Tamoxifen Citrate

Trade Names:Soltamox- Oral solution 10 mg per 5 mL

Trade Names:Tamoxifen Citrate- Tablets 10 mg- Tablets 20 mg

Pharmacology

A nonsteroidal agent with antiestrogenic properties.

Pharmacokinetics

Absorption

Tamoxifen C _max is 40 ng/mL (range, 35 to 45 ng/mL), T _max is approximately 5 h after dosing, and steady state is achieved in about 4 wk.

Metabolism

Tamoxifen is extensively metabolized. The major metabolite is N-desmethyl tamoxifen. It is a substrate of CYP450 3A, 2C9, 2D6, and an inhibitor of P-glycoprotein.

Elimination

Tamoxifen t _½ is 5 to 7 days; 65% of a dose is excreted over a 2-wk period, with fecal excretion as the primary route of elimination.

Special Populations

The effects of reduced liver function have not been determined.

Indications and Usage

Adjuvant treatment of breast carcinoma in women; metastatic breast carcinoma in men and women; reduction in risk of breast cancer in high-risk women; lower risk of invasive breast cancer in women with ductal carcinoma in situ (DCIS).

Unlabeled Uses

Ovulation stimulation in specially selected anovulatory women desiring pregnancy; management and treatment of some types of mastalgia (eg, cyclical); malignant carcinoid tumor and carcinoid syndrome; migraine associated with menstruation; metastatic malignant melanoma; oligozoospermia; McCune-Albright syndrome in female pediatric patients (in combination with other agents); metastatic melanoma; desmoid tumors; symptomatic gynecomastia.

Contraindications

Hypersensitivity to drug; women who require concomitant coumarin-type anticoagulant therapy; women with a history of deep vein thrombosis or pulmonary embolus.

Dosage and Administration

PO 20 to 40 mg daily.

PO 20 mg daily for 5 yr.

General Advice

• Divide dosages greater than 20 mg/day (morning and evening).

Storage/Stability

Do not store oral solution above 77°F. Do not refrigerate or freeze. To protect from light, store in original package. Use within 3 mo of opening. Store tablets at 68° to 77°F. Dispense in well-closed, light-resistant containers.

Drug Interactions

Tamoxifen concentrations may be reduced.

Plasma concentrations of anastrozole may be decreased. Do not coadminister.

Tamoxifen concentrations may be increased.

Increased risk of thromboembolic events.

Plasma concentrations may be decreased by tamoxifen, reducing the therapeutic effect.

Tamoxifen plasma levels may be reduced, decreasing the antiestrogenic effect.

Increased hypoprothrombinemic effect.

Laboratory Test Interactions

T ₄ elevations. Variations in the karyopyknotic index on vaginal smears and various degrees of estrogen effect on Pap smears.

Adverse Reactions

Cardiovascular

Vasodilation (41%); hypertension (11%); ischemic cerebrovascular events, ischemic CV disease (3%).

CNS

Asthenia/fatigue, mood disturbances (18%); depression (12%); insomnia (9%); dizziness, headache (8%); anxiety (6%); paresthesia (5%); fatigue (4%).

Dermatologic

Flushing (80%); skin changes (19%); rash (13%); sweating (6%); alopecia (5%); bullous pemphigoid, erythema multiforme, Stevens-Johnson syndrome (postmarketing).

EENT

Pharyngitis (14%); cataract (7%).

GI

Nausea (26%); vomiting (12%); constipation (8%); diarrhea (7%); dyspepsia (6%); GI disorder (5%); anorexia (1%).

Genitourinary

Vaginal discharge (55%); irregular menses (25%); amenorrhea, vaginal bleeding (23%); altered menses (13%); UTI (10%); leucorrhea, oligomenorrhea (9%); breast pain, menstrual disorder, vaginal hemorrhage (6%); breast neoplasm, vaginitis, vulvovaginitis (5%); ovarian cysts (3%), endometrial cancer (1%).

Hematologic-Lymphatic

Lymphedema (11%); anemia, venous thromboembolic events (5%); deep venous thromboembolic events, thrombocytopenia (2%).

Lab Tests

Increased AST (5%); increased bilirubin, increased creatinine (2%); elevated triglycerides in some cases with pancreatitis (postmarketing).

Metabolic-Nutritional

Fluid retention (32%); weight loss (23%); peripheral edema (11%); weight gain (9%); hypercholesterolemia (4%).

Musculoskeletal

Arthritis (14%); arthralgia (11%); back pain (10%); fracture, osteoporosis (7%); bone pain (6%); arthrosis, joint disorder, myalgia (5%); musculoskeletal pain (3%).

Respiratory

Cough (9%); dyspnea (8%), bronchitis, sinusitis (5%); interstitial pneumonitis (postmarketing).

Miscellaneous

Pain (16%); accidental injury (10%); abdominal pain, infection (9%); flu syndrome (6%); chest pain, cyst, neoplasm (5%); edema (4%); abdominal cramps (1%); hypersensitivity, including angioedema (postmarketing).

Precautions

Pregnancy

Category D .

Lactation

Undetermined.

Children

Safety and efficacy in children have not been established.

Amenorrhea

May occur.

Disease of bone

Increased bone pain, tumor pain, and local disease flare are sometimes associated with a good tumor response shortly after starting tamoxifen, and generally subside rapidly.

Hematologic effects

Thrombocytopenia, leukopenia, and neutropenia and/or pancytopenia have occurred.

Hepatic effects

Changes in liver enzyme levels may occur.

Hypercalcemia

If occurs, institute appropriate measures and, if severe, discontinue use.

Nonmalignant uterine effects

An increased incidence of endometrial changes, including hyperplasia and polyps, have been reported. Endometriosis and uterine fibroids have been reported.

Secondary tumors

Secondary primary tumors, occurring at sites other than the endometrium, were reported following treatment of breast cancer with tamoxifen.

Thromboembolic effects

Deep vein thrombosis and pulmonary embolism have occurred.

Visual disturbances

Visual disturbances, including corneal changes, cataracts, the need for cataract surgery, decrement in color vision perception, retinal vein thrombosis, and retinopathy, have occurred with use.

Overdosage

Symptoms

Convulsions, neurotoxicity, QT interval changes.

Patient Information

• Advise patient to review the Medication Guide before using the first time and with each refill.
• Explain tamoxifen can induce ovulation.
• Explain tamoxifen reduces the incidence of breast cancer but may not eliminate risk.
• Women should have regular gynecologic examinations and promptly inform health care provider of menstrual irregularities, abnormal vaginal bleeding, change in vaginal discharge, or pelvic pain or pressure.
• Notify health care provider of pain/swelling/tenderness of legs or calves, unexplained shortness of breath, changes in vision, new breast lumps, vaginal bleeding, gynecologic symptoms (eg, menstrual irregularities, changes in vaginal discharge, pelvic pain or pressure), sudden chest pain, or coughing up blood.
• Women should not become pregnant during therapy. Advise women to notify health care provider if pregnant, planning to become pregnant, or breast-feeding.

Copyright © 2009 Wolters Kluwer Health.