General

estrogens, conjugated (equine)
ESS-troe-jenz

• C.E.S [Canada]

• Congest [Canada]

• Premarin

estrogens, conjugated (synthetic, a)

• Cenestin

estrogens, conjugated (synthetic, b)

• Enjuvia

Pregnancy Category
Category X

Ther. class.
hormones

Pharm. class.
estrogens

Indications

• PO: Treatment of moderate to severe vasomotor symptoms of menopause

• Estrogen deficiency states, including:

» Female hypogonadism

» Ovariectomy

» Primary ovarian failure

• Prevention of postmenopausal osteoporosis

• Advanced inoperable metastatic breast and prostatic carcinoma

• IM, IV: Uterine bleeding resulting from hormonal imbalance

• Vag: Atrophic vaginitis

• Moderate to severe dyspareunia due to menopause

• Concurrent use of progestin is recommended during cyclical therapy to decrease the risk of endometrial carcinoma in patients with an intact uterus

Action

Estrogens promote the growth and development of female sex organs and the maintenance of secondary sex characteristics in women

Therapeutic Effect(s):
Restoration of hormonal balance in various deficiency states and treatment of hormone-sensitive tumors

Pharmacokinetics

Absorption: Well absorbed after oral administration. Readily absorbed through skin and mucous membranes

Distribution: Widely distributed. Crosses placenta and enters breast milk

Metabolism and Excretion: Mostly metabolized by liver and other tissues. Enterohepatic recirculation occurs, with more absorption from GI tract

Half-life: Unknown

TIME/ACTION PROFILE (estrogenic effects†)

ROUTE	ONSET	PEAK	DURATION
PO	rapid	unknown	24 hr
IM	delayed	unknown	6–12 hr
IV	rapid	unknown	6–12 hr

†Tumor response may take several weeks

Contraindication/Precautions

Contraindicated in:

• Thromboembolic disease (e.g. DVT, PE, MI, stroke)

• Undiagnosed vaginal bleeding

• History of breast cancer

• History of estrogen-dependent cancer

• Liver dysfunction

• OB: May result in harm to the fetus

• Lactation: Negatively affects quantity and quality of breast milk

Use Cautiously in:

• Long-term use (more than 4–5 yr); may ↑ risk of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, deep vein thrombosis and dementia in postmenopausal women

• Underlying cardiovascular disease

• Hypertriglyceridemia

• May ↑ risk of endometrial carcinoma

Adverse Reactions/Side Effects

(systemic use)

CNS: headache, dizziness, insomnia, lethargy, mental depression.

CV: MI, THROMBOEMBOLISM, edema, hypertension.

GI: nausea, weight changes, anorexia, increased appetite, jaundice, vomiting.

GU: women—amenorrhea, breakthrough bleeding, dysmenorrhea, cervical erosion, loss of libido, vaginal candidiasis, men—erectile dysfunction, testicular atrophy.

Derm: acne, oily skin, pigmentation, urticaria.

Endo: gynecomastia (men), hyperglycemia.

F and E: hypercalcemia, sodium and water retention.

MS: leg cramps.

Misc: breast tenderness.

*CAPITALS indicates life-threatening.
*italic indicates most frequent.

Interactions

Drug-Drug

• May alter requirement for warfarin , oral hypoglycemic agents , or insulins

• Barbiturates , carbamazepine , or rifampin may ↓ effectiveness

• Smoking ↑ risk of adverse CV reactions

• Erythromycin , clarithromycin , itraconazole , ketoconazole , and ritonavir may ↑ risk of adverse effects

Drug-Natural Products
Grapefruit juice may ↑ risk of adverse effects

Route/Dosage

• Estrogens should be used in the lowest doses for the shortest period of time consistent with desired therapeutic outcome.

Ovariectomy, Primary Ovarian Failure

• PO (Adults): 1.25 mg daily administered cyclically (3 wk on, 1 wk off).

Osteoporosis/Menopausal Symptoms

• PO (Adults): 0.3–1.25 mg daily or in a cycle.

Female Hypogonadism

• PO (Adults): 0.3–0.625 mg daily administered cyclically (3 wk on, 1 wk off).

Inoperable Breast Carcinoma—Men and Postmenopausal Women

• PO (Adults): 10 mg 3 times daily.

Inoperable Prostate Carcinoma

• PO (Adults): 1.25–2.5 mg 3 times daily.

Uterine Bleeding

• IM, IV (Adults): 25 mg, may repeat in 6–12 hr if necessary.

Atrophic Vaginitis

• PO (Adults): 0.3–1.25 mg daily.

• Vag (Adults): Conjugated estrogens (equine)–0.5–2 g cream (0.3125 mg – 1.25 g conjugated estrogens) daily for 3 wk, off for 1 wk, then repeat; Synthetic conjugated estrogens, A-1 g cream (0.3125 mg synthetic conjugated estrogens, A) daily for 1 wk, then twice weekly.

Moderate to Severe Dyspareunia

• Vag (Adults): Conjugated estrogens (equine)–0.5 g cream (0.3125 mg conjugated estrogens) twice weekly continuously or daily for 3 wk, off for 1 wk, then repeat; Synthetic conjugated estrogens, A-1 g cream (0.3125 mg synthetic conjugated estrogens, A) daily for 1 wk, then twice weekly.

Availability

• Tablets: 0.3 mg, 0.45 mg , 0.625 mg, 0.9 mg, 1.25 mg

» Cost:
Premarin: 0.3 mg $166.63/100, 0.45 mg $139.97/100, 0.625 mg $136.95/100, 0.9 mg $139.97/100, 1.25 mg $126.46/100.

• Powder for injection: 25 mg/vial

• Vaginal cream: 0.625 mg/g

» Cost: $85.99/42.5-g tube.

• In combination with: medroxyprogesterone (Prempro and Premphase [compliance package]). See combination drugs

Assessment

• Assess blood pressure before and periodically during therapy

» Monitor intake and output ratios and weekly weight. Report significant discrepancies or steady weight gain

Menopause

• Assess frequency and severity of vasomotor symptoms

Lab Test Considerations

• May cause ↑ HDL and triglycerides, and ↓ serum LDL and total cholesterol concentrations

» May cause ↑ serum glucose, sodium, cortisol, prolactin, prothrombin, and factor VII, VIII, IX, and X levels. May ↓ serum folate, pyridoxine, antithrombin III, and urine pregnanediol concentrations

» Monitor hepatic function before and periodically during therapy

» May cause false interpretations of thyroid function tests

» May cause hypercalcemia in patients with metastatic bone lesions

Potential Nursing Diagnoses

• Sexual dysfunction (Indications)

Implementation

• Estrogens should be used in the lowest doses for the shortest period of time consistent with desired therapeutic outcome

• PO: Administer with or immediately after food to reduce nausea

• Vag: Manufacturer provides applicator with cream. Dose is marked on the applicator. Wash applicator with mild soap and warm water after each use

• IM: To reconstitute, withdraw at least 5 mL of air from dry container and then slowly introduce the sterile diluent (bacteriostatic water for injection) against the container side. Gently agitate container to dissolve; do not shake vigorously. Solution is stable for 60 days if refrigerated. Do not use if precipitate is present or if solution is darkened

» IV is preferred parenteral route because of rapid response

IV Adminstration:

• Direct IV:

Diluent: Reconstitute as for IM. Inject into distal port tubing of free-flowing IV of 0.9% NaCl, D5W, or lactated Ringer's solution
Concentration: 5 mg/mL

• Rate:
Administer slowly (no faster than 5 mg/min) to prevent flushing

• Y-Site Compatibility:

» heparin

» hydrocortisone sodium succinate

» potassium chloride

» vitamin B complex with C

Patient/Family Teaching

• Instruct patient to take oral medication as directed. Take missed doses as soon as remembered, but not just before next dose. Do not double doses

» Explain dose schedule and maintenance routine. Discontinuing medication suddenly may cause withdrawal bleeding. Bleeding is anticipated during the week when conjugated estrogens are withheld

» If nausea becomes a problem, advise patient that eating solid food often provides relief

» Advise patient to report signs and symptoms of fluid retention (swelling of ankles and feet, weight gain), thromboembolic disorders (pain, swelling, tenderness in extremities; headache; chest pain; blurred vision), depression, hepatic dysfunction (yellowed skin or eyes, pruritus, dark urine, light-colored stools), or abnormal vaginal bleeding to health care professional

» Instruct patient to stop taking medication and notify health care professional if pregnancy is suspected

» Caution patient that cigarette smoking during estrogen therapy may increase risk of serious side effects, especially for women over age 35

» Caution patient to use sunscreen and protective clothing to prevent increased pigmentation

» Advise patient to notify health care professional of medication regimen before treatment or surgery

» Advise patient treated for osteoporosis that exercise has been found to arrest and reverse bone loss. The patient should discuss any exercise limitations with health care professional before beginning program

» Emphasize the importance of routine follow-up physical exams, including blood pressure; breast, abdomen, and pelvic examinations; Papanicolaou smears every 6–12 mo; and mammogram every 12 mo or as directed. Health care professional will evaluate possibility of discontinuing medication every 3–6 mo. If on continuous (not cyclical) therapy or without concurrent progestins, endometrial biopsy may be recommended if uterus is intact

• Inform patient that estrogens should not be used to decrease risk of cardiovascular disease. Estrogens may increase risk of cardiovascular disease and breast cancer

• Vag: Instruct patient in the correct use of applicator. Patient should remain recumbent for at least 30 min after administration. May use sanitary napkin to protect clothing, but do not use tampon. If a dose is missed, do not use the missed dose, but return to regular dosing schedule

Evaluation/Desired Outcomes

• Resolution of menopausal vasomotor symptoms

» Decreased vaginal and vulvar itching, inflammation, or dryness associated with menopause

• Normalization of estrogen levels in patients with ovariectomy or hypogonadism

• Control of the spread of advanced metastatic breast or prostate cancer

• Prevention of osteoporosis

• Relief of moderate to severe dyspareunia due to menopause

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