estradiol acetate

estradiol acetate

Femring, Femtrace

Pharmacologic class: Estrogen

Therapeutic class: Hormone

Pregnancy risk category X

FDA Boxed Warning

• Drug increases endometrial cancer risk in postmenopausal women.
• Drug may increase risk of cardiovascular disease, breast cancer, and dementia.
• Drug shouldn't be used during pregnancy.
• Warnings may vary somewhat among specific brands. See package insert for complete warning information.

Action

Binds to nuclear receptors in responsive tissues (such as female genital organs, breasts, and pituitary gland), enhancing DNA, RNA, and protein synthesis. In androgen-dependent prostate cancer, competes for androgen receptor sites, inhibiting androgen activity. Also decreases pituitary release of follicle-stimulating hormone and luteinizing hormone.

Availability

Injection (cypionate in oil): 5 mg/ml

Injection (valerate in oil): 10 mg/ml, 20 mg/ml, 40 mg/ml

Tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg

Tablets (film-coated): 25.8 mcg estradiol hemidrate (equivalent to 25 mcg estradiol)

Transdermal system: 25 mcg/24-hour release rate, 37.5 mcg/24-hour release rate, 50 mcg/24-hour release rate, 75 mcg/24-hour release rate, 100 mcg/24-hour release rate

Vaginal cream: 100 mcg/g

Vaginal ring: 2 mg released over 90 days

Vaginal tablets: 25 mcg

⊘Indications and dosages

➣ Symptoms of menopause, atrophic vaginitis, female hypogonadism, ovarian failure, and osteoporosis

Adults: 0.5 to 2 mg (estradiol) P.O. daily continuously or cyclically. Or 1 to 5 mg (cypionate) or 10 to 20 mg (valerate) I.M. monthly. Or 50- or 100-mcg/24-hour transdermal patch applied twice weekly (Alora, Estraderm) or weekly (Climara). Or 25-mcg/24-hour patch applied q 7 days (FemPatch) or 37.5- to 100-mcg transdermal patch applied twice weekly (Vivelle). Or 2 to 4 g (0.2 to 0.4 mg) vaginal cream (estradiol) applied daily for 1 to 2 weeks, then decreased to 1 to 2 g/day for 1 to 2 weeks, then a maintenance dose of 1 g one to three times weekly for 3 weeks, then off for 1 week; repeat cycle once vaginal mucosa has been restored. Or 2-mg vaginal ring q 3 months or 25-mcg vaginal tablet once daily for 2 weeks, then twice weekly.

➣ Postmenopausal breast cancer

Adults: 10 mg P.O. t.i.d. (estradiol)

➣ Prostate cancer

Adults: 1 to 2 mg P.O. t.i.d. (estradiol) or 30 mg I.M. q 1 to 2 weeks (valerate)

Contraindications

• Hypersensitivity to drug or its components
• Thromboembolic disease (current or previous)
• Undiagnosed vaginal bleeding
• Breast or reproductive system cancer (except in metastatic disease)
• Estrogen-dependent neoplasms
• Pregnancy

Precautions

Use cautiously in:
• cardiovascular, hepatic, or renal disease
• breastfeeding patients.

Administration

• Inject I.M. dose deep into large muscle mass; rotate injection sites.
• If switching from oral to transdermal estrogen, apply patch 1 week after withdrawal of oral therapy.

Route	Onset	Peak	Duration
P.O.	Slow	Days	Unknown
I.M.	Unknown	Unknown	Unknown
Transdermal	Unknown	Unknown	3-4 days (Estraderm) 7 days (Climara)
Vaginal ring	Unknown	Unknown	90 days
Vaginal tablet	Unknown	Unknown	3-4 days

Adverse reactions

CNS: headache, dizziness, lethargy, depression

CV: hypertension, myocardial infarction (MI), thromboembolism

EENT: contact lens intolerance, worsening of myopia or astigmatism

GI: nausea, vomiting

GU: amenorrhea, dysmenorrhea, breakthrough bleeding, cervical erosions, decreased libido, vaginal candidiasis, erectile dysfunction, testicular atrophy, gynecomastia, breast pain or tenderness

Hepatic: jaundice

Metabolic: sodium and fluid retention, hypercalcemia, hyperglycemia

Musculoskeletal: leg cramps

Skin: oily skin, acne, pigmentation changes, urticaria

Other: weight loss or gain, edema, increased appetite

Interactions

Drug-drug. Insulin, oral hypoglycemics, warfarin: altered requirements for these drugs

Drug-diagnostic tests. Antithrombin III, folate, low-density lipoproteins, pyridoxine, total cholesterol, urine pregnanediol: decreased levels

Cortisol; factors VII, VIII, IX, and X; glucose; high-density lipoproteins; phospholipids; prolactin; prothrombin; sodium; triglycerides: increased levels

Metyrapone test: false decrease

Thyroid function tests: false interpretation

Drug-behaviors. Smoking: increased risk of adverse CV reactions

Patient monitoring

☞ Monitor vital signs and cardiovascular status, especially for hypertension, thromboembolism, and MI.
• Assess vision.
• In diabetic patient, monitor blood glucose level and watch for signs and symptoms of hyperglycemia.

Patient teaching

• Instruct patient to place transdermal patch on clean, dry skin area.
• Teach proper technique for use of vaginal tablet, ring, or cream, as appropriate.
• Tell patient drug may cause loss of libido (in women) or erectile dysfunction (in men). Encourage patient to discuss these issues with prescriber.
☞ Teach patient to recognize and immediately report signs and symptoms of thromboembolism.
☞ Caution patient not to take drug if she is or plans to become pregnant.
• Advise patient that drug may worsen nearsightedness or astigmatism and make contact lenses uncomfortable.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.