DrugindexOnline^{2nd edition}

Pronouncation: (ESS-truh-janz)
Class: Estrogens Esterified Estrogen

Trade Names:
Menest
- Tablets 0.3 mg
- Tablets 0.625 mg
- Tablets 1.25 mg
- Tablets 2.5 mg

Conjugated Estrogen

Trade Names:
Premarin
- Tablets 0.3 mg
- Tablets 0.45 mg
- Tablets 0.625 mg
- Tablets 0.9 mg
- Tablets 1.25 mg

Trade Names:
Premarin IV
- Injection 25 mg

C.E.S. (Canada)
Congest (Canada)

Mechanism of Action

Pharmacology

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 phosphorus and encourages bone formation; overrides stimulatory effects of testosterone.

Pharmacokinetics

Absorption

Well absorbed from GI tract. The tablets slowly release the drug over several hours.

Distribution

Bound to sex hormone-binding globulin and albumin. Widely distributed and generally found in higher concentration in the sex hormone target organs. Crosses the placenta.

Metabolism

Metabolized in the liver and undergoes enterohepatic recirculation. Estradiol is converted reversibly to estrone, and both can be converted to estriol (major urinary metabolite).

Elimination

Estradiol, estrone, and estriol are excreted in the urine along with glucuronide and sulfate conjugates.

Indications and Usage

Management of moderate to severe vasomotor symptoms associated with menopause; treatment of atrophic vaginitis, kraurosis vulvae, female hypogonadism, symptoms of female castration, and primary ovarian failure; prevention and treatment of osteoporosis (conjugated estrogens); palliative treatment of metastatic breast or prostate cancer in selected women and men; treatment of postpartum breast engorgement and abnormal uterine bleeding (parenteral form).

Contraindications

Breast cancer (except in patients being treated for metastatic disease); estrogen-dependent neoplasia; undiagnosed abnormal genital bleeding; thrombophlebitis or thromboembolic disorders associated with previous estrogen use; known or suspected pregnancy.

Dosage and Administration

Vasomotor Symptoms
Adults

PO 1.25 mg/day.

Female Castration, Primary Ovarian Failure
Adults

PO 0.3 to 1.25 mg/day (3 wk on estrogen, 1 wk off).

Atrophic Vaginitis, Atrophic Urethritis, Kraurosis Vulvae
Adults

PO 0.3 to 1.25 mg or more/day (3 wk on estrogen, 1 wk off). Intravaginal 0.5 to 2 g/day (3 wk on estrogen, 1 wk off).

Female Hypogonadism
Adults

PO 2.5 to 7.5 mg/day in divided doses for 20 days, followed by 10-day rest period.

Prostatic Carcinoma
Adults

PO 1.25 to 2.5 mg 3 times daily.

Breast Cancer
Adults

PO 10 mg 3 times daily for 3 mo or more.

Osteoporosis
Adults

PO 0.625 mg/day (3 wk on conjugated estrogen, 1 wk off).

Postpartum Breast Engorgement
Adults

PO 3.75 mg every 4 h for 5 doses, or 1.25 mg every 4 h for 5 days.

Abnormal Uterine Bleeding
Adults

IV/IM 25 mg; may repeat in 6 to 12 h.

General Advice

Conjugated estrogen

• Administer IM injection deeply into muscle.
• Administer IV injection slowly to avoid flushing.

Esterified estrogen

• Administer as prescribed without regard to meals.
• Administer with food if GI upset occurs.

Storage/Stability

Injection

Store vials for parenteral administration in refrigerator.

Tablets

Store at controlled room temperature (59° to 86°F).

Drug Interactions

Antidepressants, tricyclic

Estrogens may alter effects and increase toxicity of these agents.

Barbiturates, modafinil, topiramate, St. John's wort, rifampin

May decrease estrogen concentration.

Corticosteroids

An increase in pharmacologic and toxicologic effects of corticosteroids may occur.

Hydantoins

Loss of seizure control or decreased estrogenic effects may occur.

Incompatibility

Infusion of conjugated estrogen with other agents is not recommended. Solution is compatible with normal saline, dextrose, and invert sugar solutions. It is not compatible with any solution with acidic pH.

Laboratory Test Interactions

Endocrine and LFT results may be affected; possible decreased PT and increased platelet aggregability; increased thyroid-binding globulin and total T ₄ ; impaired glucose tolerance; decreased serum folate concentration; increased serum triglyceride and phospholipid concentrations; increased corticosteroid binding globulin and sex-hormone binding globulin; increased plasma HDL concentrations; reduced LDL cholesterol concentrations; increased triglyceride levels.

Adverse Reactions

Cardiovascular

Thrombosis; thrombophlebitis; pulmonary embolism; MI; elevated BP.

CNS

Headache; migraine; dizziness; depression; anxiety; emotional lability.

Dermatologic

Chloasma; melasma; erythema nodosum/multiforme; scalp hair loss; hirsutism; urticaria; dermatitis; skin hypertrophy; pruritus.

EENT

Intolerance to contact lenses.

GI

Nausea; vomiting; abdominal cramps; bloating; colitis; acute pancreatitis; diarrhea; dyspepsia; flatulence; gastritis; gastroenteritis; enlarged abdomen; hemorrhoids.

Genitourinary

Increased risk of endometrial carcinoma; breakthrough bleeding; dysmenorrhea; amenorrhea; vaginal candidiasis; premenstrual-like syndrome; increased size of uterine fibromyomata; hemolytic uremic syndrome; UTI; vaginitis; vaginal discomfort/pain; cystitis; dysuria; genital pruritus; urinary incontinence.

Hepatic

Cholestatic jaundice.

Metabolic

Hyperglycemia; hypercalcemia.

Respiratory

Upper respiratory tract infection; sinusitis; rhinitis; pharyngitis; flu-like symptoms; allergy; bronchitis; chest pain.

Miscellaneous

Increase or decrease in weight; reduced glucose tolerance; edema; changes in libido; breast tenderness; acute intermittent porphyria; vaginal bleeding; hypersensitivity reactions; back pain; arthritis; arthralgia; hot flushes; leg edema; otitis media; toothache.

Precautions

Monitor Baseline examinations Ensure that breast, abdominal and pelvic examination and Pap smear have been completed and documented before starting therapy and annually thereafter during prolonged therapy. Side effects Notify health care provider of pain, swelling, redness, or warmth in calves; sudden severe headache; visual disturbances; weakness or numbness of arms or legs; signs of liver dysfunction (eg, dark urine, jaundice); abdominal pain or tenderness, abdominal mass or signs of depression.

Pregnancy

Category X .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

Hepatic Function

Metabolism may be impaired; use drug with caution.

Cardiovascular and other risks

Compared with placebo, increased risks of MI, stroke, deep vein thrombosis, pulmonary emboli, and invasive breast cancer were reported in postmenopausal women during 5 yr of treatment with conjugated equine estrogens combined with medroxyprogesterone acetate. Other combinations of estrogens and progestins were not studied; however, in the absence of comparable data, assume these risks to be similar.

Calcium/phosphorus metabolism

Use drug with caution in patients with metabolic bone diseases.

Elevated BP

BP elevation may occur. 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 careful observation when conditions that might be affected by this factor are present (eg, asthma, cardiac or renal function impairment, epilepsy).

Gallbladder disease

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

Glucose intolerance

Monitor blood glucose level in diabetic patients. Monitor blood sugar more frequently in diabetic patient when therapy is started and dose is changed. Report significant changes to health care provider.

Induction of malignant neoplasms

May increase risk of endometrial or other carcinomas.

Surgery/Immobilization

Consider discontinuing therapy during periods of prolonged immobilization and, if possible, 4 wk before surgery that is associated with an increased risk of thromboembolic disease.

Unopposed estrogen administration (eg, without progesterone)

Increases risk of uterine cancer. Therefore, when using estrogens on long-term basis in a woman with intact uterus, consider cyclic therapy with progesterone (eg, estrogen on days 1 to 25 of mo with progesterone added for last 12 days) or daily coadministration of estrogen plus progesterone on daily basis. In a woman without a uterus, use of cyclic therapy or therapy with progesterone is not necessary.

Uterine leiomyomata

Preexisting uterine leiomyomata may increase in size.

Overdosage

Symptoms

Nausea, withdrawal bleeding in women.

Patient Information

• Advise patient to review patient information leaflet before starting therapy and with each refill.
• Instruct patient to take as prescribed and to not change the dose or stop taking unless advised to do so by health care provider.
• Advise patient that medication can be taken without regard to meals, but to take with food if GI upset occurs.
• 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 that help prevent osteoporosis: 1,500 mg/day of calcium; vitamin D supplementation; exercise.
• Caution patient that this medication must not be taken during pregnancy or when pregnancy is possible. Advise patient to use reliable form of birth control while taking this drug.
• Advise patient regarding importance of smoking cessation or reduction of intake to less than 15 cigarettes/day because of risk of cardiovascular complications.
• Teach patient proper method of performing breast self-examination.
• Advise patient to avoid exposure to sunlight or other sources of UV light. Sunscreens and/or protective clothing should be used until sun tolerance is determined.
• 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 in arm or leg; severe abdominal pain; yellowing of skin or eyes; severe depression.
• Remind patient to have Pap smear every 6 to 12 mo while undergoing therapy.