Ethinyl Estradiol and Norgestimate (Lexi-Drugs)

ALERT: US Boxed Warning
  Cigarette smoke and serious cardiovascular events:
Pronunciation

(ETH in il es tra DYE ole & nor JES ti mate)

Brand Names: US

Estarylla; Femynor; Mili; Mono-Linyah; MonoNessa; Ortho Tri-Cyclen (28); Ortho Tri-Cyclen Lo; Ortho-Cyclen (28); Previfem; Sprintec 28; Tri Femynor; Tri-Estarylla; Tri-Linyah; Tri-Lo-Estarylla; Tri-Lo-Marzia; Tri-Lo-Sprintec; Tri-Mili; Tri-Previfem; Tri-Sprintec; Tri-VyLibra; Tri-VyLibra Lo; TriNessa (28) [DSC]; TriNessa Lo [DSC]; VyLibra

Brand Names: Canada

Cyclen; Tri-Cyclen; Tri-Cyclen Lo; Tricira Lo 21; Tricira Lo 28

Dosing: Adult

Females:

Acne (Ortho Tri-Cyclen, Tri-Estarylla, TriNessa, Tri-Previfem, Tri-Sprintec): Oral: Refer to dosing for contraception

Contraception: Oral: 1 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. With a Sunday start, an additional method of contraception should be used until after the first 7 days of consecutive administration.

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 breast-feeding) or after second trimester abortion or miscarriage: Therapy may be started ≥4 weeks postpartum. Pregnancy should be considered 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.

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 package insert for product specific information.

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

Females:

Acne: Oral: Adolescents ≥15 years; refer to adult dosing for contraception; not to be used prior to menarche.

Contraception: 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: Treatment of moderate acne vulgaris in females at least 15 years of age

Limitations of use: When used for acne, use only in females ≥15 years of age who achieved menarche, who also desire combination hormonal contraceptive therapy, and have no contraindications to combination hormonal contraceptive use

Contraception: Prevention of pregnancy.

Use: Off-Label: Adult

  Abnormal uterine bleedingLevel of Evidence [G]

Based on the American College of Obstetricians and Gynecologists committee opinion on the management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women, ethinyl estradiol and norgestimate (among other oral contraceptive combinations) is effective and recommended for the management of abnormal uterine bleeding Ref.

  DysmenorrheaLevel of Evidence [G]

Based on the American College of Obstetricians and Gynecologists Practice Bulletin on Noncontraceptive Uses of Hormonal Contraceptives, ethinyl estradiol and norgestimate (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 norgestimate 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 American College of Obstetricians and Gynecologists Practice Bulletin on Noncontraceptive Uses of Hormonal Contraceptives, ethinyl estradiol and norgestimate (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 norgestimate (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

Stroke:

AHA/ASA, “Guidelines for the Prevention of Stroke in Women,” 2014

Administration: Oral

Administer at the same time each day at intervals not >24 hours.

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).

According to the manufacturer, if severe diarrhea or vomiting occur within 3 to 4 hours after taking an active tablet, it should be considered a missed dose; additional contraceptive measures are recommended. Additional guidelines are also available (Curtis 2016a).

Administration: Pediatric

Oral:

Contraception: Administer at the same time each day at intervals not >24 hours.

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).

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

According to the manufacturer, if vomiting or diarrhea occurs, back-up contraceptive measures may be needed. Additional guidelines are available (Curtis 2016a).

Acne: Ortho-TriCyclen, Tri-Estarylla, TriNessa, Tri Femynor, Tri-Linyah, Tri-Previfem, Tri-Sprintec, Tri-VyLibra: Females ≥15 years: Follow administration for contraception.

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 room temperature. 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, weight gain, flatulence, anxiety, abdominal pain, enlarged breasts, menstrual changes, 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 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), 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), edema, severe dizziness, passing out, severe headache, depression, mood changes, 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, blindness, bulging eyes, 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:
  International issues:
Contraindications

Breast cancer or other estrogen- or progestin-dependent neoplasms (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/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), hypercoagulopathies (inherited or acquired), hypertension (uncontrolled), headaches with focal neurological symptoms, migraine headaches with aura or migraine headaches if >35 years of age, thrombogenic valvular or rhythm diseases of the heart (eg, subacute bacterial endocarditis with valvular disease or atrial fibrillation), women >35 years who smoke.

Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to ethinyl estradiol, norgestimate, or any component of the formulation; myocardial infarction (current or history of); persistent blood pressure ≥160 mm Hg systolic or ≥100 mm Hg diastolic; ocular lesions due to ophthalmic vascular disease including partial or complete loss of vision or defect in visual fields; steroid dependent jaundice, cholestatic jaundice or history of jaundice in pregnancy; pancreatitis associated with severe hypertriglyceridemia (current or history of); severe dyslipoproteinemia; prolonged immobilization or major surgery associated with an increased risk of postoperative thromboembolism; thrombophlebitis, thromboembolic disorders, or thrombophilic conditions (current or history of); prodromi of a thrombosis (eg, TIA, angina pectoris; current or history of); hereditary or acquired predisposition for venous or arterial thrombosis, such as Factor V Leiden mutation and 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 ombitasvir, paritaprevir, ritonavir (with or without dasabuvir)

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: 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 women 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, 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.

• 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.

• 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, 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:

• Cardiovascular disease: Use 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). Use is 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: Oral contraceptives 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). Use is contraindicated in women with diabetes mellitus and vascular disease.

• Endometrial or ovarian cancer: The risk of endometrial or 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 endometrial or ovarian cancer may use combination hormonal contraceptives (Curtis 2016b).

• Gallbladder disease: Combination hormonal contraceptives may cause a small increased risk of gallbladder disease or may worsen existing gallbladder disease (Curtis 2016b).

• 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 of this product is contraindicated in women with preexisting hepatic tumors.

• Hepatic impairment: Combination hormonal contraceptives may be poorly metabolized in women with hepatic impairment. Discontinue if jaundice develops during therapy or if liver function becomes abnormal. Use is contraindicated in women with 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).

• Hereditary angioedema: Estrogens may induce or exacerbate 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.

• 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.

• 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: Women with systemic lupus erythematosus (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, 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:

• Obese: 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).

• Pediatric: Not for use prior to menarche.

• Postmenopausal women: Use is not indicated in postmenopausal women.

• 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 over 35 years, and with the number of cigarettes smoked. For this reason, combination oral contraceptives should not be used by women who are over 35 years and smoke. Use is contraindicated in patients >35 years who smoke.

• Surgical patients: Whenever possible, should be discontinued at least 4 weeks prior to and for 2 weeks following elective surgery associated with an increased risk of thromboembolism or during periods of prolonged immobilization.

Other warnings/precautions:

• Appropriate use: When initiating a combination oral contraceptive, consideration should be given to safety, effectiveness, availability and acceptance to the patient (Curtis 2016a). 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).

• 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).

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

>10%:

Central nervous system: Headache (≤34%), migraine (≤34%)

Gastrointestinal: Nausea (≤16%), vomiting (≤16%)

Genitourinary: Breakthrough bleeding (7% to 38%)

1% to 10%:

Central nervous system: Nipple pain (≤10%), depression (≤8%), emotional lability (≤8%), mood changes (≤8%), mood disorder (≤8%), nervousness (3%), fatigue (2%)

Dermatologic: Acne vulgaris (5%), skin rash (3%)

Endocrine & metabolic: Menstrual disease (≤9%), weight changes (≤3%), weight gain (≤3%), weight loss (≤3%)

Gastrointestinal: Abdominal pain (≤9%), gastrointestinal pain (≤8%), abdominal distention (3%), flatulence (3%)

Genitourinary: Breast cyst (≤10%), breast hypertrophy (≤10%), breast swelling (≤10%), breast tenderness (≤10%), mastalgia (≤10%), nipple discharge (≤10%), dysmenorrhea (≤9%), vaginal infection (7% to 8%), genital discharge (3% to 7%), vulvovaginal infection (4%)

Frequency not defined:

Cardiovascular: Hypertension, venous thromboembolism

Central nervous system: Irritability

Endocrine & metabolic: Amenorrhea, premenstrual syndrome

Genitourinary: Abnormal uterine bleeding, cervical carcinoma (in situ), cervical dysplasia

<1%, postmarketing, and/or case reports: Angioedema, anxiety, arterial thromboembolism, asthenia, back pain, breast neoplasm (benign), cerebrovascular accident, chest pain, constipation, contact lens intolerance, deep vein thrombosis, diarrhea, dizziness, dyslipidemia, dyspnea, erythema nodosum, hepatic adenoma, hepatic focal nodular hyperplasia, hepatitis, hirsutism, hot flash, hyperhidrosis, hypersensitivity reaction, insomnia, lactation insufficiency, limb pain, malignant neoplasm of breast, muscle spasm, myalgia, myocardial infarction, night sweats, ovarian cyst, palpitations, pancreatitis, paresthesia, pruritus, pulmonary embolism, retinal thrombosis, seizure, skin photosensitivity, syncope, tachycardia, urinary tract infection, urticaria, vaginal dryness, vertigo, visual impairment, vulvar dryness, xerophthalmia

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

Asunaprevir: May decrease serum concentrations of the active metabolite(s) of Norgestimate. 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

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 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

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 serum concentrations of the active metabolite(s) of Norgestimate. Management: Use a reliable barrier contraceptive if efavirenz is used in combination with norgestimate. Continue using barrier contraception for 12 weeks after discontinuation of efavirenz. 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

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

Monitoring Parameters

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 two consecutive menstrual periods are missed, assess 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.

Advanced Practitioners Physical Assessment/Monitoring

Evaluate smoking status and educate smokers on increased risks of smoking while taking this drug. Monitor blood pressure (baseline and yearly). Obtain liver function tests, glucose (diabetics), and lipid profiles (patients with hyperlipidemia). Obtain weight at baseline. Assess results of annual gynecological exam. Assess other medicines patient may be taking; alternate therapy or dosage adjustments may be needed. Assess for vision changes, signs of thromboembolism, signs of depression, and bleeding irregularities. Rule out malignancy in cases of undiagnosed vaginal bleeding.

Nursing Physical Assessment/Monitoring

Check ordered labs and report any abnormalities. Monitor blood pressure. Instruct patient to report any vision changes, signs of depression, abnormal vaginal bleeding, or signs of thromboembolism (eg, swelling in arms or legs, chest pain, weakness on one side). Educate patient on importance of frequent self-breast exams and yearly gynecological exams. Educate patients who smoke on increased risks of smoking while taking this drug.

Dosage Forms: US

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

Tablet, Oral:

Estarylla: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #2 aluminum lake, fd&c yellow #10 aluminum lake]

Femynor: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets]

Mili: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #2 aluminum lake]

Mono-Linyah: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #1 aluminum lake, fd&c blue #2 aluminum lake, fd&c red #40 aluminum lake, fd&c yellow #5 aluminum lake]

MonoNessa: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets] [contains corn starch, fd&c blue #2 aluminum lake]

Ortho Tri-Cyclen (28): Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #2 aluminum lake]

Ortho Tri-Cyclen Lo: Day 1 to 7: Ethinyl estradiol 0.025 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.025 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.025 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #2 aluminum lake]

Ortho-Cyclen (28): Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #2 aluminum lake]

Previfem: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #1 aluminum lake, fd&c blue #2 (indigotine)]

Previfem: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #2 aluminum lake, fd&c yellow #10 aluminum lake]

Sprintec 28: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets] [contains corn starch, fd&c blue #2 aluminum lake]

Tri Femynor: Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets

Tri-Estarylla: Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #2 aluminum lake, fd&c yellow #10 aluminum lake]

Tri-Linyah: Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #1 aluminum lake, fd&c blue #2 aluminum lake, fd&c red #40 aluminum lake, fd&c yellow #5 aluminum lake]

Tri-Lo-Estarylla: Day 1 to 7: Ethinyl estradiol 0.025 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.025 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.025 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [DSC] [contains brilliant blue fcf (fd&c blue #1), fd&c blue #2 aluminum lake, fd&c yellow #5 aluminum lake, fd&c yellow #6 aluminum lake, soybean lecithin]

Tri-Lo-Estarylla: Day 1 to 7: Ethinyl estradiol 0.025 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.025 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.025 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #1 aluminum lake, fd&c blue #2 aluminum lake, fd&c yellow #5 aluminum lake, fd&c yellow #6 aluminum lake]

Tri-Lo-Marzia: Day 1 to 7: Ethinyl estradiol 0.025 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.025 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.025 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #2 aluminum lake]

Tri-Lo-Sprintec: Day 1 to 7: Ethinyl estradiol 0.025 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.025 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.025 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #2 aluminum lake]

Tri-Mili: Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #2 aluminum lake]

Tri-Previfem: Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #1 aluminum lake, fd&c blue #2 (indigotine)]

Tri-Previfem: Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #2 aluminum lake, fd&c yellow #10 aluminum lake]

Tri-Sprintec: Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains corn starch, fd&c blue #2 (indigotine), fd&c red #40, fd&c yellow #6 (sunset yellow)]

Tri-VyLibra: Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #2 aluminum lake]

Tri-VyLibra Lo: Day 1 to 7: Ethinyl estradiol 0.025 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.025 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.025 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains fd&c blue #2 aluminum lake]

TriNessa (28): Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [DSC] [contains corn starch, fd&c blue #2 aluminum lake]

TriNessa Lo: Day 1 to 7: Ethinyl estradiol 0.025 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.025 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.025 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [DSC] [contains fd&c blue #2 aluminum lake]

VyLibra: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets] [contains fd&c blue #2 aluminum lake]

Generic: Day 1 to 7: Ethinyl estradiol 0.025 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.025 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.025 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets, Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets, Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets]

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Cyclen: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets] [contains FD&C BLUE #2 ALUMINUM LAKE]

Cyclen: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [21 tablets and 7 inactive tablets] [contains FD&C BLUE #2 ALUMINUM LAKE, FD&C YELLOW #10 ALUMINUM LAKE]

Tri-Cyclen: Day 1 to 7: Ethinyl estradiol 0.035 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.035 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.035 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets

Tri-Cyclen Lo: Day 1 to 7: Ethinyl estradiol 0.025 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.025 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.025 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains FD&C BLUE #2 ALUMINUM LAKE, POLYSORBATE 80]

Tricira Lo 21: Day 1 to 7: Ethinyl estradiol 0.025 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.025 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.025 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains BRILLIANT BLUE FCF (FD&C BLUE #1), FD&C BLUE #2 ALUMINUM LAKE, FD&C YELLOW #5 ALUMINUM LAKE, FD&C YELLOW #6 ALUMINUM LAKE]

Tricira Lo 28: Day 1 to 7: Ethinyl estradiol 0.025 mg and norgestimate 0.18 mg [7 tablets]; Day 8 to 14: Ethinyl estradiol 0.025 mg and norgestimate 0.215 mg [7 tablets]; Day 15 to 21: Ethinyl estradiol 0.025 mg and norgestimate 0.25 mg [7 tablets]; Day 22 to 28: 7 inactive tablets [contains BRILLIANT BLUE FCF (FD&C BLUE #1), FD&C BLUE #2 ALUMINUM LAKE, FD&C YELLOW #5 ALUMINUM LAKE, FD&C YELLOW #6 ALUMINUM LAKE, SOYBEAN LECITHIN]

Anatomic Therapeutic Chemical (ATC) Classification
  • G03AA11
  • G03AB09
Generic Available (US)

Yes

Pricing: US

Tablets (Estarylla Oral)

0.25-35 mg-mcg (per each): $1.15

Tablets (Femynor Oral)

0.25-35 mg-mcg (per each): $1.62

Tablets (Mili Oral)

0.25-35 mg-mcg (per each): $1.15

Tablets (Mono-Linyah Oral)

0.25-35 mg-mcg (per each): $1.17

Tablets (MonoNessa Oral)

0.25-35 mg-mcg (per each): $1.22

Tablets (Norgestim-Eth Estrad Triphasic Oral)

0.18/0.215/0.25 mg-25 mcg (per each): $5.75

0.18/0.215/0.25 mg-35 mcg (per each): $1.40

Tablets (Norgestimate-Eth Estradiol Oral)

0.25-35 mg-mcg (per each): $1.15 – $1.30

Tablets (Ortho Tri-Cyclen Lo Oral)

0.18/0.215/0.25 mg-25 mcg (per each): $6.40

Tablets (Previfem Oral)

0.25-35 mg-mcg (per each): $1.15

Tablets (Sprintec 28 Oral)

0.25-35 mg-mcg (per each): $1.15

Tablets (Tri Femynor Oral)

0.18/0.215/0.25 mg-35 mcg (per each): $1.62

Tablets (Tri-Estarylla Oral)

0.18/0.215/0.25 mg-35 mcg (per each): $1.40

Tablets (Tri-Linyah Oral)

0.18/0.215/0.25 mg-35 mcg (per each): $1.40

Tablets (Tri-Lo-Estarylla Oral)

0.18/0.215/0.25 mg-25 mcg (per each): $2.20

Tablets (Tri-Lo-Marzia Oral)

0.18/0.215/0.25 mg-25 mcg (per each): $5.24

Tablets (Tri-Lo-Sprintec Oral)

0.18/0.215/0.25 mg-25 mcg (per each): $5.24

Tablets (Tri-Mili Oral)

0.18/0.215/0.25 mg-35 mcg (per each): $1.40

Tablets (Tri-Previfem Oral)

0.18/0.215/0.25 mg-35 mcg (per each): $1.40

Tablets (Tri-Sprintec Oral)

0.18/0.215/0.25 mg-35 mcg (per each): $1.40

Tablets (Tri-VyLibra Lo Oral)

0.18/0.215/0.25 mg-25 mcg (per each): $4.73

Tablets (Tri-VyLibra Oral)

0.18/0.215/0.25 mg-35 mcg (per each): $1.40

Tablets (VyLibra Oral)

0.25-35 mg-mcg (per each): $1.17

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 hormonal 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.

Pharmacodynamics/Kinetics

Absorption: Ethinyl estradiol (EE) and norgestimate (NGM): Rapid and well absorbed

Protein binding:

EE: >97% to albumin

Norelgestromin (NGMN): >97% to albumin

Norgestrel (NG): >97% to sex hormone-binding globulin (SHBG); SHBG capacity is affected by plasma ethinyl estradiol levels

Metabolism:

EE: Hepatic; forms metabolites

NGM: Hepatic; forms NGMN (major active metabolite) which is further metabolized to NG (active) and other metabolites

Half-life elimination:

EE: 10-16 hours

NGMN: 18-25 hours

NG: 38-45 hours

Time to peak, plasma: EE and NGM: ~2 hours

Excretion:

EE: Urine and feces

NGM: Urine (~47%) and feces (~37%) as metabolites

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

Ethinyl Estradiol and NGM; Norgestimate and Ethinyl Estradiol; Ortho Cyclen; Ortho Tri Cyclen

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

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.[PubMed 15105794]

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]

Cyclen (ethinyl estradiol and norgestimate) [product monograph]. Toronto, Ontario: Janssen Inc; March 2017.

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]

Estarylla (norgestimate and ethinyl estradiol) [prescribing information]. Princeton, NJ: Sandoz Inc; May 2015.

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):1931-1943. doi:10.1158/1055-9965.EPI-13-0298.[PubMed 24014598]

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

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]

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]

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]

Mono-Linyah (ethinyl estradiol and norgestimate) [prescribing information]. Memphis, TN: Northstart Rx LLC; May 2014.

MonoNessa (ethinyl estradiol and norgestimate) [prescribing information]. Corona, CA: Watson Laboratories Inc; November 2013.

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

Ortho Tri-Cyclen Lo (ethinyl estradiol and norgestimate) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; August 2017.

Ortho-Cyclen and Ortho Tri-Cyclen (ethinyl estradiol and norgestimate) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; February 2016.

Ott MA, Sucato GS; Committee on Adolescence. Contraception for adolescents. Pediatrics. 2014;134(4):e1257-e1281. 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]

Previfem (ethinyl estradiol and norgestimate) [prescribing information]. Huntsville, AL: Qualitest Pharmaceuticals; July 2015.

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

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

Sprintec (ethinyl estradiol and norgestimate) [prescribing information]. North Wales, PA: Teva Pharmaceuticals USA, Inc; May 2015.

Tri-Cyclen (ethinyl estradiol and norgestimate) [product monograph]. Toronto, Ontario: Janssen Inc; June 2018.

Tri-Cyclen Lo (ethinyl estradiol and norgestimate) [product monograph]. Toronto, Ontario: Janssen Inc; June 2018.

Tri-Linyah (ethinyl estradiol and norgestimate) [prescribing information]. Memphis, TN: Northstar RX LLS; May 2014.

Tri-Lo-Estarylla (ethinyl estradiol and norgestimate) [prescribing information]. Princeton, NJ: Sandoz Inc; August 2015.

Tri-Previfem (ethinyl estradiol and norgestimate) [prescribing information]. Huntsville, AL: Qualitest Pharmaceuticals; July 2015.

Tri-Sprintec (ethinyl estradiol and norgestimate) [prescribing information]. North Wales, PA: Teva Pharmaceuticals USA, Inc; September 2016.

Tricira Lo (ethinyl estradiol and norgestimate) [product monograph]. Toronto, Ontario: Apotex Inc; January 2015.

Tri-Estarylla (ethinyl estradiol and norgestimate) [prescribing information]. Princeton, NJ: Sandoz Inc; May 2015.

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]

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

Zuraw BL, Bernstein JA, Lang DM, et alD; 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

Cilest (AE, AR, BE, BG, BH, CH, CO, CR, CY, CZ, DE, DK, DO, EE, EG, FI, FR, GB, GT, HN, HR, IE, IT, LT, LV, MT, MX, NI, NL, PA, PE, PL, PY, QA, RO, RU, SA, SE, SI, SK, SV, TH, TR, UY); Cileste (AT); Cilique (IE); Edelsin (ES); Lizinna (GB); Mactex (PY); Ortrel (VE); Triafemi (FR); Tricilest (FR, TH)

Ethinyl Estradiol and Norgestimate (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 JES ti mate)

Brand Names: US

Estarylla; Femynor; Mili; Mono-Linyah; MonoNessa; Ortho Tri-Cyclen (28); Ortho Tri-Cyclen Lo; Ortho-Cyclen (28); Previfem; Sprintec 28; Tri Femynor; Tri-Estarylla; Tri-Linyah; Tri-Lo-Estarylla; Tri-Lo-Marzia; Tri-Lo-Sprintec; Tri-Mili; Tri-Previfem; Tri-Sprintec; Tri-VyLibra; Tri-VyLibra Lo; TriNessa (28) [DSC]; TriNessa Lo [DSC]; VyLibra

Brand Names: Canada

Cyclen; Tri-Cyclen ; Tri-Cyclen Lo; Tricira Lo

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. Do not use this drug if you smoke and are older than 35 years of age.
What is this drug used for?
  • It is used to prevent pregnancy.
  • 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?
  • If you have an allergy to ethinyl estradiol, norgestimate, 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 turned yellow during pregnancy or with estrogen-based or hormone contraceptive use.
  • 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).
  • 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?
  • 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.
  • 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.
  • This drug may cause high cholesterol and triglyceride levels. 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 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.
  • 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.
  • Do not use in children who have not had their first menstrual period.
  • If you have any signs of pregnancy or if you have a positive pregnancy test, call your doctor right away.
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).
  • Mood changes.
  • 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:
  • Weight gain.
  • Headache.
  • Upset stomach or throwing up.
  • Gas.
  • Feeling nervous and excitable.
  • Belly pain.
  • Feeling tired or weak.
  • Enlarged breasts.
  • Tender breasts.
  • Period (menstrual) changes. These include spotting or bleeding between cycles.
  • 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.
  • 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.
  • 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.
  • If you also take colesevelam, take it at least 4 hours after you take this drug.
  • 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.
What do I do if I miss 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.
  • Protect from light.
  • Store in a dry place. Do not store in a bathroom.
  • 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 Norgestimate (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 JES ti mate)

Brand Names: US

Estarylla; Femynor; Mili; Mono-Linyah; MonoNessa; Ortho Tri-Cyclen (28); Ortho Tri-Cyclen Lo; Ortho-Cyclen (28); Previfem; Sprintec 28; Tri Femynor; Tri-Estarylla; Tri-Linyah; Tri-Lo-Estarylla; Tri-Lo-Marzia; Tri-Lo-Sprintec; Tri-Mili; Tri-Previfem; Tri-Sprintec; Tri-VyLibra; Tri-VyLibra Lo; TriNessa (28) [DSC]; TriNessa Lo [DSC]; VyLibra

Brand Names: Canada

Cyclen; Tri-Cyclen ; Tri-Cyclen Lo; Tricira Lo

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.
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 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.
  • 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.
  • This drug may cause high cholesterol and triglyceride levels. 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 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.
  • Do not use in children who have not had their first menstrual period.
  • 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).
  • Mood changes.
  • 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:
  • Weight gain.
  • Headache.
  • Gas.
  • Feeling nervous and excitable.
  • Belly pain.
  • Feeling tired or weak.
  • Period (menstrual) changes. These include spotting or bleeding between cycles.
  • Enlarged breasts.
  • Tender breasts.
  • 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.
  • 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 this drug with or without food. Give with food if it causes an upset stomach.
  • If your child also takes colesevelam, give it at least 4 hours before or after your child takes this drug.
  • 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.
  • Protect from light.
  • Store in a dry place. Do not store in a bathroom.
  • 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.