GENERIC NAME: conjugated estrogens vaginal cream

BRAND NAME: Premarin Vaginal Cream

DRUG CLASS AND MECHANISM: Conjugated estrogens are a mixture of estrogen-related chemicals including estrone, equilin, 17 alpha-dihydroequilin, and others. They are derived from the urine of pregnant horses, and the exact composition of the estrogenic mixture is uncertain. The vaginal cream is used for treating the uncomfortable vaginal symptoms that may occur after menopause. Both oral and vaginal estrogens reverse postmenopausal atrophy of the vaginal lining, thickening the lining and increasing its secretions. Most individuals taking estrogens orally do not need additional vaginal estrogens. Conjugated estrogens were first approved by the FDA in 1938.

GENERIC AVAILABLE: no

PRESCRIPTION: yes

PREPARATIONS: 0.625mg per application with accompanying applicator, 42.5gm tube.

STORAGE: The cream should be stored at room temperature, 15-30°C (59-86°F).

PRESCRIBED FOR: Premarin vaginal cream is used for the relief of vaginal symptoms in post-menopausal women who have developed uncomfortable dryness of the vagina and/or vulvae.

DOSING: Vaginal products work best if used at bedtime. The hands should first be washed and the applicator filled with cream from the tube. Lying on the back with the knees bent, individuals should insert the applicator into the vagina and push the applicator's plunger to deliver the cream. The applicator and plunger then should be washed with warm, soapy water and rinsed with plain water. The hands should be washed before and after use. A small amount of the cream also can be applied to the outer skin folds or "lips" of the vagina (vulvae) to relieve dryness or irritation.

DRUG INTERACTIONS: Estrogens can inhibit the elimination of cyclosporine from the body, resulting in increased cyclosporine levels in the blood. These increased levels can result in kidney and/or liver damage. If the combination of cyclosporine and estrogens cannot be avoided, cyclosporine concentrations can be measured in the blood, and the dose of cyclosporine can be adjusted to assure that blood levels are not elevated.

Estrogens appear to increase the risk of liver disease in patients receiving dantrolene. The reason is not known. Women over 35 years of age and those who already have liver disease are especially at risk.

Estrogens increase the liver's ability to manufacture clotting factors. Because of this, patients receiving warfarin (Coumadin)--which has its beneficial effects by reducing clotting factors--need to be monitored for loss of anticoagulant (blood thinning) effect if an estrogen is begun.

Rifampin, barbiturates, carbamazepine (Tegretol), griseofulvin, phenytoin (Dilantin) and primidone (Mysoline), all can increase the elimination of estrogen by enhancing the liver's ability to metabolize it. Use of these drugs may result in reduction of the beneficial effects of estrogens.

PREGNANCY: Estrogens should be avoided during pregnancy since they increase the risk of fetal abnormalities.

NURSING MOTHERS: Estrogens are secreted in milk and cause unpredictable effects in the infant. In general, they should not be used by women who are breast-feeding.

SIDE EFFECTS: Among the most common endocrine side effects are breakthrough vaginal bleeding or spotting, loss of periods or excessively prolonged periods, breast pain or enlargement, and changes in sexuality (increases or decreases in libido). Estrogens cause gallstones, and the gallstones may result in abdominal pain and require surgery. Rarely, estrogens may cause hepatitis. Migraine headaches have been associated with estrogen therapy. Estrogens can cause retention of water (edema). Melasma--tan or brown patches-- may develop on the forehead, cheeks, or temples. These may persist even after the estrogen is stopped. Conjugated estrogens may increase the curvature of the cornea, and patients with contact lenses may develop intolerance to their lenses.

Blood clots are an occasional, serious side effect of estrogen therapy and are dose-related. (The higher the dose of estrogen, the greater the risk of blood clots.) Cigarette smokers are at a higher risk than non-smokers for blood clots, and patients requiring estrogens should be encouraged to quit smoking.

Estrogens can promote thickening of the lining of the uterus (endometrial hyperplasia) and increase the risk of uterine cancer. At diagnosis, endometrial cancers in recipients of estrogens are generally at an earlier stage and are less aggressive when they are discovered. Survival from endometrial cancer also is better in women taking estrogens than in those not taking estrogens. The addition of a progestin to estrogen therapy offsets the risk of endometrial cancer.

Conflicting data exists on the association between estrogens and breast cancer. There may be a small increase in risk. The effect of concomitant progestin therapy on the risk of estrogen-induced breast cancer is unclear.

Conjugated estrogens are well-absorbed from the vagina and into the blood. The amount absorbed depends on the frequency of use and the amount used. Thus, more frequent use or larger amounts of vaginal estrogens can have effects throughout the body (see conjugated estrogens, Premarin).

Reference: FDA Prescribing Information