Purpose: Antidepressants like the serotonin reuptake inhibitors (SRIs) are often used concomitantly with tamoxifen (e.g. for treatment of depression). This may lead to an additional prolongation of the QTc-interval, with an increased risk of cardiac side effects. Therefore we investigated whether there is a drug-drug interaction between tamoxifen and SRIs resulting in a prolonged QTc-interval. Methods: Electrocardiograms (ECGs) of 100 patients were collected at steady state tamoxifen treatment, with or without concomitant SRI co-medication. QTc-interval was manually measured and calculated using the Fridericia formula. Primary outcome was difference in QTc-interval between tamoxifen monotherapy and tamoxifen concomitantly with an SRI. Results: The mean QTc-interval was 12.4 ms longer when tamoxifen was given concomitantly with an SRI (95% CI:1.8–23.1 ms; P = 0.023). Prolongation of the QTc-interval was particularly pronounced for paroxetine (17.2 ms; 95%CI:1.4–33.0 ms; P = 0.04), escitalopram (12.5 ms; 95%CI:4.4–20.6 ms; P < 0.01) and citalopram (20.7 ms; 95%CI:0.7–40.7 ms; P = 0.047), where other agents like venlafaxine did not seem to prolong the QTc-interval. None of the patients had a QTc-interval of >500 ms. Conclusions: Concomitant use of tamoxifen and SRIs resulted in a significantly higher mean QTc-interval, which was especially the case for paroxetine, escitalopram and citalopram. When concomitant administration with an SRI is warranted venlafaxine is preferred.

Additional Metadata
Keywords drug-drug interaction, electrocardiogram, QTc-interval, serotonin reuptake inhibitors, Tamoxifen
Persistent URL dx.doi.org/10.1007/s11095-019-2746-9, hdl.handle.net/1765/122811
Journal Pharmaceutical Research
Citation
Hussaarts, K.G.A.M, Berger, F.A. (Florine A.), Binkhorst, L, Oomen - de Hoop, E, van Leeuwen, R.W.F, van Alphen, R.J, … van Gelder, T. (Teun). (2020). The Risk of QTc-Interval Prolongation in Breast Cancer Patients Treated with Tamoxifen in Combination with Serotonin Reuptake Inhibitors. Pharmaceutical Research, 37(1). doi:10.1007/s11095-019-2746-9