Estrogen Conjugated Cream Gel Cream Ointment API USP Finished Dosages

Estrogen Conjugated Cream Gel Cream Ointment API USP Finished Dosages

PRODUCT : Conjugated Estrogens Cream

Dosage and Strenth : Cream, 0.625mg/g
PACKING : 43g/tube, 1tube/box

Standard : API according to USP, finished dosages in house standard

Dossier: Ready to submit

INDICATIONS AND USAGE :

Conjugated Estrogens Vaginal Cream therapy is indicated in the treatment of atrophic vaginitis and kraurosis vulvae.

DOSAGE AND ADMINISTRATION :

Use of Conjugated Estrogens Vaginal Cream, alone or in combination with a progestin, should be limited to the shortest duration consistent with treatment goals and risks for the individual woman. Patients should be reevaluated periodically as clinically appropriate (for example at 3-month to 6-month intervals) to determine if treatment is still necessary. For women with a uterus, adequate diagnostic measures, such as endometrial sampling, when indicated, should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal vaginal bleeding.

Given cyclically for short-term use only:

For treatment of atrophic vaginitis, or kraurosis vulvae. The lowest dose that will control

symptoms should be chosen and medication should be discontinued as promptly as possible. Administration should be cyclic (three weeks on and one week off).

Usual Dosage Range:

½ to 2 g daily, intravaginally, depending on the severity of the condition.

CONTRAINDICATIONS :

Conjugated Estrogens Vaginal Cream therapy should not be used in women with any of the following

conditions:

1. Undiagnosed abnormal genital bleeding.

2. Known, suspected, or history of cancer of the breast.

3. Known or suspected estrogen-dependent neoplasia.

4. Active deep vein thrombosis, pulmonary embolism or a history of these conditions.

5. Active or recent (within past year) arterial thromboembolic disease (for example, stroke,

myocardial infarction).

6. Liver dysfunction or disease.

7. Known hypersensitivity to any of the ingredients in Conjugated Estrogens Vaginal Cream.

8. Known or suspected pregnancy.

OVERDOSAGE :

Overdosage of estrogen may cause nausea and vomiting, breast tenderness, abdominal pain, drowsiness/fatigue; and withdrawal bleeding may occur in females. Treatment of overdose consists of discontinuation of Conjugated Estrogens therapy with institution of appropriate symptomatic care.

CLINICAL PHARMACOLOGY :

Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level.

The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle. After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone by peripheral tissues. Thus, estrone and the sulfate-conjugated form, estrone sulfate, are the most abundant circulating estrogen in postmenopausal women.

Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. To date, two estrogen receptors have been identified. These vary in proportion from tissue to tissue.

Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these gonadotropins seen in postmenopausal women.

Mechanism of action :

All estrogen products mimic the effects of endogenous estrogens in the body which are responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Estrogens act by binding to estrogen receptors on a wide variety of tissues in the body and modulating the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH) through a negative feedback mechanism. Prior to menopause, the primary source of estrogen is the ovarian follicle, which secretes 70-500 micrograms of estradiol daily, depending on the phase of the menstrual cycle. However, once a woman stops ovulating there is a sharp decline in the production of progesterone and estradiol by the ovaries and a consequent fluctuation in LH and FSH due to a lack of feedback control. This shift in hormone production is largely responsible for many of the symptoms experienced during and after menopause and includes hot flashes and other vasomotor symptoms, painful intercourse, vaginal dryness, and vulvovaginal atrophy. These symptoms are able to be reduced by replacing many of the hormones lost during and following menopause with synthetic or naturally occurring forms, in a therapy known as Hormone Replacement Therapy (HRT).