Estinyl (Ethinyl Estradiol)

ESTINYL®

Schering

Ethinyl Estradiol

Estrogen

Action And Clinical Pharmacology: Ethinyl estradiol promotes growth of the endometrium; promotes thickening, stratification and cornification of the vagina. It causes enlargement of the ducts of the mammary glands and promotes the development of secondary female sex characteristics. Ethinyl estradiol inhibits pituitary gonadotropin secretion probably via action on the hypothalamus. Similar to other estrogens it influences calcium and phosphorus metabolism, possesses some anabolic action on protein metabolism and induces retention of sodium and water. In cases of advanced mammary carcinoma in postmenopausal women and in cases of prostatic carcinoma, the metastatic growth may be inhibited by high doses of estrogens.

Indications And Clinical Uses: Menopausal syndrome; abnormal uterine bleeding due to hormonal imbalance in absence of organic pathology; palliative treatment of progressing inoperable or roentgen resistant mammary carcinoma in women who are at least 5 years postmenopausal; palliative treatment of inoperable prostatic carcinoma.

Contra-Indications: Patients with active hepatic dysfunction or disease, especially of the obstructive type; or a personal history of breast or endometrial cancer, except in special circumstances.

Endometrial hyperplasia is also a contraindication for estrogen therapy without accompanying progestogen.

The drug is also contraindicated in undiagnosed vaginal bleeding; a history of cerebrovascular accident, coronary thrombosis, or the presence of classical migraine; a history of thrombophlebitis or thromboembolic disease; partial or complete loss of vision or diplopia, from ophthalmic vascular disease; suspected pregnancy.

Manufacturers’ Warnings In Clinical States: Induction of Malignant Neoplasms: At the present time the effect of replacement hormones on the risk of breast or ovarian cancer is unknown. Most studies suggest a small but significant increased risk of breast cancer after long-term use. There is a need for caution in prescribing estrogens for women with a strong family history of breast cancer or who have breast nodules, fibrocystic disease, or abnormal mammograms. Women on this therapy should have regular breast examinations and should be instructed in breast self-examination.

Independent studies have shown an increased risk of endometrial cancer in postmenopausal women treated with estrogens for prolonged periods. However, administration of a progestogen for the last 10 to 14 days of an estrogen cycle protects the endometrium from hyperplasia and reduces the risk of endometrial cancer to that of untreated women.

Thromboembolic Disease: It is now well established that users of oral contraceptives have an increased risk of various thromboembolic and thrombotic vascular diseases such as thrombophlebitis, pulmonary embolism, stroke, and myocardial infarction. Cases of retinal thrombosis, mesenteric thrombosis, and optic neuritis have been reported in oral contraceptive users. There is evidence that the risk of several of these adverse reactions is related to the dose of the drug. An increased risk of postsurgery thromboembolic complications has also been reported in users of oral contraceptives. If feasible, estrogen should be discontinued at least 4 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of immobilization.

Estrogens should not be used in persons with active thrombophlebitis or thromboembolic disorders, and they should not be used (except in treatment of malignancy) in persons with a history of such disorders in association with estrogen use. They should be used with caution in patients with cerebral vascular or coronary artery disease and only for those in whom estrogens are clearly needed.

Hepatic Adenoma: Benign hepatic adenomas appear to be associated with the use of oral contraceptives. Although benign and rare, these may rupture and may cause death through intra-abdominal hemorrhage. Such lesions have not yet been reported in association with other estrogen or progestogen preparations, but should be considered in estrogen users having abdominal pain and tenderness, abdominal mass, or hypovolemic shock. Hepatocellular carcinoma has also been reported in women taking estrogen-containing oral contraceptives. The relationship of this malignancy to these drugs is not known at this time.

Elevated Blood Pressure: Increased blood pressure is not uncommon in women using oral contraceptives. Blood pressure should be monitored with estrogen use, especially if high doses are used.

Glucose Tolerance: A worsening of glucose tolerance has been observed in a significant percentage of patients on estrogen-containing oral contraceptives. For this reason, diabetic patients should be carefully observed while receiving estrogen.

Hypercalcemia: Administration of estrogens may lead to severe hypercalcemia in patients with breast cancer and bone metastases. If this occurs, the drug should be stopped and appropriate measures taken to reduce the serum calcium level.

Precautions: A complete medical and family history should be taken prior to the initiation of any estrogen therapy. The pretreatment and periodic physical examinations should include special reference to blood pressure, breasts, abdomen and pelvic organs, and should include a Papanicolaou smear. The first follow-up examination should be done within 6 months after initiation of treatment. Thereafter, examinations should be made once a year. At each examination, repeat those procedures outlined above.

If any surgical procedures are performed, advise the pathologist of the patient’s therapy when specimens are sent for examination.

Conduct periodic liver function tests in subjects who have, or are suspected of having, hepatic disease.

If abnormal vaginal bleeding occurs during therapy, perform diagnostic aspiration biopsy or curettage to rule out the possibility of uterine malignancy.

Patients who develop visual disturbances, classical migraine, transient aphasia, paralysis, or loss of consciousness should discontinue medication.

If the patient develops any sign of phlebitis or thromboembolic complications, discontinue medication.

Because estrogens influence the metabolism of calcium and phosphorus, they should be used with caution in patients with metastatic breast carcinoma or metabolic bone diseases that are associated with hypercalcemia or in patients with renal insufficiency.

Gallbladder Disease: A recent study has reported a 2 to 3 fold increase in the risk of surgically confirmed gallbladder disease in women receiving postmenopausal estrogens similar to the 2 fold increase previously noted in users of oral contraceptives. In the case of oral contraceptives, the increased risk appeared after 2 years of use.

Development of sudden enlargement, pain or tenderness of uterine fibroids requires discontinuation of medication.

Estrogen may cause fluid retention. Therefore, particular caution is indicated in cardiac or renal dysfunction, epilepsy, or asthma.

Elevation of blood pressure in previously normotensive or hypertensive patients necessitates cessation of medication.

Diabetic patients or those with a predisposition to diabetes should be observed closely to detect any alterations in carbohydrate metabolism.

Because of the effects of estrogens on epiphyseal closure, they should be used judiciously in young patients in whom bone growth is not complete.

Drug/Laboratory Test Interactions : Certain endocrine and liver function tests may be affected by estrogen-containing oral contraceptives. The following similar changes may be expected with larger doses of estrogen: increased sulfobromophthalein retention; increased prothrombin and factors VII, VIII, IX and X; decreased antithrombin 3; increased norepinephrine-induced platelet aggregation; increased thyroid binding globulin (TGB) leading to increased circulating total thyroid hormone, as measured by PBI, T4 by column, or T4 by radioimmunoassay. Free T3 resin uptake is decreased, reflecting the elevated TBG; free T4 concentration is unaltered; impaired glucose tolerance; decreased pregnanediol excretion; reduced response to metyrapone test; reduced serum folate concentration; increased serum triglyceride and phospholipid concentration.

Pregnancy: The use of estrogens during early pregnancy may seriously damage the offspring.

Lactation: Because of the potential for tumorigenicity shown for ethinyl estradiol in animal and human studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Children: Safety and effectiveness in children have not been established.

Adverse Reactions: Although not all of the following reactions have been specifically associated with ethinyl estradiol, they have been reported with estrogens generally, including oral contraceptives, and may be encountered when giving any estrogen.

Gastrointestinal: nausea, anorexia, vomiting, abdominal cramps, bloating, cholestatic jaundice.

Genitourinary: sodium and water retention, breakthrough bleeding, spotting, and withdrawal bleeding, increased cervical mucus, reactivation of endometriosis, and cystitis like syndrome.

Endocrine: breast swelling and tenderness, possible diminution of lactation when given immediately post partum, increased blood sugar levels, and decreased glucose tolerance.

CNS: headaches, migraine, mental depression, increase or decrease of libido, nervousness, dizziness, fatigue, irritability, and malaise.

Dermatologic Hypersensitivity: chloasma or melasma which may persist when drug is discontinued; loss of scalp hair, allergic reactions and rashes, hemorrhagic eruption, itching, erythema nodosum, erythema multiforme.

Musculoskeletal: backache.

Cardiovascular: an increase in blood pressure in susceptible individuals and aggravation of migraine headaches.

Hematologic: A statistically significant association has been demonstrated between the use of estrogen containing drugs and the following reactions: thrombophlebitis, pulmonary embolism, cerebral thrombosis. Although available evidence is suggestive of an association, such a relationship has been neither confirmed nor refuted for the following serious reactions: coronary thrombosis and neuro-ocular lesions (e.g., retinal thrombosis and optic neuritis).

Ophthalmic: steepening of corneal curvature; intolerance to contact lenses.

Miscellaneous: Premenstrual like syndrome, precipitation or aggravation of porphyria cutanea tarda in predisposed individuals, increase or decrease in body weight.

Symptoms And Treatment Of Overdose: Symptoms: Other than possible nausea, no signs or symptoms are anticipated from a single excessive dose, except maybe abnormal uterine bleeding which usually is self limited and does not require any specific treatment.

Treatment: In case of accidental ingestion by a child, gastric emptying is suggested.

Dosage And Administration: In general, estrogen should be given cyclically and in some cases with progestogen or androgen to avoid overstimulation of breast and endometrial tissues. The addition of sufficient progestogen to promote conversion of the endometrium is mandatory in those patients who are receiving sufficient unopposed estrogen to cause vaginal bleeding or endometrial hyperplasia. Obviously, abnormal vaginal bleeding in such patients is an indication for prompt diagnostic measures.

For the relief of menopausal symptoms, administer 5 or 10 g of ethinyl estradiol daily for 21 days, followed by a 7 day period without medication.

Dosage may require adjustment as therapy progresses. Use the lowest effective dosage and assess the requirement for estrogen therapy periodically.

Functional Uterine Bleeding: 500 g once or twice daily until hemostasis is secured, then cyclic administration of 50 g 1 to 3 times daily during the first 2 weeks of the menstrual cycle, followed by progesterone for 5 days. Three such cycles of therapy may be given.

Carcinoma of the Breast in Postmenopausal Women (Palliative): 100 g 3 times daily.

Prostatic Carcinoma (Palliative): 0.15 to 3 mg daily taken at bedtime. Therapy may be continued with dose adjustment depending on the patient’s response.

Availability And Storage: 20 g: Each buff, coated tablet contains: ethinyl estradiol USP 20 g. Nonmedicinal ingredients: cornstarch; dye, FD & C Yellow No. 6; lactose; magnesium stearate and povidone; coating: acacia; carnauba wax; cornstarch; dye, Opalux Off-White; gelatin; tribasic calcium phosphate; sucrose and white wax. Tartrazine-free. Bottles of 100.

50 g: Each pink, coated tablet contains: ethinyl estradiol USP 50 g. Nonmedicinal ingredients: cornstarch, lactose, magnesium stearate and povidone; coating: acacia; carnauba wax; cornstarch; dye, Opalux Pink; gelatin; tribasic calcium phosphate; sucrose and white wax. Tartrazine-free. Bottles of 100.

500 g: Each peach, scored tablet contains: ethinyl estradiol USP 500 g. Nonmedicinal ingredients: cornstarch; dye, FD & C Yellow No. 6; lactose; magnesium stearate and povidone. Tartrazine-free. Bottles of 100.

Store between 2 and 30°C.

ESTINYL® Schering Ethinyl Estradiol Estrogen

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Menopause

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