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 ↓ 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., deep vein thrombosis [DVT], pulmonary embolism [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 MI, stroke, invasive breast cancer, PE, DVT, 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, DVT, MI

Derm: acne, oily skin, pigmentation, urticaria

Endo: gynecomastia (men), hyperglycemia

F and E: hypercalcemia

GI: nausea, anorexia, jaundice, vomiting

GU: womenamenorrhea, breakthrough bleeding, breast tenderness, dysmenorrhea, cervical erosion, loss of libido, vaginal candidiasis, menerectile dysfunction, testicular atrophy

Metab: weight changes, ↑appetite

MS: leg cramps

Neuro: headache, dementia, depression, dizziness, insomnia, lethargy, STROKE

Resp: PE

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 ↓ levels and effectiveness.
Smoking↑ risk of adverse CV reactions.
Erythromycin, clarithromycin, itraconazole, ketoconazole, and ritonavir may ↑ levels and risk of toxicity.

Drug-Food:

Grapefruit juice may ↑ levels and risk of toxicity.

Route/Dosage ⬆ ⬇

Estrogens should be used in the lowest doses for the shortest period of time consistent with desired therapeutic outcome. Concurrent use of progestin is recommended during cyclical therapy to ↓ the risk of endometrial carcinoma in patients with an intact uterus.

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 as single dose; may repeat in 6–12 hr if necessary.

Atrophic Vaginitis

PO (Adults ): 0.3–1.25 mg once daily.
Vag (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

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
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 for signs and symptoms of venous thromboembolism, such as PE (chest pain, dyspnea, tachycardia) or DVT (calf pain or tenderness, lower extremity edema, localized warmth or erythema), or emerging cardiovascular disease, such as MI (chest pain, dyspnea, diaphoresis, dizziness, nausea) or stroke (weakness, slurred speech, confusion, dizziness); discontinue therapy in all patients if PE, DVT, stroke, or MI is suspected.
- If persistent or recurring abnormal genital bleeding occur in postmenopausal women, directed or random endometrial sampling may need to be performed to rule out malignancy.
- Monitor for breast tenderness, lumps, or discharge. Perform baseline mammogram before starting treatment.
- Assess for signs of anaphylactic reactions and angioedema (hives; pruritus; swollen lips, tongue, or face) within minutes to hours after administration. Implement emergency medical management as needed.
- Monitor intake and output and weekly weight. Report significant discrepancies or steady weight gain.
Menopause: Assess frequency and severity of vasomotor symptoms.

Lab Test Considerations:

May ↑ HDL and triglycerides and ↓ LDL and total cholesterol concentrations.
- May ↑ 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 ↓ 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 ≥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 solution if precipitate is present or if darkened.
- IV is preferred parenteral route because of rapid response.

IV Administration:

IV Push: 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.
Y-Site Compatibility:
- heparin
- hydrocortisone
- potassium chloride
Y-Site Incompatibility:
- pantoprazole

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy. 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.
Instruct patient in the correct use of applicator. Patient should remain recumbent for >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.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications. Advise patient to avoid drinking grapefruit juice during therapy.
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.
Inform postmenopausal women that long-term use may ↑ risk of MI, stroke, invasive breast cancer, PE, DVT, and dementia.
Advise patient to report signs and symptoms of fluid retention (swelling of ankles and feet, weight gain), depression, hepatic dysfunction (yellowed skin or eyes, pruritus, dark urine, light-colored stools), or abnormal vaginal bleeding to health care provider.
Advise patient to report signs and symptoms of thromboembolic disorders (pain, swelling, tenderness in extremities, headache, chest pain, blurred vision).
Caution patient that cigarette smoking during estrogen therapy may ↑ 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 ↑ pigmentation.
Advise patient to notify health care provider 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 provider before beginning program.
Emphasize the importance of routine follow-up physical exams, including BP check; breast, abdomen, and pelvic examinations; Papanicolaou smears every 6–12 mo; and mammogram every 12 mo or as directed. Health care provider 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.
Rep: May cause fetal harm. Advise women of reproductive potential patient to stop taking medication and notify health care provider if pregnancy is planned or suspected and to avoid breastfeeding during therapy.

Evaluation/Desired Outcomes ⬆ ⬇

Restoration of hormonal balance in various deficiency states and treatment of hormone-sensitive tumors.

US Brand Names ⬆ ⬇

Canadian Brand Names ⬆ ⬇

Pill Image

Code ⬆

NDC Code

0046- Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.
- 0046-1100- Premarin
  - 0046-1100-52- 1 BLISTER PACK in 1 CARTON (0046-1100-52) / 5 TABLET, FILM COATED in 1 BLISTER PACK

0046- Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.
- 0046-1100- Premarin
  - 0046-1100-81- 100 TABLET, FILM COATED in 1 BOTTLE (0046-1100-81)

0046- Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.
- 0046-1100- Premarin
  - 0046-1100-91- 1 BOTTLE in 1 CARTON (0046-1100-91) / 1000 TABLET, FILM COATED in 1 BOTTLE

0046- Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.
- 0046-1101- Premarin
  - 0046-1101-81- 100 TABLET, FILM COATED in 1 BOTTLE (0046-1101-81)

0046- Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.
- 0046-1102- Premarin
  - 0046-1102-52- 1 BLISTER PACK in 1 CARTON (0046-1102-52) / 5 TABLET, FILM COATED in 1 BLISTER PACK

0046- Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.
- 0046-1102- Premarin
  - 0046-1102-81- 100 TABLET, FILM COATED in 1 BOTTLE (0046-1102-81)

0046- Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.
- 0046-1102- Premarin
  - 0046-1102-91- 1 BOTTLE in 1 CARTON (0046-1102-91) / 1000 TABLET, FILM COATED in 1 BOTTLE

0046- Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.
- 0046-1103- Premarin
  - 0046-1103-81- 100 TABLET, FILM COATED in 1 BOTTLE (0046-1103-81)

0046- Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.
- 0046-1104- Premarin
  - 0046-1104-81- 100 TABLET, FILM COATED in 1 BOTTLE (0046-1104-81)

0046- Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.
- 0046-1104- Premarin
  - 0046-1104-91- 1 BOTTLE in 1 CARTON (0046-1104-91) / 1000 TABLET, FILM COATED in 1 BOTTLE

22552- Symbiotec Pharmalab Private Limited
- 22552-0017-
  - 22552-0017-1- 1 BAG in 1 CONTAINER (22552-0017-1) / 25000 g in 1 BAG

22552- Symbiotec Pharmalab Private Limited
- 22552-0018-
  - 22552-0018-1- 1 BAG in 1 CONTAINER (22552-0018-1) / 25000 g in 1 BAG

50090- A-S Medication Solutions
- 50090-0167- Premarin
  - 50090-0167-0- 100 TABLET, FILM COATED in 1 BOTTLE (50090-0167-0)

50090- A-S Medication Solutions
- 50090-0167- Premarin
  - 50090-0167-5- 30 TABLET, FILM COATED in 1 BOTTLE (50090-0167-5)

50090- A-S Medication Solutions
- 50090-1853- PREMARIN
  - 50090-1853-3- 30 TABLET, FILM COATED in 1 BOTTLE (50090-1853-3)

60870- Aspen Oss B.V.
- 60870-0422-
  - 60870-0422-0- 1 BAG in 1 DRUM (60870-0422-0) / 1000 g in 1 BAG

60870- Aspen Oss B.V.
- 60870-0479-
  60870-0479-0- 1 BAG in 1 DRUM (60870-0479-0) / 1000 g in 1 BAG

64918- Sterling S.p.A.
- 64918-1410-
  64918-1410-0- 20 kg in 1 BOX (64918-1410-0)

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇