Conjugated Estrogens-Medroxyprogesterone

Conjugated Estrogens-Medroxyprogesterone is a prescription medication used to treat the symptoms of Menopause. 

• Conjugated Estrogens-Medroxyprogesterone is available under the following different brand names: Premphase, Prempro

Common side effects of Conjugated Estrogens-Medroxyprogesterone include:

• Nausea, 
• Gas,
• Stomach pain,
• Headache,
• Back pain,
• Depression,
• Weakness,
• Breast pain,
• Itching,
• Thinning scalp hair,
• Vaginal itching or discharge,
• Changes in your menstrual periods, and
• Breakthrough bleeding

Serious side effects of Conjugated Estrogens-Medroxyprogesterone include:

• Hives,
• Difficulty breathing,
• Swelling of the face, lips, tongue, or throat,
• Chest pain or pressure,
• Pain spreading to the jaw or shoulder,
• Nausea,
• Sweating,
• Sudden numbness or weakness (especially on one side of the body),
• Sudden severe headache,
• Slurred speech,
• Problems with vision or balance,
• Sudden vision loss,
• Stabbing chest pain,
• Shortness of breath,
• Coughing up blood,
• Pain or warmth in one or both legs,
• Swelling or tenderness in the stomach,
• Yellowing of the skin or eyes (jaundice),
• Memory problems,
• Confusion,
• Unusual behavior,
• Unusual vaginal bleeding,
• Pelvic pain,
• Lump in the breast,
• Vomiting,
• Constipation,
• Increased thirst or urination,
• Muscle weakness,
• Bone pain, and
• Lack of energy

Rare side effects of conjugated Estrogens-Medroxyprogesterone include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out. 

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 0.3 mg/1.5 mg
• 0.45 mg/1.5 mg
• 0.625 mg/2.5 mg
• 0.625 mg/5 mg
• 0.625 mg/ 5mg plus conjugated estrogen 0.625 mg (Premphase)

Menopause

Adult dosage

• Premphase (biphasic regimen)
  • 1 pure estrogen tablet once a day, Days 1-14, THEN
  • 1 combo tablet orally once a day on days 15-28 of the cycle
• Prempro
  • 1 tablet orally once a day.

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Conjugated Estrogens-Medroxyprogesterone has severe interactions with the following drugs.
  • ospemifene
• Conjugated Estrogens-Medroxyprogesterone has serious interactions with at least 52 other drugs.
• Conjugated Estrogens-Medroxyprogesterone has moderate interactions with at least 187 other drugs.
• Conjugated Estrogens-Medroxyprogesterone has minor interactions with at least 42 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice or health questions or concerns.

Contraindications

• Undiagnosed abnormal genital bleeding
• Known, suspected, or history of breast cancer.
• Known or suspected estrogen-dependent neoplasiaActive DVT, PE, or a history of these conditions
• Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions
• Known anaphylactic reaction or angioedema to PREMPRO/PREMPHASE
• Known liver dysfunction or disease.
• Known protein C, protein S, antithrombin deficiency, or other known thrombophilia disorders.
• Known or suspected pregnancy

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Conjugated Estrogens-Medroxyprogesterone?”

Long-Term Effects

See “What Are Side Effects Associated with Using Conjugated Estrogens-Medroxyprogesterone?”

Cautions

• An increased risk of PE, DVT, stroke, and MI reported with estrogen plus progestin therapy; an increased risk of stroke and DVT reported with estrogen-alone therapy; should any of these occur or be suspected, estrogen with or without progestin therapy should be discontinued immediately
• Use caution in patients with bone mineral density changes, current/history of depression, diabetes mellitus, HTN, hyperlipidemia, hypertriglyceridemia, obesity, endometriosis, family history of breast cancer, and/or DVT/PE, smoking, severe hypocalcemia.
• If feasible, estrogens should be discontinued at least 4 to 6 weeks before surgery or prolonged immobilization or if there are any symptoms of VTE, massive BP increase, unusually severe migraines or first-time migraines, or depression.
• Retinal vascular thrombosis reported in patients receiving estrogens; discontinue medication pending examination if there is a sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine; if examination reveals papilledema or retinal vascular lesions, estrogens should be discontinued.
• Increased risk of post-op thromboembolic complications, MI, stroke, pulmonary emboli, DVT, Alzheimer's disease, cardiovascular disorders, probable dementia, and endometrial cancer
• Increased risk of endometrial cancer reported with the use of unopposed estrogen therapy in a woman with a uterus; the reported endometrial cancer risk among unopposed estrogen users is about 2 to 12 times greater than in non-users and appears dependent on the duration of treatment and estrogen dose.
• Manage appropriately risk factors for arterial vascular disease (. g., hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (.g, personal history or family history of VTE, obesity, and systemic lupus erythematosus)
• Use caution in patients with conditions exacerbated by fluid retention (. g, asthma, migraine, cardiac/renal dysfunction, epilepsy)
• Estrogen therapy may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions.
• Patients on warfarin/oral anticoagulants: estrogens increase thromboembolic risk; an increase in anticoagulant dose may be warranted.
• Angioedema involving the tongue, larynx, face, hands, and feet requiring medical intervention has occurred postmarketing in patients taking this therapy; if angioedema involves the tongue, glottis, or larynx, airway obstruction may occur; patients who develop an anaphylactic reaction with or without angioedema after treatment should permanently discontinue therapy.
• Not for use with conditions that predispose to hyperkalemia.
• Estrogen administration may lead to severe hypercalcemia in women with breast cancer and bone metastases; if hypercalcemia occurs, use of the drug should be stopped, and appropriate measures are taken to reduce serum calcium level
• Increased risk of ovarian cancer was reported in women who used hormonal therapy for menopausal symptoms
• Clinical surveillance of all women using estrogen-alone or estrogen plus progestin therapy is important; adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding
• A 2 to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens was reported.
• There are, possible risks that may be associated with the use of progestins with estrogens compared to estrogen-alone regimens, including a possible increased risk of breast cancer, adverse effects on lipoprotein metabolism (e.g., lowering HDL, raising LDL), and impairment of glucose tolerance.
• In patients with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis and other complications
• Estrogens may be poorly metabolized in patients with impaired liver function; exercise caution in patients with a history of cholestatic jaundice associated with past estrogen use or with pregnancy; in the case of recurrence, discontinue the medication.
• Patients dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of thyroid replacement therapy; these patients should have their thyroid function monitored to maintain their free thyroid hormone levels in an acceptable range.
• All women should receive yearly breast examinations by a healthcare provider and perform monthly breast self-examinations; in addition, mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results.
• Studies of the addition of progestin for 10 or more days of a cycle of estrogen administration or daily with estrogen in a continuous regimen, have reported a lowered incidence of endometrial hyperplasia than would be induced by estrogen treatment alone; endometrial hyperplasia may be a precursor to endometrial cancer; there are, however, possible risks that may be associated with the use of progestins with estrogens compared to estrogen-alone regimens; these include an increased risk of breast cancer
• The use of estrogen-alone and estrogen plus progestin has been reported to increase abnormal mammograms requiring further evaluation.
• There is no evidence that using natural estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen dose; adding progestin to estrogen therapy in postmenopausal women has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer.

Pregnancy and Lactation

• This drug combination should not be used during pregnancy; there appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins as an oral contraceptives inadvertently during early pregnancy
• Lactation
  • This drug combination 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 estrogen and progestin have been identified in the breast milk of women receiving these drugs; caution should be exercised when this drug combination is administered to a nursing woman.