TAMOXIFEN CITRATE

(ta-mox'i-fen)

Nolvadex, Nolvadex-D

, Tamofen

Classifications: antineoplastic agent; hormone; selective estrogen receptor modulator (serm);
Therapeutic: antineoplastic; antiestrogen; serm
Pregnancy Category: D

Availability

10 mg, 20 mg tablets

Action

Nonsteroidal gonad-stimulating drug with potent antiestrogenic as well as estrogenic activity on various tissues. Competes with estradiol at estrogen receptor (ER-positive) sites in target tissues such as breast, uterus, vagina, anterior pituitary. Estrogen is thought to increase breast cancer in ER-positive tumors. Tamoxifen has no effect on the development of ER-negative breast cancer disease.

Therapeutic Effect

Has effects on tumor with high concentration of estrogen receptors. Tamoxifen-receptor complexes move into the cell nucleus, decreasing DNA synthesis and estrogen responses. Ovulation may be induced by stimulation of the release of hypothalamic gonadotropic-releasing factor.

Uses

Palliative treatment of advanced with metastatic estrogen receptors (ER)-positive breast cancer in postmenopausal women, adjunctively with surgery in the treatment of breast carcinoma with positive lymph nodes.

Unlabeled Uses

Investigationally to stimulate ovulation in selected anovulatory women desiring pregnancy.

Contraindications

Anticoagulant therapy, pregnancy (category D), especially during first trimester; preexisting endometrial hyperplasia; intramuscular injections if platelets <50,000/mm³; history of thromboembolic disease; lactation; children.

Cautious Use

Vision disturbances; cataracts, visual disturbance; leukopenia, bone marrow suppression; thrombocytopenia; hypercalcemia; hypercholesterolemia, lipid protein abnormalities.

Route & Dosage

Breast Carcinoma
Adult: PO 10–20 mg 1–2 times/d (morning and evening)

Stimulation of Ovulation
Adult: PO 5–40 mg b.i.d. for 4 d

Administration

Oral

With severe adverse effects, a simple reduction in dosage gives sufficient relief without losing control of disease. Consult physician.
Store at 15°–30° C (59°–86° F); protect from light.

Adverse Effects (≥1%)

Body as a Whole: Increased bone pain, and transient local disease flair; loss of hair, weight gain, shortness of breath, photosensitivity, hot flashes. CNS: Depression, light-headedness, dizziness, headache, mental confusion, sleepiness. CV: Thrombosis, pulmonary embolism, increased risk of stroke. GI: Nausea and vomiting (about 25% of patients), distaste for food, anorexia. Hematologic: Leukopenia, thrombocytopenia. Metabolic: Hypercalcemia. Skin: Skin rash or dryness. Special Senses: Retinopathy, decreased visual acuity, blurred vision. Urogenital: Changes in menstrual period, milk production and leaking from breasts, vaginal discharge and bleeding, pruritus vulvae, risk of uterine malignancies.

Diagnostic Test Interference

Tamoxifen may produce transient increase in serum calcium.

Interactions

Drug: May enhance hypoprothrombinemic effects of warfarin; may increase risk of thromboembolic events with cytotoxic agents; bromocriptine may elevate tamoxifen levels, SSRI antidepressants may decrease effectiveness of tamoxifen.

Pharmacokinetics

Absorption: Slowly from GI tract. Peak: 3–6 h. Metabolism: In liver, enterohepatically cycled. Elimination: Primarily in feces. Half-Life: 7 d.

Nursing Implications

Assessment & Drug Effects

Monitor therapeutic effectiveness. An objective response may require 4–10 wk of therapy, longer if there is bone metastasis.
Administer analgesics for pain relief as necessitated by bone and tumor pain or local disease flair. Reassure patient that this discomfort frequently signals a good tumor response.
Be aware that local swelling and marked erythema over preexisting lesions or the development of new lesions may signal soft-tissue disease response to tamoxifen. These symptoms rapidly subside.
Lab tests: Assess CBC, including platelet counts, periodically. Transient leukopenia and thrombocytopenia (50,000–100,000/mm³) without hemorrhagic tendency have been reported. Monitor serum calcium periodically.

Patient & Family Education

Do not change established dose schedule.
Report to physician occurrence of marked weakness, sleepiness, mental confusion, edema, dyspnea, blurred vision.
Understand the possibility of drug-induced menstrual irregularities before starting treatment.
Avoid prolonged sun exposure, especially if skin is unprotected. Apply sunscreen lotions (SPF 12 or greater) to all exposed skin surfaces.
Avoid OTC drugs unless specifically prescribed by the physician; particularly OTC pain medicines.
Report onset of tenderness or redness in an extremity.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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