you are allergic to tartrazine, talk with your doctor. Some products have tartrazine.
  • If you drink grapefruit juice or eat grapefruit often, talk with your doctor.
  • This drug may affect certain lab tests. Tell all of your health care providers and lab workers that you take this drug.
  • Certain drugs, herbal products, or health problems could cause this drug to not work as well. Be sure your doctor knows about all of your drugs and health problems.
  • Birth control:
  • This drug does not stop the spread of diseases like HIV or hepatitis that are passed through blood or having sex. Do not have any kind of sex without using a latex or polyurethane condom. Do not share needles or other things like toothbrushes or razors. Talk with your doctor.
  • This drug may raise the chance of blood clots. The chance is highest during the first year of using this drug. The chance is also highest when starting to use hormone-based birth control again after not using it for 4 weeks or more. Talk with the doctor.
  • If you are taking this drug for pimples (acne), you need to be at least 15 years of age.
  • If you have any signs of pregnancy or if you have a positive pregnancy test, call your doctor right away.
  • Hormone replacement therapy (HRT):
  • This drug works best when used with calcium/vitamin D and weight-bearing workouts like walking or PT (physical therapy).
  • Follow the diet and workout plan that your doctor told you about.
  • Do not give to a child. Talk with your doctor.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
  • Signs of gallbladder problems like pain in the upper right belly area, right shoulder area, or between the shoulder blades; yellow skin or eyes; fever with chills; bloating; or very upset stomach or throwing up.
  • Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
  • Low mood (depression).
  • Feeling very tired or weak.
  • Swelling.
  • Not able to pass urine or change in how much urine is passed.
  • A lump in the breast, breast soreness, or nipple discharge.
  • Vaginal itching or discharge.
  • Spotting or vaginal bleeding that is very bad or does not go away.
  • Bulging eyes.
  • Change in eyesight.
  • Loss of eyesight.
  • Change in how contact lenses feel in the eyes.
  • Call your doctor right away if you have signs of a blood clot like chest pain or pressure; coughing up blood; shortness of breath; swelling, warmth, numbness, change of color, or pain in a leg or arm; or trouble speaking or swallowing.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • All products:
  • Feeling more or less hungry.
  • Dizziness.
  • Weight gain.
  • Headache.
  • Upset stomach or throwing up.
  • Cramps.
  • Bloating.
  • Enlarged breasts.
  • Breast soreness.
  • Hair loss.
  • Lowered interest in sex.
  • This drug may cause dark patches of skin on your face. Avoid sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects you from the sun.
  • Birth control:
  • Period (menstrual) changes. These include spotting or bleeding between cycles.
  • Hormone replacement therapy (HRT):
  • Diarrhea.
  • Vaginal bleeding or spotting.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Follow how to use as you have been told by the doctor or read the package insert.
  • Take this drug at the same time of day.
  • Take with or without food. Take with food if it causes an upset stomach.
  • Birth control:
  • Do not skip doses, even if you do not have sex very often.
  • If you throw up or have diarrhea, this drug may not work as well to prevent pregnancy. Use an extra form of birth control, like condoms, until you check with your doctor.
  • If you miss 2 periods in a row, take a pregnancy test before starting a new cycle.
  • Chewable tablet:
  • Chew well before swallowing.
  • Some brands may be swallowed whole. Check with your pharmacist to see if your brand may be swallowed whole.
  • Some brands need to be taken with a full glass of water. Some brands need to be taken without water. Check with your pharmacist to see if you need to take your drug with water.
What do I do if I miss a dose?
  • Birth control:
  • If a dose is missed, check the package insert or call the doctor to find out what to do. If using this drug to prevent pregnancy, another form of birth control may need to be used for some time to prevent pregnancy.
  • Hormone replacement therapy (HRT):
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
  • If you miss taking this drug for a few days in a row, call your doctor before you start taking it again.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Protect from light.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Ethinyl Estradiol and Norethindrone (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(ETH in il es tra DYE ole & nor eth IN drone)

Brand Names: US

Alyacen 1/35; Alyacen 7/7/7; Aranelle; Balziva; Blisovi 24 Fe; Blisovi Fe 1.5/30; Blisovi FE 1/20; Brevicon (28) [DSC]; Briellyn; Cyclafem 1/35; Cyclafem 7/7/7; Dasetta 1/35; Dasetta 7/7/7; Estrostep Fe; Femcon Fe [DSC]; Femhrt Low Dose; Fyavolv; Generess FE; Gildagia [DSC]; Gildess 1.5/30 [DSC]; Gildess 1/20 [DSC]; Gildess 24 FE [DSC]; Gildess FE 1.5/30 [DSC]; Gildess FE 1/20 [DSC]; Hailey 24 Fe; Jevantique Lo [DSC]; Jinteli; Junel 1.5/30; Junel 1/20; Junel FE 1.5/30; Junel FE 1/20; Junel Fe 24; Kaitlib Fe; Larin 1.5/30; Larin 1/20; Larin 24 FE; Larin Fe 1.5/30; Larin Fe 1/20; Layolis FE; Leena; Lo Loestrin Fe; Loestrin 1.5/30 (21); Loestrin 1/20 (21); Loestrin Fe 1.5/30; Loestrin Fe 1/20; Lomedia 24 FE [DSC]; Melodetta 24 Fe; Mibelas 24 Fe; Microgestin 1.5/30; Microgestin 1/20; Microgestin 24 Fe [DSC]; Microgestin FE 1.5/30; Microgestin FE 1/20; Minastrin 24 Fe; Modicon (28) [DSC]; Necon 0.5/35 (28); Necon 1/35 (28) [DSC]; Necon 10/11 (28) [DSC]; Necon 7/7/7 [DSC]; Norinyl 1+35 (28) [DSC]; Nortrel 0.5/35 (28); Nortrel 1/35 (21); Nortrel 1/35 (28); Nortrel 7/7/7; Ortho-Novum 1/35 (28); Ortho-Novum 7/7/7 (28); Ovcon-35 (28) [DSC]; Philith; Pirmella 1/35; Pirmella 7/7/7; Tarina 24 Fe; Tarina FE 1/20; Tarina FE 1/20 EQ; Taytulla; Tilia Fe; Tri-Legest Fe; Tri-Norinyl (28); Vyfemla; Wera; Wymzya Fe; Zenchent FE [DSC]; Zenchent [DSC]

Brand Names: Canada

Brevicon 0.5/35; Brevicon 1/35; FemHRT; Loestrin 1.5/30; Lolo; Minestrin 1/20; Ortho 0.5/35; Ortho 1/35; Ortho 7/7/7; Select 1/35; Synphasic

Warning
  • Smoking cigarettes while using this drug raises the chance of very bad heart and blood-related side effects. This chance is raised with age (mainly in women older than 35 years of age). It is also raised with the number of cigarettes smoked. It is strongly advised not to smoke.
What is this drug used for?
  • It is used to prevent pregnancy.
  • It is used to treat pimples (acne).
  • It may be given to your child for other reasons. Talk with the doctor.
  • Hormone replacement therapy (HRT):
  • If your child has been given this form of this drug, talk with the doctor for information about the benefits and risks. Talk with the doctor if you have questions or concerns about giving this drug to your child.
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child has had any of these health problems: Blood clots, blood clotting problem, breast cancer or other cancer where hormones make it grow, diseased blood vessels in the brain or heart, disease of a heart valve with problems, endometrial cancer, cancer of the cervix or vagina, heart disease, chest pain caused by angina, heart attack, stroke, high blood pressure, liver disease, liver tumor, very bad headache or migraine, diabetes that affects blood flow, or vaginal bleeding where the cause is not known.
  • If your child has surgery and needs bedrest.
  • If your child has turned yellow during pregnancy or with estrogen-based or hormone contraceptive use.
  • If your child has not had her first period.
  • If your child is taking ombitasvir, paritaprevir, and ritonavir (with or without dasabuvir).
  • If your child is pregnant:
  • Do not give this drug to your child if she is pregnant.
  • If your child is breast-feeding a baby:
  • Talk with the doctor if your child is breast-feeding a baby or plans to breast-feed a baby.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists. This drug may need to be stopped before certain types of surgery as the doctor has told you. If this drug is stopped, the doctor will tell you when to start giving this drug again after your child’s surgery or procedure.
  • This drug may raise the chance of blood clots, a stroke, or a heart attack. Talk with the doctor.
  • Talk with the doctor if your child will need to be still for long periods of time like long trips, bedrest after surgery, or illness. Not moving for long periods may raise the chance of blood clots.
  • Some studies have shown the risk of breast cancer is raised in women taking birth control pills, especially at a younger age. This includes birth control pills that have drugs like this one in them. The risk was also linked to how long the birth control pills were taken. One study showed the risk of breast cancer was also raised in women who took birth control pills within the past 10 years. Talk with the doctor.
  • If your child has high blood sugar (diabetes), talk with the doctor. This drug can raise blood sugar.
  • Have your child’s blood sugar checked as you have been told by your child’s doctor.
  • High blood pressure has happened with drugs like this one. Have your child’s blood pressure checked as you have been told by the doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Be sure that your child has regular breast exams and gynecology check-ups. The doctor will tell you how often your child needs to have these. Your child will also need to do breast self-exams as the doctor has told you. Talk with the doctor.
  • If your child is allergic to tartrazine, talk with your child’s doctor. Some products have tartrazine.
  • If your child drinks grapefruit juice or eats grapefruit often, talk with your child’s doctor.
  • This drug may affect certain lab tests. Tell all of your child’s health care providers and lab workers that your child takes this drug.
  • Certain drugs, herbal products, or health problems could cause this drug to not work as well. Be sure the doctor knows about all of your child’s drugs and health problems.
  • This drug may raise the chance of blood clots. The chance is highest during the first year of using this drug. The chance is also highest when starting to use hormone-based birth control again after not using it for 4 weeks or more. Talk with the doctor.
  • If your child is taking this drug for pimples (acne), she needs to be at least 15 years of age.
  • If your child is or may be sexually active:
  • This drug does not stop the spread of diseases like HIV or hepatitis that are passed through having sex. Be sure your child does not have any kind of sex without using a latex or polyurethane condom. Talk with the doctor.
  • If your child has any signs of pregnancy or if she has a positive pregnancy test, call the doctor right away.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
  • Signs of gallbladder problems like pain in the upper right belly area, right shoulder area, or between the shoulder blades; yellow skin or eyes; fever with chills; bloating; or very upset stomach or throwing up.
  • Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
  • Low mood (depression).
  • Feeling very tired or weak.
  • Swelling.
  • Not able to pass urine or change in how much urine is passed.
  • A lump in the breast, breast soreness, or nipple discharge.
  • Vaginal itching or discharge.
  • Spotting or vaginal bleeding that is very bad or does not go away.
  • Bulging eyes.
  • Change in eyesight.
  • Loss of eyesight.
  • Change in how contact lenses feel in the eyes.
  • Call the doctor right away if your child has signs of a blood clot like chest pain or pressure; coughing up blood; shortness of breath; swelling, warmth, numbness, change of color, or pain in a leg or arm; or trouble speaking or swallowing.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • Feeling more or less hungry.
  • Dizziness.
  • Weight gain.
  • Headache.
  • Upset stomach or throwing up.
  • Cramps.
  • Bloating.
  • Period (menstrual) changes. These include spotting or bleeding between cycles.
  • Enlarged breasts.
  • Breast soreness.
  • Hair loss.
  • This drug may cause dark patches of skin on your child’s face. Avoid lots of sun, sunlamps, and tanning beds. Use sunscreen and dress your child in clothing and eyewear that protects him/her from the sun.
  • If your child is or may be sexually active:
  • Lowered interest in sex.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • Follow how to give this drug as you have been told by your child’s doctor or read the package insert.
  • Give this drug at the same time of day.
  • Give after the evening meal or at bedtime.
  • Give this drug with or without food. Give with food if it causes an upset stomach.
  • Do not skip doses, even if your child does not have sex or does not have sex very often.
  • If your child throws up or has diarrhea, this drug may not work as well. Your child needs to use an extra form of birth control, like condoms, until you check with the doctor.
  • If your child misses 2 periods in a row, have your child take a pregnancy test before starting a new dosing cycle.
What do I do if my child misses a dose?
  • If a dose is missed, check the package insert or call the doctor to find out what to do. If using this drug to prevent pregnancy, another form of birth control may need to be used for some time to prevent pregnancy.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Protect from light.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.