Norelgestromin, Ethinyl Estradiol Transdermal

ORTHO EVRA is a combination transdermal contraceptive system with a contact surface area of 20 cm². It contains 6 mg NGMN and 0.75 mg EE. Systemic exposures (as measured by area under the curve [AUC] and steady state concentration [Css]) of NGMN and EE during use of ORTHO EVRA are higher and the Cmax is lower than those produced by an oral contraceptive containing NGM 250 mcg / EE 35 mcg. [see BOXED WARNING and CLINICAL PHARMACOLOGY].

ORTHO EVRA is a thin, matrix-type transdermal contraceptive patch consisting of three layers. The backing layer is composed of a beige flexible film consisting of a low-density pigmented polyethylene outer layer and a polyester inner layer. It provides structural support and protects the middle adhesive layer from the environment. The middle layer contains polyisobutylene/polybutene adhesive, crospovidone, non-woven polyester fabric and lauryl lactate as inactive components. The active components in this layer are the hormones, NGMN and EE. The third layer is the release liner, which protects the adhesive layer during storage and is removed just prior to application. It is a transparent polyethylene terephthalate (PET) film with a polydimethylsiloxane coating on the side that is in contact with the middle adhesive layer.

The outside of the backing layer is heat-stamped “ORTHO EVRA®.”

The structural formulas of the components are:

Molecular weight, NGMN: 327.47

Molecular weight, EE: 296.41

Chemical name for NGMN: 18, 19-Dinorpregn-4-en-20-yn-3-one, 13-ethyl-17-hydroxy-,3-oxime,(17α)

Chemical name for EE: 19-Norpregna-1,3,5(10)-trien-20-yne-3, 17-diol,(17α)

Dosage Forms And Strengths

Transdermal system

ORTHO EVRA is a 20 cm² beige, thin, matrix-type transdermal system containing 6 mg norelgestromin (NGMN) and 0.75 mg EE.

The outside of the backing layer is heat-stamped “ORTHO EVRA®.”

Storage And Handling

Each beige ORTHO EVRA patch contains 6 mg NGMN and 0.75 mg EE.

Each patch surface is heat stamped with ORTHO EVRA. Each patch is packaged in a protective pouch.

ORTHO EVRA is available in folding cartons of 1 cycle each (NDC 50458-192-15); each cycle contains 3 patches.

ORTHO EVRA is available for clinic usage in folding cartons of 1 cycle each (NDC 50458-192-24); each cycle contains 3 patches.

ORTHO EVRA is also available in folding cartons containing a single patch (NDC 50458-192-01), intended for use as a replacement in the event that a patch is inadvertently lost or destroyed.

Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F).

Store patches in their protective pouches. Apply immediately upon removal from the protective pouch.

Do not store in the refrigerator or freezer.

Used patches still contain some active hormones. The sticky sides of the patch should be folded together and the folded patch placed in a sturdy container, preferably with a child-resistant cap, and the container thrown in the trash. Used patches should not be flushed down the toilet.

Mfd. by: Janssen Ortho, LLC Manati, Puerto Rico 00674. Mfd. for: Janssen Pharmaceuticals, Inc. Titusville, New Jersey 08560. Revised June 2013

Included as part of the PRECAUTIONS section.

This medication can cause birth defects. Do not use if you are pregnant. Tell your doctor right away if you become pregnant, or if you miss two menstrual periods in a row. If you have recently had a baby, wait at least 4 weeks before using this medication.

You should not use this medication if you have:

• untreated or uncontrolled high blood pressure;
• heart disease (coronary artery disease, uncontrolled heart valve disorder, history of heart attack, stroke, or blood clot);
• a blood-clotting disorder or circulation problems;
• problems with your eyes, kidneys or circulation caused by diabetes;
• a history of hormone-related cancer such as breast or uterine cancer;
• unusual vaginal bleeding that has not been checked by a doctor;
• liver disease or liver cancer;
• severe migraine headaches (with aura, numbness, weakness, or vision changes), especially if you are older than 35;
• a history of jaundice caused by pregnancy or birth control pills; or
• if you smoke and are over 35 years old.

To make sure you can safely use this medication, tell your doctor if you have any of these other conditions:

• high blood pressure, varicose veins;
• high cholesterol or triglycerides, or if you are overweight;
• a history of depression;
• underactive thyroid;
• gallbladder disease;
• diabetes;
• seizures or epilepsy;
• a history of irregular menstrual cycles;
• tuberculosis; or
• a history of fibrocystic breast disease, lumps, nodules, or an abnormal mammogram.

The hormones in this medication can pass into breast milk and may harm a nursing baby. This medication may also slow breast milk production. Do not use if you are breast-feeding a baby.

Your risk of serious blood clot may be higher with the use of birth control skin patches than with the use of birth control pills.

Your pharmacist can provide more information about ethinyl estradiol and norelgestromin.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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The following serious adverse reactions with the use of combination hormonal contraceptives, including ORTHO EVRA, are discussed elsewhere in the labeling:

• Serious cardiovascular events and stroke [see BOXED WARNING and WARNINGS AND PRECAUTIONS]
• Vascular events, including venous and arterial thromboembolic events [see WARNINGS AND PRECAUTIONS]
• Liver disease [see WARNINGS AND PRECAUTIONS]

Adverse reactions commonly reported by users of combination hormonal contraceptives are:

• Irregular uterine bleeding
• Nausea
• Breast tenderness
• Headache

Clinical Trials 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 data described below reflect exposure to ORTHO EVRA in 3330 sexually active women (3322 of whom had safety data) who participated in three Phase 3 clinical trials designed to evaluate contraceptive efficacy and safety. These subjects received six or 13 cycles of contraception (ORTHO EVRA or an oral contraceptive comparator in 2 of the trials). The women ranged in age from 18 to 45 years and were predominantly white (91%).

The most common adverse reactions ( ≥ 5%) reported during clinical trials were breast symptoms, nausea/vomiting, headache, application site disorder, abdominal pain, dysmenorrhea, vaginal bleeding and menstrual disorders, and mood, affect and anxiety disorders. The most common events leading to discontinuation were application site reaction, breast symptoms (including breast discomfort, engorgement and pain), nausea and/or vomiting, headache and emotional lability.

Adverse drug reactions reported by ≥ 2.5% of ORTHO EVRA-treated subjects in these trials are shown in Table 3.

Table 3: Adverse Drug Reactions Reported by ≥ 2.5% of ORTHO EVRA-treated Subjects in Three Phase 3 Clinical Trials

Additional adverse drug reactions that occurred in < 2.5% of ORTHO EVRA-treated subjects in the above clinical trials datasets are:

• Gastrointestinal disorders: Abdominal distension
• General disorders and administration site conditions: Fluid retention1, malaise
• Hepatobiliary disorders: Cholecystitis
• Investigations: Blood pressure increased, lipid disorders1
• Musculoskeletal and connective tissue disorders: Muscle spasms
• Psychiatric disorders: Insomnia, libido decreased, libido increased
• Reproductive system and breast disorders: Galactorrhea, genital discharge, premenstrual syndrome, uterine spasm, vaginal discharge, vulvovaginal dryness
• Respiratory, thoracic and mediastinal disorders: Pulmonary embolism
• Skin and subcutaneous tissue disorders: Chloasma, dermatitis contact, erythema, skin irritation

Postmarketing Experience

The following adverse reactions (Table 4) have been identified during postapproval use of ORTHO EVRA. 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.

Table 4: Alphabetical List of Adverse Drug Reactions Identified During Postmarketing Experience with ORTHO EVRA/EVRA by System Organ Class*

REFERENCES

1Represents a bundle of similar terms

Read the entire FDA prescribing information for Ortho Evra (Norelgestromin, Ethinyl Estradiol Transdermal)