FDA

Tyblume

Approved 30 Mar 2020OralTablet

Indications

TYBLUME 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. ( 1 )

Contraindications

TYBLUME 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 [see Boxed Warning and Warnings and Precautions (5.1) ] Have current or history of deep vein thrombosis or pulmonary embolism [see Warnings and Precautions (5.1) ] Have cerebrovascular disease [see Warnings and Precautions (5.1) ] Have coronary artery disease [see Warnings and Precautions (5.1) ] Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see Warnings and Precautions (5.1) ] Have inherited or acquired hypercoagulopathies [see Warnings and Precautions (5.1) ] Have uncontrolled hypertension or hypertension with vascular disease [see Warnings and Precautions (5.3) ] 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 [see Warnings and Precautions (5.6) ] Have headaches with focal 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 [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.

( 4 ) Breast cancer or other estrogen- or progestin-sensitive cancer. ( 4 ) Liver tumors, acute viral hepatitis or decompensated cirrhosis. ( 4 ) Undiagnosed abnormal uterine bleeding. ( 4 ) Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. ( 4 )

Warnings and precautions

Vascular risks : Stop if a thrombotic or thromboembolic event occurs. Stop TYBLUME at least 4 weeks before and through 2 weeks after major surgery. Start no earlier than 4 weeks after delivery, in females who are not breast-feeding. Consider cardiovascular risk factors before initiating in all females, particularly those over 35 years. ( 5.1 , 5.4 ) Liver disease : Discontinue TYBLUME if jaundice occurs. ( 5.2 ) Hypertension : If used in females with well-controlled hypertension, monitor blood pressure.

At a glance

Brand name: Tyblume
Active substance: ethinyl estradiol
Route: Oral
Dosage form: Tablet
Applicant: Exeltis USA Inc
Status: Prescription
FDA approval: 30 Mar 2020
Application: NDA209405-001

Indications

Contraindications

Warnings and precautions

Interactions

The sections below provide information on substances for which data on drug interactions with CHCs are available. There is little information available about the clinical effect of most drug interactions that may affect CHCs. However, based on the known pharmacokinetic effects of these drugs, clinical strategies to minimize any potential adverse effect on contraceptive effectiveness or safety are suggested. Consult the approved product labeling of all concurrently used drugs to obtain further information about interactions with CHCs or the potential for metabolic enzyme or transporter system alterations.

No drug-drug interaction studies were conducted with TYBLUME. Enzyme inducers (e.g., CYP3A4) : May decrease the effectiveness of TYBLUME or increase breakthrough bleeding. Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with TYBLUME. ( 7.1 , 7.2 )

7.1Effects 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 [see Clinical Pharmacology (12.3) ] .

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 [see Clinical Pharmacology (12.3) ].

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).

7.2Effects 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 [see Clinical Pharmacology (12.3) ]. 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 [see Warnings and Precautions (5.11) ].

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. [See Warnings and Precautions (5.11) ]. 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.

7.3Effect 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.

7.4Concomitant 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 [see Contraindications (4) ]. 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.

Adverse reactions

The following serious adverse reactions with the use of CHCs are discussed elsewhere in labeling: Serious cardiovascular events [see Boxed Warning and Warnings and Precautions (5.1 and 5.4) ] Vascular events [see Warnings and Precautions (5.1) ] Liver disease [see Warnings and Precautions (5.2) ] Hypertension [see Warnings and Precautions (5.3) ] Gallbladder disease [see Warnings and Precautions (5.5) ] Adverse carbohydrate and lipid metabolic effects [see Warnings and Precautions (5.6) ] Headache [see Warnings and Precautions (5.7) ] Bleeding irregularities and amenorrhea [see Warnings and Precautions (5.8) ] Depression [see Warnings and Precautions (5.9) ] Cervical cancer [see Warnings and Precautions (5.10) ] Effect on binding globulins [see Warnings and Precautions (5.11) ] Hereditary angioedema [see Warnings and Precautions (5.12) ] Chloasma [see Warnings and Precautions (5.13) ] Risk of liver enzyme elevations with concomitant hepatitis C treatment [see Warnings and Precautions (5.14) ] 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 [see Warnings and Precautions (5.13) ] 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.

( 6 ) 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.

Tyblume

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Tyblume

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

5.1Thromboembolic Disorders and Other Vascular Problems

5.2Liver Disease Elevated Liver Enzymes

5.3Hypertension

5.4Age-related Considerations

5.5Gallbladder Disease

5.6Adverse Carbohydrate and Lipid Metabolic Effects Hyperglycemia

5.7Headache

Interactions

7.1Effects of Other Drugs on Combined Hormonal Contraceptives

7.2Effects of Combined Hormonal Contraceptives on Other Drugs Table

7.3Effect on Laboratory Tests

7.4Concomitant Use with HCV Combination

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

Composition

Official product information