Brand and Other Names:Soltamox
Dosing & Uses
Dosage Forms & Strengths
- 10mg/5mL (Soltamox)
Breast Cancer Treatment
20-40 mg/day PO; doses >20mg/day should be divided BID (ie, morning and evening)
Although the FDA has approved a dosage range of 20-40 mg/day, clinical benefit for doses >20 mg/day has not been demonstrated
Continue with adjuvant therapy for at least 5 years
For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10 (ATLAS trial, Lancet 2013;381:805-816; aTTom trial; ASCO Annual Meeting 2013;31:5)
- Treatment of metastatic breast cancer in women and men; in premenopausal women, alternative to oophorectomy or ovarian irradiation; estrogen receptor positive tumors more likely to benefit
- Adjuvant treatment of node-positive breast cancer in postmenopausal women following total mastectomy or segmental mastectomy, axillary dissection, and breast irradiation; most benefit in the subgroup with 4 or more positive axillary nodes
- Adjuvant treatment of axillary node-negative breast cancer in women following total mastectomy or segmental mastectomy, axillary dissection, and breast irradiation
- Reduces occurrence of contralateral breast cancer in patients receiving adjuvant treatment
Ductal Carcinoma in Situ
Indicated in women with ductal carcinoma in situ following breast surgery and radiation to reduce the risk of invasive breast cancer
20 mg PO qDay for 5 years
Breast Cancer Prevention
Indicated to reduce the incidence of breast cancer in women at high risk for breast cancer; high risk is defined as women aged ≥35 years with a 5-year predicted risk of breast cancer ≥1.67% (calculated by the Gail Model)
20 mg PO qDay for 5 years
Data are limited for use >5 yr in the risk-reduction setting (NCCN guidelines)
Ovulation Induction (Off-label)
5-40 mg PO q12hr for 4 days
10 mg PO qDay for 4 months
Other Indications & Uses
Safety and efficacy not established
Serious - Use Alternative
Significant - Monitor Closely
Hot flashes (64%)
Vaginal discharge (30%)
Menstrual changes (13%)
Bone pain (6%)
Musculoskeletal pain (3%)
Ovarian cyst (3%)
Abdominal cramps (1%)
Loss of libido
Retinal vein thrombosis
Black Box Warnings
For women with ductal carcinoma in situ (DCIS) and women at high risk for breast cancer:
Uterine malignancies, stroke, and pulmonary embolism reported with use in risk-reduction setting (women with ductal carcinoma in situ and women at high risk for breast cancer).
Undiagnosed vaginal bleeding
History of thromboembolism (prevention, DCIS)
Coumarin anticoagulation (prevention, DCIS)
History of thromboembolism (CA treatment); tamoxifen significantly increases risk of venous thromboembolism
Coumarin anticoagulation (CA treatment)
CYP2D6 polymorphism-CYP2D6 converts tamoxifen to active metabolite endoxifen; lowered CYP2D6 activity or concomitant CYP2D6 inhibitors may reduce tamoxifen efficacy
Cholestasis, fatty liver, hepatic necrosis, and hepatitis reported
Postmarketing cases of hyperlipidemia reported
Decreased visual acuity, corneal changes, retinal vein thrombosis
Flushing and increased bone pain and/or tumor pain sometimes associated with good tumor response
Chronic use for prevention may result in increased risk of stroke, pulmonary embolism, endometrial cancer, uterine sarcoma, cataract
Pregnancy & Lactation
Pregnancy Category: D
Lactation: not known if excreted in breast milk, do not nurse
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Mechanism of Action
Selective estrogen receptor modulator: nonsteroid with potent antiestrogenic effects in breast (but may be estrogen agonist in uterus); has cytostatic effect rather than cytocidal effects (cells accumulate in Go and G1 phase of the cell cycle)
Half-Life: 7-14 hr
Peak Plasma Time: 3-6 hr
Protein binding: 99%
Peak Plasma Concentration: 40 ng/mL
Metabolism: by hepatic P450 enzyme CYP2C9, CYP2D6, CYP3A4
Metabolites: N-desmethyl tamoxifen, endoxifen
Excretion: Feces (65%), urine (9%)
Metabolized via CYP2D6 into endoxifen (4-OH-N-desmethyl-tamoxifen), its primary active metabolite
Lowered CYP2D6 activity or concomitant CYP2D6 inhibitors may reduce tamoxifen efficacy
Poor CYP2D6 metabolizers are defined as those with *4/*4 alleles
On October 18, 2006, the Pharmaceutical Science Clinical Pharmacology Subcommittee of the FDA recommended including information on CYP2D6 genotypes and their potential effect on patient outcomes in the label for tamoxifen, but they did not come to consensus on whether testing should be recommended or considered optional
Subsequent to that recommendation, branded tamoxifen (Nolvadex) was discontinued and no further guidance was given by FDA on whether to amend the label for generic tamoxifen
Recent data presented at the 2010 San Antonio Breast Cancer Symposium found the CYP2D6 allele status had no effect on any outcomes, including disease recurrence, distant recurrence, and overall survival
Further research will help elucidate the potential effect of strong CYP2D6 inhibitors, such as SSRIs, on tamoxifen metabolism, but there is no evidence to suggest that the use of such medications should influence the use of tamoxifen
Therefore, based on the data available to date, routine testing for CYP2D6 variants is not recommended
CYP2C19 heterozygous *2 carriership may be a predictive factor for patients with breast cancer using tamoxifen; this factor was associated with a longer survival among tamoxifen users in a recent study (Pharmacogenomics. 2010;11:1367-75)
Genetic testing laboratories
- The Roche Cytochrome AmpliChip P450 2D6/2C19 Genotyping and Phenotyping Assay can be used to identify 26 different alleles of CYP2D6, including *4
- The following companies offer testing for CYP2D6 variants
- DxS (http://www.dxsdiagnostics.com/)
- LabCorp (http://www.labcorp.com/)
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