mechanism. Use Caution/Monitor. teriflunomide increases levels of ethinylestradiol by unknown mechanism. Use Caution/Monitor.tesamorelinMonitor Closely (1)tesamorelin will decrease the level or effect of levonorgestrel oral by altering metabolism. Use Caution/Monitor. Use alternative contraceptiontetracyclineMonitor 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.topiramateMonitor Closely (1)topiramate decreases levels of levonorgestrel oral by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - 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 (2)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. tucatinib will increase the level or effect of levonorgestrel oral 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 (2)levonorgestrel oral 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. 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 (2)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. voxelotor will increase the level or effect of levonorgestrel oral 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. Frequency Not Defined Amenorrhea Arterial thromboembolism Benign or malignant neoplasm of liver Bloating Breakthrough bleeding Breast changes (enlargement, tenderness, secretion) Cerebral hemorrhage Cerebral thrombosis Disorder of gallbladder Disorder of menstruation Headache Hypertension Mood swings Myocardial infarction Nausea and vomiting Pulmonary embolism (PE) Scanty vaginal bleeding Stomach cramps Thrombophlebitis Weight change (increased or decreased) Postmarketing Reports Pancreatitis Cholestatic jaundice Retinal vein thrombosis Hirsutism Erythema multiforme Erythema nodosum Hemorrhagic eruption Melasma/chloasma Migraine Urticaria Angioedema Respiratory Circulatory symptoms Black Box Warnings Cigarette smoking & risk of cardiovascular disease Cigarette smoking increases risk of serious cardiovascular adverse effects from combination hormonal contraceptive use Risk increases with age (>35 years) and with heavy smoking (≥15 cigarettes/day) Advise women who use hormonal oral contraceptives not to smoke Not for the treatment of patients who use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations Contraindications Documented hypersensitivity Breast cancer or other estrogen- or progestin-sensitive cancer, now or in the past Arterial thromboembolic disease (stroke, myocardial infarction [MI]), thrombophlebitis, deep vein thrombosis or pulmonary embolism (DVT)/PE, thrombogenic valvular disease Estrogen-dependent neoplasia Liver tumors, benign or malignant, or liver disease Undiagnosed abnormal vaginal bleeding Undiagnosed abnormal uterine bleeding Uncontrolled hypertension or hypertension with vascular disease Diabetes mellitus and over age 35, diabetes mellitus with hypertension or vascular disease or other end-organ damage, or diabetes mellitus of >20 years duration Inherited or acquired hypercoagulopathies, smokers aged >35 years (Natazia) Renal insufficiency, hepatic dysfunction, adrenal insufficiency Headaches with focal neurological symptoms or have migraine headaches with aura Women >35 with any migraine headaches Smoking >15 cigarettes/day at age >35 years Major surgery with prolonged immobilization Cerebrovascular or coronary artery disease (current or past history) Thrombogenic rhythm disorders Hereditary or acquired thrombophilias Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia Undiagnosed abnormal vagina/uterine bleeding Cholestatic jaundice of pregnancy or jaundice with prior pill use Receiving Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir Acute viral hepatitis, or severe (decompensated) cirrhosis Cautions Before starting therapy evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy; therapy is contraindicated in females with a high risk of arterial or venous thrombotic/thromboembolic diseases Use caution in patients with family history of breast cancer, DVT/PE, or both; 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) Risk of VTE is highest during first year of use of a COCs and when restarting oral contraception after a break of 4 weeks or longer; risk of thromboembolic disease due to COCs gradually disappears after COC use is discontinued; use of COCs increases risk of arterial thromboses that result in strokes and myocardial infarctions, especially in women with other risk factors for these events; COCs have been shown to increase both relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes); risk increases with age, particularly in women over 35 years of age who smoke Consider presence of underlying risk factors that may increase risk of cardiovascular disease or VTE, particularly before initiating therapy for women over 35 years, such as hypertension, diabetes, dyslipidemia, obesity Discontinue therapy if an arterial thrombotic event or venous thromboembolic (VTE) event occurs; if feasible, stop therapy at least 4 weeks before and through 2 weeks after major surgery or other surgeries known to have an elevated risk of VTE as well as during and following prolonged immobilization; initiate therapy no earlier than 4 weeks after delivery in women who are not breastfeeding; risk of postpartum VTE decreases after third postpartum week, whereas risk of ovulation increases after third postpartum week Discontinue if the following develop: Jaundice, visual problems (may cause contact lens intolerance), any signs of VTE, 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 Discontinue drug prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir; therapy can be restarted approximately 2 weeks following completion of treatment with the hepatitis C combination drug regimen Use of warfarin or other oral anticoagulants (increase in anticoagulant dose may be warranted) Estrogen component of COCs may raise serum concentrations of thyroxine-binding globulin, sex hormone- binding globulin, and cortisol-binding globulin; dose of replacement thyroid hormone or cortisol therapy may need to be increased Increased risk of cervical cancer with oral contraceptive use, however, human papillomavirus (HPV) remains primary risk factor for this cancer 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 Long-term (≥5 years) 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 CDC guidelines recommend waiting ≥3 weeks after vaginal birth or ≥6 weeks after cesarean section to decrease risk of VTE before initiating combined hormonal contraceptives; women with additional risk factors for VTE (besides postpartum status) should not use combined hormonal contraceptives Scheduled withdrawal bleeding does not occur with therapy; the absence of withdrawal bleeding cannot be used as a sign of an unexpected pregnancy and as such, unexpected pregnancy may be difficult to recognize; if pregnancy suspected, a pregnancy test should be performed Benign hepatic adenomas are associated with oral contraceptive use; rupture of rare, benign, hepatic adenomas may cause death through intraabdominal hemorrhage Retinal thrombosis associated with use of oral contraceptives that may lead to partial or complete loss of vision reported; oral contraceptives should be discontinued if there is unexplained partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or retinal vascular lesions; appropriate diagnostic and therapeutic measures should be undertaken immediately Increased risk of myocardial infarction attributed to oral contraceptive use; risk is primarily in smokers or women with other underlying risk factors for coronary-artery disease such as hypertension, hypercholesterolemia, morbid obesity, and diabetes An increased risk of venous thromboembolic and thrombotic disease associated with use of oral contraceptives is well established; the excess risk is highest during the first year a woman ever uses a combined oral contraceptive In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation while receiving therapy Oral contraceptives have been shown to increase both relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes), although, in general, risk is greatest among older (>35 years), hypertensive women who also smoke Not for use in women with liver disease, such as acute viral hepatitis or severe (decompensated) cirrhosis of liver; acute or chronic disturbances of liver function may necessitate discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded; discontinue therapy if jaundice develops Certain conditions, such as smoking and migraine headache without aura, that do not contraindicate COC use in younger females, are contraindications to use in women over 35 years of age; women with migraine (particularly migraine/ headaches with focal neurological symptoms such as aura) who take combination oral contraceptives may be at increased risk of stroke A positive association has been observed between the