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Nolvadex
Classes
Cytostatic Anti-Estrogens
Selective Estrogen Receptor Modulators (SERMs)
Administration
Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 1
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure.
Tamoxifen may be taken with or without food.
If a dose of tamoxifen is missed, administer the dose as soon as possible. If it is almost time for the next dose, skip the missed dose and administer the next dose at the regularly scheduled time.[63589]
Adverse Reactions
hot flashes / Early / 0-45.0
vaginal discharge / Delayed / 0-12.3
thromboembolism / Delayed / 0-5.0
stroke / Early / 0.5-3.0
new primary malignancy / Delayed / 0-1.0
endometrial cancer / Delayed / 0-1.0
thrombocytopenia / Delayed / 0-0.7
pulmonary embolism / Delayed / 0.3-0.5
spontaneous fetal abortion / Delayed / Incidence not known
teratogenesis / Delayed / Incidence not known
fetal death / Delayed / Incidence not known
thrombosis / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
retinopathy / Delayed / Incidence not known
retinal thrombosis / Delayed / Incidence not known
visual impairment / Early / Incidence not known
hepatic necrosis / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
pancreatitis / Delayed / Incidence not known
peripheral vasodilation / Rapid / 0-41.0
fluid retention / Delayed / 0-32.0
vaginal bleeding / Delayed / 6.0-23.0
depression / Delayed / 2.0-12.0
hypertension / Early / 11.0-11.0
peripheral edema / Delayed / 0-11.0
cataracts / Delayed / 7.0-8.1
constipation / Delayed / 4.4-8.0
dyspnea / Early / 0-8.0
bone pain / Delayed / 0-6.0
vaginitis / Delayed / 0-5.0
elevated hepatic enzymes / Delayed / 0-5.0
chest pain (unspecified) / Early / 5.0-5.0
edema / Delayed / 0-4.0
hypercholesterolemia / Delayed / 0-3.0
hyperbilirubinemia / Delayed / 0-2.0
phlebitis / Rapid / 0-0.4
endometrial hyperplasia / Delayed / Incidence not known
bleeding / Early / Incidence not known
leukopenia / Delayed / Incidence not known
anemia / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
steatosis / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
impotence (erectile dysfunction) / Delayed / Incidence not known
bullous rash / Early / Incidence not known
pneumonitis / Delayed / Incidence not known
hypertriglyceridemia / Delayed / Incidence not known
erythema / Early / Incidence not known
tumor flare / Delayed / Incidence not known
hypercalcemia / Delayed / Incidence not known
flushing / Rapid / 0-33.0
arthralgia / Delayed / 11.0-29.0
nausea / Early / 5.0-26.0
menstrual irregularity / Delayed / 6.0-25.0
weight loss / Delayed / 0-23.0
fatigue / Early / 0-18.0
asthenia / Delayed / 0-18.0
amenorrhea / Delayed / 0-16.0
pharyngitis / Delayed / 0-14.0
infection / Delayed / 5.0-14.0
rash / Early / 0-13.0
vomiting / Early / 0-12.0
back pain / Delayed / 0-10.0
oligomenorrhea / Delayed / 0-9.0
leukorrhea / Delayed / 0-9.0
weight gain / Delayed / 0-9.0
abdominal pain / Early / 0-9.0
insomnia / Early / 0-9.0
cough / Delayed / 4.0-9.0
headache / Early / 0-8.0
dizziness / Early / 0-8.0
diarrhea / Early / 0-7.0
influenza / Delayed / 0-6.0
dyspepsia / Early / 0-6.0
anxiety / Delayed / 0-6.0
hyperhidrosis / Delayed / 0-6.0
mastalgia / Delayed / 0-6.0
alopecia / Delayed / 0-5.2
myalgia / Early / 0-5.0
sinusitis / Delayed / 0-5.0
paresthesias / Delayed / 0-5.0
throat irritation / Early / 5.0-5.0
musculoskeletal pain / Early / 0-3.0
anorexia / Delayed / 0-1.0
pruritus / Rapid / Incidence not known
libido decrease / Delayed / Incidence not known
dysgeusia / Early / Incidence not known
Boxed Warning
There is an increased incidence of thromboembolic events, including DVT and PE, during tamoxifen therapy; this risk is increased when tamoxifen is coadministered with chemotherapy. Tamoxifen is contraindicated in patients who require concomitant anticoagulant therapy or have a history of thromboembolism (e.g., deep vein thrombosis (DVT), pulmonary embolus (PE), stroke) if the indication is risk reduction for high-risk patients or risk reduction of invasive breast cancer after ductal carcinoma in situ (DCIS) treatment. For the treatment of breast cancer, carefully consider the risks and benefits of tamoxifen in patients with a history of thromboembolic events. Discuss the potential benefits of tamoxifen versus the potential risks of these serious events with women at high risk for breast cancer and women with DCIS considering tamoxifen to reduce the risk of developing invasive breast cancer. For most patients already diagnosed with breast cancer, the benefits of tamoxifen outweigh its risks. Advise patients to seek medical attention immediately if signs or symptoms of a thromboembolic event occur. During the NSABP P-1 trial, women without a history of PE had a statistically significant increase in the incidence of PE. In this same population, there was a nonstatistically significant increase in DVT and stroke in the patients randomized to tamoxifen. The majority (87%) of the cases of PE and stroke occurred in women at least 50 years of age at randomization; the relative risk of DVT was not statistically different depending on age. Women with thromboembolic events were at risk for a second related event and were at risk for treatment-related complications. In a small substudy of the NSABP-1 trial (n = 81), there appeared to be no benefit to screening women for Factor V Leiden and prothrombin mutations G20210A as a means to identify those who may not be appropriate candidates for tamoxifen therapy.[63589]
An increased risk of endometrial changes (including hyperplasia and polyps) and new primary malignancy (endometrial cancer and uterine cancer) has been reported in association with tamoxifen treatment for any indication. The underlying mechanism is unknown, but may be related to the estrogen-like effect of tamoxifen. Most uterine malignancies seen in association with tamoxifen therapy are classified as adenocarcinoma of the endometrium; however, rare uterine sarcomas including malignant mixed mullerian tumors have also been reported. Uterine sarcoma has been reported to occur more frequently among long-term tamoxifen users (more than 2 years) versus non-users. Use tamoxifen with caution in patients with preexisting endometrial hyperplasia. Discuss the risks versus benefits of tamoxifen therapy with women at high risk of breast cancer considering tamoxifen preventative therapy, as well as with women who have ductal carcinoma in situ (DCIS) considering tamoxifen to decrease the risk of developing invasive breast cancer. The benefits of tamoxifen therapy for the adjuvant treatment of breast cancer or for advanced breast cancer generally outweigh the risks in most patients. Patients receiving or having previously received tamoxifen should have annual gynecological examinations and should promptly inform their health care professional if they experience any abnormal gynecological symptoms (e.g., menstrual irregularities, abnormal vaginal bleeding, changes in vaginal discharge, or pelvic pain or pressure). There are no data to suggest that routine endometrial sampling in asymptomatic women taking tamoxifen is beneficial. Second primary tumors at sites other than the endometrium have been reported following the treatment of breast cancer with tamoxifen in clinical trials; however, data from the NSABP B-14 and P-1 studies show no increase in non-uterine cancers. Whether an increased risk for non-uterine cancers is associated with tamoxifen is still unknown.[63589]
Common Brand Names
Nolvadex, Soltamox
Dea Class
Rx
Description
Selective estrogen receptor modulator; estrogen agonist/antagonist
Used for the prevention and treatment of specific types of breast cancer
Discuss benefits vs. serious risks with patients at high risk for breast cancer and patients with DCIS
Dosage And Indications
20 mg once daily for 5 to 10 years. Doses greater than 20 mg daily do not provide additional clinical benefit. The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) conducted worldwide overviews of systemic adjuvant therapy for early breast cancer in 1985, 1990, 1995, 1998 and 2011. Women with ER-positive or ER-unknown breast cancer were entered into trials comparing tamoxifen to no adjuvant therapy (n =17,076), or trials comparing tamoxifen plus chemotherapy to chemotherapy alone (n = 12,365). Treatment with tamoxifen for approximately 5 years significantly improved overall survival at 10 years compared to control in both node-positive (n = 15,898; 61.4% vs. 50.5%) and node-negative (n = 13,543; 78.9% vs. 73.3%) disease. The recurrence-free survival rate at 10 years was also significantly improved in both node-positive (59.7% vs. 44.5%) and node-negative (79.2% vs. 64.3%) patients. In women with ER-positive or ER-unknown breast cancer who received 1 year or less, 2 years, or about 5 years of tamoxifen, the proportional reductions in mortality were 12%, 17%, and 26%, respectively; corresponding reductions in breast cancer recurrence were 21%, 29%, and 47%, respectively. The benefit is less clear for women with ER-poor breast cancer, in whom the proportional reduction in recurrence was 10% for all durations taken together, or 9% if contralateral breast cancers are excluded; the reduction in mortality was 6%. These effects were similar regardless of age and concurrent chemotherapy. Continuing tamoxifen for up to 10 years has had conflicting results, with an improved risk of recurrence in one study (ATLAS) and no benefit in two others including NSABP-B14.[63589]
20 to 40 mg PO daily; doses greater than 20 mg per day should be given in divided doses (morning and evening). In 3 prospective, randomized studies in premenopausal women with advanced breast cancer, the objective response rate, time to treatment failure, and survival were similar with tamoxifen compared to ovarian ablation (oophorectomy or ovarian irradiation); limited patient accrual prevented a demonstration of equivalence. A limited number of patients with disease progression during tamoxifen therapy responded to subsequent ovarian ablation. Published results from 119 evaluable patients and 13 evaluable case reports demonstrated that tamoxifen is effective for the palliative treatment of men with metastatic breast cancer, with a 50% objective response rate.[63589]
20 mg PO once daily for 5 years. In a randomized, double-blind study (NSABP B-24), the incidence of invasive breast cancer was reduced by 43% in women randomized to receive tamoxifen. Survival was similar for both the placebo and tamoxifen treatment groups. In a randomized, double-blind clinical trial in women with DCIS (NSABP B-24; n = 1,804), treatment with tamoxifen following lumpectomy and radiation significantly reduced the incidence of invasive breast cancer by 43% compared with placebo; no data are available regarding the estrogen receptor (ER) status of the invasive cancers. The stage distribution of the invasive cancers at diagnosis was similar to that reported anually in the SEER database. Fewer deaths occurred in the tamoxifen arm (28 vs. 32 patients); however, patients in the tamoxifen arm experienced more uterine malignancies (9 vs. 4 patients), strokes (7 vs. 2 patients), and thromboembolic events (15 vs. 5 patients).
20 mg PO once daily plus everolimus 10 mg PO once daily until disease progression or unacceptable toxicity. In a randomized phase 2 study in postmenopausal women with estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer and primary or secondary resistance to aromatase inhibitors (n = 111), treatment with tamoxifen plus everolimus significantly improved clinical benefit rate (61.1% vs. 42.1%), time to progression (TTP) (7.6 months vs. 4.5 months), and overall survival (OS) (16 vs. 31 events) compared with tamoxifen alone. In exploratory analyses, a statistically significant TTP and OS benefit was observed with combination therapy in women with secondary resistance (TTP, 14.8 months vs. 5.5 months; OS, 4 events vs. 16 events) but not primary resistance (TTP, 5.4 months vs. 3.8 months; OS, 12 events vs. 15 events). A higher incidence of grade 3 and 4 stomatitis and anorexia was reported in the combination therapy arm; 22% of patients receiving combination therapy and 7% of patients treated with tamoxifen alone discontinued treatment due to adverse events.
20 mg once daily for 5 to 10 years. Doses greater than 20 mg daily do not provide additional clinical benefit. The incidence of contralateral breast cancer was reduced in both premenopausal and postmenopausal breast cancer patients receiving adjuvant tamoxifen compared to placebo in a large overview analysis including 32,422 patients. In this analysis, proportional reductions in the incidence of contralateral breast cancer among women receiving tamoxifen for 1 year or less, 2 years, and about 5 years duration were 13%, 26%, and 47%, respectively, independent of age and estrogen receptor (ER)-status of the primary tumor; the reduction in the incidence of contralateral breast cancer was significant with longer tamoxifen duration. Treatment with about 5 years of tamoxifen reduced the annual incidence of contralateral breast cancer from 7.6 per 1,000 patients in the control group to 3.9 per 1,000 patients in the tamoxifen group. At an increased daily dose of 40 mg in a Sweedish Breast Cancer Cooperative Group trial, the reduction in second primary breast cancers was similar (40%).
20 mg PO once daily for 5 years. In a double-blind, placebo-controlled clinical trial (the Breast Cancer Prevention Trial), women older than 35 years of age and at high risk for invasive breast cancer were randomized to receive either tamoxifen or placebo for 5 years (n = 13,388); "high risk" was defined as a 5-year predicted risk of breast cancer of 1.67% or higher. Treatment with tamoxifen significantly reduced the incidence of invasive breast cancer by 44% after a median follow-up of 4.2 years; this reduction was significant in each age group (49 years or less, 50 to 59 years, and 60 years or more), in women with or without LCIS, and in each absolute risk level. The decrease was evident in the incidence of small estrogen receptor-positive tumors, but not in the incidence of ER-negative tumors or larger tumors. A nonsignificant decrease in the incidence in DCIS was observed (RR 0.66). There was no significant difference in overall mortality, breast cancer-related mortality, or acute ischemic cardiac events. A subgroup analysis suggested a difference in effect on bone mineral density (BMD) related to menopausal status: there was no evidence of bone loss of the lumbar spine and hip in postmenopausal women, but there was significant bone loss in premenopausal women. Tamoxifen increased the risk for endometrial cancer, DVT, PE, stroke, cataract formation, and cataract surgery.[63589]
10 mg PO twice daily or 20 mg PO once daily in combination with carmustine, dacarbazine, and cisplatin (DBCT regimen). First-line treatment with DBCT did not significantly improve the median overall survival (OS) time (7.7 vs 6.3 months), 1-year OS rate (22% vs 27%), or overall response rate (ORR) (16.8% vs 9.9%) compared with single-agent dacarbazine in 240 patients in a multicenter, randomized phase III trial. Additionally, the DBCT regimen did not significantly improve median OS time (202 vs 199 days), 1-year OS rate (22.6% vs 30.6%), or ORR (26.4% vs 17.3%) compared with dacarbazine and interferon alfa-2a in 105 patients in another randomized phase III trial. In this study, treatment with DBCT was associated with significantly longer hospitalization and 2 treatment-related deaths. Serious toxicity that occurred significantly more often with DBCT included grade 3 and 4 hematologic toxicity and increased serum creatinine levels.
Several dosage regimens have been employed. Continuous daily dosing of 20 mg or 20 mg/m2 (rounded to nearest 10 mg) PO daily in conjunction with other chemotherapy agents has been used. In clinical trials, response rates with tamoxifen added to combination therapy range from 14.3—31.9%. Few trials have reported a significant improvement in OS with the addition of tamoxifen.
Multiple dosage regimens have been studied. Salvage tamoxifen 80 mg/m2 PO once daily (or divided twice daily) produced an ORR of 17% in a phase II trial of 24 patients with recurrent anaplastic astrocytomas. Tamoxifen 100 mg PO once daily in combination with procarbazine 100 mg/m2 PO once daily produced an ORR of 29.5% in the second-line treatment of patients with high-grade gliomas. Additionally, tamoxifen 20 mg/m2 PO every 6 hours (escalated 20 mg/day until target reached) was given until disease progression in combination with radiation therapy (30 fractions x 2.0 Gy). Among 75 patients with supratentorial glioblastoma multiforme, combination treatment produced a median overall survival of 9.7 months.
Studies have used 20 mg PO twice daily. Of 105 patients with advanced ovarian cancer treated with tamoxifen, 10% demonstrated a complete response (CR) and 8% a partial response; 38% had disease stabilization. Of the 9 patients with a CR, 8 (89%) had elevated estrogen receptor levels, as compared to patients with stable or progressive disease where only 59% had measurable estrogen receptors. In a reanalysis of this trial, 77 patients with cisplatin-refractory disease had an ORR of 13% with tamoxifen.
Tamoxifen 120 mg PO once daily in combination with sulindac 300 mg PO once daily for the treatment of desmoid tumors. In a study of 25 patients (17 familial adenomatous polyposis-associated, 8 sporadic) with desmoid tumors, among 20 patients administered tamoxifen and sulindac, 3 complete responses, 3 partial responses, and 8 cases of stable disease were observed.]
In a small case series, 6 pediatric patients with desmoid tumors underwent multimodality treatment that included tamoxifen 1 mg/kg PO once daily in combination with diclofenac 2 mg/kg per rectum twice daily. Patients ranged in age from 11 months to 9 years. With varying periods of follow-up, 2 patients achieved no evidence of disease (2.6 years, 3.7 years follow-up), 2 patients had minimal residual tumor (1.1 years, 7.5 years), and 2 patients had stable disease (1 year, 11 years).
Limited data suggest 20 to 80 mg/day PO for 5 days may be as effective as clomiphene in ovulation induction. In one study, tamoxifen induced ovulation in 44.2% of patients compared to 45.1% induction with clomiphene (P=NS). Studies have typically started at doses of 20 mg/day PO and titrated up after a lack of ovulation for 1 to 2 cycles. Administering tamoxifen on cycle days 2 thru 6, 3 thru 7, or 5 thru 9 have been studied during clinical trials.
10 to 20 mg/day PO for 3 to 6 months has been shown to be effective in the treatment of mastalgia. A meta-analysis found significant pain relief with tamoxifen as compared to placebo (RR 1.92, 95% CI 1.52—2.59).
Trials suggest 20 mg/day PO for up to 1 year in men taking bicalutamide is effective in reducing the incidence of gynecomastia and breast pain. Patients randomized to bicalutamide only or tamoxifen plus bicalutamide experienced a rate of gynecomastia of 73% vs. 10%, respectively (p < 0.001), and a rate of breast pain of 39% vs. 6%, respectively (p = 0.006). In another study, lower doses of tamoxifen (1 to 10 mg/day PO) were not as effective as 20 mg/day PO.
In a randomized, double-blind trial of postmenopausal women with breast cancer, tamoxifen 10 mg PO twice daily for 2 years increased bone density of lumbar spine but not radial bone density. The risk or incidence of fractures in this study population was not assessed.
A single, uncontrolled trial of tamoxifen 20 mg PO once daily for 12 months was conducted in 28 female patients with McCune-Albright Syndrome and precocious puberty manifested by physical signs of pubertal development, episodes of vaginal bleeding, and/or advanced bone age. Tamoxifen treatment was associated with a 50% reduction in frequency of vaginal bleeding. Not all patients improved on treatment and a few patients not reporting vaginal bleeding in the 6 months prior to enrollment reported menses on treatment. Tamoxifen was associated with a reduction in mean rate of increase of bone age. Linear growth rate was decreased during tamoxifen treatment in the majority of patients. This change was not seen uniformly across all stages of bone maturity; all recorded response failures occurred in patients with bone ages < 7 years at screening. Mean uterine volume increased after 6 months of treatment and doubled at the end of the one-year study. A causal relationship has not been established; however, as an increase in the incidence of endometrial adenocarcinoma and uterine sarcoma has been noted in adult females treated with tamoxifen, continued monitoring of McCune-Albright patients treated with tamoxifen for long-term uterine effects is recommended. The safety and efficacy of tamoxifen in these patients beyond one year of treatment has not been studied.
Limited data suggest that 40 mg PO twice daily may be effective in decreasing the Young Mania Rating Scale (YMRS) and Clinical Global Impression-Mania (CGI-Mania) scores. In a double-blind, placebo-controlled study of 66 patients, tamoxifen (N=35) was compared to placebo (n = 31) for 3 weeks; patients were able to take adjunctive oral lorazepam up to 5 mg/day. The YMRS score decreased from a mean of 38.6 to 20.3 by the end of week 3 in patients treated with tamoxifen and increased from a baseline mean of 37.2 to 40.1 in placebo treated patients; in patients treated with tamoxifen, the weekly YMRS score decreased by an average of 5.85 points while the score increased by 1.5 points per week in patients taking placebo (p < 0.001). Similarly, improvements in the CGI-Mania score were better in patients taking tamoxifen (decrease of 0.73 points/week for tamoxifen vs. an increase of 0.1 points/week for placebo, p < 0.001). The treatment was well-tolerated by all patients. It should be noted that patients were hospitalized for the entire 3 weeks of the study and that the majority of patients in the tamoxifen group (88%) were still symptomatic after 3 weeks of tamoxifen. The authors note that the population studied consisted of patients considered to be difficult to treat (baseline YMRS score higher than similarly designed studies), and patients receiving placebo in other studies have not experienced a worsening of symptoms as they did in the current evaluation. Longer studies are needed to determine the full impact of tamoxifen on bipolar disorder as 3-week studies typically can demonstrate an improvement in symptoms, but not function.
†Indicates off-label use
Dosing Considerations
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Drug Interactions
Adagrasib: (Major) Concomitant use of adagrasib and tamoxifen increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Alfuzosin: (Moderate) Concomitant use of tamoxifen and alfuzosin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Amiodarone: (Major) Concomitant use of tamoxifen and amiodarone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
Amisulpride: (Major) Concomitant use of tamoxifen and amisulpride increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Concomitant use of tamoxifen and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Anagrelide: (Major) Concomitant use of tamoxifen and anagrelide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Anastrozole: (Major) Avoid coadministration of tamoxifen with anastrozole, as there is no benefit when compared to tamoxifen alone. Additionally, in the ATAC trial, coadministration of anastrozole and tamoxifen in breast cancer patients reduced the anastrozole plasma concentration by 27% compared to that achieved with anastrozole alone; the tamoxifen concentration was not altered.
Apalutamide: (Major) Avoid coadministration of apalutamide with tamoxifen due to decreased exposure to tamoxifen which may affect efficacy. Tamoxifen is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC and Cmax of tamoxifen by 86% and 55%, respectively.
Apomorphine: (Moderate) Concomitant use of tamoxifen and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Aripiprazole: (Moderate) Concomitant use of aripiprazole and tamoxifen may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Arsenic Trioxide: (Major) Concomitant use of tamoxifen and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Artemether; Lumefantrine: (Major) Concomitant use of tamoxifen and artemether increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Asenapine: (Major) Concomitant use of tamoxifen and asenapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Atomoxetine: (Moderate) Concomitant use of tamoxifen and atomoxetine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Azithromycin: (Major) Concomitant use of azithromycin and tamoxifen increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bedaquiline: (Major) Concomitant use of tamoxifen and bedaquiline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and tamoxifen may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and tamoxifen may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Buprenorphine: (Major) Concomitant use of tamoxifen and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Buprenorphine; Naloxone: (Major) Concomitant use of tamoxifen and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bupropion: (Moderate) Monitor for decreased efficacy of tamoxifen if coadministration with bupropion is necessary. Tamoxifen is metabolized by CYP2D6 to endoxifen and 4-hydroxytamoxifen, both of which are minor metabolites but have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen. Bupropion is a strong CYP2D6 inhibitor. In one study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. In another study, the mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors were 3.6-fold higher compared to normal metabolizers who were receiving strong CYP2D6 inhibitors; plasma levels in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to levels observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors. Some studies have shown that the efficacy of tamoxifen may be reduced when concomitant drugs decrease the levels of potent active metabolites; however, others have failed to demonstrate such an effect. The clinical significance is not well established.
Bupropion; Naltrexone: (Moderate) Monitor for decreased efficacy of tamoxifen if coadministration with bupropion is necessary. Tamoxifen is metabolized by CYP2D6 to endoxifen and 4-hydroxytamoxifen, both of which are minor metabolites but have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen. Bupropion is a strong CYP2D6 inhibitor. In one study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. In another study, the mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors were 3.6-fold higher compared to normal metabolizers who were receiving strong CYP2D6 inhibitors; plasma levels in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to levels observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors. Some studies have shown that the efficacy of tamoxifen may be reduced when concomitant drugs decrease the levels of potent active metabolites; however, others have failed to demonstrate such an effect. The clinical significance is not well established.
Cabotegravir; Rilpivirine: (Moderate) Concomitant use of tamoxifen and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Carbamazepine: (Major) Avoid coadministration of carbamazepine with tamoxifen due to decreased exposure to tamoxifen which may affect efficacy. Tamoxifen is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC and Cmax of tamoxifen by 86% and 55%, respectively.
Ceritinib: (Major) Concomitant use of tamoxifen and ceritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Chloroquine: (Major) Concomitant use of tamoxifen and chloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Chlorpromazine: (Major) Concomitant use of tamoxifen and chlorpromazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ciprofloxacin: (Moderate) Concomitant use of tamoxifen and ciprofloxacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Cisapride: (Contraindicated) Avoid concomitant use of tamoxifen and cisapride due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Citalopram: (Major) Concomitant use of tamoxifen and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clarithromycin: (Major) Concomitant use of tamoxifen and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clofazimine: (Moderate) Concomitant use of clofazimine and tamoxifen may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Clozapine: (Moderate) Concomitant use of tamoxifen and clozapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Cocaine: (Major) Monitor for decreased efficacy of tamoxifen if the patient uses cocaine. Tamoxifen is metabolized by CYP2D6 to endoxifen and 4-hydroxytamoxifen, both of which are minor metabolites but have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen. Cocaine is a strong CYP2D6 inhibitor. In one study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. In another study, the mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors were 3.6-fold higher compared to normal metabolizers who were receiving strong CYP2D6 inhibitors; plasma levels in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to levels observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors. Some studies have shown that the efficacy of tamoxifen may be reduced when concomitant drugs decrease the levels of potent active metabolites; however, others have failed to demonstrate such an effect. The clinical significance is not well established.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of tamoxifen and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Codeine; Promethazine: (Moderate) Concomitant use of tamoxifen and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Conjugated Estrogens; Medroxyprogesterone: (Minor) Medroxyprogesterone reduces plasma concentrations of N-dimethyltamoxifen, the metabolite of tamoxifen, but not tamoxifen.
Crizotinib: (Major) Concomitant use of tamoxifen and crizotinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cyclophosphamide: (Moderate) Monitor for signs and symptoms of thrombosis if coadministration of cyclophosphamide with tamoxifen is necessary; concomitant use of tamoxifen with chemotherapy may increase the risk of thromboembolic complications.
Dacomitinib: (Moderate) Monitor for decreased efficacy of tamoxifen if coadministration with dacomitinib is necessary. Tamoxifen is metabolized by CYP2D6 to endoxifen and 4-hydroxytamoxifen, both of which are minor metabolites but have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen. Dacomitinib is a strong CYP2D6 inhibitor. In one study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. In another study, the mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors were 3.6-fold higher compared to normal metabolizers who were receiving strong CYP2D6 inhibitors; plasma levels in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to levels observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors. Some studies have shown that the efficacy of tamoxifen may be reduced when concomitant drugs decrease the levels of potent active metabolites; however, others have failed to demonstrate such an effect. The clinical significance is not well established.
Dasatinib: (Moderate) Concomitant use of tamoxifen and dasatinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Degarelix: (Moderate) Concomitant use of tamoxifen and androgen deprivation therapy (i.e., degarelix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Desflurane: (Major) Concomitant use of tamoxifen and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Deutetrabenazine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and tamoxifen. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses.
Dexmedetomidine: (Moderate) Concomitant use of dexmedetomidine and tamoxifen may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Dextromethorphan; Bupropion: (Moderate) Monitor for decreased efficacy of tamoxifen if coadministration with bupropion is necessary. Tamoxifen is metabolized by CYP2D6 to endoxifen and 4-hydroxytamoxifen, both of which are minor metabolites but have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen. Bupropion is a strong CYP2D6 inhibitor. In one study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. In another study, the mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors were 3.6-fold higher compared to normal metabolizers who were receiving strong CYP2D6 inhibitors; plasma levels in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to levels observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors. Some studies have shown that the efficacy of tamoxifen may be reduced when concomitant drugs decrease the levels of potent active metabolites; however, others have failed to demonstrate such an effect. The clinical significance is not well established.
Dextromethorphan; Quinidine: (Major) Coadministration of quinidine with tamoxifen may result in additive QT prolongation and decreased efficacy of tamoxifen. When administered as quinidine; dextromethorphan, coadministration with tamoxifen is contraindicated. Quinidine is a CYP2D6 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Tamoxifen is a CYP2D6 substrate that has also been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Tamoxifen is metabolized by CYP2D6 to endoxifen and 4-hydroxytamoxifen, both of which are minor metabolites but have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen. In one study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. In another study, the mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors were 3.6-fold higher compared to normal metabolizers who were receiving strong CYP2D6 inhibitors; plasma levels in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to levels observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors. Some studies have shown that the efficacy of tamoxifen may be reduced when concomitant drugs decrease the levels of potent active metabolites; however, others have failed to demonstrate such an effect. The clinical significance is not well established.
Disopyramide: (Major) Concomitant use of tamoxifen and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dofetilide: (Major) Concomitant use of tamoxifen and dofetilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dolasetron: (Moderate) Concomitant use of tamoxifen and dolasetron may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Dolutegravir; Rilpivirine: (Moderate) Concomitant use of tamoxifen and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Donepezil: (Moderate) Concomitant use of tamoxifen and donepezil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Donepezil; Memantine: (Moderate) Concomitant use of tamoxifen and donepezil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Dronedarone: (Contraindicated) Avoid concomitant use of tamoxifen and dronedarone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Droperidol: (Major) Concomitant use of tamoxifen and droperidol increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Efavirenz: (Moderate) Concomitant use of tamoxifen and efavirenz may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of tamoxifen and efavirenz may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of tamoxifen and efavirenz may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Eliglustat: (Major) Concomitant use of tamoxifen and eliglustat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Concomitant use of tamoxifen and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of tamoxifen and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Encorafenib: (Major) Concomitant use of tamoxifen and encorafenib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Entrectinib: (Major) Concomitant use of tamoxifen and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Enzalutamide: (Major) Avoid coadministration of enzalutamide with tamoxifen due to decreased exposure to tamoxifen which may affect efficacy. Tamoxifen is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC and Cmax of tamoxifen by 86% and 55%, respectively.
Eribulin: (Major) Concomitant use of tamoxifen and eribulin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Erythromycin: (Major) Concomitant use of tamoxifen and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Escitalopram: (Moderate) Concomitant use of tamoxifen and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Everolimus: (Moderate) Monitor for decreased efficacy of tamoxifen if coadministration with everolimus is necessary. Tamoxifen is metabolized by CYP2D6 to endoxifen and 4-hydroxytamoxifen, both of which are minor metabolites but have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen. Everolimus is a CYP2D6 inhibitor. In one study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. In another study, the mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors were 3.6-fold higher compared to normal metabolizers who were receiving strong CYP2D6 inhibitors; plasma levels in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to levels observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors. Some studies have shown that the efficacy of tamoxifen may be reduced when concomitant drugs decrease the levels of potent active metabolites; however, others have failed to demonstrate such an effect. The clinical significance is not well established.
Fingolimod: (Moderate) Concomitant use of tamoxifen and fingolimod may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Flecainide: (Major) Concomitant use of tamoxifen and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluconazole: (Moderate) Concomitant use of tamoxifen and fluconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fluoroestradiol F 18: (Major) Administer fluoroestradiol F 18 before starting an estrogen-receptor (ER) modifier; however, do not delay indicated therapy to administer fluoroestradiol F 18. ER modifiers may block ER for up to 8 weeks and reduce the uptake of fluoroestradiol F 18 and detection of ER-positive lesions.
Fluoxetine: (Moderate) Monitor for QT prolongation and decreased efficacy of tamoxifen if coadministration with fluoxetine is necessary. Concomitant use may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Tamoxifen is metabolized by CYP2D6 to endoxifen and 4-hydroxytamoxifen, both of which are minor metabolites but have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen. XXX is a strong CYP2D6 inhibitor. In one study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. In another study, the mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors were 3.6-fold higher compared to normal metabolizers who were receiving strong CYP2D6 inhibitors; plasma concentrations in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to concentrations observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors. Some studies have shown that the efficacy of tamoxifen may be reduced when concomitant drugs decrease the concentrations of potent active metabolites; however, others have failed to demonstrate such an effect. The clinical significance is not well established.
Fluphenazine: (Minor) Use caution if coadministration of fluphenazine with tamoxifen is necessary due to the risk of QT prolongation. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Fluphenazine is also associated with a possible risk for QT prolongation. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Fluvoxamine: (Moderate) Concomitant use of tamoxifen and fluvoxamine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Foscarnet: (Major) Concomitant use of tamoxifen and foscarnet increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fosphenytoin: (Major) Avoid coadministration of fosphenytoin with tamoxifen due to decreased exposure to tamoxifen which may affect efficacy. Tamoxifen is a CYP3A4 substrate and fosphenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC and Cmax of tamoxifen by 86% and 55%, respectively.
Fostemsavir: (Moderate) Concomitant use of tamoxifen and fostemsavir may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with fostemsavir is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 4 times the recommended daily dose.
Gemifloxacin: (Moderate) Concomitant use of tamoxifen and gemifloxacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Gemtuzumab Ozogamicin: (Moderate) Concomitant use of tamoxifen and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Gilteritinib: (Moderate) Concomitant use of tamoxifen and gilteritinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Glasdegib: (Major) Concomitant use of tamoxifen and glasdegib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and tamoxifen as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); tamoxifen is a P-gp inhibitor.
Goserelin: (Moderate) Concomitant use of tamoxifen and androgen deprivation therapy (i.e., goserelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Granisetron: (Moderate) Concomitant use of tamoxifen and granisetron may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Halogenated Anesthetics: (Major) Concomitant use of tamoxifen and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Haloperidol: (Moderate) Concomitant use of tamoxifen and haloperidol may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Histrelin: (Moderate) Concomitant use of tamoxifen and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Hydroxychloroquine: (Major) Concomitant use of tamoxifen and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase the risk of retinal toxicity. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Moderate) Concomitant use of tamoxifen and hydroxyzine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ibutilide: (Major) Concomitant use of tamoxifen and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Iloperidone: (Major) Concomitant use of tamoxifen and iloperidone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Inotuzumab Ozogamicin: (Major) Concomitant use of tamoxifen and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Isoflurane: (Major) Concomitant use of tamoxifen and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of rifampin with tamoxifen due to decreased exposure to tamoxifen which may affect efficacy. Tamoxifen is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the AUC and Cmax of tamoxifen by 86% and 55%, respectively.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of rifampin with tamoxifen due to decreased exposure to tamoxifen which may affect efficacy. Tamoxifen is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the AUC and Cmax of tamoxifen by 86% and 55%, respectively.
Itraconazole: (Moderate) Concomitant use of tamoxifen and itraconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ivosidenib: (Major) Concomitant use of tamoxifen and ivosidenib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and tamoxifen due to an increased risk for QT/QTc prolongation and torsade de pointes (TdP). Ketoconazole has an established risk for QT prolongation and TdP; QT prolongation with tamoxifen has been reported in the published literature.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Concomitant use of tamoxifen and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lapatinib: (Moderate) Concomitant use of tamoxifen and lapatinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lefamulin: (Major) Concomitant use of tamoxifen and lefamulin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lenvatinib: (Major) Concomitant use of tamoxifen and lenvatinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Letrozole: (Major) Coadministration of letrozole with tamoxifen is not recommended because the efficacy of the combination in the treatment of breast cancer has not been established. Additionally, tamoxifen reduced the plasma concentration of letrozole by 38% when the drugs were coadministered.
Leuprolide: (Moderate) Concomitant use of tamoxifen and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Leuprolide; Norethindrone: (Moderate) Concomitant use of tamoxifen and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Levofloxacin: (Moderate) Concomitant use of tamoxifen and levofloxacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and tamoxifen due to an increased risk for QT/QTc prolongation and torsade de pointes (TdP). Ketoconazole has an established risk for QT prolongation and TdP; QT prolongation with tamoxifen has been reported in the published literature.
Lithium: (Moderate) Concomitant use of tamoxifen and lithium may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lofexidine: (Moderate) Concomitant use of tamoxifen and lofexidine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Loperamide: (Moderate) Concomitant use of tamoxifen and loperamide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Loperamide; Simethicone: (Moderate) Concomitant use of tamoxifen and loperamide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lopinavir; Ritonavir: (Major) Concomitant use of tamoxifen and lopinavir increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of lumacaftor; ivacaftor with tamoxifen due to decreased exposure to tamoxifen which may affect efficacy. Tamoxifen is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC and Cmax of tamoxifen by 86% and 55%, respectively.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of lumacaftor; ivacaftor with tamoxifen due to decreased exposure to tamoxifen which may affect efficacy. Tamoxifen is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC and Cmax of tamoxifen by 86% and 55%, respectively.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as tamoxifen. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses.
Maprotiline: (Major) Concomitant use of tamoxifen and maprotiline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Medroxyprogesterone: (Minor) Medroxyprogesterone reduces plasma concentrations of N-dimethyltamoxifen, the metabolite of tamoxifen, but not tamoxifen.
Methadone: (Major) Concomitant use of tamoxifen and methadone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Metronidazole: (Moderate) Concomitant use of metronidazole and tamoxifen may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Midostaurin: (Major) Concomitant use of tamoxifen and midostaurin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mifepristone: (Major) Concomitant use of tamoxifen and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mirtazapine: (Moderate) Concomitant use of tamoxifen and mirtazapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Mitotane: (Major) Avoid coadministration of mitotane with tamoxifen due to decreased exposure to tamoxifen which may affect efficacy. Tamoxifen is a CYP3A4 substrate and mitotane is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC and Cmax of tamoxifen by 86% and 55%, respectively.
Mobocertinib: (Major) Concomitant use of tamoxifen and mobocertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Moxifloxacin: (Major) Concomitant use of tamoxifen and moxiflocacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Nilotinib: (Major) Concomitant use of tamoxifen and nilotinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ofloxacin: (Moderate) Concomitant use of tamoxifen and ofloxacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine: (Moderate) Concomitant use of tamoxifen and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine; Fluoxetine: (Moderate) Concomitant use of tamoxifen and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (Moderate) Monitor for QT prolongation and decreased efficacy of tamoxifen if coadministration with fluoxetine is necessary. Concomitant use may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Tamoxifen is metabolized by CYP2D6 to endoxifen and 4-hydroxytamoxifen, both of which are minor metabolites but have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen. XXX is a strong CYP2D6 inhibitor. In one study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. In another study, the mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors were 3.6-fold higher compared to
normal metabolizers who were receiving strong CYP2D6 inhibitors; plasma concentrations in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to concentrations observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors. Some studies have shown that the efficacy of tamoxifen may be reduced when concomitant drugs decrease the concentrations of potent active metabolites; however, others have failed to demonstrate such an effect. The clinical significance is not well established.
Olanzapine; Samidorphan: (Moderate) Concomitant use of tamoxifen and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ondansetron: (Major) Concomitant use of ondansetron and tamoxifen increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Osilodrostat: (Moderate) Concomitant use of tamoxifen and osilodrostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Osimertinib: (Major) Concomitant use of tamoxifen and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ospemifene: (Major) Ospemifene should not be used concomitantly with estrogen agonists/antagonists such as tamoxifen. The safety of concomitant use of ospemifene with estrogen agonists/antagonists has not been studied.
Oxaliplatin: (Major) Concomitant use of tamoxifen and oxaliplatin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking tamoxifen due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses.
Pacritinib: (Major) Concomitant use of pacritinib and tamoxifen increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Concomitant use of tamoxifen and paliperidone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paroxetine: (Moderate) Monitor for decreased efficacy of tamoxifen if coadministration with paroxetine is necessary. Tamoxifen is metabolized by CYP2D6 to endoxifen and 4-hydroxytamoxifen, both of which are minor metabolites but have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen. Paroxetine is a strong CYP2D6 inhibitor. In one study, the mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors were 3.6-fold higher compared to normal metabolizers who were receiving strong CYP2D6 inhibitors (e.g., paroxetine); plasma levels in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to levels observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors. In another study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. Some studies have shown that the efficacy of tamoxifen may be reduced when concomitant drugs decrease the levels of potent active metabolites; however, others have failed to demonstrate such an effect. The clinical significance is not well established.
Pasireotide: (Moderate) Concomitant use of tamoxifen and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Pazopanib: (Major) Concomitant use of tamoxifen and pazopanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pentamidine: (Major) Concomitant use of tamoxifen and pentamidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Perphenazine: (Minor) Use caution if coadministration of perphenazine with tamoxifen is necessary. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have been described when tamoxifen is used at lower doses. Perphenazine is also associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Perphenazine; Amitriptyline: (Minor) Use caution if coadministration of perphenazine with tamoxifen is necessary. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have been described when tamoxifen is used at lower doses. Perphenazine is also associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Phenobarbital: (Major) Avoid coadministration of phenobarbital with tamoxifen due to decreased exposure to tamoxifen which may affect efficacy. Tamoxifen is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC and Cmax of tamoxifen by 86% and 55%, respectively.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of phenobarbital with tamoxifen due to decreased exposure to tamoxifen which may affect efficacy. Tamoxifen is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC and Cmax of tamoxifen by 86% and 55%, respectively.
Phenytoin: (Major) Avoid coadministration of phenytoin with tamoxifen due to decreased exposure to tamoxifen which may affect efficacy. Tamoxifen is a CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC and Cmax of tamoxifen by 86% and 55%, respectively.
Pimavanserin: (Major) Concomitant use of tamoxifen and pimavanserin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pimozide: (Contraindicated) Avoid concomitant use of tamoxifen and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Pitolisant: (Major) Concomitant use of tamoxifen and pitolisant increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking tamoxifen due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses.
Posaconazole: (Moderate) Concomitant use of tamoxifen and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Primaquine: (Moderate) Concomitant use of tamoxifen and primaquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Primidone: (Major) Avoid coadministration of primidone with tamoxifen due to decreased exposure to tamoxifen which may affect efficacy. Tamoxifen is a CYP3A4 substrate and primidone is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC and Cmax of tamoxifen by 86% and 55%, respectively.
Procainamide: (Major) Concomitant use of tamoxifen and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Prochlorperazine: (Minor) Use caution if coadministration of prochlorperazine with tamoxifen is necessary due to the risk of QT prolongation. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have been described when tamoxifen is used at lower doses. Prochlorperazine is also associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Promethazine: (Moderate) Concomitant use of tamoxifen and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Dextromethorphan: (Moderate) Concomitant use of tamoxifen and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Phenylephrine: (Moderate) Concomitant use of tamoxifen and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Propafenone: (Major) Concomitant use of tamoxifen and propafenone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quetiapine: (Major) Concomitant use of tamoxifen and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinidine: (Major) Coadministration of quinidine with tamoxifen may result in additive QT prolongation and decreased efficacy of tamoxifen. When administered as quinidine; dextromethorphan, coadministration with tamoxifen is contraindicated. Quinidine is a CYP2D6 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Tamoxifen is a CYP2D6 substrate that has also been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Tamoxifen is metabolized by CYP2D6 to endoxifen and 4-hydroxytamoxifen, both of which are minor metabolites but have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen. In one study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. In another study, the mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors were 3.6-fold higher compared to normal metabolizers who were receiving strong CYP2D6 inhibitors; plasma levels in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to levels observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors. Some studies have shown that the efficacy of tamoxifen may be reduced when concomitant drugs decrease the levels of potent active metabolites; however, others have failed to demonstrate such an effect. The clinical significance is not well established.
Quinine: (Major) Concomitant use of tamoxifen and quinine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quizartinib: (Major) Concomitant use of quizartinib and tamoxifen increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ranolazine: (Moderate) Concomitant use of tamoxifen and ranolazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Relugolix: (Moderate) Concomitant use of tamoxifen and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Concomitant use of tamoxifen and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ribociclib: (Major) Avoid coadministration of ribociclib with tamoxifen due to the risk of QT prolongation; an increase in tamoxifen exposure may also occur. Ribociclib is not indicated for concomitant use with tamoxifen. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner; these ECG changes occurred within the first four weeks of treatment and were reversible with dose interruption. Tamoxifen has also been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have been described when tamoxifen is used at lower doses. Additionally, data from a clinical trial in patients wtih breast cancer indicated that the Cmax and AUC of tamoxifen increased approximately 2-fold after coadministration of 600 mg of ribociclib.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with tamoxifen due to the risk of QT prolongation; an increase in tamoxifen exposure may also occur. Ribociclib is not indicated for concomitant use with tamoxifen. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner; these ECG changes occurred within the first four weeks of treatment and were reversible with dose interruption. Tamoxifen has also been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have been described when tamoxifen is used at lower doses. Additionally, data from a clinical trial in patients wtih breast cancer indicated that the Cmax and AUC of tamoxifen increased approximately 2-fold after coadministration of 600 mg of ribociclib. (Major) Coadministration of letrozole with tamoxifen is not recommended because the efficacy of the combination in the treatment of breast cancer has not been established. Additionally, tamoxifen reduced the plasma concentration of letrozole by 38% when the drugs were coadministered.
Rifampin: (Major) Avoid coadministration of rifampin with tamoxifen due to decreased exposure to tamoxifen which may affect efficacy. Tamoxifen is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the AUC and Cmax of tamoxifen by 86% and 55%, respectively.
Rifapentine: (Major) Avoid coadministration of rifapentine with tamoxifen due to decreased exposure to tamoxifen which may affect efficacy. Tamoxifen is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC and Cmax of tamoxifen by 86% and 55%, respectively.
Rilpivirine: (Moderate) Concomitant use of tamoxifen and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Risperidone: (Moderate) Concomitant use of tamoxifen and risperidone may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Romidepsin: (Moderate) Concomitant use of tamoxifen and romidepsin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Saquinavir: (Major) Concomitant use of tamoxifen and saquinavir increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Selpercatinib: (Major) Concomitant use of tamoxifen and selpercatinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sertraline: (Moderate) Concomitant use of tamoxifen and sertraline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Sevoflurane: (Major) Concomitant use of tamoxifen and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Siponimod: (Major) Concomitant use of tamoxifen and siponimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and tamoxifen may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Solifenacin: (Moderate) Concomitant use of tamoxifen and solifenacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Sorafenib: (Major) Concomitant use of tamoxifen and sorafenib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sotalol: (Major) Concomitant use of tamoxifen and sotalol increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Soy Isoflavones: (Major) Theoretically, the soy isoflavones may compete with drugs that selectively modulate estrogen receptors. The soy isoflavones have a diphenolic structure similar to that of the potent synthetic and natural estrogens. All isoflavones are competitive ligands of in vitro estrogen receptor assays and appear to function as selective estrogen receptor modifiers (SERMs). Soy isoflavones should be used with caution in patients taking selective estrogen receptor modulators (SERMs, e.g., raloxifene, tamoxifen, or toremifene), as not much is known about how soy might influence side effects or therapeutic efficacy of the SERMs.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of St. Johns wort with tamoxifen due to decreased exposure to tamoxifen which may affect efficacy. Tamoxifen is a CYP3A4 substrate and St. Johns wort is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC and Cmax of tamoxifen by 86% and 55%, respectively.
Sunitinib: (Moderate) Concomitant use of tamoxifen and sunitinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tacrolimus: (Moderate) Concomitant use of tamoxifen and tacrolimus may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Telavancin: (Moderate) Concomitant use of tamoxifen and telavancin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Terbinafine: (Moderate) Monitor for decreased efficacy of tamoxifen if coadministration with terbinafine is necessary. Tamoxifen is metabolized by CYP2D6 to endoxifen and 4-hydroxytamoxifen, both of which are minor metabolites but have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen. Terbinafine is a strong CYP2D6 inhibitor. In one study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. In another study, the mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors were 3.6-fold higher compared to normal metabolizers who were receiving strong CYP2D6 inhibitors; plasma levels in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to levels observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors. Some studies have shown that the efficacy of tamoxifen may be reduced when concomitant drugs decrease the levels of potent active metabolites; however, others have failed to demonstrate such an effect. The clinical significance is not well established.
Tetrabenazine: (Major) Concomitant use of tetrabenazine and tamoxifen increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Thioridazine: (Contraindicated) Avoid concomitant use of thioridazine and tamoxifen due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Tipranavir: (Moderate) Monitor for decreased efficacy of tamoxifen if coadministration with tipranavir is necessary. Tamoxifen is metabolized by CYP2D6 to endoxifen and 4-hydroxytamoxifen, both of which are minor metabolites but have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen. Tipranavir is a strong CYP2D6 inhibitor. In one study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. In another study, the mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors were 3.6-fold higher compared to normal metabolizers who were receiving strong CYP2D6 inhibitors; plasma levels in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to levels observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors. Some studies have shown that the efficacy of tamoxifen may be reduced when concomitant drugs decrease the levels of potent active metabolites; however, others have failed to demonstrate such an effect. The clinical significance is not well established.
Tolterodine: (Moderate) Caution is advised with the concomitant use of tamoxifen and tolterodine due to an increased risk of QT prolongation. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
Toremifene: (Major) Concomitant use of toremifene and tamoxifen increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Trazodone: (Major) Concomitant use of tamoxifen and trazodone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Triclabendazole: (Moderate) Concomitant use of triclabendazole and tamoxifen may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Trifluoperazine: (Minor) Caution is advised with the concomitant use of tamoxifen and trifluoperazine due to an increased risk of QT prolongation. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Triptorelin: (Moderate) Concomitant use of tamoxifen and androgen deprivation therapy (i.e., triptorelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Vandetanib: (Major) Concomitant use of vandetanib and tamoxifen increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vardenafil: (Moderate) Concomitant use of tamoxifen and vardenafil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Vemurafenib: (Major) Concomitant use of vemurafenib and tamoxifen increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Venlafaxine: (Moderate) Concomitant use of tamoxifen and venlafaxine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Voclosporin: (Moderate) Concomitant use of tamoxifen and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Concomitant use of tamoxifen and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Voriconazole: (Moderate) Concomitant use of tamoxifen and voriconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Vorinostat: (Moderate) Concomitant use of tamoxifen and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Warfarin: (Major) Closely monitor PT/INR if coadministration of warfarin with tamoxifen for the treatment of metastatic breast cancer or as adjuvant therapy is necessary; a marked increase in anticoagulant effect may occur. Tamoxifen is contraindicated with warfarin therapy if the indication for tamoxifen is reduction of breast cancer incidence in high-risk patients or risk reduction of invasive breast cancer after treatment of DCIS.
Ziprasidone: (Major) Concomitant use of ziprasidone and tamoxifen increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
How Supplied
Nolvadex/Tamoxifen/Tamoxifen Citrate Oral Tab: 10mg, 20mg
Soltamox Oral Sol: 5mL, 10mg
Maximum Dosage
FDA-approved dosing: 20 mg PO twice daily.
Off-label dosing: Up to 120 mg PO once daily or 80 mg/m2 PO once daily (or divided twice daily).
FDA-approved dosing: 20 mg PO twice daily.
Off-label dosing: Up to 120 mg PO once daily or 80 mg/m2 PO once daily (or divided twice daily).
FDA labelling: Safety and efficacy have not been established.
Off-label dosing: Up to 120 PO once daily.
FDA labelling: Safety and efficacy have not been established.
Off-label dosing: Up to 1 mg/kg PO once daily or 20 mg PO once daily.
FDA labelling: Safety and efficacy have not been established.
Off-label dosing: Up to 1 mg/kg PO once daily.
Safety and efficacy have not been established.
Mechanism Of Action
Tamoxifen is an estrogen agonist/antagonist. It competes with estrogen for binding to the estrogen receptor (ER), which can result in a decrease in estrogen receptor signaling-dependent growth in breast tissue.[63589] After tamoxifen binds to the estrogen receptor, the expression of estrogen-dependent genes (RNA transcription) is blocked or altered, resulting in reduced DNA polymerase activity, impaired thymidine utilization, blockade of estradiol uptake, and decreased estrogen response. Most of tamoxifen's activity occurs in the G2-phase; it is cytostatic, with cell cycling slowed by its activity in the nucleus. Tamoxifen also decreases insulin-like growth factor type 1 (IGF-1) which stimulates cancer cell growth and development, and induces the secretion of transforming growth factor-beta (TGF-beta) which is associated with inhibiting the activity of breast cancer cells. It also induces the re-expression of maspin, a tumor suppressor gene, in breast cancer tissue. Maspin gene expression is diminished or lost in breast cancer, whereas it is abundant in normal breast cells. The presence of maspin has been shown to prevent tumor invasion and metastasis; the use of tamoxifen reintroduces maspin into breast cancer cells and may cause the carcinoma to be less invasive.[27874] Tamoxifen has demonstrated antitumor activity against human breast cancer cell lines xenografted in mice. It has also been shown to inhibit the induction of rat mammary carcinoma induced by dimethylbenzanthracene (DMBA) and to cause the regression of already established DMBA-induced tumors.[63589]
Tamoxifen also can be used to induce ovulation in anovulatory women. Tamoxifen stimulates the hypothalamus to release gonadotropin-releasing hormone, thereby prompting the release of hormones from the pituitary. The subsequent effect on the ovaries results in ovulation.[34101] [34102]
Pharmacokinetics
Tamoxifen is administered orally as tablets or a solution. The decline in plasma concentrations of tamoxifen is biphasic, with a terminal elimination half-life of about 5 to 7 days. After initiation of therapy, steady-state for tamoxifen is achieved in approximately 4 weeks; steady-state for N-desmethyl tamoxifen occurs in approximately 8 weeks, suggesting a half-life of approximately 14 days for this metabolite. Studies in women receiving radiolabelled tamoxifen showed that approximately 65% of a radiolabeled dose was excreted from the body over a period of 2 weeks, with fecal excretion as the primary route of elimination. Tamoxifen is excreted mainly as polar conjugates, with unchanged drug and unconjugated metabolites accounting for less than 30% of the total fecal radioactivity.[63589]
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2B6
Tamoxifen is extensively metabolized in the liver by the CYP450 system, including CYP3A, CYP2D6, CYP2C9, CYP2C19, and CYP2B6. The main metabolite found in plasma is N-desmethyl tamoxifen, which has similar pharmacological activity to tamoxifen and is formed predominantly via CYP3A. CYP2D6 is involved in the formation of endoxifen and 4-hydroxytamoxifen, both minor metabolites that have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen.[63589] Endoxifen concentrations may be up to 20-fold higher than concentrations of 4-hydroxytamoxifen.[41246] Phase 2 enzymes, such as SULT1A1, UGT2B7, and UGT1A4, are associated with tamoxifen clearance from plasma.[63589]
Following a single oral dose of tamoxifen 20 mg, an average peak plasma concentration (Cmax) of 40 ng/mL (range, 35 to 45 ng/mL) occurs in approximately 5 hours; the average Cmax of N-desmethyl tamoxifen, the major metabolite, is 15 ng/mL (range, 10 to 20 ng/mL). Chronic administration of tamoxifen 10 mg twice daily for 3 months results in average steady-state tamoxifen plasma concentrations of 120 ng/mL (range, 67 to 183 ng/mL) for tamoxifen and 336 ng/mL (range, 148 to 654 ng/mL) for N-desmethyl tamoxifen. The average steady-state plasma concentrations of tamoxifen and N-desmethyl tamoxifen after administration of tamoxifen 20 mg once daily for 3 months are similar, at 122 ng/mL (range, 71 to 183 ng/mL) and 353 ng/mL (range, 152 to 706 ng/mL), respectively. Steady-state plasma concentrations of endoxifen and 4-hydroxytamoxifen area 29.1 ng/mL (95% CI, 24.6 to 33.6) and 3.7 ng/mL (95% CI, 3.3 to 4.1), respectively.[63589]
The rate and extent of tamoxifen citrate oral solution (n = 30) in healthy perimenopausal and postmenopausal female subjects was bioequivalent to tamoxifen citrate tablets (n = 33) under fasting conditions in a pharmacokinetic study. Food did not affect the bioavailability (Cmax and AUC) of tamoxifen oral solution (n = 16); tamoxifen may be given without regard to meals. In a steady-state crossover study, tamoxifen 10 mg tablets given twice daily were bioequivalent to tamoxifen 20 mg tablets given once daily.[63589]
Pregnancy And Lactation
Pregnancy should be avoided by females of reproductive potential during tamoxifen treatment and for at least 2 months after the last dose. Although there are no adequately controlled studies in pregnant humans, tamoxifen can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies, including the potential long-term risk of a DES-like syndrome. Women who are pregnant or who become pregnant while receiving tamoxifen should be apprised of the potential hazard to the fetus. There are limited 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. In rats, a lower incidence of embryo implantation and a higher incidence of fetal death or delayed in utero growth occurred in rats at doses of 0.01 to 0.03 times the recommended human dose on a mg/m2 basis; slower learning behavior in rat pups also occurred. Abortion and premature delivery occurred in rabbits at doses greater than 0.05 times the daily maximum recommended human dose on a mg/m2 basis when administered during organogenesis. Although reversible nonteratogenic skeletal variations occurred in rat reproductive studies at doses less than or equal to the human dose, there were no teratogenic changes in either rats or rabbits. In pregnant marmosets, approximately 2 times the daily maximum recommended human dose on a mg/m2 basis during organogenesis or in the last half of pregnancy resulted in termination of pregnancy; in pregnancies that continued, there were no malformations or deformations in offspring. Rodent models of fetal reproductive tract development indicated that tamoxifen caused changes in both sexes similar to those caused by estradiol, ethynylestradiol, and diethylstilbestrol at doses 0.002 to 2.4 times the daily maximum recommended human dose on a mg/m2 basis; the clinical relevance of these changes is unknown. Additionally, rodent models showed reproductive tract changes often associated with diethylstilbestrol (DES) in offspring of both sexes.[63589]
Counsel patients about the reproductive risk and contraception requirements during tamoxifen treatment. Tamoxifen can cause spontaneous abortions, birth defects, and fetal death if taken by the mother during pregnancy. Females of reproductive potential should avoid pregnancy and use effective non-hormonal contraception during and for at least 2 months after treatment with tamoxifen. Females of reproductive potential should undergo pregnancy testing prior to initiation of tamoxifen. Women who become pregnant while receiving tamoxifen should be apprised of the potential hazard to the fetus. Based on animal studies, tamoxifen may impair embryo implantation in females of reproductive potential, however, may not reliably cause infertility, even in the presence of menstrual irregularity.