Delestrogen (Estradiol Valerate)

DELESTROGEN®

Squibb

Estradiol Valerate

Estrogen

Indications And Clinical Uses: In nonpregnant women, Delestrogen is indicated in the treatment of amenorrhea (primary and secondary); disturbances of the menstrual cycle (hypomenorrhea, oligomenorrhea, irregular cycles, metrorrhagia); deficiency syndromes (castration, primary ovarian failure, menopause); local manifestations of estrogen deficiency (senile vaginitis, pruritus vulvae); abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology; and for the production of secretory endometrium and desquamation.

Also indicated for the treatment of advanced mammary carcinoma in women 5 years or more postmenopausal and in the relief of postpartum breast engorgement and inhibition of lactation. May also be used in the palliative treatment of inoperable progressing prostatic carcinoma in males.

Contra-Indications: Estrogens should not be administered to patients with active hepatic dysfunction or disease, especially of the obstructive type; patients with known or suspected endometrial carcinoma or carcinoma of the cervix uteri, carcinoma of the breast except in special circumstances (see Indications); patients with endometrial hyperplasia without accompanying progestogen; hypersensitivity to estrogens.

Estrogens are also contraindicated in the following situations: undiagnosed vaginal bleeding; a history of cerebrovascular accident, coronary thrombosis, or in the presence of classical migraine; thrombophlebitis or thromboembolic disease or a history of these conditions; partial or complete loss of vision or diplopia, from ophthalmic vascular disease; suspected pregnancy.

Steroidal suppression of lactation, in the immediate postpartum period is contraindicated in patients over 35 years of age or in the face of circumstances that predispose to puerperal thromboembolism such as a history of thromboembolism, operative delivery, infection, obesity, multiparity or varicose veins.

Precautions: Before estradiol is administered, the patient should have a complete physical examination including a blood pressure determination. Breasts and pelvic organs should be examined and a Papanicolaou smear should be taken.

The first follow-up examination should be done within 6 months after initiation of treatment. Thereafter, examinations should be made at least once a year. At each annual visit, 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. Liver function tests should be made periodically in subjects who have, or are suspected of having, hepatic disease.

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

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

If the patient develops any sign of phlebitis or thromboembolic complications, papilledema or retinal vascular lesions, discontinue medication.

Because normal endogenous hormone production varies individually, certain patients may be unusually responsive to estrogenic therapy and may respond with undesirable manifestations of excessive estrogenic stimulation such as abnormal or excessive uterine bleeding, mastodynia, edema.

When large doses of estrogens are used, urinary stress incontinence may occur.

Lactation: Estrogen may be excreted in the mother’s milk and an estrogenic effect upon the nursing infant has been described.

In patients with metastatic carcinoma and hypercalcemia, estrogen medication should be used with caution.

Close medical supervision is mandatory when estrogens are used for the treatment of mammary or prostatic carcinoma. Therapy should be immediately discontinued if there is a recurrence or an acceleration of the condition.

Continuous use of estrogens will result in prolonged stimulation of the endometrium and breast. To avoid this in the menopausal or hypogonadal patient, estrogens should be administered cyclically (see Dosage).

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

Estrogen may cause fluid retention. 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.

When liver or endocrine function tests are indicated, the results should not be considered reliable unless therapy has been discontinued for 2 to 4 months.

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

Prolonged high doses of estrogens will inhibit anterior pituitary function. This should be borne in mind when treating patients in whom fertility is desired.

Estrogens should be used with caution in patients with certain metabolic bone diseases that are associated with hypercalcemia or in patients with renal insufficiency.

Discontinue the medication in patients with a history of psychiatric abnormalities if exaggeration of symptoms occur.

Adverse Reactions: The following adverse effects have been reported with estrogens generally and may be encountered when giving any estrogen: Gastrointestinal: nausea, anorexia, vomiting, abdominal cramps, bloating, cholestatic jaundice, increase or decrease in body weight.

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

Endocrine: breast swelling and tenderness, increased blood sugar concentrations, and decreased glucose tolerance; in males: gynecomastia, reduced potency and feminization.

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

Dermatologic: hypersensitivity: loss of scalp hair, allergic reactions and rashes, chloasma or melasma; hemorrhagic eruption, itching, erythema nodosum and erythema multiforme.

Musculoskeletal: backache.

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

Hematologic: A statistically significant association between the use of estrogen-progestin preparations and the following serious reactions has been demonstrated: thrombophlebitis, pulmonary embolism and cerebral thrombosis. Coagulation tests may give altered results (increased prothrombin, and Factors VII, VIII, IX and X).

While available evidence suggests an association with the following serious reactions, such a relationship has been neither confirmed nor refuted: coronary thrombosis and neuro-ocular lesions, e.g., retinal thrombosis and optic neuritis.

Miscellaneous: pain at the injection site, sterile abscess, incomplete suppression of breast engorgement, mastodynia, premenstrual like syndrome, precipitation or aggravation of porphyria cutanea tarda in predisposed individuals.

Symptoms And Treatment Of Overdose: Symptoms: Accidental overdosage may result in nausea, vomiting and abdominal cramps, headache, dizziness and general malaise. The transient hyperestrogenic effects may include severe temporary sodium and water retention in some susceptible individuals.

Treatment: Symptomatic. For severe temporary sodium and water retention, administer diuretics.

Dosage And Administration: Care should be taken to inject deeply into the upper, outer quadrant of the gluteal muscle following the usual precautions for i.m. administration. By virtue of the low viscosity of the vehicle, Delestrogen may be administered with a small gauge needle. A dry needle and syringe should be used. Use of a wet needle or syringe may cause the solution to become cloudy; however, this does not affect the potency of the material.

In general, estrogens 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.

The lowest effective dosage should be used and the requirement for estrogen therapy should be assessed periodically.

Castration, Primary Ovarian Failure, Menopausal Syndrome, Senile Vaginitis, Kraurosis Vulvae With or Without Pruritus: The cyclic therapy schedule should be used, starting anytime and continuing through 4 cycles. Continuous therapy with estrogen alone may induce dysfunctional uterine bleeding.

Inoperable Prostatic Carcinoma: 30 mg or more every 1 to 2 weeks. Close medical supervision is mandatory. Suspend therapy if there is a relapse. Soreness of the breast or gynecomastia may occur; hypercalcemia may develop.

Inhibition of Lactation; Postpartum Breast Engorgement: 10 to 25 mg as a single injection at the end of the first stage of labor.

Amenorrhea, Production of Secretory Endometrium and Desquamation: administer 375 mg of hydroxyprogesterone caproate injection anytime. After 4 days of desquamation or, if there is no bleeding 21 days after hydroxyprogesterone alone, start cyclic therapy schedule. Repeat cyclic therapy every 4 weeks; stop after 4 cycles for amenorrhea, or when cyclic therapy is no longer required for production of secretory endometrium and desquamation. Exclude genital malignancy before hormone therapy is started. To determine onset of normal cyclic function, patient should be observed for 2 to 3 cycles after cessation of therapy.

Disturbances of the Menstrual Cycle (hypomenorrhea, oligomenorrhea, irregular cycles, metrorrhagia): The cyclic therapy schedule should be used, starting at the beginning of the cycle and repeated for 4 cycles. To determine the onset of normal cyclic function, the patient should be observed for 2 to 3 cycles without any hormone therapy.

Advanced Mammary Carcinoma in Women 5 Years or More Postmenopausal: 20 to 40 mg every 2 or 3 weeks. Close medical supervision is mandatory. Suspend therapy if there is a relapse. Therapy may be discontinued briefly after each course of 4 months, to permit the endometrium to regress. Estrogen therapy may induce vaginal bleeding; hypercalcemia may develop.

Cyclic Therapy Schedule: Cyclic therapy is a 28 day cycle which is repeated every 4 weeks. The cyclic therapy schedule is as follows: 20 mg of estradiol valerate injection is administered on Day 1 of each cycle. Two weeks after Day 1, 250 mg of hydroxyprogesterone caproate injection and 5 mg of estradiol valerate injection are administered; 4 weeks after Day 1 is Day 1 of next cycle.

Availability And Storage: Each mL of sterile suspension contains: estradiol valerate 10 mg in sesame oil plus 0.5% chlorobutanol as a preservative. Nonmedicinal ingredients: chlorobutanol 0.5% w/v and sesame oil. Vials of 5 mL. Delestrogen may be stored at room temperature. Low temperatures may result in separation of some crystalline material which redissolves readily on warming.

DELESTROGEN® Squibb Estradiol Valerate Estrogen

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