tamoxifen

High Alert

Estrogen-receptor positive metastatic breast cancer.
Adjuvant treatment of early-stage estrogen-receptor positive breast cancer.
To reduce the occurrence of contralateral breast cancer when used as adjuvant therapy for breast cancer.
Prevention of breast cancer in high-risk patients.
To reduce risk of invasive breast cancer in women with ductal carcinoma in situ following breast surgery and radiation.

Action ⬆ ⬇

Competes with estrogen for binding sites in breast and other tissues.
Reduces DNA synthesis and estrogen response.

Therapeutic effects:

Suppression of tumor growth.
Reduced incidence of breast cancer in high-risk patients.

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed after oral administration.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A isoenzyme into N-desmethyltamoxifen and via the CYP2D6 isoenzyme into 4-hydroxytamoxifen. Both of these metabolites are further metabolized into endoxifen (N-desmethyltamoxifen via CYP2D6 and 4-hydroxytamoxifen via CYP3A). Both endoxifen and 4-hydroxytamoxifen are 30- to 100-fold more potent than tamoxifen in suppressing estrogen-dependent cell proliferation. The CYP2D6 enzyme system exhibits genetic polymorphism (∼7% of population may be poor metabolizers and may have significantly ↓ endoxifen concentrations and ↓ effectiveness of tamoxifen). Slowly eliminated in the feces. Minimal amounts excreted in the urine.

Half-Life: 7 days.

Time/Action Profile ⬆ ⬇

(tumor response)

ROUTE	ONSET	PEAK	DURATION
PO	4–10 wk	several mo	several wk

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Concurrent warfarin therapy with history of deep vein thrombosis (DVT) or pulmonary embolism (PE) (patients with ductal carcinoma in situ or at high risk for breast cancer only);
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

↓bone marrow reserve;
History of thromboembolic events
;
Rep: Women of reproductive potential.

Adv. Reactions/Side Effects ⬆ ⬇

CV: DVT, edema

Derm: hot flashes

EENT: blurred vision

F and E: hypercalcemia

GI: nausea, vomiting

GU: UTERINE MALIGNANCIES, vaginal bleeding

Hemat: leukopenia, thrombocytopenia

MS: bone pain

Neuro: confusion, depression, headache, STROKE, weakness.

Resp: PE

Misc: tumor flare

Interactions ⬆ ⬇

Drug-drug:

Estrogens may ↓ effectiveness.
Bromocriptine may ↑ levels and risk of toxicity.
May ↑ the anticoagulant effect of warfarin.
Risk of thromboembolic events is ↑ by concurrent use of other antineoplastics.

Route/Dosage ⬆ ⬇

Metastatic Breast Cancer

PO (Adults ): 20 mg once daily or 20 mg twice daily.

Adjuvant Treatment of Breast Cancer

PO (Adults ): 20 mg once daily for 5–10 yr.

Prevention of Breast Cancer in High-Risk Women or Ductal Carcinoma in Situ

PO (Adults ): 20 mg once daily for 5 yr.

Availability ⬆ ⬇

(Generic available)

Oral solution licorice aniseed flavor: 10 mg/5 mL
Tablets: 10 mg; 20 mg

Assessment ⬆ ⬇

Assess for an ↑ in bone or tumor pain. Confer with health care provider regarding analgesics. This transient pain usually resolves despite continued therapy.
Monitor for signs and symptoms of venous thromboembolism such as PE (chest pain, dyspnea, tachycardia), DVT (calf pain or tenderness, lower extremity edema, localized warmth or erythema), or stroke (headache, facial numbness, unilateral weakness, aphasia, eye pain or swelling, vision changes). Discontinue therapy if suspected.
Gynecologic examinations should be performed at initiation of therapy and annually to monitor for uterine malignancies; abnormal vaginal bleeding, menstrual irregularities, changes in vaginal discharge, or pelvic pain or pressure should be monitored; breast exam and mammogram should occur at baseline and periodically.
Dual energy x-ray absorptiometry scans should be completed at baseline and every 1–2 yr. Evaluate osteoporosis and fracture risk in all patients. Risk of ↓ bone mineral density in premenopausal women.
X-ray of thoracic and lumbar spine to rule out vertebral facture should be done in patients with kyphosis, height loss ≥6 cm, acute severe back pain, and in age ≥65 yr.
Optical coherence tomography should be done at baseline and every 6 mo to detect tamoxifen maculopathy during treatment.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
An estrogen receptor assay should be assessed before initiation of therapy.
Monitor CBC and platelets at baseline and periodically during therapy. May cause leukopenia and thrombocytopenia.
Monitor serum cholesterol and triglyceride concentrations in patients with pre-existing hyperlipidemia. May cause ↑ concentrations.
Bone mineral density panel (serum albumin, calcium and alkaline phosphatase, and phosphate and osteocalcin measurements) should be measured at baseline and periodically. May cause transient hypercalcemia in patients with metastases to the bone. If severe hypercalcemia develops, discontinue tamoxifen.
Monitor hepatic function tests and thyroxine (T₄) periodically during therapy. May ↑ liver enzymes and thyroxine concentrations.

Implementation ⬆ ⬇

Handle intact tablets or capsules with single gloves; use double gloves, respiratory protection, and a protective gown in the preparation of tablets or capsules, including cutting, crushing, or manipulating, or the handling of uncoated tablets; optimally prepare in a ventilated control device. During administration, wear single gloves, and wear eye/face protection if the formulation is hard to swallow or if the patient may resist, vomit, or spit up.
PO: Administer with food or fluids if GI irritation becomes a problem. Consult health care provider if patient vomits shortly after administration of medication to determine need for repeat dose.

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of tamoxifen. Instruct patient to take medication as directed. If a dose is missed, it should be omitted. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
If skin lesions are present, inform patient that lesions may temporarily ↑ in size and number and may have ↑ erythema.
Advise patient to report bone pain to health care provider promptly. This pain may be severe. Analgesics should be ordered to control pain. Inform patient that this may be an indication of the drug’s effectiveness and will resolve over time.
Instruct patient to monitor weight weekly. Weight gain or peripheral edema should be reported to health care provider.
Advise patient that medication may cause hot flashes. Notify health care provider if these become bothersome.
Instruct patient to notify health care provider promptly if pain or swelling of legs, shortness of breath, weakness, sleepiness, confusion, nausea, vomiting, weight gain, dizziness, headache, loss of appetite, or blurred vision occurs. Patient should also report menstrual irregularities, vaginal bleeding, or pelvic pain or pressure.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Rep: May cause fetal harm. Advise women of reproductive potential to use a nonhormonal method of contraception during therapy and for 2 mo after last dose and to avoid breastfeeding for 3 mo after last dose. May cause female infertility.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇