conjugated equine estrogens and medroxyprogesterone acetate

Prempro and Premphase are combinations of conjugated estrogens (Premarin) and medroxyprogesterone (Provera). Estrogens and progestins are the two major classes of female hormones. Conjugated estrogens are a mixture of several different estrogens (estrogen salts) that are derived from natural sources and blended to approximate the composition of estrogens in the urine of pregnant horses. The main components are sodium estrone sulphate and sodium equilin sulfate. Estrogens have widespread effects on many tissues in the body. Estrogens cause growth and development of the female sexual organs and maintain female sexual characteristics such as the growth of underarm and pubic hair, body contours, and skeleton. Estrogens also increase secretions from the cervix and growth of the inner lining of the uterus (endometrium). Medroxyprogesterone is a derivative of progesterone, a naturally occurring female progestin. Progestins are responsible for changes in the mucus and inner lining of the uterus (endometrium) during the second half (secretory phase) of the menstrual cycle. Progestins prepare the endometrium for implantation of the embryo. Once an embryo implants in the endometrium, for example, and pregnancy occurs, progestins help maintain the pregnancy. At high doses, progestins can prevent ovulation (release of the egg from the ovary) and thereby prevent pregnancy. The FDA approved Prempro and Premphase in June 2003.

Prempro, Premphase

GENERIC AVAILABLE: No

Yes

The most common side effects of Prempro and Premphase are:

• nausea,
• vomiting,
• stomach pain,
• tenderness,
• bloating, and
• fluid accumulation
• (edema).

Other important side effects include:

• Headaches,
• breakthrough bleeding, and
• spotting.

The Women's Health Initiative found that postmenopausal women (50-79 years old) taking conjugated estrogens, 0.625 mg daily, in combination with medroxyprogesterone, 2.5 mg daily, for five years, had an increased risk of heart attacks, stroke, breast cancer, and blood clots, while postmenopausal women taking conjugated estrogens without progesterone experienced only increased strokes but not increased blood clots, heart disease, or breast cancer. There was an increased risk of impaired cognition and/or dementia among women over age 65 treated with either estrogens or estrogens and medroxyprogesterone.

One tablet of Prempro should be taken daily. The lowest effective dose should be used. For either hot flashes or osteoporosis, patients are most often started at a dose of 0.3 mg/1.5 mg. For women with hot flashes, the dose is adjusted depending on the response of the hot flashes.

Patients should take one tablet of Premphase daily starting with the 0.625 mg conjugated estrogen tablets for 14 days (days 1 to 14) followed by one tablet daily of the 0.625/5 mg conjugated estrogen/medroxyprogesterone tablets for 14 days (days 14 to 28).

Drugs such as St. John's Wort (Hypericum perforatum), phenobarbital, carbamazepine (Tegretol, Tegretol XR, Equetro, Carbatrol), and rifampin may increase break-down of estrogens in the liver, reducing blood levels of estrogens and possibly reducing the effect of estrogens. Erythromycin, clarithromycin (Biaxin, Biaxin XL), ketoconazole (Nizoral, Extina, Xolegel, Kuric), itraconazole (sporanox), ritonavir (Norvir) and grapefruit juice may reduce break-down of estrogens in the liver, increasing blood concentrations of estrogens and possibly increasing side effects of estrogens.

Prempro and Premphase should not be given to pregnant women due to the risk of harm to the fetus.

Estrogens are secreted in breast milk and cause unpredictable effects in the infant. They should not be taken by women who are breastfeeding.

What preparations of conjugated equine estrogens and medroxyprogesteron are available?

• Prempro: Tablets 0.3/1.5, 0.45/1.5, 0.625/2.5, and 0.625/5 (mg conjugated estrogen/mg medroxyprogesterone).
• Premphase: Tablets, 28 day pack containing 14 tablets of 0.625 mg conjugated estrogens and 14 tablets of 0.625 mg/5 mg (conjugated estrogen/medroxyprogesterone).

How should I keep conjugated equine estrogens and medroxyprogesteron stored?

Prempro and Premphase should be stored at room temperature between 15-30 C (59-86 F).