ta-MOX-i-fen

Therapeutic Classification: antineoplastics

Pharmacologic Classification: antiestrogens

• 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.

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

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

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.

(tumor response)

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
• Women of reproductive potential

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.

Drug-Drug:

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

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.

(Generic available)

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

• Assess for an increase in bone or tumor pain. Confer with health care professional regarding analgesics. This transient pain usually resolves despite continued therapy.

• Verify negative pregnancy test before starting therapy.Monitor CBC, platelets, and calcium levels before and during therapy. May cause transient hypercalcemia in patients with metastases to the bone. An estrogen receptor assay should be assessed before initiation of therapy.
  • Monitor serum cholesterol and triglyceride concentrations in patients with pre-existing hyperlipidemia. May cause ↑ concentrations.
  • Monitor hepatic function tests and thyroxine (T₄) periodically during therapy. May cause ↑ serum hepatic enzyme and thyroxine concentrations.
  • Gynecologic examinations should be performed regularly; may cause variations in Papanicolaou and vaginal smears.

• PO: Administer with food or fluids if GI irritation becomes a problem. Consult health care professional if patient vomits shortly after administration of medication to determine need for repeat dose.

• 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 increase in size and number and may have increased erythema.
• Advise patient to report bone pain to health care professional 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 professional.
• Advise patient that medication may cause hot flashes. Notify health care professional if these become bothersome.
• Instruct patient to notify health care professional 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, pelvic pain or pressure.
• May cause fetal harm. Advise females of reproductive potential to use a nonhormonal method of contraception during and for 2 mo after last dose of tamoxifen and to avoid breastfeeding for 3 mo after last dose. May cause female infertility.

• Decrease in the size or spread of breast cancer. Observable effects of therapy may not be seen for 4–10 wk after initiation.
• Reduced incidence of breast cancer in high-risk patients.

Soltamox