CONTRAINDICATIONS

Do not prescribe XULANE to females who are known to have or develop the following conditions:

• A high risk of arterial or venous thrombotic diseases including women who:
  • * smoke, if over age 35
  • * have now or have had deep vein thrombosis or pulmonary embolism
  • * have inherited or acquired hypercoagulopathies
  • * have cerebrovascular disease
  • * have coronary artery disease
  • * have thrombogenic valvular or thrombogenic rhythm diseases of the heart including atrial fibrillation
  • * have uncontrolled hypertension
  • * have diabetes mellitus with vascular disease
  • * have headaches with focal neurological symptoms or have migraine headaches with aura
  • * women over age 35 with any migraine headaches;
• Body Mass Index ≥30 kg/m²
• Liver tumors or liver disease;
• Undiagnosed abnormal uterine bleeding;
• Pregnancy;
• Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive;
• Use Hepatitis C drug combinations containing ombitasvir/paritaprevir/
  ritonavir.

WARNINGS AND PRECAUTIONS

Thromboembolic Disorders and Other Vascular Conditions

• Do not use XULANE in women at high risk for arterial or venous thromboembolism diseases.
• Combination hormonal contraceptives (CHCs) increase the risk of thromboembolic disorders including venous thromboembolism (VTE). Known risk factors for VTE include smoking, obesity and family history of VTE. The risk of VTE is highest during the first year of CHC use and when restarting hormonal contraception after a break of 4 weeks or longer.
• Use of CHCs also increases the risk of arterial thromboses (e.g., stroke and myocardial infarction). The risk is greatest among hypertensive women who are >35 years old and smoke. Use CHCs with caution in women with cardiovascular disease risk factors.
• Stop XULANE if:
  • * an arterial or VTE occurs;
  • * there is unexplained loss of vision, proptosis, diplopia, papilledema, or retina vascular lesions;
  • * at least 4 weeks before and through 2 weeks after major surgery or surgeries known to have an elevated risk of VTE.
• Start XULANE no earlier than 4 weeks after delivery in women who are not breastfeeding.

Ethinyl Estradiol Exposure

• Higher estrogen exposure may increase the risk of adverse reactions, including VTE.
• The Area Under the Curve (AUC) for Ethinyl Estradiol (EE) is approximately 60% higher in women using XULANE compared to oral contraceptives containing EE 35 mcg. In contrast, the peak concentration (C_max) for EE is approximately 25% lower in women using norelgestromin and Ethinyl Estradiol transdermal system. [See Section 12.3 of the PI.]

Liver Disease

• Do not use XULANE in women with liver disease or tumors.
• Discontinue XULANE if jaundice or acute or chronic disturbances of liver function develop.
• Hepatic adenomas are associated with CHC use. Rupture of hepatic adenomas may cause death.
• Studies have shown an increased risk of developing hepatocellular carcinoma in long-term (> 8 years) CHC users.

Risk of liver enzyme elevations with concomitant hepatitis C treatment

• Discontinue XULANE prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/
  ritonavir, with or without dasabuvir.

High Blood Pressure

• XULANE is contraindicated in women with uncontrolled hypertension or hypertension with vascular disease.
• For women with well-controlled hypertension, monitor blood pressure and stop XULANE if blood pressure rises significantly.

Gallbladder Disease

• Studies suggest a small increased relative risk of developing gallbladder disease among CHC users. Use of CHCs may also worsen existing gallbladder disease.

Carbohydrate and Lipid Metabolic Effects

• Carefully monitor prediabetic and diabetic women on XULANE. CHCs may decrease glucose tolerance in a dose-related fashion.
• Consider alternative contraception for women with uncontrolled dyslipidemia.
• Women with (or family history of) hypertriglyceridemia may be at increased risk of pancreatitis.

Headache

• If a patient develops new headaches that are recurrent, persistent or severe, evaluate the cause and discontinue XULANE if indicated. Consider discontinuation of XULANE in the case of increased frequency or severity of migraines.

Bleeding Irregularities

• Women may experience unscheduled bleeding and spotting on XULANE. Rule out malignancy, other pathology or pregnancy.
• In the event of amenorrhea, consider the possibility of pregnancy.

Other Warnings and Precautions

• Discontinue XULANE use if pregnancy is confirmed.
• Carefully observe women with a history of depression and discontinue XULANE if depression recurs to a serious degree.
• XULANE is contraindicated in females who currently have or have had breast cancer because breast cancer may be hormonally sensitive. Some studies report a small increase in the risk of breast cancer among current or recent users (<6 months since last use) and current users with longer duration of Combination Oral Contraceptive (COC) use.
• Some studies suggest that COC use has been associated with an increase in the risk of cervical cancer or intraepithelial neoplasia.
• The estrogen component of CHCs may raise the serum concentrations of thyroxine-binding globulin, sex hormone-binding globulin and cortisol-binding globulin. The dose of replacement thyroid hormone or cortisol therapy may need to be increased.
• A woman who is taking hormonal contraceptive should have routine visits with her healthcare provider for a blood pressure check and for other indicated healthcare.
• In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema.
• Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum.

ADVERSE REACTIONS

• The most common adverse reactions (≥ 5%) reported during clinical trials of norelgestromin and Ethinyl Estradiol transdermal system were breast symptoms, nausea/vomiting, headache, application site disorder, abdominal pain, dysmenorrhea, vaginal bleeding and menstrual disorders, and mood, affect and anxiety disorders.

Patients should be counseled that XULANE does not protect against HIV infection (AIDS) and other sexually transmitted infections.

DRUG INTERACTIONS

• Drugs or herbal products that induce certain enzymes (for example CYP3A4) may decrease the effectiveness of CHCs or increase breakthrough bleeding. Counsel patients to use a back-up or alternative method of contraception.
• Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because serum concentration of thyroid-binding globulin increases with use of CHCs.

USE IN SPECIAL POPULATIONS

• The effects of XULANE in nursing mothers have not been evaluated and are unknown. Advise women to use other forms of contraception while nursing.
• XULANE has not been studied in postmenopausal women or in women before menarche and should not be used in these populations.

INDICATION AND USAGE: XULANE is indicated for the prevention of pregnancy in women with a body mass index (BMI) <30 kg/m² for whom a combined hormonal contraceptive is appropriate.

Limitations of Use: XULANE may be less effective in preventing pregnancy in women who weigh 198 lbs. (90 kg) or more. XULANE is contraindicated for use in women with BMI ≥ 30 kg/m² [see Contraindications (4), Warnings and Precautions (5.1) and Clinical Studies (14)].

This is not all of the information you should read prior to prescribing XULANE. Please see the Full Prescribing Information, including Boxed WARNING.