Estracon 0.625 mg

INDICATIONS

Conjugated Estrogen is indicated in-

Moderate-to-severe vasomotor symptoms associated with estrogen deficiency.
Prevention and management of osteoporosis associated with estrogen deficiency.
Decrease of the risk of coronary heart disease and its associated mortality in postmenopausal women.
Atrophic vaginitis and atrophic arthritis.
Female hypoestrogenism.

PHARMACOLOGY

Conjugated estrogens for oral administration is a mixture of estrogens, obtained exclusively from natural sources, blended to represent the average composition of material derived from pregnant mares’ urine. It contains the sodium salts of water-soluble sulfate esters of estrone, equilin, and 17alpha-dihydroequilin, together with smaller amounts of 17 alpha-estradiol, equilenin, 17 alpha-dihydroequilenin, 17 beta-dihydroequilin, 17 beta-dihydroequilenin, 17beta-estradiol, and delta 8,9-dehydroestrone.Estrogens are important in the development and maintenance of the female urogenital system and secondary sex characteristics. They promote growth and development of the vagina, uterus, and fallopian tubes, and enlargement of the breasts. Indirectly, they contribute to the shaping of the skeleton, maintenance of tone and elasticity of urogenital structures, changes in the epiphyses of the long bones associated with the pubertal growth spurt and its termination, growth of axillary and pubic hair, and pigmentation of the nipples and genital tissues. Decline of ovarian estrogenic and progestogenic activity at the end of the menstrual cycle can result in menstruation, although the cessation of progesterone secretion is the most important factor in the mature ovulatory cycle. However, in the preovulatory or anovulatory cycle, estrogen is the primary determinant in the onset menstruation. Eestrogen also affects the release of pituitary gonadotropins. The pharmacologic effects of conjugated estrogens are similar to those of endogenous estrogens. In responsive tissues (female urogenital organs, breasts, hypothalamus, pituitary) estrogens enter the cell and are transported into the nucleus. As a result of estrogenic activity, specific RNA and protein synthesis occurs. Oral administration of Conjugated Estrogens to postmenopausal women increases serum high density lipoprotein cholesterol (HDL-C) levels and decreases low density lipoprotein cholesterol (LDL-C) levels. This improves the lipid profile and is recognized as a factor responsible for the beneficial effects of Conjugated Estrogens on the risk of coronary heart disease in postmenopausal women. Conjugated Estrogens are soluble in water and are well absorbed from the gastrointestinal tract. Metabolism and inactivation occur primarily in the liver. Some estrogens are excreted in bile; however, they are reabsorbed from the intestine and returned to the liver through the portal venous system. Water-soluble estrogen conjugates are strongly acidic and are ionized in body fluids, which favors excretion through the kidneys since tubular reabsorption is minimal.

DOSAGE & ADMINISTRATION

Osteoporosis: 0.625 mg daily. This dose is required for bone mass conservation.Cardiovascular benefit: 0.625 mg-1.25 mg daily.Female hypoestrogenism: 0.3 mg-1.25 mg daily. Doses are adjusted depending on the severity of symptoms and responsiveness of the endometrium. Dose should be individualized to achieve optimum patient response.Administration of Conjugated Estrogen may be continuous (e.g., without a break in therapy) or cyclic (e.g., three weeks on and one week off.) The lowest effective dose should be administered. Conjugated Estrogen can be used concomitantly with progestogen.The addition of a progestogen during estrogen administration reduces the risk of endometrial hyperplasia and endometrial carcinoma, which have been associated with the use of unoposed estrogen. Morphological and biochemical studies of the endometrium suggest that an adequate dose of progestogen for at least 10-14 days per cycle will significantly reduce hyperplastic changes. Since progestogens are administered to reduce the risk of hyperplastic hanges of the endometrium, patients without a uterus do not require a progestogen for this purpose.Numerous reports of ingestion of large doses of estrogen-containing oral contraceptives by young children indicate that acute serious ill effects have not been observed. Overdosage of estrogens may cause nausea, and withdrawal bleeding may occur in females.

INTERACTION

Rifampin reportedly decreases estrogenic activity during concomitant use with estrogen. This effect has been attributed to enhanced metabolism of estrogen, presumably by induction of hepatic microsomal enzymes.

SIDE EFFECTS

The most serious adverse reactions associated with the use of estrogen are indicated under Warnings and Precautions. The following additional adverse reactions have been reported with estrogenic therapy.

Genitourinary system: Breakthrough bleeding, spotting, change in menstrual flow, amenorrhea.
Breasts: Tenderness, enlargement, secretion.
Gastrointestinal: Nausea, vomiting, abdominal cramps, bloating, cholestatic jaundice.
Skin: Chloasma or melasma which may persist when drug is discontinued, alopecia, rash.
Eyes: Steepening of the corneal curvature; intolerance to contact lenses.
Central nervous system: Headache, migraine, dizziness; chorea.
Miscellaneous: Increase or decrease in wiehgt; edema; changes in libido, aggravation of porphyria.

PREGNANCY & LACTATION

As a general principle the administration of any drug to nursing mothers should be done only when clearly necessary since many drugs are excreted in human milk.

PRECAUTIONS & WARNINGS

A complete medical and family history should be obtained 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. Patients with a uterus should be monitored at least annually for signs of endometrial hyperplasia or endometrial cancer. When concurrent progestogen therapy is used in women with a uterus, monitoring should include endometrial sampling. Certain patients may develop undesirable manifestations of excessive estrogenic stimulation, such as abnormal or excessive uterine bleeding, mastodynia, etc. In the event of abnormal vaginal bleeding, adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy. Where no pathologic cause is found for abnormal vaginal bleeding, dose reduction of cycling may be indicated. Pre-existing uterine leiomyomata may increase in size during estrogen use. Women on estrogen replacement therapy have not been reported to have an increased risk of thrombophlebitis and/or thromboembolic disease. However, there is insufficient information regarding women who have a history of thromboembolic disease to determine risk. There is no adequate evidence that estrogens are effective for nervous symptoms or depression which may occur during menopause and they should not be used to treat such conditions. If feasible, estrogen should be discontinued at least four weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization. Because estrogens may cause some degree of fluid retention, conditions which might be influenced by this factor such as asthma, epilepsy, migraine and cardiac or renal dysfunction require careful observation. Estrogen may be poorly metabolized in patients with impaired liver function and they should be administered with caution in such patients. Estrogen should be used with caution in patients with metabolic bone diseases associated with hypercalcemia. Patients should be advised that the resumption of menses associated with estrogen replacement therapy in postmenopausal women is not indicative of fertility. Conjugated Estrogens is not a contraceptive. Women of child bearing potential desiring contraception should be advised to adhere to non-hormonal contraceptive methods.

THERAPEUTIC CLASS

Female Sex hormones

STORAGE CONDITIONS

Store in a cool and dry place, protected from light and moisture, temperature below 25ºC.