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|Estrogens, Conjugated/Medroxyprogesterone Acetate

Estrogens, Conjugated/Medroxyprogesterone Acetate

Trade Names:
Premphase
- Tablets 0.625 mg conjugated estrogens and 0.625 mg conjugated estrogens/5 mg medroxyprogesterone acetate

Trade Names:
Prempro
- Tablets 0.625 mg conjugated estrogens/5 mg medroxyprogesterone acetate
- Tablets 0.625 mg conjugated estrogens/2.5 mg medroxyprogesterone acetate

Mechanism of Action

Pharmacology

Conjugated estrogens: promotes growth and development of female reproductive system and secondary sex characteristics; affects release of pituitary gonadotropins; inhibits ovulation and prevents postpartum breast engorgement; conserves calcium and phosphorous and encourages bone formation; overrides stimulatory effects of testosterone; progesterone: inhibits secretion of pituitary gonadotropins, thereby preventing follicular maturation and ovulation (contraceptive effect); inhibits spontaneous uterine contraction; transforms proliferative endometrium into secretory endometrium.

Indications and Usage

Treatment of moderate-to-severe vasomotor symptoms associated with menopause; treatment of vulval and vaginal atrophy; osteoporosis prevention.

Unlabeled Uses

Treatment of hypercholesterolemia in postmenopausal women.

Contraindications

Do not use combined estrogens/progestins in conditions or circumstances of: 1) known or suspected pregnancy; 2) known or suspected cancer of the breast; 3) known or suspected estrogen-dependent neoplasm; 4) undiagnosed abnormal genital bleeding; 5) active or past history of thrombophlebitis; thromboembolic disorders, or stroke; 6) liver dysfunction or disease; 7) hypersensitivity to ingredients of tablets.

Dosage and Administration

Revaluate patient at 3- to 6-mo intervals to determine need for continued treatment.

Monitor women with intact uterus closely for signs of endometrial cancer, evaluate recurrent or persistent abnormal vaginal bleeding to rule out malignancy.

PO One 0.625 mg conjugated estrogen/2.5 mg medroxyprogesterone once daily.

PO One 0.625 mg conjugated estrogen once daily on days 1 through 14 and one 0.625 mg conjugated estrogen/5 mg medroxyprogesterone once daily on days 15 through 28.

General Advice

• Administer without regard to meals.
• Remove 1 tablet at a time from provided dispensing dial. When dial is empty, begin new dial the following day.

Storage/Stability

Store at controlled room temperature. Do not remove tablet from dispensing dial until ready to administer.

Drug Interactions

May decrease estrogen levels.

Pharmacologic and adverse effects of corticosteroids may be increased.

Loss of seizure control or decreased estrogenic effects may occur.

Estrogens may alter effects and increase toxicity.

May increase metabolism and decrease effect of medroxyprogesterone.

Laboratory Test Interactions

Endocrine and liver function test results may be affected; possible increased PT and increased platelet aggregability; increased thyroid binding globulin and total T ₄ ; impaired glucose tolerance; increased corticosteroid binding globulin and sex-hormone binding globulin; increased plasma HDL concentration; reduced LDL cholesterol concentrations; increased triglyceride levels; reduced response to metyrapone test; reduced folate concentration.

Adverse Reactions

Cardiovascular

Change in BP; thrombophlebitis; cerebral thrombosis and embolism; pulmonary embolism.

CNS

Headache; depression; dizziness; hypertonia; nervousness; migraine; chorea; insomnia; somnolence; change in libido.

Dermatologic

Pruritus; rash; chloasma; erythema multiforme; erythema nodosum; hemorrhagic eruption; alopecia; hirsutism; itching; urticaria; acne.

EENT

Pharyngitis; rhinitis; sinusitis; retinal thrombosis; optic neuritis; contact lenses intolerance.

GI

Abdominal pain and cramps; diarrhea; dyspepsia; flatulence; nausea; changes in appetite; vomiting; bloating.

Genitourinary

Breast pain; cervix disorder; dysmenorrhea; leukorrhea; vaginal hemorrhage; vaginitis; abnormal withdrawal bleeding or flow; breakthrough bleeding; spotting; changes in cervical secretion; premenstrual-like syndrome; cystitis-like syndrome; vaginal candidiasis; amenorrhea; changes in cervical erosion; breast tenderness and enlargement; galactorrhea.

Hepatic

Cholestatic jaundice.

Metabolic

Peripheral edema; increase or decrease in weight; edema; reduced carbohydrate tolerance.

Miscellaneous

Accidental injury; back pain; flu-like syndrome; infection; pain; pelvic pain; arthralgia; leg cramps; gallbladder disease; pancreatitis; fatigue; aggravation of porphyria; anaphylactoid reaction; anaphylaxis.

Precautions

Pregnancy

Category X .

Lactation

Excreted in breast milk.

Depression

Carefully observe patients with history of depression.

Elevated BP

Increased BP during estrogen replacement has been attributed to idiosyncratic reactions. Assess BP at beginning of therapy and periodically during treatment.

Familial hyperlipoproteinemia

May be associated with massive elevations of plasma triglycerides.

Fluid retention

Use with caution when conditions that might be affected by fluid retention are present (eg, asthma, cardiac, or renal dysfunction, epilepsy).

Gallbladder disease

Risk of gallbladder disease may increase in women receiving postmenopausal estrogens.

Glucose intolerance

Monitor blood sugar in diabetic patient when drug is started or dose is changed. Report significant changes to health care provider. A worsening of glucose tolerance has occurred.

Hypercalcemia

In patients with breast cancer or bone metastases, severe hypercalcemia has occurred with estrogen therapy.

Induction of malignant neoplasm

May increase risk of endometrial cancer or other carcinomas.

Uterine bleeding

Certain patients may develop abnormal uterine bleeding.

Visual abnormalities

Discontinue medication if there are any sudden changes in vision, sudden onset of proptosis, diplopia, migraine, papilledema, or retinal vascular lesions.

Overdosage

Symptoms

Nausea, vomiting, withdrawal bleeding.

Patient Information

• Explain name, dose, action, and potential side effects of drug.
• Instruct patient to take 1 tablet every day from the dispensing dial.
• Advise patient that medication can be taken without regard to meals, but to take with food if GI upset occurs.
• Caution patient not to take tablets out of sequence and when dispensing dial is empty, to begin a new cycle of tablets the next day.
• Advise patient to keep tablets in provided plastic dispensing device until dose is needed.
• Caution patient to not change brands without consulting health care provider. Products made by different companies may not be equally effective.
• Instruct diabetic patient to monitor blood glucose more frequently when drug is started or dose is changed and to inform health care provider of significant changes in readings.
• Review nonhormonal modalities, which help prevent osteoporosis: 1500 mg/day of calcium; vitamin D supplementation; and exercise.
• Instruct patient to report these symptoms to health care provider: pain in groin or calves; sharp chest pain or sudden shortness of breath; abnormal vaginal bleeding; breast lumps; sudden severe headache; dizziness or fainting; vision or speech problems; weakness or numbness of arms or legs; severe abdominal pain; yellowing of skin or eyes; or severe depression.
• Instruct patients to notify health care provider if they become pregnant, plan on becoming pregnant, or are breastfeeding.
• Teach patient proper method of breast self-examination.
• Advise patient that follow-up visits and examinations, including Pap smear, at least once a year will be required to monitor therapy and to keep appointments.