FDA

Levora 0.15/30-28

Approved 13 Dec 1993OralTablet

Indications

LEVORA 0.15/30-28 is indicated for use by females of reproductive potential to prevent pregnancy.

Contraindications

LEVORA 0.15/30-28 is contraindicated in females who are known to have the following conditions: A high risk of arterial or venous thrombotic diseases. Examples include women who are known to: Smoke, if over age 35 [see BOXED WARNING and WARNINGS (1) ]. Have current or history of deep vein thrombosis or pulmonary embolism [see WARNINGS (1) ] . Have cerebrovascular disease [see WARNINGS (1) ] . Have coronary artery disease [see WARNINGS (1) ] .

Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see WARNINGS (1) ] . Have inherited or acquired hypercoagulopathies [see WARNINGS (1) ] . Have uncontrolled hypertension or hypertension with vascular disease [see WARNINGS (4) ] . 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 (8) ] .

Have headaches with focal neurological symptoms, migraine headaches with aura, or over age 35 with any migraine headaches [see WARNINGS (9) ] . Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive. Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis [see WARNINGS (2) ] . Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations [see WARNINGS (6) ] .

Undiagnosed abnormal uterine bleeding [see WARNINGS (10) ] .

Warnings and precautions

1. Thromboembolic Disorders and Other Vascular Conditions Stop LEVORA 0.15/30-28 if an arterial or venous thrombotic/thromboembolic event occurs. Stop LEVORA 0.15/30-28 if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis immediately. Discontinue LEVORA 0.15/30-28 during prolonged immobilization. If feasible, stop LEVORA 0.15/30-28 at least four weeks before and through two weeks after major surgery, or other surgeries known to have an elevated risk of thromboembolism.

Start LEVORA 0.15/30-28 no earlier than four weeks after delivery in females who are not breast-feeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the likelihood of ovulation increases after the third postpartum week. Before starting LEVORA 0.15/30-28 evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy.

At a glance

Brand name: Levora 0.15/30-28
Active substance: ethinyl estradiol
Route: Oral
Dosage form: Tablet
Applicant: DR Reddys Labs SA
Status: Prescription
FDA approval: 13 Dec 1993
Application: ANDA073594-001

Contraindications

Undiagnosed abnormal uterine bleeding [see WARNINGS (10) ] .

Warnings and precautions

Interactions

4. Drug Interactions The sections below provide information on substances for which data on drug interactions with COCs are available. There is little information available about the clinical effect of most drug interactions that may affect COCs. 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 COCs or the potential for metabolic enzyme or transporter system alterations . No drug-drug interaction studies were conducted with LEVORA 0.15/30-28.

4.1 Effects of Other Drugs on Combined Oral Contraceptives Substances Decreasing the Plasma Concentrations of COCs and Potentially Diminishing the Efficacy of COCs Table 1 includes substances that demonstrated an important drug interaction with LEVORA 0.15/30-28. Table 1: Significant Drug Interactions Involving Substances That Affect COCs Metabolic Enzyme Inducers Clinical effect Concomitant use of COCs with metabolic enzyme inducers may decrease the plasma concentrations of the estrogen and/or progestin component of COCs.

Decreased exposure of the estrogen and/or progestin component of COCs may potentially diminish the effectiveness of COCs 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 COCs. 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, rifabutin, rufinamide, topiramate, products containing St. John's wort Induction potency of St. John's wort may vary widely based on preparation. , and certain protease inhibitors (see separate section on protease inhibitors below). Colesevelam Clinical effect Concomitant use of COCs with colesevelam significantly decreases systemic exposure of ethinyl estradiol.

Decreased exposure of the estrogen component of COCs may potentially reduce contraceptive efficacy or result in an increase in breakthrough bleeding, depending on the strength of ethinyl estradiol in the COC. Prevention or management Administer 4 or more hours apart to attenuate this drug interaction. Substances increasing the systemic exposure of COCs Co-administration of atorvastatin or rosuvastatin and COCs 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, or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of COCs. 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 COCs 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 COCs 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).

4.2Effects of Combined Oral Contraceptives on Other Drugs Table

2 provides significant drug interaction information for drugs co-administered with LEVORA 0.15/30-28. Table 2: Significant Drug Interaction Information for Drugs Co-Administered With COCs Lamotrigine Clinical effect Concomitant use of COCs 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 COCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid- binding and cortisol-binding globulin (see Warnings, EFFECT ON BINDING GLOBULINS ).

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, EFFECT ON BINDING GLOBULINS ). Other Drugs Clinical effect Concomitant use of COCs may decrease systemic exposure of acetaminophen, morphine, salicylic acid, and temazepam. Concomitant use with ethinyl estradiol- containing COCs 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.

4.3Concomitant Use with Hepatitis C Virus (HCV) Combination Therapy-Liver Enzyme Elevation Do

not co-administer LEVORA 0.15/30-28 with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, [see WARNINGS (6) ], and glecaprevir/pibrentasvir due to potential for ALT elevations.

4.4Effect on Laboratory Tests

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

Adverse reactions

Post Marketing Experience Five studies that compared breast cancer risk between ever-users (current or past use) of COCs and never-users of COCs reported no association between ever use of COCs and breast cancer risk, with effect estimates ranging from 0.90 - 1.12 (Figure 2). Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 2). One of these studies reported no association between breast cancer risk and COC use.

The other two studies found an increased relative risk of 1.19 - 1.33 with current or recent use. Both of these studies found an increased risk of breast cancer with current use of longer duration, with relative risks ranging from 1.03 with less than one year of COC use to approximately 1.4 with more than 8-10 years of COC use. Figure 2: Risk of Breast Cancer with Combined Oral Contraceptive Use The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling: Serious cardiovascular adverse events [see BOXED WARNING and WARNINGS (1) ] Vascular events [see WARNINGS (1) ] Liver disease [see WARNINGS (2) ] Hypertension [see WARNINGS (4) ] Gallbladder disease [see WARNINGS (7) ] Carbohydrate and lipid effects [see WARNINGS (8) ] Headache [see WARNINGS (9) ] Carcinoma of the cervix [see WARNINGS (3) ] Adverse reactions reported by COC users and described elsewhere in the labeling are: Bleeding irregularities and amenorrhea [see WARNINGS (10) ] Mood changes, including depression [see WARNINGS (11) ] Melasma/chloasma which may persist [see WARNINGS (14) ] Edema/fluid retention [see PRECAUTIONS (2) ] Diminution in lactation when given immediately postpartum [see PRECAUTIONS (7) ] The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug-related: Breast tenderness, pain, enlargement, secretion; Nausea, vomiting and gastrointestinal symptoms (such as abdominal pain, cramps and bloating); Change in menstrual flow; Temporary infertility after discontinuation of treatment; Change in weight or appetite (increase or decrease); Change in cervical erosion and secretion; Cholestatic jaundice; Rash (allergic); Vaginitis, including candidiasis; Change in corneal curvature (steepening); Intolerance to contact lenses; Mesenteric thrombosis; Decrease in serum folate levels; Exacerbation of systemic lupus erythematosus; Exacerbation of porphyria; Exacerbation of chorea; Aggravation of varicose veins; Anaphylactic/anaphylactoid reactions, including urticaria, angioedema, and severe reactions with respiratory and circulatory symptoms.

The following adverse reactions have been reported in users of oral contraceptives, and the association has been neither confirmed nor refuted: Congenital anomalies; Premenstrual syndrome; Cataracts; Optic neuritis, which may lead to partial or complete loss of vision; Cystitis-like syndrome; Nervousness; Dizziness; Hirsutism; Loss of scalp hair; Erythema multiforme; Erythema nodosum; Hemorrhagic eruption; Impaired renal function; Hemolytic uremic syndrome; Budd-Chiari syndrome; Acne; Changes in libido; Colitis; Sickle-cell disease; Cerebral-vascular disease with mitral valve prolapse; Lupus-like syndromes; Pancreatitis; Dysmenorrhea.

Figure 2

Levora 0.15/30-28

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Levora 0.15/30-28

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Interactions

4.2Effects of Combined Oral Contraceptives on Other Drugs Table

4.3Concomitant Use with Hepatitis C Virus (HCV) Combination Therapy-Liver Enzyme Elevation Do

4.4Effect on Laboratory Tests

Pregnancy and breastfeeding

Adverse reactions

Composition

Official product information