FDA

Nexesta Fe

Approved 2 Feb 2017OralTablet

Indications

Nexesta Fe is indicated for use by females of reproductive potential to prevent pregnancy. Nexesta Fe is a progestin/estrogen COC indicated for use by females of reproductive potential to prevent pregnancy. ( 1 )

Contraindications

Nexesta Fe is contraindicated in females who are known to have or develop the following conditions:

A high risk of arterial or venous thrombotic diseases. Examples include women who are known to: o Smoke, if over age 35 [see Boxed Warning and Warnings and Precautions (5.1) ] o Have deep vein thrombosis or pulmonary embolism, now or in the past [see Warnings and Precautions (5.1) ] o Have inherited or acquired hypercoagulopathies [see Warnings and Precautions (5.1) ] o Have cerebrovascular disease [see Warnings and Precautions (5.1) ] o Have coronary artery disease [see Warnings and Precautions (5.1) ] o 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) ] o Have uncontrolled hypertension [see Warnings and Precautions (5.4) ] o Have diabetes mellitus with vascular disease [see Warnings and Precautions (5.6) ] o Have headaches with focal neurological symptoms or have migraine headaches with aura [see Warnings and Precautions (5.7) ]
Women over age 35 with any migraine headaches [see Warnings and Precautions (5.7) ]
Liver tumors, benign or malignant, or liver disease [see Warnings and Precautions (5.2) ]
Undiagnosed abnormal uterine bleeding [see Warnings and Precautions (5.8) ]
Pregnancy, because there is no reason to use COCs during pregnancy [see Warnings and Precautions (5.9) and Use in Specific Populations (8.1) ]
Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see Warnings and Precautions (5.11) ].
Hypersensitivity to any of the components.
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 (5.3) ] A high risk of arterial or venous thrombotic diseases ( 4 ) Liver tumors or liver disease ( 4 ) Undiagnosed abnormal uterine bleeding ( 4 ) Pregnancy ( 4 ) Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive ( 4 ) Co-administration with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir ( 4 )

Warnings and precautions

At a glance

Brand name: Nexesta Fe
Active substance: ethinyl estradiol
Route: Oral
Dosage form: Tablet
Applicant: Aurobindo Pharma
Status: Prescription
FDA approval: 2 Feb 2017
Application: ANDA207535-001

Contraindications

Nexesta Fe is contraindicated in females who are known to have or develop the following conditions:

A high risk of arterial or venous thrombotic diseases. Examples include women who are known to: o Smoke, if over age 35 [see Boxed Warning and Warnings and Precautions (5.1) ] o Have deep vein thrombosis or pulmonary embolism, now or in the past [see Warnings and Precautions (5.1) ] o Have inherited or acquired hypercoagulopathies [see Warnings and Precautions (5.1) ] o Have cerebrovascular disease [see Warnings and Precautions (5.1) ] o Have coronary artery disease [see Warnings and Precautions (5.1) ] o 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) ] o Have uncontrolled hypertension [see Warnings and Precautions (5.4) ] o Have diabetes mellitus with vascular disease [see Warnings and Precautions (5.6) ] o Have headaches with focal neurological symptoms or have migraine headaches with aura [see Warnings and Precautions (5.7) ]
Women over age 35 with any migraine headaches [see Warnings and Precautions (5.7) ]
Liver tumors, benign or malignant, or liver disease [see Warnings and Precautions (5.2) ]
Undiagnosed abnormal uterine bleeding [see Warnings and Precautions (5.8) ]
Pregnancy, because there is no reason to use COCs during pregnancy [see Warnings and Precautions (5.9) and Use in Specific Populations (8.1) ]
Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see Warnings and Precautions (5.11) ].
Hypersensitivity to any of the components.
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 (5.3) ] A high risk of arterial or venous thrombotic diseases ( 4 ) Liver tumors or liver disease ( 4 ) Undiagnosed abnormal uterine bleeding ( 4 ) Pregnancy ( 4 ) Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive ( 4 ) Co-administration with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir ( 4 )

Interactions

Consult the labeling of concurrently used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. Drugs or herbal products that induce certain enzymes, including CYP3A4, may decrease the effectiveness of COCs or increase breakthrough bleeding. Counsel patients to use a back-up method or alternative method of contraception when enzyme inducers are used with COCs ( 7.1 )

7.1Effects of Other Drugs on Combined Oral Contraceptives

Substances decreasing the plasma concentrations of COCs and potentially diminishing the efficacy of COCs : Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the plasma concentrations of COCs and potentially diminish the effectiveness of COCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St.

John’s wort. Interactions between hormonal contraceptives and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative method of contraception or a back-up method when enzyme inducers are used with COCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability. Colesevelam: Colesevelam, a bile acid sequestrant, given together with a COC, has been shown to significantly decrease the AUC of EE.

The drug interaction between the contraceptive and colesevelam was decreased when the two drug products were given 4 hours apart. Substances increasing the plasma concentrations of COCs: Co-administration of atorvastatin or rosuvastatin and certain COCs containing EE increase AUC values for EE by approximately 20 to 25%. Ascorbic acid and acetaminophen may increase plasma EE concentrations, possibly by inhibition of conjugation.

CYP3A4 inhibitors, such as itraconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. Human immunodeficiency virus (HIV)/Hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors: Significant changes (increase or decrease) in the plasma concentrations of estrogen and/or progestin have been noted in some cases of co-administration with HIV protease inhibitors (decrease [e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir] or increase [e.g., indinavir and atazanavir/ritonavir])/HCV protease inhibitors (decrease [e.g., nevirapine] or increase [e.g., etravirine]).

7.2Effects of Combined Oral Contraceptives on Other Drugs

COCs containing EE may inhibit the metabolism of other compounds (e.g., cyclosporine prednisolone, theophylline, tizanidine, and voriconazole) and increase their plasma concentrations. COCs have been shown to decrease plasma concentrations of acetaminophen, clofibric acid, morphine, salicylic acid, temazepam and lamotrigine. Significant decrease in plasma concentration of lamotrigine has been shown, likely due to induction of lamotrigine glucuronidation.

This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because the serum concentration of thyroid-binding globulin increases with use of COCs [see Warnings and Precautions (5.12) ].

7.3Concomitant Use with HCV Combination

Therapy – Liver Enzyme Elevation Do not co-administer Nexesta Fe with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [see Warnings and Precautions (5.3) ].

7.4Interference with Laboratory Tests

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

Adverse reactions

The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling: Serious cardiovascular events and stroke [see Boxed Warning and Warnings and Precautions (5.1) ] Vascular events [see Warnings and Precautions (5.1) ] Liver disease [see Warnings and Precautions (5.2) ] The following adverse reactions are commonly reported by COC users. Because these reactions are voluntarily reported by from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Irregular uterine bleeding Nausea Breast tenderness Headache The most common adverse reactions were: irregular uterine bleeding, nausea, breast tenderness, and headache.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Postmarketing 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 to 1.12 (Figure 1).

Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 1). 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 to 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 to 10 years of COC use.

Figure 1: Risk of Breast Cancer with Combined Oral Contraceptive Use RR = relative risk; OR = odds ratio; HR = hazard ratio. “ever COC” are females with current or past COC use; “never COC use” are females that never used COCs. Figure 1: Risk of Breast Cancer with Combined Oral Contraceptive Use

Nexesta Fe

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Nexesta Fe

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

5.1Thrombotic Disorders and Other Vascular

5.2Liver Disease Impaired Liver Function Do

5.3Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment

5.4High Blood Pressure Nexesta

5.5Gallbladder Disease

5.6Carbohydrate and Lipid Metabolic Effects

5.7Headache If

5.8Bleeding Irregularities and Amenorrhea Unscheduled Bleeding and Spotting Unscheduled (breakthrough

5.9COC Use Before or During Early Pregnancy

5.10Depression

5.11Malignant Neoplasms Breast Cancer Nexesta

Interactions

7.1Effects of Other Drugs on Combined Oral Contraceptives

7.2Effects of Combined Oral Contraceptives on Other Drugs

7.3Concomitant Use with HCV Combination

7.4Interference with Laboratory Tests

Pregnancy and breastfeeding

8.1Pregnancy

Adverse reactions

Composition

Official product information