The clinical significance of QT prolongation associated with tamoxifen: A review of the literature

Objective To review the literature discussing QT prolongation associated with the use of tamoxifen in order to evaluate the clinical significance. Data sources A search of PubMed (1946 to 2017), MEDLINE (1946 to 2017) and EMBASE (1947 to 2017) was performed using a combination of the following search terms: tamoxifen, estrogen antagonist, selective estrogen receptor modulator, QT prolongation, QT interval, long QT syndrome and torsades de pointes. All searches were limited to human subjects. Reference lists of the literature found were also reviewed but did not reveal any further articles. Study selection Articles reviewed were relating to humans only and included clinical trials and case reports that mentioned QT prolongation in association with the use of tamoxifen. Data synthesis It can be common for patients on tamoxifen to also be on a number of different medications being used to treat comorbid medical conditions. Such combinations of medications increase the potential risk for drug interactions, such as drug-induced QT prolongation. Tamoxifen is often flagged by tertiary drug information sources as a drug with indeterminate effects on the QT interval. However, the risk may be elevated when combined with other QT-prolonging agents. A total of five publications were identified, including two phase I clinical trials and three case reports, which discussed the association between tamoxifen and QT prolongation. Conclusions Tertiary drug information sources identify tamoxifen as an agent that may cause QT prolongation when used in combination with other QT-prolonging agents. However, based on the limited number of published reports found, it would suggest that the use of tamoxifen concurrently with other agents known to prolong the QT interval is likely to be of low risk for causing a clinically significant QT-prolonging event, especially at a dose of 20mg daily.