No

Antineoplastic Agent, Miscellaneous

Palliative or adjunctive treatment of advanced breast cancer; reduce the incidence of breast cancer in women at high risk (taking into account age, number of first-degree relatives with breast cancer, previous breast biopsies, age at first live birth, age at first menstrual period, and a history of lobular carcinoma in situ); induction of ovulation

D

Hypersensitivity to tamoxifen

Use with caution in patients with leukopenia, thrombocytopenia, or hyperlipidemias; ovulation may be induced; "hot flashes" may be countered by Bellergal-S® tablets; decreased visual acuity, retinopathy and corneal changes have been reported with use for more than 1 year at doses above recommended; hypercalcemia in patients with bone metastasis; hepatocellular carcinomas have been reported in animal studies; endometrial hyperplasia and polyps have occurred

>10%:

Cardiovascular: Flushing

Dermatologic: Skin rash

Gastrointestinal: Little to mild nausea (10%), vomiting, weight gain

Hematologic: Myelosuppressive: Transient thrombocytopenia occurs in ~24% of patients receiving 10-20 mg/day; platelet counts return to normal within several weeks in spite of continued administration; leukopenia has also been reported and does resolve during continued therapy; anemia has also been reported

WBC: Rare

Platelets: None

Hepatic: Hepatotoxicity

Neuromuscular & skeletal: Increased bone and tumor pain and local disease flare shortly after starting therapy; this will subside rapidly, but patients should be aware of this since many may discontinue the drug due to the side effects

1% to 10%:

Cardiovascular: Thromboembolism: Tamoxifen has been associated with the occurrence of venous thrombosis and pulmonary embolism; arterial thrombosis has also been described in a few case reports

Central nervous system: Lightheadedness, depression, dizziness, headache, lassitude, mental confusion

Dermatologic: Rash

Endocrine & metabolic: Hypercalcemia may occur in patients with bone metastases; galactorrhea and vitamin deficiency, menstrual irregularities

Genitourinary: Vaginal bleeding or discharge, endometriosis, priapism, possible endometrial cancer

Neuromuscular & skeletal: Weakness

Ocular: Ophthalmologic effects (visual acuity changes, cataracts, or retinopathy), corneal opacities

Symptoms of overdose include hypercalcemia, edema

General supportive care

CYP1A2, 2A6, 2B6, 2C, 2D6, 2E1, and 3A3/4 enzyme substrate

Tablets are stored at room temperature

Competitively binds to estrogen receptors on tumors and other tissue targets, producing a nuclear complex that decreases DNA synthesis and inhibits estrogen effects; nonsteroidal agent with potent antiestrogenic properties which compete with estrogen for binding sites in breast and other tissues; cells accumulate in the G₀ and G₁ phases; therefore, tamoxifen is cytostatic rather than cytocidal.

Absorption: Well absorbed from GI tract

Time to peak serum concentration: Oral: Within 4-7 hours

Distribution: High concentrations found in uterus, endometrial and breast tissue

Metabolism: In the liver

Half-life: 7 days

Elimination: Undergoes enterohepatic recycling; excreted in feces with only small amounts appearing in urine

Oral (refer to individual protocols):

Breast cancer: Refer to individual protocols

Adjunct to surgery/radiation therapy: 20-40 mg/day; dosages >20 mg/day in divided doses

Females >50 years with positive axillary nodes: 10 mg twice daily

Metastatic: 20-40 mg/day; dosages >20 mg/day in divided doses

Prevention (in high-risk females): 20 mg/day

Males: 20 mg/day

Higher dosages (up to 700 mg/day) have been investigated for use in modulation of multidrug resistance (MDR), but are not routinely used in clinical practice

Induction of ovulation: 5-40 mg twice daily for 4 days

Monitor WBC and platelet counts, tumor

T₄ elevations (no clinical evidence of hyperthyroidism)

May cause dizziness, drowsiness, or confusion

May cause leukopenia; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

Take as directed, morning and night and maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience menstrual irregularities, vaginal bleeding, hot flashes, hair loss, loss of libido (these will subside when treatment is completed). Bone pain may indicate a good therapeutic responses (consult prescriber for mild analgesics). For nausea, vomiting small, frequent meals, chewing gum, or sucking lozenges may help. You may experience photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight). Report unusual bleeding or bruising, severe weakness, sedation, mental changes, swelling or pain in calves, difficulty breathing, or any changes in vision. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication; use appropriate contraceptive measures. Do not breast-feed.

Increase of bone pain usually indicates a good therapeutic response

Tablet, as citrate: 10 mg, 20 mg

Allan SG, Rodger A, Smyth JF, et al, "Tamoxifen as Primary Treatment of Breast Cancer in Elderly or Frail Patients: A Practical Management," Br Med J [Clin Res], 1985, 290:358.

Buckley MM and Goa KL, "Tamoxifen. A Reappraisal of Its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Use," Drugs, 1989, 37(4):451-90.

Catherino WH and Jordan VC, "A Risk-Benefit Assessment of Tamoxifen Therapy," Drug Saf, 1993, 8(5):381-97.

Cohen I, Altaras MM, Lew S, et al, "Ovarian Endometrioid Carcinoma and Endometriosis Developing in a Postmenopausal Breast Cancer Patient During Tamoxifen Therapy: A Case Report and Review of the Literature," Gynecol Oncol, 1994, 55(3 Pt 1):443-7.

Cutuli B, Petit JC, Fricker JP et al, "Thromboembolic Accidents in Postmenopausal Patients Treated by Tamoxifen and Adjuvant Treatment: Frequency, Risk Factors, and Prevention," Bull Cancer, 1995, 82(1):51-6.

Cuzick J, Allen D, Baum M, et al, "Long Term Effects of Tamoxifen: Biological Effects of Tamoxifen Working Party," Eur J Cancer, 1992, 29A(1):15-21.

Dew JE and Eden JA, "Gynaecological Complications of Women Treated With Tamoxifen for Breast Cancer," Aust N Z J Obstet Gynaecol, 1995, 35(2):198-200.

Fernando IN and Tobias JS, "Priapism in Patient on Tamoxifen," Lancet, 1989, 1(8635):436.

Folk JJ, Mazur MT, Eddy GL, et al, "Secretory Endometrial Adenocarcinoma in a Patient on Tamoxifen for Breast Cancer: A Report of a Case," Gynecol Oncol, 1995, 58(1):133-5.

Gelmann EP, "Tamoxifen for the Treatment of Malignancies Other Than Breast and Endometrial Carcinoma," Semin Oncol, 1997, 24(1 Suppl 1):S1-65-S1-70.

Hochner-Celnikier D, Anteby E, and Yagel S, "Ovarian Cysts in Tamoxifen-Treated Premenopausal Women With Breast Cancer - A Management Dilemma," Am J Obstet Gynecol, 1995, 172(4 Pt 1):1323-4.

Jeffrey LP, Chairman, National Study Commission on Cytotoxic Exposure. Position Statement. "The Handling of Cytotoxic Agents by Women Who Are Pregnant, Attempting to Conceive, or Breast-Feeding," January 12, 1987.

Jordan VC, "Tamoxifen: Toxicities and Drug Resistance During Treatment and Prevention of Breast Cancer," Annu Rev Pharmacol Toxicol, 1995, 35:195-211.

LiVolsi VA, Salhany KE, and Dowdy YG, "Endocervical Adenocarcinoma in Tamoxifen-Treated Patient," Am J Obstet Gynecol, 1995, 172(3):1065.

Nease RF Jr and Ross JM, "The Decision to Enter a Randomized Trial of Tamoxifen for the Prevention of Breast Cancer in Healthy Women: An Analysis of the Tradeoffs," Am J Med, 1995, 99(2):180-9.

Parry BR, "Radiation Recall Induced by Tamoxifen," Lancet, 1992, 340(8810):49.

Pratt DS, Knox TA, and Erban J, "Tamoxifen-Induced Steatohepatitis," Ann Intern Med, 1995, 123(3):236.

Rabinowicz AL, Hinton DR, Dyck P, et al, "High-Dose Tamoxifen in Treatment of Brain Tumors: Interaction With Antiepileptic Drugs," Epilepsia, 1995, 36(5):513-5.

Ritchie LD and Grant SM, "Tamoxifen-Warfarin Interaction: The Aberdeen Hospitals Drug File," BMJ, 1989, 298(6682):1253.

Rutqvist LE, Johansson H, Signomklao T, et al, "Adjuvant Tamoxifen Therapy for Early Stage Breast Cancer and Second Primary Malignancies. Stockholm Breast Cancer Study Group," J Natl Cancer Inst, 1995, 87(9):645-51.

Rutqvist LE, "Long-Term Toxicity of Tamoxifen," Recent Results Cancer Res, 1993, 127:257-66.

Spooner D and Evans BD, "Tamoxifen and Life-Threatening Hypercalcaemia," Lancet, 1979, 2(8139):413-4.

Taylor SG, Gelman RS, Falkson G, et al, "Combination Chemotherapy Compared to Tamoxifen as Initial Therapy for Stage IV Breast Cancer in Elderly Women," Ann Intern Med, 1986, 104:455-61.

Wogan GN, "Review of the Toxicology of Tamoxifen," Semin Oncol, 1997, 24(1 Suppl 1):S1-87-S1-97.