reliability.salicylic acid acneMonitor Closely (1)levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of salicylic acid acne by unknown mechanism. Use Caution/Monitor.saquinavirSerious - Use Alternative (1)saquinavir, levonorgestrel oral/ethinylestradiol/ferrous bisglycinate. 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.secobarbitalMonitor Closely (1)secobarbital will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. The efficacy of hormonal contraceptives may be reduced. Use an alternative method of contraception or a backup method when enzyme inducers are used with combined hormonal contraceptives (CHCs), and continue backup contraception for 28 days after discontinuing enzyme inducer to ensure contraceptive reliability.somapacitanMonitor Closely (1)levonorgestrel oral/ethinylestradiol/ferrous bisglycinate 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)levonorgestrel oral/ethinylestradiol/ferrous bisglycinate 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)levonorgestrel oral/ethinylestradiol/ferrous bisglycinate 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 WortMonitor Closely (1)St John's Wort will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. The efficacy of hormonal contraceptives may be reduced. Use an alternative method of contraception or a backup method when enzyme inducers are used with combined hormonal contraceptives (CHCs), and continue backup contraception for 28 days after discontinuing enzyme inducer to ensure contraceptive reliability.sulfadiazineMonitor Closely (1)sulfadiazine will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.sulfamethoxazoleMonitor Closely (1)sulfamethoxazole will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.sulfisoxazoleMonitor Closely (1)sulfisoxazole will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.temazepamMonitor Closely (1)levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of temazepam by unknown mechanism. Use Caution/Monitor.tetracyclineMonitor Closely (1)tetracycline will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.theophyllineMonitor Closely (1)levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will increase the level or effect of theophylline by decreasing metabolism. Use Caution/Monitor. Combined oral contraceptives containing EE may inhibit the metabolism and increase plasma concentrations of cyclosporine.thyroid desiccatedMonitor Closely (1)levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of thyroid desiccated by unknown mechanism. Modify Therapy/Monitor Closely. The estrogen component of combined hormonal contraceptives (CHCs) may raise the serum concentrations of thyroxine-binding globulin. Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone with use of CHCs.ticarcillinMonitor Closely (1)ticarcillin will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.tigecyclineMonitor Closely (1)tigecycline will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.tipranavirSerious - Use Alternative (1)tipranavir, levonorgestrel oral/ethinylestradiol/ferrous bisglycinate. 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)levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will increase the level or effect of tizanidine by decreasing metabolism. Use Caution/Monitor. Combined oral contraceptives containing EE may inhibit the metabolism and increase plasma concentrations of cyclosporine.topiramateMonitor Closely (1)topiramate will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. The efficacy of hormonal contraceptives may be reduced. Use an alternative method of contraception or a backup method when enzyme inducers are used with combined hormonal contraceptives (CHCs), and continue backup contraception for 28 days after discontinuing enzyme inducer to ensure contraceptive reliability.triazolamMonitor Closely (1)levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will increase the level or effect of triazolam by 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 levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.valoctocogene roxaparvovecMonitor Closely (1)levonorgestrel oral/ethinylestradiol/ferrous bisglycinate 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.voriconazoleMonitor Closely (2)levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will increase the level or effect of voriconazole by decreasing metabolism. Use Caution/Monitor. Combined oral contraceptives containing EE may inhibit the metabolism and increase plasma concentrations of cyclosporine. voriconazole will increase the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase the plasma hormone concentrations. Use of a nonhormonal contraceptive is recommended.warfarinMonitor Closely (1)levonorgestrel oral/ethinylestradiol/ferrous bisglycinate increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor. >10% Headache (14%) 1-10% Metrorrhagia (8%) Dysmenorrhea (7%) Nausea (7%) Abdominal pain (4%) Breast pain (4%) Emotional lability (3%) Acne (3%) Depression (2%) Amenorrhea (2%) Vaginal moniliasis (2%) <1% Hypertension Hypercholesterolemia Weight gain Dysmenorrhea Flatulence Postmarketing Reports Cardiac disorder: Chest pain, dyspnea, palpitations Gastrointestinal disorders: Abdominal pain, nausea, vomiting, diarrhea General disorders and administration site conditions: Chest pain, fatigue, pain, malaise, injection site pain or erythema, feeling abnormal, pyrexia, condition aggravated, asthenia Immune system disorders: Hypersensitivity reactions, including pruritus, rash, urticaria, erythema Injury, poisoning, and procedural complications: Injury Investigations: Decreased weight Musculoskeletal and connective-tissue disorders: Pain in extremity, arthralgia, back pain, muscle spasm Nervous system disorders: Headache, migraine, dizziness, hypoesthesia, paresthesia Psychiatric disorders: Depression, insomnia, anxiety Reproductive system and breast disorders: Metrorrhagia, menorrhagia, hot flush, vaginal hemorrhage Respiratory, thoracic, and mediastinal disorders: Nasopharyngitis, cough Sleep disorders and disturbances: Somnolence Vascular disorders: Deep vein thrombosis, pulmonary embolism Black Box Warnings Cigarette smoking & risk of cardiovascular disease Cigarette smoking increases risk of serious cardiovascular adverse effects from combination hormonal contraceptive use This risk increases with age (>35 years) and with heavy smoking (15 or more cigarettes/day) For this reason, combined hormonal contraceptives (CHCs) are contraindicated in women aged >35 years who smoke Contraindications Liver tumors, benign or malignant, or liver disease (acute viral hepatitis or severe, decompensated, cirrhosis of the liver) Undiagnosed abnormal uterine bleeding Pregnancy (no reason to use CHCs during pregnancy) History or current breast cancer or other estrogen- or progestin-sensitive cancer Hypersensitivity Coadministration with ombitasvir/paritaprevir/ritonavir, with or without dasabuvir High risk of arterial or venous thrombotic disease Smoking, if older than 35 years (see Black Box Warnings) History or current deep vein thrombosis or pulmonary embolism Inherited or acquired hypercoagulopathies Cerebrovascular disease Coronary artery disease Thrombogenic valvular or thrombogenic rhythm diseases of the heart (eg, subacute bacterial endocarditis with valvular disease, atrial fibrillation) Uncontrolled hypertension Diabetes mellitus with vascular disease Headaches with focal neurological symptoms or have migraine headaches with aura Women over age 35 with any migraine headaches Cautions Risk of postpartum VTE decreases after third postpartum week, whereas risk of ovulation increases after third postpartum week; start contraceptive therapy no earlier than 4 weeks after delivery, in women who are not breastfeeding Acute or chronic disturbances of liver function may necessitate the discontinuation of CHCs use until liver function resolves to normal and CHC causation has been excluded Hepatic adenomas are associated with CHCs use; studies have shown an increased risk of developing hepatocellular carcinoma in long-term (>8 years) combined oral contraceptive (COC) users (see Contraindications) Studies suggest a small increased relative risk of developing gallbladder disease among CHC users; use of CHCs may worsen existing gallbladder disease; past history of CHC-related cholestasis predicts an increased risk with subsequent CHC use; women with a history of pregnancy-related cholestasis may be at an increased risk for CHC-related cholestasis CHCs may decrease glucose tolerance; carefully monitor in prediabetes and diabetes Consider alternative contraception for women with uncontrolled dyslipidemia Small proportion of women will have adverse lipid changes while on CHCs; women with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using CHCs If new headaches that are recurrent, persistent, or severe develop in women taking the drug, evaluate the cause and discontinue therapy if indicated (see Contraindications) This product contains FD&C yellow no. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons Carefully observe women with a history of depression, and discontinue therapy if depression recurs to a serious degree 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 light Bleeding irregularities and amenorrhea Unscheduled (breakthrough or intracyclic) bleeding and spotting may occur, especially during the first 3 months of use; if bleeding persists or occurs after previously regular cycles, check for causes such as pregnancy or malignancy; if pathology and pregnancy are excluded, bleeding irregularities may resolve over time or with a change to a different contraceptive product If scheduled (withdrawal) bleeding does not occur, consider possibility of pregnancy; if patient has not adhered to prescribed dosing schedule (missed one or more active tablets or started taking them on a day later than she should have), consider possibility of pregnancy at time of first missed period and take appropriate diagnostic measures; if patient has adhered to prescribed regimen and misses two consecutive periods, rule out pregnancy In clinical trial, 2.6% of the evaluable cycles were amenorrheic; women may experience amenorrhea or oligomenorrhea after discontinuation of CHCs, especially when such a condition was preexistent Thrombotic disorders and other vascular problems Use of CHCs also increases the risk of arterial thromboses such as strokes and myocardial infarctions, especially in women with other risk factors for these events CHCs have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes) If feasible, discontinue CHC 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 the following prolonged immobilization An increase in blood pressure has been reported in women taking CHCs, and this increase is more likely in older women with extended duration of use (see Contraindications); incidence of hypertension increases with increasing concentrations of progestin; monitor blood pressure periodically; stop therapy in women with well-controlled hypertension if blood pressure rises significantly Drug interactions overview During clinical trials with the hepatitis C combination drug regimen containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, incidences of elevated ALT >5x ULN, including some cases >20x ULN, were significantly more frequent in women using ethinyl estradiol (EE)-containing medications, such as CHCs (see Contraindications) Drugs or herbal products that induce certain enzymes, including CYP3A4, may decrease plasma concentrations of CHCs and potentially diminish the effectiveness of CHCs or increase breakthrough bleeding Coadministration of atorvastatin or rosuvastatin and certain CHCs containing EE increase AUC values for EE by approximately 20-25% Ascorbic acid and acetaminophen may increase plasma EE concentrations, possibly by inhibition of conjugation CYP3A4 inhibitors (eg, itraconazole, voriconazole, fluconazole, grapefruit juice, ketoconazole) may increase plasma hormone concentrations Significant changes (increase or decrease) in the plasma concentrations of estrogen and/or progestin have been noted in some cases of coadministration with HIV/HCV protease inhibitors and nonnucleoside reverse-transcriptase inhibitors CHCs containing EE may inhibit the metabolism of other compounds