Premarin

INDICATIONS AND USAGE Premarin Intravenous (conjugated estrogens, USP) for injection is indicated in the treatment of abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology. Premarin Intravenous is indicated for short-term use only, to provide a rapid and temporary increase in estrogen levels.

DOSAGE AND ADMINISTRATION For treatment of abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology: One 25 mg injection, intravenously or intramuscularly. Intravenous use is preferred since more rapid response can be expected from this mode of administration. Repeat in 6 to 12 hours if necessary. The use of Premarin Intravenous for injection does not preclude the advisability of other appropriate measures. One should adhere to the usual precautionary measures governing intravenous administration. Injection should be made SLOWLY to obviate the occurrence of flushes. Infusion of Premarin Intravenous for injection with other agents is not generally recommended. In emergencies, however, when an infusion has already been started it may be expedient to make the injection into the tubing just distal to the infusion needle. If so used, compatibility of solutions must be considered. COMPATIBILITY OF SOLUTIONS Premarin Intravenous is compatible with normal saline, dextrose, and invert sugar solutions. It is not compatible with protein hydrolysate, ascorbic acid, or any solution with an acid pH.

WARNINGS See BOXED WARNINGS . Premarin Intravenous for injection is indicated for short-term use. However, warnings, precautions and adverse reactions associated with oral Premarin treatment should be taken into account. 1. Cardiovascular Disorders An increased risk of stroke and DVT has been reported with estrogen-alone therapy. An increased risk of PE, DVT, stroke, and MI has been reported with estrogen plus progestin therapy. Should any of these events occur or be suspected, estrogen with or without progestin therapy should be discontinued immediately. Risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE) (for example, personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately. a. Stroke In the WHI estrogen-alone substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily CE (0.625 mg)-alone compared to women in the same age group receiving placebo (45 versus 33 per 10,000 women-years). (See CLINICAL STUDIES .) The increase in risk was demonstrated in year 1 and persisted. Should a stroke occur or be suspected, estrogen-alone therapy should be discontinued immediately. Subgroup analyses of women 50 to 59 years of age suggest no increased risk of stroke for those women receiving CE (0.625 mg)-alone versus those receiving placebo (18 versus 21 per 10,000 women-years). In the WHI estrogen plus progestin substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women in the same age group receiving placebo (33 versus 25 per 10,000 women-years). (See CLINICAL STUDIES .) The increase in risk was demonstrated after the first year and persisted. Should a stroke occur or be suspected, estrogen plus progestin therapy should be discontinued immediately. b. Coronary heart disease In the WHI estrogen-alone substudy, no overall effect on CHD events (defined as nonfatal MI, silent MI, or CHD death) was reported in women receiving estrogen-alone compared to placebo. (See CLINICAL STUDIES .) In the WHI estrogen plus progestin substudy, there was a non-statistically significant increased risk of CHD events reported in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (41 versus 34 per 10,000 women-years). An increase in relative risk was demonstrated in year 1, and a trend toward decreasing relative risk was reported in years 2 through 5. In postmenopausal women with documented heart disease (n = 2,763, average 66.7 years of age), in a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estrogen/Progestin Replacement Study; HERS), treatment with daily CE 0.625 mg/MPA 2.5 mg demonstrated no cardiovascular benefit. During an average follow-up of 4.1 years, treatment with CE plus MPA did not reduce the overall rate of CHD events in postmenopausal women with established coronary heart disease. There were more CHD events in the CE plus MPA-treated group than in the placebo group in year one, but not during the subsequent years. Two thousand three hundred and twenty-one (2,321) women from the original HERS trial agreed to participate in an open-label extension of HERS, HERS II. Average follow-up in HERS II was an additional 2.7 years, for a total of 6.8 years overall. Rates of CHD events were comparable among women in the CE plus MPA group and the placebo group in the HERS, the HERS II, and overall. c. Venous thromboembolism In the WHI estrogen-alone substudy, the risk of VTE (DVT and PE), was increased for women receiving daily CE (0.625 mg)-alone compared to placebo (30 versus 22 per 10,000 women-years), although only the increased risk of DVT reached statistical significance (23 versus 15 per 10,000 women-years). The increase …

CONTRAINDICATIONS Premarin Intravenous therapy should not be used in individuals with any of the following conditions: 1. Undiagnosed abnormal genital bleeding. 2. Known, suspected, or history of breast cancer. 3. Known or suspected estrogen-dependent neoplasia. 4. Active DVT, PE or a history of these conditions. 5. Active arterial thromboembolic disease (for example, stroke and MI) or a history of these conditions. 6. Known anaphylactic reaction and angioedema to Premarin Intravenous therapy. 7. Known liver dysfunction or disease. 8. Known protein C, protein S, or antithrombin deficiency or other known thrombophilic disorders. 9. Known or suspected pregnancy.

F. Pregnancy Premarin Intravenous should not be used during pregnancy. (See CONTRAINDICATIONS .)

G. Nursing Mothers Premarin Intravenous should not be used during lactation. Estrogen administration to nursing women has been shown to decrease the quantity and quality of the breast milk. Detectable amounts of estrogens have been identified in the breast milk of women receiving estrogens. Caution should be exercised when Premarin Intravenous is administered to a nursing woman.

ADVERSE REACTIONS See BOXED WARNINGS , WARNINGS , and PRECAUTIONS . Premarin Intravenous for injection is indicated for short-term use. However, the warnings, precautions and adverse reactions associated with oral Premarin treatment should be taken into account. The following adverse reactions have been identified during post-approval use of oral or intravenous Premarin. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Genitourinary system Abnormal uterine bleeding/spotting. Dysmenorrhea or pelvic pain. Increase in size of uterine leiomyomata. Vaginitis, including vaginal candidiasis. Change in amount of cervical secretion. Change in cervical ectropion. Ovarian cancer. Endometrial hyperplasia. Endometrial cancer. Breasts Tenderness, enlargement, pain, discharge, galactorrhea. Fibrocystic breast changes. Breast cancer. Cardiovascular Deep and superficial venous thrombosis. Pulmonary embolism. Thrombophlebitis. Myocardial infarction. Stroke. Increase in blood pressure. Gastrointestinal Nausea, vomiting. Abdominal cramps, bloating. Cholestatic jaundice. Increased incidence of gallbladder disease. Pancreatitis. Enlargement of hepatic hemangiomas. Ischemic colitis. Skin Chloasma or melasma that may persist when drug is discontinued. Erythema multiforme. Erythema nodosum. Hemorrhagic eruption. Loss of scalp hair. Hirsutism. Pruritis. Rash. Eyes Retinal vascular thrombosis. Intolerance to contact lenses. Central Nervous System Headache. Migraine. Dizziness. Mental depression. Exacerbation of chorea. Nervousness. Exacerbation of epilepsy. Dementia. Possible growth potentiation of benign meningioma. Miscellaneous Increase or decrease in weight. Glucose intolerance. Aggravation of porphyria. Edema. Arthralgia. Leg cramps. Changes in libido. Urticaria. Hypocalcemia (preexisting condition). Injection site pain. Injection site edema. Phlebitis (injection site). Exacerbation of asthma. Increased triglycerides.