norelgestromin/ethinyl estradiol

norelgestromin/ethinyl estradiol Warning - Hazardous drug!

Evra (UK), Ortho Evra

Pharmacologic class: Estrogen

Therapeutic class: Hormone

Pregnancy risk category X

Action

Suppresses gonadotropin and inhibits ovulation by causing changes in cervical mucus and endometrium, thereby preventing egg implantation

Availability

Transdermal patch: 6 mg norelgestromin and 0.75 mg ethinyl estradiol (releases 150 mcg norelgestromin and 20 mcg ethinyl estradiol q 24 hours)

⊘Indications and dosages

➣ To prevent pregnancy

Adults: Apply patch on day 1 of menstrual cycle (or first Sunday after period begins). Change patch weekly thereafter for 3 weeks (on same day each week), and then remove patch for fourth week. Repeat q month.

Contraindications

• Hypersensitivity to drug or its components
• Undiagnosed vaginal bleeding
• Breast or reproductive system cancer
• Thromboembolism, history of thromboembolic disease
• Coronary artery disease
• Valvular heart disease with complications
• Severe hypertension, diabetes with vascular involvement
• Cerebrovascular disease
• Headache with focal neurologic symptoms
• Cholestatic jaundice of pregnancy, jaundice with previous hormonal contraceptive use
• Acute or chronic hepatic disease with abnormal liver function tests
• Hepatic adenomas or carcinomas
• Major surgery with prolonged immobilization
• Pregnancy or breastfeeding

Precautions

Use cautiously in:
• cardiovascular disease, severe hepatic or renal disease, asthma, bone disease, migraine, lipid disorders, fibrocystic breasts, increased risk for endometrial cancer, sexually transmitted diseases
• family history of breast or genital tract cancer
• abnormal mammogram.

Administration

• Apply patch to clean, dry, intact skin on buttock, abdomen, upper torso, or upper outer arm.
• Change patch on same day each week (except for fourth week, when patch is removed).

Route	Onset	Peak	Duration
Transdermal	Rapid	2 days	Unknown

Adverse reactions

CNS: headache, dizziness, lethargy, depression, emotional lability, increased risk of cerebrovascular accident

CV: edema, hypertension, myocardial infarction, thromboembolism

EENT: contact lens intolerance, worsening of myopia or astigmatism

GI: nausea, vomiting, jaundice, abdominal cramps, bloating, anorexia, gallbladder disease, pancreatitis

GU: amenorrhea, dysmenorrhea, breakthrough bleeding, cervical erosion, vaginal candidiasis, breast tenderness, breast enlargement or secretion, menstrual cramps, libido loss, increased risk of breast or endometrial cancer

Hepatic: cholestatic jaundice, hepatic adenoma

Metabolic: hyperglycemia, hypercalcemia, sodium and water retention

Musculoskeletal: leg cramps

Respiratory: upper respiratory infection, pulmonary embolism

Skin: acne, oily skin, increased pigmentation, urticaria, patch site reaction

Other: increased appetite, weight changes

Interactions

Drug-drug. Acetaminophen, ascorbic acid, atorvastatin, miconazole (vaginal capsules): increased ethinyl estradiol blood level

Antibiotics, barbiturates, carbamazepine, fosphenytoin, phenobarbital, phenytoin, rifampin: decreased contraceptive efficacy

Corticosteroids: enhanced corticosteroid effects

Cyclosporine: increased risk of cyclosporine toxicity

CYP3A4 inhibitors (such as ketoconazole, itraconazole): increased hormone level

Dantrolene, other hepatotoxic drugs: increased risk of hepatotoxicity

Insulin, oral hypoglycemics, warfarin: altered requirements for these drugs

Protease inhibitors: increased contraceptive metabolism

Tamoxifen: interference with tamoxifen effects

Drug-diagnostic tests. Antithrombin III, folate, low-density lipoproteins, pyridoxine, total cholesterol, urine pregnanediol: decreased levels

Cortisol; factors VII, VIII, IX, and X; glucose; high-density lipoproteins; phospholipids; prolactin; prothrombin; sodium; triglycerides: increased levels

Metyrapone test: false decrease

Thyroid function tests: false interpretation

Drug-food. Caffeine: increased blood caffeine level

Drug-herbs. Black cohosh: increased adverse drug effects

Red clover: interference with hormonal therapy

Saw palmetto: antiestrogenic effects

St. John's wort: decreased drug blood level and effects

Drug-behaviors. Smoking (15 or more cigarettes daily): increased risk of adverse cardiovascular reactions

Patient monitoring

• Evaluate menstrual pattern.
☞ Monitor blood pressure. Watch for signs and symptoms of thromboembolic disease (swelling or warmth in calf, sudden chest pain, shortness of breath).
• Check blood glucose level in diabetic patient.

Patient teaching

• Instruct patient to start using patch on first day of menstrual period or on first Sunday after period starts. Advise her to use calendar to keep track of which day each week to change patch.
• Tell patient to remove patch during fourth week of each cycle. Explain that she will have bleeding that week.
• Advise patient to check daily to ensure that patch is attached firmly to skin. Explain that if patch is detached for 1 day or less, she should try to reattach it more firmly. If patch is detached for more than 1 day or for an unknown length of time, she should start with new patch and new calendar.
• Instruct patient to use alternative contraception during first week of patch use.
☞ Inform patient that smoking while using patch increases risk of thromboembolic disease and other serious cardiovascular reactions. Stress importance of not smoking. Tell her to immediately report swelling or warmth in calf, chest pain, or shortness of breath.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, herbs, and behaviors mentioned above.