tamoxifen (Rx)

Brand and Other Names:Soltamox
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet (generic)

  • 10mg
  • 20mg

oral solution

  • 10mg/5mL (Soltamox)
more...

Breast Cancer

Metastatic breast cancer

  • 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
  • 20-40 mg/day PO; doses >20mg/day should be divided BID (ie, morning and evening)
  • Although approved a dosage range of 20-40 mg/day, clinical benefit for doses >20 mg/day has not been demonstrated

Adjuvant breast cancer

  • 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 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
  • 20-40 mg/day PO; doses >20mg/day should be divided BID (ie, morning and evening)
  • Although approved 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

Ductal Carcinoma in Situ

Indicated in women with ductal carcinoma in situ (DCIS) 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

Mastalgia (Off-label)

10 mg PO qDay for 4 months

Other Indications & Uses

Gynecomastia

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and tamoxifen

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            >10%

            Hot flashes (64%)

            Vaginal discharge (30%)

            Amenorrhea (16%)

            Menstrual changes (13%)

            1-10%

            Oligomenorrhea (9%)

            Cataracts (8%)

            Bone pain (6%)

            Nausea (5%)

            Cough (4%)

            Edema (4%)

            Fatigue (4%)

            Musculoskeletal pain (3%)

            Ovarian cyst (3%)

            Depression (2%)

            Abdominal cramps (1%)

            Anorexia (1%)

            <1%

            Angioedema

            Corneal changes

            Loss of libido

            Endometrial cancer

            Pancreatitis

            Retinal vein thrombosis

            Stroke

            Uterine fibroids

            Previous
            Next:

            Warnings

            Black Box Warnings

            Women with DCIS and women at high risk for breast cancer

            • Serious and life-threatening events associated with tamoxifen in the risk reduction setting (women at high risk for cancer and women with DCIS) include uterine malignancies, stroke and pulmonary embolism
            • Fatal cases of each type of event have occurred
            • Discuss potential benefits versus risks of these serious events with women at high risk of breast cancer and women with DCIS considering tamoxifen to reduce their risk of developing breast cancer; benefits of tamoxifen citrate tablets outweigh its risks in women already diagnosed with breast cancer

            Contraindications

            Hypersensitivity

            Pregnancy

            Undiagnosed vaginal bleeding

            Patients who require concomitant warfarin therapy or have a history of deep vein thrombosis or pulmonary embolus if indication for treatment is either reduction of breast cancer incidence in high-risk patients or risk reduction of invasive breast cancer after treatment of DCIS

            Cautions

            Liver cancer and changes in liver enzyme levels reported with use; on rare occasions, a spectrum of more severe liver abnormalities including fatty liver, cholestasis, hepatitis and hepatic necrosis, that have included fatalities, also reported; monitor liver function periodically

            Unknown whether an increased risk for other (non-uterine) cancers is associated with tamoxifen

            Hypercalcemia reported in some breast cancer patients with bone metastases within a few weeks of starting treatment; if hypercalcemia occurs, treat as appropriate; if hypercalcemia is severe, discontinue therapy

            CYP2D6 polymorphism-CYP2D6 converts tamoxifen to active metabolite endoxifen; lowered CYP2D6 activity or concomitant CYP2D6 inhibitors may reduce tamoxifen efficacy

            Decreases in platelet counts, usually to 50,000-100,000/mm3, infrequently lower, reported in patients receiving therapy for breast cancer; hemorrhagic episodes have occurred, but not certain if episodes were due to tamoxifen therapy; leukopenia, sometimes in association with anemia and/or thrombocytopenia reported; neutropenia and pancytopenia also reported; perform periodic complete blood counts, including platelet counts

            Ocular disturbances, including corneal changes, decrement in color vision perception, retinal vein thrombosis, and retinopathy reported; an increased incidence of cataracts and need for cataract surgery reported; patients should seek medical attention if they experience visual disturbance

            There is increased incidence of thromboembolic events, including deep vein thrombosis and pulmonary embolism, during tamoxifen therapy; when tamoxifen is coadministered with chemotherapy, there is further increase in risk of thromboembolic events; for treatment of breast cancer, carefully consider risks and benefits of tamoxifen in women with a history of thromboembolic events; advise patients to seek medical attention immediately if signs or symptoms of a thromboembolic event occur

            Increased incidence of uterine malignancies (endometrial adenocarcinoma and uterine sarcoma), including fatal cases, reported with treatment; underlying mechanism unknown, most uterine malignancies seen with tamoxifen are classified as adenocarcinoma of the endometrium; however, uterine sarcomas, including malignant mixed mullerian tumors (MMMT), generally associated with a higher FIGO stage (III/IV), also reported; uterine sarcoma at diagnosis usually associated with poor prognosis, and short survival; uterine sarcoma reported to occur more frequently among long-term users (≥2 years) of tamoxifen than non-users; promptly evaluate patient receiving or who has previously received therapy who reports abnormal vaginal bleeding; patients receiving or who have previously received tamoxifen should have annual gynecological examinations

            Therapy can cause fetal harm when administered to pregnant woman; there are postmarketing reports of vaginal bleeding, spontaneous abortions, birth defects, and fetal deaths in pregnant women taking tamoxifen; in primate model, administration of drug at doses 2 times maximum recommended human dose resulted in spontaneous abortion; advise pregnant women of potential risks to a fetus, including potential long-term risk of a DES-like syndrome; advise females of reproductive potential to use effective non-hormonal contraception during treatment with tamoxifen and for 9 months following the last dose

            Previous
            Next:

            Pregnancy & Lactation

            Pregnancy

            Fetal harm may occur when administered to a pregnant woman

            There are postmarketing reports of vaginal bleeding, spontaneous abortions, birth defects, and fetal deaths in pregnant women taking tamoxifen

            In a primate model, administration of tamoxifen at doses 2 times the maximum recommended human dose resulted in spontaneous abortion

            Advise pregnant women of potential risks to a fetus, including potential long term risk of a DES-like syndrome

            Prior to initiating treatment, a negative pregnancy test should be confirmed

            Animal studies

            • In rat and rabbit studies, doses of tamoxifen less than or equal to human doses resulted in increased embryotoxicity, abortions, and altered learning behaviors in the offspring; rodent models showed reproductive tract changes often associated with diethylstilbestrol (DES) in offspring of both sexes
            • Based on animal studies, tamoxifen may impair embryo implantation in females of reproductive potential, however, may not reliably cause infertility; advise women that tamoxifen does not always cause infertility, even in the presence of menstrual irregularity

            Contraception

            • Advise females of reproductive potential to use effective nonhormonal contraception during treatment with tamoxifen and for 9 months following last dose
            • Because of potential for genotoxicity, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 6 months following last dose

            Lactation

            Tamoxifen reported to inhibit lactation

            Two placebo-controlled studies in over 150 women have shown that tamoxifen significantly inhibits early postpartum milk production; both studies tamoxifen was administered within 24 hr of delivery for between 5 and 18 days; effect of tamoxifen on established milk production is not known

            There are no data that address whether tamoxifen is excreted into human milk; direct neonatal exposure of tamoxifen to mice and rats (not via breast milk) produced 1) reproductive tract lesions in female rodents (similar to those seen in humans after intrauterine exposure to diethylstilbestrol) and 2) functional defects of the reproductive tract in male rodents such as testicular atrophy and arrest of spermatogenesis

            Unknown if tamoxifen is excreted in human milk

            Because of potential for serious adverse reactions in nursing infants from tamoxifen, women taking tamoxifen should not breast feed

            Pregnancy Categories

            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.

            more...
            Previous
            Next:

            Pharmacology

            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)

            Pharmacokinetics

            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%)

            Pharmacogenomics

            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[10]: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/)
            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.