TY - JOUR
T1 - The Risk of QTc-Interval Prolongation in Breast Cancer Patients Treated with Tamoxifen in Combination with Serotonin Reuptake Inhibitors
AU - Hussaarts, Koen G.A.M.
AU - Berger, Florine A.
AU - Binkhorst, Lisette
AU - Oomen - de Hoop, Esther
AU - van Leeuwen, Roelof W.F.
AU - van Alphen, Robbert J.
AU - Mathijssen - van Stein, Daniëlle
AU - de Groot, Natasja M.S.
AU - Mathijssen, Ron H.J.
AU - van Gelder, Teun
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/16
Y1 - 2019/12/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85076519935&partnerID=8YFLogxK
U2 - 10.1007/s11095-019-2746-9
DO - 10.1007/s11095-019-2746-9
M3 - Article
C2 - 31845095
SN - 0724-8741
VL - 37
SP - 1
EP - 8
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 7
M1 - 7
ER -
