ethinyl estradiol
Estinyl

Available forms
Available by prescription only
Tablets: 0.02 mg, 0.05 mg, 0.5 mg

Indications and dosages
 Palliative treatment of metastatic breast cancer (at least 5 years after menopause). Adults: 1 mg P.O. t.i.d. for at least 3 months.
 Female hypogonadism. Adults: 0.05 mg P.O. daily to t.i.d. for 2 weeks monthly, followed by 2 weeks progesterone therapy; continue for three to six monthly dosing cycles, followed by 2 months off.
 Vasomotor menopausal symptoms. Adults: 0.02 to 0.05 mg P.O. daily for cycles of 3 weeks on, 1 week off.
 Palliative treatment of metastatic inoperable prostatic cancer. Adults: 0.15 to 2 mg P.O. daily.

Pharmacodynamics
Estrogenic action: Ethinyl estradiol mimics the action of endogenous estrogen in treating female hypogonadism and menopausal symptoms. It inhibits growth of hormone-sensitive tissue in advanced, inoperable prostatic cancer and in certain carefully selected cases of breast cancer in men and postmenopausal women.

Pharmacokinetics
Absorption: After oral administration, estradiol is well absorbed but substantially inactivated by the liver.
Distribution: About 50% to 80% plasma protein- bound, particularly estradiol-binding globulin. Distribution occurs throughout the body, with highest levels appearing in fat.
Metabolism: Steroidal estrogens, including estradiol, are metabolized primarily in the liver, where they are conjugated with sulfate and glucuronide. Because of the rapid metabolism, nonesterified forms of estrogen, including estradiol, must usually be administered daily.
Excretion: The majority of estrogen elimination occurs through the kidneys in the form of sulfate or glucuronide conjugates.

Contraindications and precautions
Contraindicated in pregnant patients and patients with thrombophlebitis or thromboembolic disorders, estrogen-dependent neoplasia, breast or reproductive organ cancer (except for palliative treatment), and undiagnosed abnormal genital bleeding.
 Use cautiously in patients with cerebrovascular or coronary artery disease, gallbladder disease, hypertension, asthma, mental depression, bone disease, or cardiac, hepatic, or renal dysfunction. Also use cautiously in women who have a family history (mother, grandmother, sister) of breast or genital tract cancer or who have breast nodules, fibrocystic disease, or abnormal mammographic findings.

Interactions
Drug-drug. Drugs that induce hepatic metabolism (such as barbiturates, carbamazepine, primidone, and rifampin): May decrease estrogenic effects and accelerate the metabolism of certain other drugs. Use together cautiously.
Insulin, hormonal antidiabetics: Alters blood glucose levels. Adjust dosage if needed.
Tamoxifen: Decreases tamoxifen effects. Monitor patient closely.
Warfarin-type anticoagulants: Decreases anticoagulant effect. Dosage adjustment may be needed.
Drug-food. Caffeine: May increase serum caffeine levels. Discourage caffeine use.
Grapefruit juice: Elevates estrogen levels. Advise patient to take drug with liquid other than grapefruit juice.
Drug-lifestyle. Smoking: Increases risk of adverse CV effects. Discourage smoking.

Adverse reactions
CNS: headache, dizziness, chorea, depression, seizures, CVA.
CV: thrombophlebitis, thromboembolism, hypertension, edema, pulmonary embolism, MI.
EENT: worsening of myopia or astigmatism, intolerance of contact lenses.
GI: nausea, vomiting, abdominal cramps, bloating, anorexia, increased appetite, gallbladder disease.
GU: breakthrough bleeding, altered menstrual flow, dysmenorrhea, amenorrhea, endometrial cancer, cervical erosion, altered cervical secretions, enlargement of uterine fibromas, vaginal candidiasis, testicular atrophy, impotence.
Hepatic: cholestatic jaundice, hepatic adenoma.
Metabolic: hypercalcemia, weight changes.
Skin: melasma, urticaria, flushing (with rapid I.V. administration), hirsutism or hair loss, erythema nodosum, dermatitis.
Other: possible breast cancer, breast changes (tenderness, enlargement, secretion), gynecomastia in men.

Effects on lab test results
• May increase levels of triglyceride, glucose, calcium, phospholipid,and clotting factors VII, VIII, IX, and X. May decrease serum folate, pyridoxine, and antithrombin III levels.
• May increase PT, INR, and norepinephrine-induced platelet aggregability.

Overdose and treatment
Serious toxicity after overdose of this drug hasn’t been reported. Nausea may occur.
 Provide appropriate supportive care.

Special considerations
• Make sure patient has thorough physical examination before starting estrogen therapy. Patients receiving long-term therapy should have examinations yearly.
• Because of risk of thromboembolism, therapy should be discontinued at least 1 month before procedures that cause prolonged immobilization or raise the risk of thromboembolism, such as knee or hip surgery.
• Notify pathologist about estrogen therapy when sending specimens to laboratory for evaluation.
Pregnant patients
• Drug is contraindicated for use during pregnancy.
Breast-feeding patients
• Drug is contraindicated in breast-feeding women.
Geriatric patients
• Use cautiously in patients whose condition may be aggravated by fluid retention.

Patient education
• Provide patient with a package insert describing adverse reactions of estrogen as well as a verbal explanation.
• Emphasize importance of regular physical examinations and breast self-examinations.
• Warn patient to immediately report abdominal pain; pain, numbness, or stiffness in legs or buttocks; pressure or pain in chest; shortness of breath; severe headaches; visual disturbances such as blind spots, flashing lights, or blurriness; vaginal bleeding or discharge; breast lumps; swelling of hands or feet; yellow skin or sclera; dark urine; or light-colored stools.
• Tell diabetic patient to report elevated blood glucose level; antidiabetic dosage may be adjusted.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use