Drospirenone and Estradiol

Use estrogen, alone or in combination with a progestogen, at the lowest effective dose and the shortest duration consistent with treatment goals and risks for the individual woman. Re-evaluate postmenopausal women periodically as clinically appropriate to determine whether treatment is still necessary. Angeliq is a combination of an estrogen and progestin indicated in a woman with a uterus for the treatment of: Moderate to severe vasomotor symptoms due to menopause. Moderate to severe vulvar and vaginal atrophy symptoms due to menopause. Limitation of Use When prescribing solely for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy, first consider the use of topical vaginal products.

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 (E2) 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 in the peripheral tissues. Thus, estrone and the sulfate-conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women.

Each pack of Angeliq covers 28 days of treatment. Treatment is continuous, which means that the next pack follows immediately without a break. The tablets are to be swallowed whole with some liquid irrespective of food intake and should preferably be taken at the same time every day. In case a tablet is forgotten, it should be taken as soon as possible. If more than 24 hours have elapsed, the missed tablet should not be taken. If several tablets are forgotten, bleeding may occur. Women who do not take estrogens or women who change from a continuous combination product may start treatment at any time. Women changing from a continuous sequential or cyclic hormone therapy (HT) should complete the current cycle of therapy before initiating Angeliq therapy.

Angeliq is contraindicated in women with any of the following conditions: Undiagnosed abnormal genital bleeding. Breast cancer or a history of breast cancer. Estrogen-dependent neoplasia. Active DVT, PE or history of these conditions. Active arterial thromboembolic disease (for example, stroke and MI) or history of these conditions. Renal Impairment. Hepatic impairment or disease. Adrenal insufficiency. Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders Known anaphylactic reaction, angioedema, or hypersensitivity to Angeliq or any of its ingredients Undiagnosed abnormal genital bleeding. Active DVT, PE, or a history of these conditions. Renal impairment.

Boxed warning (cardiovascular disorders, probable dementia, breast cancer, and endometrial cancer): Estrogen Plus Progestin Therapy Cardiovascular Disorders and Probable Dementia The Women's Health Initiative (WHI) estrogen plus progestin substudy reported increased risks of pulmonary embolism (PE), deep vein thrombosis (DVT), stroke, and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo. Do not use with conditions that predispose to hyperkalemia ( Estrogens increase the risk of gallbladder disease. Discontinue estrogen if severe hypercalcemia, loss of vision, severe hypertriglyceridemia or cholestatic jaundice occurs. Monitor thyroid function in women on thyroid hormone replacement therapy

The following serious adverse reactions are discussed elsewhere in the labeling: Cardiovascular Disorders Malignant Neoplasms The most common adverse reactions with Angeliq that occurred in at least 1% of users in clinical trials are: gastrointestinal and abdominal pain, female genital tract bleeding, breast pain and discomfort, and headache.

Inducers and inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration. Serum potassium concentration may increase in women taking drospirenone with other drugs that have the potential to increase potassium.

Store at 20° to 25° C (68° to 77° F), excursions permitted to 15°–30° C (59°–86° F).