BE THE FIRST TO KNOW!

Sign up to receive product information and helpful resources and tools.

First Name required
LastName required
Email Address required Invalid email
Zip code required

Intended for US residents only. Mylan Pharmaceuticals, a VIATRIS™ Company understands that your personal and health information is private. The information you provide will only be used by Mylan Pharmaceuticals, a Viatris Company and parties acting on its behalf to send you the materials you requested and other helpful information and updates on XULANE, as well as related treatments, products, offers and service. You may remove yourself from this mailing list at any time by clicking "unsubscribe" on any e-newsletters or other communications that you receive. To learn about how Viatris uses your information, please view our Privacy Statement.

THANK YOU FOR
SIGNING UP!
Failed!
Image of front cover of FDA's draft guidance for hormonal drugs for the prevention of pregnancy

What is the
Pearl Index?

FDA has recommended in draft guidance that companies developing hormonal contraceptives use the Pearl Index (PI) during the first year of use of the product as a primary endpoint.

The PI is the number of pregnancies per 100 woman-years and is associated with a 95% confidence interval. FDA has recommended that this analysis be calculated only using women 35 years of age and younger.1

How is the Pearl Index calculated?

To calculate the Pearl Index, divide the number of pregnancies times 13 cycles by the number of 28 day cycles. Multiply the result by 100

Each cycle lasts 28 days, so there are approximately 13 cycles in one year.

The Pearl Index calculation typically includes all pregnancies for which conception is estimated to have occurred while the woman was using the drug (i.e., on-treatment pregnancies), but only includes cycles where the woman had vaginal intercourse and did not use backup or emergency contracepton.1

What is the Pearl Index of XULANE transdermal patch?

In clinical trials, NGMN/EE transdermal patch had a Pearl Index of 1.07 (95% CI, 0.60, 1.76)*, and is 99% effective2† when used as directed.

The pregnancy rate in women aged 18 to 35 years was 1.07 (95% CI 0.60, 1.76) per 100 woman-years. To achieve maximum contraceptive effectiveness, XULANE must be used exactly as directed. XULANE must adhere securely to the skin to work properly. See Limitations of Use.

*Differences exist from inclusion criteria from the more recent FDA Draft Guidance on calculations of Pearl Index. The impact on Pearl Index may be minimal. †In 3 large clinical trials lasting 12 months, 3,330 women (ages 18 to 45) completed 2,155 cycles of NGMN/EE (Ortho Evra®) transdermal system use.

Patient talking to Doctor

Pharmacokinetic overview

The systemic delivery rate of norelgestromin (NGMN) and ethinyl estradiol (EE) transdermal system is approximately 150 mcg of NGMN and 35 mcg of EE per day based on a comparative analysis with intravenous (IV) data. Following a single application of NGMN and EE transdermal system, both NGMN and EE reach a plateau by approximately 48 hours. Pooled data from the three clinical studies have demonstrated that steady state is reached within 2 weeks of application.2

Transdermal and Combined Oral Contraceptive (COC) PK profiles

In general, overall exposure for NGMN and EE (AUC and Css) was higher in subjects treated with norelgestromin and Ethinyl Estradiol transdermal system for both Cycle 1 and Cycle 2, compared to that for the oral contraceptive. Cmax values were higher in subjects administered the oral contraceptive. Under steady state conditions, AUC0-168 and Css for EE were approximately 55% and 60% higher, respectively, for norelgestromin and Ethinyl Estradiol transdermal system, and the Cmax was about 35% higher for the oral contraceptive, respectively.

Inter-subject variability (%CV) for PK parameters following delivery from NGMN and EE transdermal system was higher relative to the variability determined from the oral contraceptive. The mean PK profiles are different between the two products and caution should be exercised when making a direct comparison of these PK parameters.

Ethinyl Estradiol Exposure

Higher estrogen exposure may increase the risk of adverse reactions, including venous thromboembolism (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 (Cmax) for EE is approximately 25% lower in women using norelgestromin and Ethinyl Estradiol transdermal system [See Section 12.3 (Clinical Pharmacology) in the XULANE PI for more information].

The figures below present mean PK profiles for NGMN and EE, respectively, following once-daily administration of an oral contraceptive (containing NGM 250 mcg /EE 35 mcg) compared to the 7-day norelgestromin and Ethinyl Estradiol transdermal system (containing NGMN 4.86 mg/EE 0.53 mg) during Cycle 2 in 32 healthy female volunteers.


Image of chart showing Mean serum concentration - Time profiles of NGMN of TDS versus a COC. See below for results

Image of chart showing Mean serum concentration - Time profiles of EE of TDS versus a COC. See below for results

*Following once-daily administration of an oral contraceptive for two cycles or application of NGM for two cycles to the buttock in healthy female volunteers.

[Oral contraceptive: Cycle 2, Days 15 to 21, XULANE: Cycle 2, Week 3]

Image of chart showing Mean (%CV) NGMN and EE steady state pharmacokinetic parameters. See below for results

* Mean (%CV) NGMN and EE steady state pharmacokinetic parameters following application of norelgestromin and Ethinyl Estradiol transdermal system and once-daily administration of an oral contraceptive (containing NGM 250 mcg /EE 35 mcg) in healthy female volunteers
** Cycle 2, Week 3
† Cycle 2, Day 21
‡ NGM is rapidly metabolized to NGMN following oral administration
§ Average weekly exposure, calculated as AUC24 x 7
¶ Cavg
VTE: Venous Thromboembolism; COCs: Combined Oral Contraceptives; AUC: Area Under the Curve; EE: Ethinyl Estradiol; NGMN: Norelgestromin. TDS: Transdermal System

References:

  1. FDA. Establishing Effectiveness and Safety for Hormonal Drug Products Intended to Prevent Pregnancy – Guidance for Industry. Available from: https://www.fda.gov/media/128792/download Accessed April 22 2020.
  2. XULANE Prescribing Information. March 2022. Mylan Pharmaceuticals Inc. Morgantown, WV.

Scroll for Important Safety Information

IMPORTANT
SAFETY INFORMATION
sarrows sarrows

WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS and CONTRAINDICATED IN WOMEN WITH A BMI ≥ 30 kg/m2

• Cigarette Smoking and Serious Cardiovascular Events

Cigarette smoking increases the risk of serious cardiovascular events from hormonal contraceptive use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, CHCs, including XULANE, are contraindicated in women who are over 35 years of age and smoke [see Contraindications (4) and Warnings and Precautions (5.1)].

• Contraindicated in Women with a BMI ≥ 30 kg/m2

XULANE is contraindicated in women with a BMI ≥ 30 kg/m2. The risk of VTE may be greater with XULANE in women with a BMI > 30 kg/m2 compared to women with a lower BMI. [see Contraindications (4) and Warnings and Precautions (5.1)].

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 (Cmax) 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.