What is the usage and considerations for prescribing Xulane (ethinyl estradiol and norelgestromin) to a female of reproductive age for pregnancy prevention, given a potential history of blood clots, stroke, or breast cancer?

Xulane (Ethinyl Estradiol/Norelgestromin Transdermal Patch)

Primary Indication and Efficacy

Xulane is indicated for pregnancy prevention in women of reproductive age with a typical-use failure rate of approximately 9% and perfect-use failure rate of <1%, comparable to combined oral contraceptives. 1

• The patch delivers 20 μg ethinyl estradiol and 150 μg norelgestromin daily through transdermal absorption 2
• Applied once weekly for 3 consecutive weeks, followed by 1 patch-free week 3, 2
• Prevents pregnancy primarily by suppressing ovulation through gonadotropin inhibition, with secondary mechanisms including cervical mucus thickening and endometrial changes 2

Absolute Contraindications (Do NOT Prescribe)

Xulane is absolutely contraindicated in women with any history of blood clots, stroke, or breast cancer—these are FDA black-box contraindications that represent unacceptable health risks. 1

Thromboembolic Disease Contraindications:

• Current or history of deep vein thrombosis or pulmonary embolism 1, 3
• Current or history of cerebrovascular disease (stroke) or coronary artery disease 1, 3
• Known thrombogenic mutations (Factor V Leiden, prothrombin mutation) 4
• Valvular heart disease with complications 1, 3
• Major surgery with prolonged immobilization 1, 4

Cardiovascular Risk Factors:

• Age ≥35 years AND smoking ≥15 cigarettes daily (Category 4 - unacceptable risk) 4, 5
• Severe or uncontrolled hypertension (systolic ≥160 mmHg OR diastolic ≥100 mmHg) 3, 4
• Multiple atherosclerotic risk factors present simultaneously 4
• Diabetes with vascular complications (nephropathy, retinopathy, neuropathy, or duration ≥20 years) 4
• Migraine headaches with aura at any age 3, 4

Cancer Contraindications:

• Current breast cancer or personal history of breast cancer 1, 3, 4
• Carcinoma of the endometrium or other estrogen-dependent neoplasia 1

Other Absolute Contraindications:

• Acute or chronic hepatocellular disease with abnormal liver function 1
• Hepatic adenomas or carcinomas 1, 4
• Undiagnosed abnormal genital bleeding 1
• Known or suspected pregnancy 1

Critical Stroke Risk Considerations

The transdermal patch contains higher estrogen exposure (1.6 times) compared to oral contraceptives, which increases venous thromboembolism risk with odds ratios of 1.2 to 2.2 in some studies. 3

• The 2024 American Heart Association/American Stroke Association guidelines classify transdermal patches as having mild to moderate stroke risk increase depending on estrogen content 3
• Women aged 45-49 years using combined hormonal contraceptives have higher VTE incidence compared to younger users, though age-related interaction with baseline risk remains unclear 3
• The patch received FDA label revisions in 2012 with a black box warning citing possible increased VTE risk compared to 20-35 μg oral contraceptives 3

Relative Contraindications (Strong Caution Required)

• Age ≥35 years AND smoking <15 cigarettes daily (Category 3 - risks generally outweigh benefits; strongly prefer progestin-only methods) 4, 5
• Adequately controlled hypertension on medication (systolic 140-159 OR diastolic 90-99 mmHg) 4
• History of VTE with no current risk factors for recurrence 4
• Past breast cancer with no evidence of disease for 5 years 4

Safer Alternative Contraceptive Options

For women with thromboembolic history, stroke history, breast cancer history, or age ≥35 who smoke, progestin-only methods are the appropriate first-line contraceptive choices. 3, 4, 5

Category 1 Options (No Restrictions):

• Copper IUD 3, 4
• Levonorgestrel IUD 3, 4
• Etonogestrel contraceptive implant 3, 4
• Progestin-only pills (norethindrone or drospirenone) 3, 4
• Depo-medroxyprogesterone injection (Depo-Provera) - particularly appropriate for smokers over 40 with <0.05% failure rate 5

Required Baseline Screening Before Prescribing

Before initiating Xulane, assess pregnancy status and measure blood pressure—these are the only mandatory screenings required. 3

• Pregnancy test to rule out current pregnancy 3
• Blood pressure measurement to identify undiagnosed hypertension 3
• Detailed personal and family history of thromboembolic events, stroke, cardiovascular disease, and breast cancer 1
• Smoking status and quantity (critical for women ≥35 years) 4, 5
• Migraine history, specifically presence of aura 3, 4

Universal screening for thrombogenic mutations before initiating combined hormonal contraceptives is NOT cost-effective and is not recommended due to rarity of conditions and high screening costs. 3

Practical Prescribing Details

• Apply one patch weekly to abdomen, upper torso, upper outer arm, or buttocks 3
• Use for 3 consecutive weeks, then 1 patch-free week during which withdrawal bleeding occurs 3, 2
• Patch adhesion is excellent: only 1.8% require replacement for complete detachment and 2.9% for partial detachment 2
• Physical exercise, water immersion, and humid climates do not affect adhesion 2
• Provide or prescribe up to 1-year supply (13 cycles) at initial visit to maximize continuation rates 3

Ongoing Monitoring Requirements

• Assess satisfaction with method, concerns about use, and changes in health status at routine follow-up 3
• Monitor blood pressure at follow-up visits 3
• Evaluate any changes in medical conditions or medications that could affect medical eligibility 3
• Address breakthrough bleeding or spotting, which are common reasons for discontinuation 3

Duration of Use in Reproductive-Age Women

Contraception should be continued until confirmed menopause (12 months without menses) or age 50-55 years, as spontaneous pregnancies can occur in women >44 years. 3, 4

• Median age of menopause is approximately 51 years but ranges from 40-60 years 3
• No reliable laboratory tests confirm definitive loss of fertility; FSH levels are not accurate 3, 4
• Pregnancy risks in advanced reproductive age include higher maternal complications (hemorrhage, VTE, death) and fetal complications (spontaneous abortion, stillbirth, congenital anomalies) 3

Common Pitfalls to Avoid

• Never prescribe Xulane to women ≥35 years who smoke ≥15 cigarettes daily—this represents an absolute contraindication with dramatically increased MI and stroke risk 4, 5
• Do not overlook personal or family history of blood clots or stroke—any positive history is an absolute contraindication 1
• Do not assume breast cancer history from >5 years ago is safe—current or any history of breast cancer is an absolute contraindication 1, 3
• Always measure blood pressure before prescribing—undiagnosed hypertension is common and represents a major contraindication 4
• Do not prescribe for migraine with aura at any age—this combination dramatically increases stroke risk 3, 4

Non-Contraceptive Benefits

• May improve acne vulgaris (though not FDA-approved for this indication with Xulane specifically) 3, 6
• Reduces dysmenorrhea and heavy menstrual bleeding 6
• May be used for extended cycling by replacing patch monthly rather than using patch-free weeks 3
• Potential reduction in ovarian and endometrial cancer risk with long-term use 6