tamoxifen citrate
Nolvadex, Nolvadex-D ◆, Tamofen ◆

Available forms
Available by prescription only
Tablets: 10 mg, 20 mg
Tablets (enteric-coated): 20 mg ◆

Indications and dosages
 Dosages and indications may vary. Check current literature for recommended protocol.
 Breast cancer. Adults: 20 to 40 mg P.O. daily. Give amounts greater than 20 mg in divided doses (morning and evening).
 Reduction of breast cancer risk in high-risk women. Adults: 20 mg P.O. daily for 5 years.
 Ductal carcinoma in situ. Adults: 20 mg P.O. daily for 5 years.
 Stimulation of ovulation ◇. Adults: 5 to 40 mg P.O. b.i.d. for 4 days.

Pharmacodynamics
Antineoplastic action: Exact mechanism of action is unclear. Tamoxifen may exert its cytotoxic action by blocking estrogen receptors within tumor cells that require estrogen to thrive. The estrogen receptor-tamoxifen complex may be translocated into the nucleus of the tumor cell, where it inhibits DNA synthesis.

Pharmacokinetics
Absorption: Appears to be well absorbed across the GI tract after oral administration. Steady state serum levels usually occur after 3 to 4 weeks.
Distribution: Distribution of drug and its metabolites into body tissues and fluids hasn’t been fully established.
Metabolism: Metabolized extensively in the liver to several metabolites.
Excretion: Excreted primarily in feces, mostly as metabolites. Drug has a distribution phase half-life of 7 to 14 hours. Half-life of the terminal elimination phase is longer than 7 days.

Contraindications and precautions
Contraindicated in pregnant women and in patients hypersensitive to drug. Also contraindicated for risk reduction in high-risk women who also take coumarin-type anticoagulants or who have a history of deep vein thrombosis or pulmonary edema.
  Use cautiously in patients who have leukopenia or thrombocytopenia.

Interactions
Drug-drug. Antacids: May affect absorption of enteric-coated tablets. Give drugs 2 hours apart.
Bromocriptine: Increases tamoxifen levels. Dosage adjustment may be needed. Monitor patient closely.
Coumadin: Significantly increases anticoagulation effect. Monitor PT and INR. Dosage adjustment may be needed.
Cytotoxic drugs: Increases risk of thromboembolic events. Avoid use together.

Adverse reactions
CNS: CVA.
GI: nausea, vomiting, diarrhea.
GU: vaginal discharge and bleeding, irregular menses, amenorrhea, endometrial cancer, uterine sarcoma.
Hematologic: leukopenia, thrombocytopenia.
Metabolic: hypercalcemia, increased serum triglycerides and cholesterol, increased thyroxine level, weight changes.
Musculoskeletal: temporary bone or tumor pain, brief exacerbation of pain from osseous metastases.
Respiratory: pulmonary embolism.
Skin: skin changes.
Other: hot flashes, fluid retention.

Effects on lab test results
• May increase BUN, calcium, and liver enzyme levels.
• May decrease WBC and platelet counts.

Overdose and treatment
Acute overdose hasn’t been reported.
 No specific treatment is known. Treatment should include supportive measures. In advanced metastatic cancer, patients receiving loading doses above 400 mg/m² followed by 150 mg/m² b.i.d. have an increased risk of acute neurotoxicity (tremor, hyperreflexia, unsteady gait, and dizziness). Symptoms may arise within 3 to 5 days of starting therapy; they’re expected to clear 2 to 5 days after stopping therapy. QT interval may be prolonged as well.

Special considerations
• Tamoxifen acts as an antiestrogen. Best results occur in patients with positive estrogen receptors.
• Adverse reactions are usually minor and well tolerated. They usually can be controlled by dose reduction.
 ALERT Serious, life-threatening, or fatal events associated with tamoxifen in the risk reduction setting include endometrial cancer, uterine sarcoma, stroke, and pulmonary embolism.
 ALERT Discuss the potential benefits versus the potential risks with women considering treatment to reduce their risk of developing breast cancer. Benefits of therapy outweigh risks in women diagnosed with breast cancer.
• Clotting factor abnormalities may occur with prolonged tamoxifen therapy at usual doses.
• Variations on karyopyknotic index in vaginal smears and various degrees of estrogen effect on Papanicolaou smears have been seen in some postmenopausal patients. May increase serum thyroxine concentrations and may be explained by increases in thyroxine-binding globulin.
• Initial adverse reactions (increased bone pain) may be a sign of good tumor response shortly after starting tamoxifen therapy.
• Monitor WBC count, platelet count, and periodic liver function tests results.
• Monitor serum calcium levels; hypercalcemia may occur early in therapy in patients with bone metastases.
Pregnant patients
• Drug shouldn’t be used during pregnancy or for at least 2 months before pregnancy because of risks to fetus.
Breast-feeding patients
• It isn’t known whether drug appears in breast milk. However, because of the potential for serious adverse reactions and carcinogenicity in the infant, breast-feeding isn’t recommended.
Pediatric patients
• Safety and efficacy haven’t been established for use in children.
Geriatric patients
• The risk of serious adverse effects for women age 65 and older is the same as for women age 50 and older (the group identified in one study as being at highest risk for serious adverse effects).

Patient education
• Stress the importance of swallowing enteric-coated tablets without crushing or breaking them.
• Urge patient to continue taking drug despite nausea and vomiting.
• Tell patient to promptly report vomiting if it occurs shortly after dose ingestion.
• Reassure patient that acute exacerbation of bone pain during tamoxifen therapy usually indicates that drug will produce good response.
• Advise women to avoid becoming pregnant during drug therapy. Also recommend barrier or nonhormonal contraceptive measures for sexually active patients during treatment period.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use