Tyblume Drug Information

is indicated for use by females of reproductive potential to prevent pregnancy. TYBLUME (levonorgestrel and ethinyl estradiol tablets) is a combination of levonorgestrel, a progestin, and ethinyl estradiol, an estrogen, indicated for use by females of reproductive potential to prevent pregnancy.

The following serious adverse reactions with the use of CHCs are discussed elsewhere in labeling: Serious cardiovascular events Vascular events Liver disease Hypertension Gallbladder disease Adverse carbohydrate and lipid metabolic effects Headache Bleeding irregularities and amenorrhea Depression Cervical cancer Effect on binding globulins Hereditary angioedema Chloasma Risk of liver enzyme elevations with concomitant hepatitis C treatment The following adverse reactions associated with the use of oral CHCs were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Common adverse reactions associated with oral CHCs are headache, abdominal pain, nausea, metrorrhagia, vaginal moniliasis and pain, acne, and vaginitis.

Additional adverse reactions that have been reported include the following: Eye disorder: intolerance to contact lenses, steepening of corneal curvature Gastrointestinal disorders: Abdominal bloating, vomiting General disorders and administration site condition: Edema, fluid retention Hepatobiliary disorders: Cholestatic jaundice Psychiatric disorders: Change in libido, mood changes Reproductive system and breast disorders: Amenorrhea, breast tenderness, breast pain, breast enlargement, increased cervical mucous, change in menstrual flow, unscheduled bleeding Skin and subcutaneous tissue disorders: Acne, melasma Vascular disorders: Budd-Chiari syndrome, aggravation of varicose veins Common adverse reactions are: headache, abdominal pain, nausea, metrorrhagia, vaginal moniliasis and pain, acne, and vaginitis. To report SUSPECTED ADVERSE REACTIONS, contact Exeltis USA, Inc. at 1-877-324-9349 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Effects of Other Drugs on Combined Hormonal Contraceptives Substances decreasing the Plasma

Concentration of CHCs and Potentially Diminishing the Efficacy of CHCs Table 3 Significant Drug Interactions Involving Substances That Affect CHCs a Induction potency of St. John's wort may vary widely based on preparation. Metabolic Enzyme Inducers Clinical effect Concomitant use of CHCs with metabolic enzyme inducers may decrease the plasma concentrations of the estrogen and/or progestin component of CHCs . Decreased exposure of the estrogen and/or progestin component of CHCs may potentially diminish the effectiveness of CHCs and may lead to contraceptive failure or an increase in breakthrough bleeding.

Prevention or management Counsel females to use an alternative method of contraception or a backup method when enzyme inducers are used with CHCs. Continue backup contraception for 28 days after discontinuing the enzyme inducer to maintain contraceptive reliability. Examples Aprepitant, barbiturates, bosentan, carbamazepine, efavirenz, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, primidone, phenylbutazone, rifabutin, rufinamide, topiramate, products containing St.

John's wort, and certain protease inhibitors (see separate section on protease inhibitors below). Colesevelam Clinical effect Concomitant use of CHCs with colesevelam significantly decreases systemic exposure of ethinyl estradiol. Decreased exposure of the estrogen component of CHCs may potentially reduce contraceptive efficacy or result in an increase in breakthrough bleeding, depending on the strength of ethinyl estradiol in the CHC. Prevention or management Administer 4 or more hours apart to attenuate this drug interaction. 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.

Ascorbic acid and acetaminophen may increase systemic exposure of ethinyl estradiol, possibly by inhibition of conjugation. 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. Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors: Significant decreases in systemic exposure of the estrogen and/or progestin have been noted when CHCs are co-administered with some HIV protease inhibitors (e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir), some HCV protease inhibitors (e.g., boceprevir and telaprevir), and some non-nucleoside reverse transcriptase inhibitors (e.g., nevirapine). In contrast, significant increases in systemic exposure of the estrogen and/or progestin have been noted when CHCs are co-administered with certain other HIV protease inhibitors (e.g., indinavir and atazanavir/ritonavir) and with other non-nucleoside reverse transcriptase inhibitors (e.g., etravirine).

Effects of Combined Hormonal Contraceptives on Other Drugs Table 4 provides significant

drug interaction information for drugs co-administered with TYBLUME. 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. Decreased systemic exposure of lamotrigine may reduce seizure control. Prevention or management Dose adjustment may be necessary.

Consult the approved product labeling for lamotrigine. 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. Prevention or management The dose of replacement thyroid hormone or cortisol therapy may need to be increased.

Consult the approved product labeling for the therapy in use.. Other Drugs Clinical effect Concomitant use of CHCs may decrease systemic exposure of acetaminophen, morphine, salicylic acid, and temazepam. Concomitant use with ethinyl estradiol-containing CHCs may increase systemic exposure of other drugs (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole). Prevention or management The dosage of drugs that can be affected by this interaction may need to be increased. Consult the approved product labeling for the concomitantly used drug.

Effect on Laboratory Tests

The use of CHCs may influence the results of certain laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins.

Concomitant Use with

HCV Combination Therapy – Liver Enzyme Elevation CHCs are contraindicated for use with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. Discontinue TYBLUME prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. TYBLUME can be restarted approximately 2 weeks following completion of treatment with the Hepatitis C combination drug regimen.

Pregnancy Risk Summary There is no use for contraception in pregnancy; therefore, TYBLUME should be discontinued during pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to CHCs before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4 percent and 15 to 20 percent, respectively.

Pediatric Use The safety and effectiveness of TYBLUME have been established in females of reproductive potential. Efficacy is expected to be the same for post-menarchal females under the age of 17 as for users 17 years and older. The use of TYBLUME before menarche is not indicated.

is contraindicated in females who are known to have the following conditions: A high risk of arterial or venous thrombotic diseases. Examples include females who are known to: Smoke, if over age 35 Have current or history of deep vein thrombosis or pulmonary embolism Have cerebrovascular disease Have coronary artery disease Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) Have inherited or acquired hypercoagulopathies Have uncontrolled hypertension or hypertension with vascular disease Have diabetes mellitus and are over age 35, diabetes mellitus with hypertension or vascular disease or other end-organ damage, or diabetes mellitus of > 20 years duration Have headaches with focal neurological symptoms, migraine headaches with aura, or over age 35 with any migraine headaches Current or history of breast cancer or other estrogen- or progestin-sensitive cancer Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis Undiagnosed abnormal uterine bleeding Use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations High risk of arterial or venous thrombotic diseases. Breast cancer or other estrogen- or progestin-sensitive cancer.

Liver tumors, acute viral hepatitis or decompensated cirrhosis. Undiagnosed abnormal uterine bleeding. Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir.

Overdose may cause nausea and uterine bleeding in females.