estrogens, conjugated

IM:

BEERS REMS

PO: Moderate to severe vasomotor symptoms of menopause.
Vulvar and vaginal atrophy associated with menopause.
Estrogen deficiency states, including:
- Female hypogonadism,
- Ovariectomy,
- Primary ovarian failure.
Prevention of postmenopausal osteoporosis.
Advanced inoperable metastatic breast and prostatic carcinoma.
IV: Uterine bleeding resulting from hormonal imbalance.
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 effects:

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. IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Mostly metabolized by liver via the CYP3A4 isoenzyme. 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 wk.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

History of anaphylaxis or angioedema to estrogen;
Thromboembolic disease (e.g., DVT, PE, MI, stroke);
Undiagnosed vaginal bleeding;
History of breast cancer;
History of estrogen-dependent cancer;
Hepatic impairment;
Protein C, protein S, or antithrombin deficiency or other thrombophilic disorder;
OB: Pregnancy;
Lactation: Lactation.

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;
History of hereditary angioedema
Geri: Appears on Beers list. risk of breast and endometrial cancer, heart disease, thromboembolic events, and dementia in older adults. Avoid use of systemic estrogens in older adults. Vaginal cream is acceptable to use for treatment of dyspareunia, recurrent lower urinary tract infections, and other vaginal symptoms in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

(Systemic use)

CV: edema, hypertension, MI, THROMBOEMBOLISM

Derm: acne, oily skin, pigmentation, urticaria

Endo: gynecomastia (men), hyperglycemia

F and E: hypercalcemia

GI: nausea, weight changes, anorexia, jaundice, vomiting

GU:

women

amenorrhea, breakthrough bleeding, breast tenderness, dysmenorrhea, cervical erosion, loss of libido, vaginal candidiasis,

men

erectile dysfunction, testicular atrophy

Metab: ↑appetite

MS: leg cramps

Neuro: headache, depression, dizziness, insomnia, lethargy

Misc: ANAPHYLAXIS, ANGIOEDEMA, MALIGNANCY (BREAST, ENDOMETRIAL, OVARIAN)

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.

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 once daily administered cyclically (3 wk on, 1 wk off).

Osteoporosis/Menopausal Symptoms

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

Female Hypogonadism

PO (Adults ): 0.3–0.625 mg once 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 once daily.
(Adults ): 0.5–2 g cream (0.3125 mg–1.25 g conjugated estrogens) once daily for 3 wk, off for 1 wk, then repeat.

Moderate to Severe Dyspareunia

(Adults ): 0.5 g cream (0.3125 mg conjugated estrogens) twice weekly continuously or daily for 3 wk, off for 1 wk, then repeat.

Availability ⬆ ⬇

Tablets: 0.3 mg; 0.45 mg; 0.625 mg; 0.9 mg; 1.25 mg
Powder for injection: 25 mg/vial
Vaginal cream: 0.625 mg/g
In combination with: bazedoxifene (Duavee); medroxyprogesterone (Prempro and Premphase [compliance package]). See Appendix [not included in this PDA edition].

Assessment ⬆ ⬇

Assess BP 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.

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.
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 Administration:

Reconstitution: 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.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take oral medication as directed. Advise patient to avoid drinking grapefruit juice during therapy. Take missed doses as soon as remembered, but not just before next dose. Do not double doses.Inform patient that estrogens should not be used to decrease risk of cardiovascular disease. Estrogens may increase risk of cardiovascular disease and breast cancer.
- Explain dose schedule and maintenance routine. Discontinuing medication suddenly may cause withdrawal bleeding. Bleeding is anticipated during the wk 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.
- Caution patient that cigarette smoking during estrogen therapy may increase risk of serious side effects, especially for women over age 35.
- Inform patient that Premarin tablet may appear in stool; this is not harmful.
- Caution patient to use sunscreen and protective clothing to prevent increased pigmentation.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- 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.
- May cause fetal harm. Instruct patient to stop taking medication and notify health care professional if pregnancy is planned or suspected, and to avoid breastfeeding during therapy.
- Emphasize the importance of routine follow-up physical exams, including BP; breast, abdomen, and pelvic examinations; Papanicolaou (Pap) 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.
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.

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇