FDA

Sprintec

Approved 25 Sept 2002OralTablet

Indications

Sprintec ® (norgestimate and ethinyl estradiol tablets) is an estrogen/progestin COC, indicated for use by women to prevent pregnancy. ( 1.1 )

1.1Oral Contraceptive

Sprintec ® (norgestimate and ethinyl estradiol tablets) is indicated for use by females of reproductive potential to prevent pregnancy [see Clinical Studies( 14 )].

Contraindications

Do not prescribe Sprintec to women 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 and Precautions ( 5.1 )]
Have deep vein thrombosis or pulmonary embolism, now or in the past [see Warnings and Precautions ( 5.1 )]
Have inherited or acquired hypercoagulopathies [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 uncontrolled hypertension [see Warnings and Precautions ( 5.3 )]
Have diabetes mellitus with vascular disease [see Warnings and Precautions ( 5.5 )]
Have headaches with focal neurological symptoms or migraine headaches with aura [see Warnings and Precautions ( 5.6 )]
Women over age 35 with any migraine headaches [see Warnings and Precautions ( 5.6 )]
Liver tumors, benign or malignant, or liver disease [see Warnings and Precautions ( 5.2 )]
Undiagnosed abnormal uterine bleeding [see Warnings and Precautions ( 5.7 )]
Pregnancy, because there is no reason to use COCs during pregnancy [see Warnings and Precautions ( 5.8 ) and Use in Specific Populations ( 8.1 )]
Breast cancer or other estrogen-or progestin-sensitive cancer, now or in the past [see Warnings and Precautions ( 5.10 )]
A high risk of arterial or venous thrombotic diseases ( 4 )
Liver tumors or liver disease ( 4 )
Undiagnosed abnormal uterine bleeding ( 4 )
Pregnancy ( 4 )
Breast cancer or other estrogen-or progestin-sensitive cancer ( 4 )

At a glance

Brand name: Sprintec
Active substance: ethinyl estradiol
Route: Oral
Dosage form: Tablet
Applicant: Barr
Status: Prescription
FDA approval: 25 Sept 2002
Application: ANDA075804-001

Indications

Sprintec ® (norgestimate and ethinyl estradiol tablets) is an estrogen/progestin COC, indicated for use by women to prevent pregnancy. ( 1.1 )

1.1Oral Contraceptive

Sprintec ® (norgestimate and ethinyl estradiol tablets) is indicated for use by females of reproductive potential to prevent pregnancy [see Clinical Studies( 14 )].

Contraindications

Do not prescribe Sprintec to women 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 and Precautions ( 5.1 )]
Have deep vein thrombosis or pulmonary embolism, now or in the past [see Warnings and Precautions ( 5.1 )]
Have inherited or acquired hypercoagulopathies [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 uncontrolled hypertension [see Warnings and Precautions ( 5.3 )]
Have diabetes mellitus with vascular disease [see Warnings and Precautions ( 5.5 )]
Have headaches with focal neurological symptoms or migraine headaches with aura [see Warnings and Precautions ( 5.6 )]
Women over age 35 with any migraine headaches [see Warnings and Precautions ( 5.6 )]
Liver tumors, benign or malignant, or liver disease [see Warnings and Precautions ( 5.2 )]
Undiagnosed abnormal uterine bleeding [see Warnings and Precautions ( 5.7 )]
Pregnancy, because there is no reason to use COCs during pregnancy [see Warnings and Precautions ( 5.8 ) and Use in Specific Populations ( 8.1 )]
Breast cancer or other estrogen-or progestin-sensitive cancer, now or in the past [see Warnings and Precautions ( 5.10 )]
A high risk of arterial or venous thrombotic diseases ( 4 )
Liver tumors or liver disease ( 4 )
Undiagnosed abnormal uterine bleeding ( 4 )
Pregnancy ( 4 )
Breast cancer or other estrogen-or progestin-sensitive cancer ( 4 )

Interactions

Consult the labeling of concurrently used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. No drug-drug interaction studies were conducted with Sprintec. 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 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: 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 ethinyl estradiol (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, voriconazole, 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., boceprevir and telaprevir]) or with non-nucleoside reverse transcriptase 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.

7.3Interference 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 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 )] Adverse reactions commonly reported by COC users are:
Irregular uterine bleeding
Nausea
Breast tenderness
Headache The most common adverse reactions reported during clinical trials (≥2%) were: headache/migraine, abdominal/gastrointestinal pain, vaginal infection, genital discharge, breast issues (including breast pain, discharge, and enlargement), mood disorders (including depression and mood altered), flatulence, nervousness, rash. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact TEVA USA, PHARMACOVIGILANCE at 1-866-832-8537 or drug.safety@tevapharm.com; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of norgestimate and ethinyl estradiol was evaluated in 1,647 healthy women of child-bearing potential who participated in 3 clinical trials and received at least 1 dose of norgestimate and ethinyl estradiol for contraception.

Two trials were randomized active-controlled trials and 1 was an uncontrolled open-label trial. In all 3 trials, subjects were followed for up to 24 cycles. Common Adverse Reactions (≥ 2% of subjects) : The most common adverse reactions reported by at least 2% of the 1,647 women were the following in order of decreasing incidence: headache/migraine (32.9%), abdominal/gastrointestinal pain (7.8%), vaginal infection (8.4%), genital discharge (6.8%), breast issues (including breast pain, discharge, and enlargement) (6.3%), mood disorders (including depression and mood altered) (5%), flatulence (3.2%), nervousness (2.9%), and rash (2.6%).

Adverse Reactions Leading to Study Discontinuation : Over the three trials, between 11 to 21% of subjects discontinued the trial due to an adverse reaction. The most common adverse reactions (≥1%) leading to discontinuation were: metrorrhagia (6.9%), nausea/vomiting (5%), headache (4.1%), mood disorders (including depression and mood altered) (2.4%), premenstrual syndrome (1.7%), hypertension (1.4%), breast pain (1.4%), nervousness (1.3%), amenorrhea (1.1%), dysmenorrhea (1.1%), weight increased (1.1%), and flatulence (1.1%).

Serious Adverse Reactions : breast cancer (1 subject), mood disorders including depression, irritability, and mood swings (1 subject), myocardial infarction (1 subject), and venous thromboembolic events including pulmonary embolism (1 subject) and deep vein thrombosis (DVT) (1 subject).

6.2Postmarketing Experience

The following additional adverse drug reactions have been reported from worldwide postmarketing experience with norgestimate/ethinyl estradiol. Because these reactions are 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. Infections and Infestations : Urinary tract infection; Neoplasms Benign, Malignant and Unspecified (Incl.

Cysts and Polyps) : Breast cancer, benign breast neoplasm, hepatic adenoma, focal nodular hyperplasia, breast cyst; Immune System Disorders : Hypersensitivity; Metabolism and Nutrition Disorders : Dyslipidemia; Psychiatric Disorders : Anxiety, insomnia; Nervous System Disorders : Syncope, convulsion, paresthesia, dizziness; Eye Disorders : Visual impairment, dry eye, contact lens intolerance; Ear and Labyrinth Disorders : Vertigo; Cardiac Disorders : Tachycardia, palpitations; Vascular Events : Deep vein thrombosis, pulmonary embolism, retinal vascular thrombosis, hot flush; Arterial Events : Arterial thromboembolism, myocardial infarction, cerebrovascular accident; Respiratory, Thoracic and Mediastinal Disorders : Dyspnea; Gastrointestinal Disorders : Pancreatitis, abdominal distension, diarrhea, constipation; Hepatobiliary Disorders : Hepatitis; Skin and Subcutaneous Tissue Disorders : Angioedema, erythema nodosum, hirsutism, night sweats, hyperhidrosis, photosensitivity reaction, urticaria, pruritus, acne; Musculoskeletal, Connective Tissue, and Bone Disorders : Muscle spasms, pain in extremity, myalgia, back pain; Reproductive System and Breast Disorders : Ovarian cyst, suppressed lactation, vulvovaginal dryness; General Disorders and Administration Site Conditions : Chest pain, asthenic conditions.

Sprintec

Indications

1.1Oral Contraceptive

Contraindications

At a glance

Two medicines in one question?

Sprintec

Indications

1.1Oral Contraceptive

Contraindications

At a glance

Two medicines in one question?

Warnings and precautions

5.1Thromboembolic Disorders and Other Vascular

5.2Liver Disease Impaired Liver Function Do

5.3High Blood Pressure

5.4Gallbladder Disease

5.5Carbohydrate and Lipid Metabolic Effects

5.6Headache If

5.7Bleeding Irregularities and Amenorrhea Unscheduled Bleeding and Spotting Unscheduled (breakthrough

5.8COC Use Before or During Early Pregnancy

5.9Depression

5.11Effect on Binding Globulins

Interactions

7.1Effects of Other Drugs on Combined Oral Contraceptives

7.2Effects of Combined Oral Contraceptives on Other

7.3Interference with Laboratory Tests

Pregnancy and breastfeeding

8.1Pregnancy

Adverse reactions

6.1Clinical Trial Experience

6.2Postmarketing Experience

Composition

Official product information