Levonorgestrel and ethinyl estradiol interactions

Estrogen Estrogen-containing therapies should not be used with ARIMIDEX as they may diminish its pharmacological action. (Anastrozole label, Drug interactions)

…neurological symptoms, migraine headaches with aura, or over age 35 with any migraine headaches [see Warnings and Precautions (5.7) ] Current or history of breast cancer or other estrogen- or progestin-sensitive cancer Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis [see Warnings and Precautions (5.2) ] Undiagnosed abnormal uterine bleeding… (Levonorgestrel and ethinyl estradiol label, Contraindications)

…symptoms, migraine headaches with aura, or over age 35 with any migraine headaches [see Warnings and Precautions (5.7) ] Current or history of breast cancer or other estrogen- or progestin-sensitive cancer Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis [see Warnings and Precautions (5.2) ] Undiagnosed abnormal uterine bleeding [see… (Levonorgestrel and ethinyl estradiol label, Contraindications)

…neurological symptoms, migraine headaches with aura, or over age 35 with any migraine headaches [see Warnings and Precautions (5.7) ] Current or history of breast cancer or other estrogen- or progestin-sensitive cancer Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis [see Warnings and Precautions (5.2) ] Undiagnosed abnormal uterine bleeding… (Levonorgestrel and ethinyl estradiol label, Contraindications)

Women taking estrogen-containing oral contraceptives may be at increased risk of becoming pregnant while on griseofulvin (see also PRECAUTIONS, Drug Interactions ) . (Griseofulvin label, Contraindications)

…symptoms, migraine headaches with aura, or over age 35 with any migraine headaches [see Warnings and Precautions (5.7) ] Current or history of breast cancer or other estrogen- or progestin-sensitive cancer Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis [see Warnings and Precautions (5.2) ] Undiagnosed abnormal uterine bleeding [see… (Levonorgestrel and ethinyl estradiol label, Contraindications)

…symptoms, migraine headaches with aura, or over age 35 with any migraine headaches [see Warnings and Precautions (5.7) ] Current or history of breast cancer or other estrogen- or progestin-sensitive cancer Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis [see Warnings and Precautions (5.2) ] Undiagnosed abnormal uterine bleeding [see… (Levonorgestrel and ethinyl estradiol label, Contraindications)

…symptoms, migraine headaches with aura, or over age 35 with any migraine headaches [see Warnings and Precautions (5.7) ] Current or history of breast cancer or other estrogen- or progestin-sensitive cancer Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis [see Warnings and Precautions (5.2) ] Undiagnosed abnormal uterine bleeding [see… (Levonorgestrel and ethinyl estradiol label, Contraindications)

• is capable of complying with effective contraceptive measures. (Misoprostol label, Boxed warning)

…cirrhosis [see Warnings and Precautions (5.2) ] Undiagnosed abnormal uterine bleeding [see Warnings and Precautions (5.8) ] Use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations [see Warnings and Precautions (5.14) ] High risk of arterial or venous thrombotic diseases. (Levonorgestrel and ethinyl estradiol label, Contraindications)

…symptoms, migraine headaches with aura, or over age 35 with any migraine headaches [see Warnings and Precautions (5.7) ] Current or history of breast cancer or other estrogen- or progestin-sensitive cancer Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis [see Warnings and Precautions (5.2) ] Undiagnosed abnormal uterine bleeding [see… (Levonorgestrel and ethinyl estradiol label, Contraindications)

…symptoms, migraine headaches with aura, or over age 35 with any migraine headaches [see Warnings and Precautions (5.7) ] Current or history of breast cancer or other estrogen- or progestin-sensitive cancer Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis [see Warnings and Precautions (5.2) ] Undiagnosed abnormal uterine bleeding [see… (Levonorgestrel and ethinyl estradiol label, Contraindications)

…symptoms, migraine headaches with aura, or over age 35 with any migraine headaches [see Warnings and Precautions (5.7) ] Current or history of breast cancer or other estrogen- or progestin-sensitive cancer Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis [see Warnings and Precautions (5.2) ] Undiagnosed abnormal uterine bleeding [see… (Levonorgestrel and ethinyl estradiol label, Contraindications)

…symptoms, migraine headaches with aura, or over age 35 with any migraine headaches [see Warnings and Precautions (5.7) ] Current or history of breast cancer or other estrogen- or progestin-sensitive cancer Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis [see Warnings and Precautions (5.2) ] Undiagnosed abnormal uterine bleeding [see… (Levonorgestrel and ethinyl estradiol label, Contraindications)

Concomitant Use with Systemic Estrogens : Not recommended. (Raloxifene label, Warnings and precautions)

…cirrhosis [see Warnings and Precautions (5.2) ] Undiagnosed abnormal uterine bleeding [see Warnings and Precautions (5.8) ] Use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations [see Warnings and Precautions (5.14) ] High risk of arterial or venous thrombotic diseases. (Levonorgestrel and ethinyl estradiol label, Contraindications)

St. John's wort can make birth control pills less effective. (NCCIH, St. John's Wort)

Moderate or Weak CYP1A2 Inhibitors Concomitant use of Zanaflex with moderate or weak CYP1A2 inhibitors (e.g., zileuton, antiarrhythmics [amiodarone, mexiletine, propafenone, and verapamil], cimetidine, famotidine, oral contraceptives, acyclovir, and ticlopidine) should be avoided. (Tizanidine label, Drug interactions)

WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS Cigarette smoking increases the risk of serious cardiovascular events from combined hormonal contraceptive (CHC) use. (Levonorgestrel and ethinyl estradiol label, Boxed warning)

Concomitant use of combined hormonal contraceptives ( 4.1 ) (Tranexamic acid label, Contraindications)

John's Wort (CYP450 inducer; P-gp inducer) Significantly Reduced Contraindicated Oral Contraceptives containing ethinyl estradiol and norethindrone (CYP2C19 Inhibition) Increased Monitoring for adverse reactions and toxicity related to voriconazole is recommended for concomitant administration with oral contraceptives. (Voriconazole label, Drug interactions)

Ascorbic acid and acetaminophen may increase systemic exposure of ethinyl estradiol, possibly by inhibition of conjugation. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Concomitant use with ethinyl estradiol-containing CHCs may increase systemic exposure of other drugs (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole). (Levonorgestrel and ethinyl estradiol label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Amoxicillin may reduce the efficacy of oral contraceptives. (Amoxicillin label, Drug interactions)

Amoxicillin and Clavulanate Potassium Extended Release Tablets may reduce efficacy of oral contraceptives. (Amoxicillin and clavulanate label, Drug interactions)

Oral Contraceptives : May be less effective and increased breakthrough bleeding may occur. (Ampicillin label, Drug interactions)

Enzyme inducers (e.g., CYP3A4) : May decrease the effectiveness of TYBLUME or increase breakthrough bleeding. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Enzyme inducers (e.g., CYP3A4) : May decrease the effectiveness of TYBLUME or increase breakthrough bleeding. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Other Drugs Clinical effect Concomitant use of CHCs may decrease systemic exposure of acetaminophen, morphine, salicylic acid, and temazepam. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Other Drugs Clinical effect Concomitant use of CHCs may decrease systemic exposure of acetaminophen, morphine, salicylic acid, and temazepam. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Substances increasing the systemic exposure of CHCs: Co-administration of atorvastatin or rosuvastatin and CHCs containing ethinyl estradiol increase systemic exposure of ethinyl estradiol by approximately 20 to 25 percent. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy Clinical effect Concomitant use of CHCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin [see Warnings and Precautions (5.11) ]. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy Clinical effect Concomitant use of CHCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin [see Warnings and Precautions (5.11) ]. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Other Drugs Clinical effect Concomitant use of CHCs may decrease systemic exposure of acetaminophen, morphine, salicylic acid, and temazepam. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Enzyme inducers (e.g., CYP3A4) : May decrease the effectiveness of TYBLUME or increase breakthrough bleeding. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy Clinical effect Concomitant use of CHCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin [see Warnings and Precautions (5.11) ]. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy Clinical effect Concomitant use of CHCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin [see Warnings and Precautions (5.11) ]. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Ascorbic acid and acetaminophen may increase systemic exposure of ethinyl estradiol, possibly by inhibition of conjugation. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Enzyme inducers (e.g., CYP3A4) : May decrease the effectiveness of TYBLUME or increase breakthrough bleeding. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Enzyme inducers (e.g., CYP3A4) : May decrease the effectiveness of TYBLUME or increase breakthrough bleeding. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Drug Interactions Cholestyramine for Oral Suspension USP may delay or reduce the absorption of concomitant oral medication such as phenylbutazone, warfarin, thiazide diuretics (acidic), or propranolol (basic), as well as tetracycline, penicillin G, phenobarbital, thyroid and thyroxine preparations, estrogens and progestins, and digitalis. (Cholestyramine label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Enzyme inducers (e.g., CYP3A4) : May decrease the effectiveness of TYBLUME or increase breakthrough bleeding. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy Clinical effect Concomitant use of CHCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin [see Warnings and Precautions (5.11) ]. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Colesevelam Clinical effect Concomitant use of CHCs with colesevelam significantly decreases systemic exposure of ethinyl estradiol [see Clinical Pharmacology (12.3) ]. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Concomitant use with ethinyl estradiol-containing CHCs may increase systemic exposure of other drugs (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole). (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Enzyme inducers (e.g., CYP3A4) : May decrease the effectiveness of TYBLUME or increase breakthrough bleeding. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy Clinical effect Concomitant use of CHCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin [see Warnings and Precautions (5.11) ]. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Chronic increase in serum prolactin levels (although not evaluated in the AUSTEDO XR, AUSTEDO, or tetrabenazine development programs) has been associated with low levels of estrogen and increased risk of osteoporosis. (Deutetrabenazine label, Warnings and precautions)

Enzyme inducers (e.g., CYP3A4) : May decrease the effectiveness of TYBLUME or increase breakthrough bleeding. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives, methotrexate: Monitoring of valproate concentrations is recommended ( 7.1 ) (Divalproex (valproate) label, Drug interactions)

…following drugs can be coadministered with dolutegravir without a dose adjustment: atazanavir/ritonavir, darunavir/ritonavir, elbasvir/grazoprevir, methadone, midazolam, omeprazole, oral contraceptives containing norgestimate and ethinyl estradiol, prednisone, rifabutin, rilpivirine, sofosbuvir/velpatasvir, and tenofovir [see Clinical Pharmacology ( 12.3 )] . (Dolutegravir label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Therefore, an increase or decrease in the metabolism of CYP3A substrates (e.g., oral contraceptives and other steroidal agents) resulting from induction or inhibition is not anticipated, although clinical studies have not been performed. (Duloxetine label, Drug interactions)

For patients with CF taking hormonal contraceptives who develop rash, consider interrupting TRIKAFTA and hormonal contraceptives. (Elexacaftor, tezacaftor, and ivacaftor label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Enzyme inducers (e.g., CYP3A4) : May decrease the effectiveness of TYBLUME or increase breakthrough bleeding. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Concomitant use with ethinyl estradiol-containing CHCs may increase systemic exposure of other drugs (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole). (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Effects of Felbatol ® on Low-Dose Combination Oral Contraceptives A group of 24 nonsmoking, healthy white female volunteers established on an oral contraceptive regimen containing 30 µg ethinyl estradiol and 75 µg gestodene for at least 3 months received 2400 mg/day of felbamate from midcycle (day 15) to midcycle (day 14) of two consecutive oral contraceptive… (Felbamate label, Drug interactions)

Weak CYP3A4 Inhibitors Examples Oral contraceptives, cimetidine, fluoxetine, ginkgo, ranitidine Clinical Implications The concomitant use of ADDYI with multiple weak CYP3A4 inhibitors may increase the risk of adverse reactions. (Flibanserin label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy Clinical effect Concomitant use of CHCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin [see Warnings and Precautions (5.11) ]. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy Clinical effect Concomitant use of CHCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin [see Warnings and Precautions (5.11) ]. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy Clinical effect Concomitant use of CHCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin [see Warnings and Precautions (5.11) ]. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy Clinical effect Concomitant use of CHCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin [see Warnings and Precautions (5.11) ]. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Oral Contraceptive Based on AUC and half-life, multiple-dose pharmacokinetic profiles of norethindrone and ethinyl estradiol following administration of tablets containing 2.5 mg of norethindrone acetate and 50 mcg of ethinyl estradiol were similar with and without coadministration of gabapentin (400 mg three times a day; N=13). (Gabapentin label, Drug interactions)

…somatropin, protease inhibitors, atypical antipsychotic medications (e.g., olanzapine and clozapine), barbiturates, diazoxide, laxatives, rifampin, thiazides and other diuretics, corticosteroids, phenothiazines, thyroid hormones, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics (e.g., epinephrine, albuterol, terbutaline), and isoniazid. (Glimepiride label, Drug interactions)

…GLUCOTROL XL, leading to worsening glycemic control: atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline),… (Glipizide label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy Clinical effect Concomitant use of CHCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin [see Warnings and Precautions (5.11) ]. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Ascorbic acid and acetaminophen may increase systemic exposure of ethinyl estradiol, possibly by inhibition of conjugation. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy Clinical effect Concomitant use of CHCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin [see Warnings and Precautions (5.11) ]. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

…Glucose Lowering Effect of Insulin Aspart Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline),… (Insulin aspart label, Drug interactions)

…Glucose Lowering Effect of Insulin Degludec Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline),… (Insulin degludec label, Drug interactions)

…Blood Glucose Lowering Effect of LEVEMIR Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline),… (Insulin detemir label, Drug interactions)

…Lowering Effect of Insulin Glargine-yfgn Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline),… (Insulin glargine label, Drug interactions)

…Blood Glucose Lowering Effect of LYUMJEV Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline),… (Insulin lispro label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Table 4 Significant Drug Interaction Information for Drugs Co-Administered with CHCs Lamotrigine Clinical effect Concomitant use of CHCs with lamotrigine may significantly decrease systemic exposure of lamotrigine due to induction of lamotrigine glucuronidation [see Clinical Pharmacology (12.3) ]. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Teriflunomide may increase exposure of ethinylestradiol and levonorgestrel. (Leflunomide label, Drug interactions)

The dose of replacement thyroid hormone or cortisol therapy may need to be increased. (Levonorgestrel and ethinyl estradiol label, Warnings and precautions)

The dose of replacement thyroid hormone or cortisol therapy may need to be increased. (Levonorgestrel and ethinyl estradiol label, Warnings and precautions)

Other Drugs Clinical effect Concomitant use of CHCs may decrease systemic exposure of acetaminophen, morphine, salicylic acid, and temazepam. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Other Drugs Clinical effect Concomitant use of CHCs may decrease systemic exposure of acetaminophen, morphine, salicylic acid, and temazepam. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

The dose of replacement thyroid hormone or cortisol therapy may need to be increased. (Levonorgestrel and ethinyl estradiol label, Warnings and precautions)

Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy Clinical effect Concomitant use of CHCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin [see Warnings and Precautions (5.11) ]. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Enzyme inducers (e.g., CYP3A4) : May decrease the effectiveness of TYBLUME or increase breakthrough bleeding. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy Clinical effect Concomitant use of CHCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin [see Warnings and Precautions (5.11) ]. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Other Drugs Clinical effect Concomitant use of CHCs may decrease systemic exposure of acetaminophen, morphine, salicylic acid, and temazepam. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

MYHIBBIN may reduce effectiveness of oral contraceptives. (Mycophenolate label, Drug interactions)

Advise women taking oral hormonal contraceptives experiencing vomiting, diarrhea, or other conditions where the drug absorption may be reduced to use alternative highly effective contraception. (Nintedanib label, Warnings and precautions)

Enzyme inducers (e.g., CYP3A4) : May decrease the effectiveness of TYBLUME or increase breakthrough bleeding. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Ascorbic acid and acetaminophen may increase systemic exposure of ethinyl estradiol, possibly by inhibition of conjugation. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Concomitant use with ethinyl estradiol-containing CHCs may increase systemic exposure of other drugs (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole). (Levonorgestrel and ethinyl estradiol label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Enzyme inducers (e.g., CYP3A4) : May decrease the effectiveness of TYBLUME or increase breakthrough bleeding. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Enzyme inducers (e.g., CYP3A4) : May decrease the effectiveness of TYBLUME or increase breakthrough bleeding. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Enzyme inducers (e.g., CYP3A4) : May decrease the effectiveness of TYBLUME or increase breakthrough bleeding. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Sensitive CYP3A4 Substrates (including hormonal contraceptives): WAKIX may reduce effectiveness of sensitive CYP3A4 substrates. (Pitolisant label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Concomitant use with ethinyl estradiol-containing CHCs may increase systemic exposure of other drugs (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole). (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy Clinical effect Concomitant use of CHCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin [see Warnings and Precautions (5.11) ]. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Enzyme inducers (e.g., CYP3A4) : May decrease the effectiveness of TYBLUME or increase breakthrough bleeding. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

The dose of replacement thyroid hormone or cortisol therapy may need to be increased. (Levonorgestrel and ethinyl estradiol label, Warnings and precautions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Enzyme inducers (e.g., CYP3A4) : May decrease the effectiveness of TYBLUME or increase breakthrough bleeding. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

The concomitant use of strong or moderate CYP1A2 inhibitors (e.g., ciprofloxacin, enoxacin, fluvoxamine, methoxsalen, mexiletine, oral contraceptives, thiabendazole, vemurafenib, zileuton) with TIGLUTIK may increase the risk of TIGLUTIK - associated adverse reactions [see Clinical Pharmacology (12.3) ]. (Riluzole label, Drug interactions)

Oral Contraceptives Containing Gestodene and Ethinyl Estradiol The co-administration of DALIRESP (500 mcg) with oral contraceptives containing gestodene and ethinyl estradiol may increase roflumilast systemic exposure and may result in increased side effects. (Roflumilast label, Drug interactions)

Estrogens Population pharmacokinetic analysis revealed that higher doses of estrogens (usually associated with hormone replacement therapy) reduced the clearance of ropinirole. (Ropinirole label, Drug interactions)

Substances increasing the systemic exposure of CHCs: Co-administration of atorvastatin or rosuvastatin and CHCs containing ethinyl estradiol increase systemic exposure of ethinyl estradiol by approximately 20 to 25 percent. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Other Drugs Clinical effect Concomitant use of CHCs may decrease systemic exposure of acetaminophen, morphine, salicylic acid, and temazepam. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (Tacrolimus label, Drug interactions)

Hypercalcemia in Patients with Metastatic Breast Cancer As with other additive hormonal therapy (estrogens and androgens), hypercalcemia has been reported in some breast cancer patients with bone metastases within a few weeks of starting treatment with tamoxifen. (Tamoxifen label, Warnings and precautions)

Other Drugs Clinical effect Concomitant use of CHCs may decrease systemic exposure of acetaminophen, morphine, salicylic acid, and temazepam. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Teriflunomide may increase exposure of ethinylestradiol and levonorgestrel. (Teriflunomide label, Drug interactions)

Chronic increase in serum prolactin levels (although not evaluated in the tetrabenazine development program) has been associated with low levels of estrogen and increased risk of osteoporosis. (Tetrabenazine label, Warnings and precautions)

Concomitant use with ethinyl estradiol-containing CHCs may increase systemic exposure of other drugs (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole). (Levonorgestrel and ethinyl estradiol label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Advise patients using oral hormonal contraceptives to switch to a non-oral contraceptive method, or add a barrier method of contraception for 4 weeks after initiation with ZEPBOUND and for 4 weeks after each dose escalation. (Tirzepatide label, Drug interactions)

Exercise caution when coadministering TOFIDENCE with CYP3A4 substrate drugs where decrease in effectiveness is undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, etc. (Tocilizumab label, Drug interactions)

Enzyme inducers (e.g., CYP3A4) : May decrease the effectiveness of TYBLUME or increase breakthrough bleeding. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy Clinical effect Concomitant use of CHCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin [see Warnings and Precautions (5.11) ]. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Drugs Affecting Lipid Metabolism Estrogens, oral contraceptives, and clofibrate (and perhaps other lipid-lowering drugs) increase hepatic cholesterol secretion and encourage cholesterol gallstone formation and hence may counteract the effectiveness of URSO 250 and URSO Forte. (Ursodiol label, Drug interactions)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Valproic acid label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

…carbamazepine, phenobarbital, rifampin CYP1A2 acyclovir, allopurinol, caffeine, cimetidine, ciprofloxacin, disulfiram, enoxacin, famotidine, fluvoxamine, methoxsalen, mexiletine, norfloxacin, oral contraceptives, phenylpropanolamine, propafenone, propranolol, terbinafine, thiabendazole, ticlopidine, verapamil, zileuton montelukast, moricizine, omeprazole, phenobarbital,… (Warfarin label, Drug interactions)

These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel-blocking drugs, and isoniazid. (Acarbose label, Drug interactions)

Advise women of reproductive potential to use effective birth control for the duration of ALBENZA therapy and for one month after end of therapy. (Albendazole label, Warnings and precautions)

Moderate or weak CYP1A2 inhibitors include oral contraceptives and caffeine. (Clozapine label, Drug interactions)

Oral Contraceptives The effect of oral contraceptives on the pharmacokinetics of Dihydroergotamine Mesylate Injection, USP has not been studied. (Dihydroergotamine label, Drug interactions)

Concurrent use of tetracyclines, including doxycycline hyclate may render oral contraceptives less effective. (Doxycycline label, Drug interactions)

These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. (Empagliflozin and metformin label, Drug interactions)

For oral medications that are dependent on threshold concentrations for efficacy, such as contraceptives and antibiotics, patients should be advised to take those drugs at least 1 hour before BYETTA injection. (Exenatide label, Drug interactions)

These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. (Glyburide label, Drug interactions)

Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (Glyburide and metformin label, Drug interactions)

Atypical Antipsychotics (e.g., olanzapine and clozapine), Corticosteroids, Danazol, Diuretics, Estrogens, Glucagon, Isoniazid, Niacin, Oral Contraceptives, Phenothiazines, Progestogens (e.g., in oral contraceptives), Protease inhibitors, Somatropin, Sympathomimetic Agents (e.g., albuterol, epinephrine, terbutaline) and Thyroid Hormones. (Insulin regular (human) label, Drug interactions)

Oral Contraceptives Isotretinoin Capsules did not result in clinically significant changes in the pharmacokinetics of norethindrone and ethinyl estradiol when used concomitantly with a norethindrone and ethinyl estradiol oral contraceptive [see Clinical Pharmacology ( 12.3 )]. (Isotretinoin label, Drug interactions)

Potential pharmacokinetic interactions of or with levetiracetam were assessed in clinical pharmacokinetic studies (phenytoin, valproate, warfarin, digoxin, oral contraceptive, probenecid) and through pharmacokinetic screening in the placebo-controlled clinical studies in epilepsy patients. (Levetiracetam label, Drug interactions)

Advise patients who can become pregnant to use effective contraceptive methods prior to initiation of treatment, during treatment, and for one month after discontinuation of treatment with OPSUMIT. (Macitentan label, Warnings and precautions)

Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (Metformin label, Drug interactions)

…performed, the following concomitant drugs were used in at least 10% of patients in either or both Sjogren's efficacy studies: acetylsalicylic acid, artificial tears, calcium, conjugated estrogens, hydroxychloroquine sulfate, ibuprofen, levothyroxine sodium, medroxyprogesterone acetate, methotrexate, multivitamins, naproxen, omeprazole, paracetamol, and prednisone. (Pilocarpine label, Drug interactions)

These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (Pioglitazone and metformin label, Drug interactions)

No pharmacokinetic interactions were observed between LYRICA and carbamazepine, gabapentin, lamotrigine, oral contraceptive, phenobarbital, phenytoin, topiramate, and valproic acid. (Pregabalin label, Drug interactions)

Examples: Atypical antipsychotics (e.g., olanzapine and clozapine), calcium channel antagonists, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and… (Repaglinide label, Drug interactions)

Hormone Therapy Concomitant use of Risedronate sodium delayed-release with estrogens and estrogen agonist/antagonists has not been studied. (Risedronate label, Drug interactions)

Examples Aprepitant, barbiturates, bosentan, carbamazepine, efavirenz, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, primidone, phenylbutazone, rifabutin, rufinamide, topiramate, products containing St. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (Sitagliptin and metformin label, Drug interactions)

There is no information available from adequate drug-drug interaction studies with the following classes of drugs: oral contraceptives, hormone replacement therapies, hypoglycemics, phenytoins, thiazide diuretics, and calcium channel blockers. (Terbinafine label, Drug interactions)

Concurrent use of tetracycline may render oral contraceptives less effective. (Tetracycline label, Drug interactions)

Oral Contraceptives In vivo studies have revealed no effect of ziprasidone on the pharmacokinetics of estrogen or progesterone components. (Ziprasidone label, Drug interactions)

Another study showed that alosetron had no clinically significant effect on plasma concentrations of the oral contraceptive agents ethinyl estradiol and levonorgestrel (CYP3A4 substrates). (Alosetron label, Drug interactions)

Combination oral contraceptives Darifenacin (10 mg three times daily) had no effect on the pharmacokinetics of the combination oral contraceptives containing levonorgestrel and ethinyl estradiol [see Clinical Pharmacology (12.3)] . (Darifenacin label, Drug interactions)

Other Drugs: In healthy volunteers, amlodipine, phenytoin, glyburide, ranitidine, omeprazole, hormone replacement therapy (a combination of conjugated estrogens and medroxyprogesterone), antacid (aluminum and magnesium hydroxides), and theophylline did not affect the pharmacokinetics of dofetilide. (Dofetilide label, Drug interactions)

No clinically significant drug interactions have been either observed or are expected when DESCOVY is combined with the following drugs: buprenorphine, itraconazole, ketoconazole, lorazepam, methadone, midazolam, naloxone, norbuprenorphine, norgestimate/ethinyl estradiol, and sertraline. (Emtricitabine and tenofovir label, Drug interactions)

Oral Contraceptives In the presence of fesoterodine, there are no clinically significant changes in the plasma concentrations of combined oral contraceptives containing ethinyl estradiol and levonorgestrel [see Clinical Pharmacology (12.3) ] . (Fesoterodine label, Drug interactions)

No dose adjustment is needed when SINGULAIR is co-administered with theophylline, prednisone, prednisolone, oral contraceptives, fexofenadine, digoxin, warfarin, gemfibrozil, itraconazole, thyroid hormones, sedative hypnotics, non-steroidal anti-inflammatory agents, benzodiazepines, decongestants, and Cytochrome P450 (CYP) enzyme inducers [see Clinical Pharmacology… (Montelukast label, Drug interactions)

…clinically significant drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir:… (Sofosbuvir and velpatasvir label, Drug interactions)

Oral Contraceptives : Multiple dose administration of tiagabine (8 mg/day monotherapy) did not alter the pharmacokinetics of oral contraceptives in healthy women of child-bearing age. (Tiagabine label, Drug interactions)

In a single-blind, parallel-group, 3-week study in 39 healthy female subjects taking oral contraceptives, 40 mg twice daily of zafirlukast had no significant effect on ethinyl estradiol plasma concentrations or contraceptive efficacy. (Zafirlukast label, Precautions)