estrogens, conjugated (equine) (ess-troe-jenz con-joo-gae-ted) C.E.S, Congest, Premarin estrogens, conjugated (synthetic, A) Cenestin

 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 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.

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.

Contraindications/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: 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); mayqrisk of myocardial infarction, stroke, invasive

breast cancer, pulmonary emboli, deep vein

thrombosis, and dementia in postmenopausal women;

Underlying cardiovascular disease; Hypertriglyceridemia;

Mayqrisk of endometrial carcinoma; History of

hereditary angioedema.

Adverse Reactions/Side Effects

(Systemic use) CNS: headache, dizziness, insomnia,

lethargy, mental depression. CV: MI, THROMBOEMBOLISM,

edema, hypertension. GI: nausea, weight

changes, anorexia,qappetite, 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: ANAPHYLAXIS, ANGIOEDEMA, breast tenderness.

Interactions

Drug-Drug: May alter requirement for warfarin,

oral hypoglycemic agents, or insulins. Barbiturates,

carbamazepine, or rifampin maypeffectiveness.

Smokingqrisk of adverse CV reactions. Erythromycin,

clarithromycin, itraconazole,

ketoconazole, and ritonavir mayqrisk of adverse

effects.

Drug-Food: Grapefruit juice mayqrisk 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): 0.5–2 g cream (0.3125 mg–1.25 g

conjugated estrogens) daily for 3 wk, off for 1 wk, then

repeat.

Moderate to Severe Dyspareunia

Vag (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.

Cost: Premarin—0.3 mg $299.14/100, 0.45 mg

$299.14/100, 0.625 mg $299.14/100, 0.9 mg $311.87/

100, 1.25 mg $298.45/100. Powder for injection: 25

estrogens, conjugated (equine) 531

 Canadian drug name.  Genetic implication. Strikethrough  Discontinued.

*CAPITALS indicates life-threatening; underlines indicate most frequent.

E

mg/vial. Vaginal cream: 0.625 mg/g. Cost: $208.20/

30 g. In combination with: medroxyprogesterone

(Prempro and Premphase [compliance package]); bazedoxifene

(Duavee). See Appendix B.