receptor binding competition. Use Caution/Monitor.ropiniroleMonitor Closely (2)ethinylestradiol will increase the level or effect of ropinirole by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. ethinylestradiol increases levels of ropinirole by unspecified interaction mechanism. Use Caution/Monitor.rosuvastatinMinor (1)rosuvastatin increases levels of ethinylestradiol by unspecified interaction mechanism. Minor/Significance Unknown.rucaparibMonitor Closely (1)rucaparib will increase the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.rufinamideMonitor Closely (1)rufinamide decreases effects of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Rufinamide is a weak inducer of the CYP 3A4 enzyme and can decrease exposure of drugs that are substrates of CYP3A4. .ruxolitinibMinor (1)ethinylestradiol will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.ruxolitinib topicalMinor (1)ethinylestradiol will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.saquinavirSerious - Use Alternative (2)saquinavir will increase the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. saquinavir, ethinylestradiol. Other (see comment). Avoid or Use Alternate Drug. Comment: Significant changes (increase or decrease) can occur in estrogen plasma levels. Efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended. .secobarbitalSerious - Use Alternative (1)secobarbital will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.selegilineMonitor Closely (1)ethinylestradiol increases levels of selegiline by Other (see comment). Use Caution/Monitor. Comment: Oral contraceptives inhibit the N demethylatin of selegiline.selegiline transdermalMonitor Closely (1)ethinylestradiol increases levels of selegiline transdermal by Other (see comment). Use Caution/Monitor. Comment: Oral contraceptives inhibit the N demethylatin of selegiline.siltuximabMonitor Closely (2)siltuximab, norgestimate. Other (see comment). Use Caution/Monitor. Comment: CYP450 activity in the liver is down regulated by infection and inflammation stimuli including cytokines (eg, IL-6); inhibition of IL-6 by siltuximab may restore CYP450 enzymatic activity; caution if coadministered with CYP substrates that have a narrow therapeutic index. siltuximab, ethinylestradiol. Other (see comment). Use Caution/Monitor. Comment: CYP450 activity in the liver is down regulated by infection and inflammation stimuli including cytokines (eg, IL-6); inhibition of IL-6 by siltuximab may restore CYP450 enzymatic activity; caution if coadministered with CYP substrates that have a narrow therapeutic index.somapacitanMonitor Closely (1)ethinylestradiol will decrease the level or effect of somapacitan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Oral estrogens may reduce serum insulin-like growth factor I (IGF-1) response to growth hormone (GH) analogs. Higher GH dose may be requiredsomatrogonMonitor Closely (1)ethinylestradiol will decrease the level or effect of somatrogon by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Oral estrogens may reduce serum insulin-like growth factor I (IGF-1) response to growth hormone (GH) analogs. Higher GH dose may be requiredsomatropinMonitor Closely (1)ethinylestradiol will decrease the level or effect of somatropin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Oral estrogens may reduce serum insulin-like growth factor I (IGF-1) response to growth hormone (GH) analogs. Higher GH dose may be requiredSt John's WortSerious - Use Alternative (1)St John's Wort will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.stiripentolMonitor Closely (1)stiripentol, ethinylestradiol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.sugammadex sodiumSerious - Use Alternative (1)sugammadex sodium decreases effects of ethinylestradiol by receptor binding competition. Avoid or Use Alternate Drug. In vitro binding studies showed that sugammadex may bind to progestogen, thereby decreasing progestogen exposure. Therefore, a sugammadex bolus dose is considered to be equivalent to missing dose(s) of hormonal contraceptives containing an estrogen or progestogen. If an oral contraceptive is taken on the same day of sugammadex, or the patient has a transdermal or implant hormonal contraceptive, the patient must use an additional, nonhormonal contraceptive method or back-up method of contraception (eg, condoms and spermicides) for the next 7 days.sulfadiazineMonitor Closely (1)sulfadiazine will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.sulfamethoxazoleMonitor Closely (1)sulfamethoxazole will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.sulfisoxazoleMonitor Closely (1)sulfisoxazole will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.tacrolimusMonitor Closely (1)ethinylestradiol will increase the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tazemetostatMonitor Closely (2)tazemetostat will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. ethinylestradiol will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tecovirimatMonitor Closely (1)tecovirimat will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.teriflunomideMonitor Closely (1)teriflunomide increases levels of ethinylestradiol by unknown mechanism. Use Caution/Monitor.tetracyclineMonitor Closely (1)tetracycline will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.theophyllineMonitor Closely (1)ethinylestradiol will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.ticarcillinMonitor Closely (1)ticarcillin will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.tigecyclineMonitor Closely (1)tigecycline will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.tinidazoleMonitor Closely (1)ethinylestradiol will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tipranavirSerious - Use Alternative (1)tipranavir, ethinylestradiol. Other (see comment). Avoid or Use Alternate Drug. Comment: Significant changes (increase or decrease) can occur in estrogen plasma levels. Efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended. .tizanidineMonitor Closely (1)ethinylestradiol will increase the level or effect of tizanidine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Monitor for tizanidine adverse effects (eg, hypotension or bradycardia)Minor (1)ethinylestradiol increases levels of tizanidine by unspecified interaction mechanism. Minor/Significance Unknown.tolterodineMonitor Closely (1)ethinylestradiol will increase the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.topiramateSerious - Use Alternative (1)topiramate will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.tranexamic acid oralContraindicated (1)tranexamic acid oral, ethinylestradiol. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Coadministration of tranexamic acid oral and combination hormonal contraceptives increases thrombotic risk.trazodoneMinor (1)ethinylestradiol, trazodone. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Oxidative metabolism of TCAs may be decreased by ethinyl estradiol. Increased antidepressant serum concentrations may occur. Potential for increased TCA adverse effects.triazolamMonitor Closely (1)ethinylestradiol will increase the level or effect of triazolam by Mechanism: decreasing metabolism. Use Caution/Monitor. Ethinyl estradiol may inhibit the clearance of benzodiazepines that undergo oxidation, thereby increasing serum concentrations of concomitantly administered benzodiazepines.trimethoprimMonitor Closely (1)trimethoprim will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.trimipramineMinor (1)ethinylestradiol, trimipramine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Oxidative metabolism of TCAs may be decreased by ethinyl estradiol. Increased antidepressant serum concentrations may occur. Potential for increased TCA adverse effects.tucatinibSerious - Use Alternative (1)tucatinib will increase the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.ursodiolMonitor Closely (1)ethinylestradiol decreases effects of ursodiol by pharmacodynamic antagonism. Use Caution/Monitor.valoctocogene roxaparvovecMonitor Closely (1)ethinylestradiol and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.valproic acidMonitor Closely (1)ethinylestradiol will decrease the level or effect of valproic acid by increasing elimination. Modify Therapy/Monitor Closely. May lead to increased seizure frequencyvoriconazoleMonitor Closely (1)voriconazole will increase the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.voxelotorSerious - Use Alternative (1)voxelotor will increase the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.warfarinMonitor Closely (1)norgestimate increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor. Frequency Not Defined Amenorrhea Anorexia Aterial thromboembolism Cerebral hemorrhage Crebral thrombosis Retinal thrombosis Breakthrough bleeding Change in menstrual flow Gallbladder disease Edema Spotting Weakness Abdominal pain Breast tenderness Cholestatic jaundice Deep vein thrombosis (DVT) Depression Dizziness Galactorrhea Headache Nausea Nervousness Somnolence Thrombophlebitis Varicose vein aggravation Vomiting Weight change Postmarketing Reports Immune system disorders: Anaphylactic reaction, hypersensitivity Black Box Warnings Cigarette smoking and risk of cardiovascular disease Cigarette smoking increases risk of serious cardiovascular adverse effects from use of combination hormonal contraceptives Risk increases with age (>35 years) and with heavy smoking (≥15 cigarettes/day) Women who use hormonal oral contraceptives are advised not to smoke Contraindications Documented hypersensitivity Active or history of breast cancer Arterial thromboembolic disease (stroke, myocardial infarction [MI]), thrombophlebitis, DVT/pulmonary embolism (PE), thrombogenic valvular disease Estrogen-dependent neoplasia Liver disease, liver tumors Undiagnosed abnormal uterine bleeding Uncontrolled hypertension (ie, persistent BP values >160 mm Hg systolic or >100 mg Hg diastolic) Diabetes mellitus with vascular involvement Jaundice with previous oral contraceptive use Receiving hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir Women > 35 years who smoke Cerebrovascular and/or coronary artery disease, disease, headaches with focal neurological symptoms, migraine headaches with auro or migraine headaches if >35 years of age Cautions Use caution in family history of breast cancer and or DVT/PE, current or previous depression, endometriosis, diabetes mellitus, hypertension, bone mineral density changes, renal or hepatic impairment, bone metabolic disease, systemic lupus erythematosus (SLE), conditions exacerbated by fluid retention (eg, migraine, asthma, epilepsy) Monitor prediabetic and diabetic women on therapy; consider alternate contraceptive method for women with uncontrolled dyslipidemia Headache: Evaluate significant change in headaches and discontinue therapy if indicated Women with a history of hypertension or hypertension-related diseases, or renal disease should be encouraged to use another method of contraception Discontinue if any of the following develop: Jaundice, visual problems (may cause contact lens intolerance), signs of venous thromboembolism, migraine with unusual severity, significant blood pressure increase, severe depression, increased risk of thromboembolic complications after surgery Discontinue 4 weeks before major surgery or prolonged immobilization Patients on warfarin or oral anticoagulants: Increase in anticoagulant dosage may be warranted Some studies link oral contraceptive use with increased risk of breast cancer, whereas others do not; risk depends on conditions where naturally high hormone levels persist for long periods, including early-onset menstruation (age <12 years), late-onset menopause (age >55 years), first child after age 30 years, nulliparity Increased risk of cervical cancer with oral contraceptive use, however, human papillomavirus (HPV) remains primary risk factor for this cancer Long-term (≥5years) use of oral contraceptives may be associated with increased risk Increased risk of liver cancer with oral contraceptive use; risk increases with duration of use Discontinue hormonal therapy prior to starting therapy with combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir; may restart approximately 2 weeks following completion of treatment with combination drug regimen Chloasma associated with combination hormonal contraceptives, as well as pregnancy and sun exposure; avoid sun exposure or ultraviolet radiation during therapy Risk of cholestasis increased with prior history of cholestasis with prior contraceptive use or previous cholestasis of pregnancy Combination hormonal contraceptives may adversely affect lipid levels; consider alternative contraception for women with uncontrolled dyslipidemia Retinal vascular thrombosis reported in patients receiving estrogens; discontinue medication pending examination if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine; if examination reveals papilledema or retinal vascular lesions, estrogens should be discontinued Breakthrough