Electrocardiographic Changes After Granisetron Administration for Chemotherapy Induced Nausea and Vomiting
Abstract
Cancer patient receive various cytotoxic drugs in association with antiemetic drugs such as 5HT3 receptor antagonists as their chemotherapy regimen. 5HT3 receptor antagonists have been reported to produce changes in ECG parameter. There are only a few studies about cardiovascular events of these drugs in patient receiving potentially cardiotoxic chemotherapies. The subject of this study is to evaluate ECG changes after administration of chemotherapeutic agents and granisetron (the most commonly used 5HT3 antagonist in Iran) in adults with cancer. For this clinical trial study, all cancer patients referred to department of radiation oncology of Imam Hossein Hospital since August 2005 to March 2006 were evaluated if they had inclusion criteria. Granisetron (3 mg) was infused intravenously over 30 seconds just a few minutes before chemotherapeutic agent administration. The 12-lead ECG recording was obtained before and 90 minutes after infusion of granisetron. One cardiologist determined PR, QRS, QTc intervals and heart rate of all ECGs. During the study period 54 patients fulfilled our criteria. With paired t-test, the PR and QTc intervals, but not QRS interval showed statistically significant prolongation after drug infusion (P < 0.0001), and heart rate showed statistically significant decrease (P < 0.0001). The ECG findings of chemotherapeutic agents and granisetron administration were prolongation of PR and QTc intervals and decrease of heart rate (P < 0.0001). Although these changes did not cause clinical signs, with keeping in mind that there may be possible drug-drug interactions and preexisting cardiac comorbidities in cancer patient, it seems reasonable and necessary to consider physical condition specifically cardiac condition and drug usage of each patient, while designing chemotherapy regimen and supportive drugs.
Schnell FM. Chemotherapy-induced nausea and vomiting: the importance of acute antiemetic control. Oncologist 2003; 8(2): 187-98.
Aksoylar S, Akman SA, Ozgenç F, Kansoy S. Comparison of tropisetron and granisetron in the control of nausea and vomiting in children receiving combined cancer chemotherapy. Pediatr Hematol Oncol 2001; 18(6): 397-406.
Dupuis LL, Nathan PC. Options for the prevention and management of acute chemotherapy-induced nausea and vomiting in children. Paediatr Drugs 2003; 5(9): 597-613.
Kasinath NS, Malak O, Tetzlaff J. Atrial fibrillation after ondansetron for the prevention and treatment of postoperative nausea and vomiting: a case report. Can J Anaesth 2003; 50(3): 229-31.
Watanabe H, Hasegawa A, Shinozaki T, Arita S, Chigira M. Possible cardiac side effects of granisetron, an antiemetic agent, in patients with bone and soft-tissue sarcomas receiving cytotoxic chemotherapy. Cancer Chemother Pharmacol 1995; 35(4): 278-82.
Jantunen IT, Kataja VV, Muhonen TT, Parviainen T. Effects of granisetron with doxorubicin or epirubicin on ECG intervals. Cancer Chemother Pharmacol 1996; 37(5): 502-4.
Navari RM, Koeller JM. Electrocardiographic and cardiovascular effects of the 5-hydroxytryptamine3 receptor antagonists. Ann Pharmacother 2003; 37(9): 1276-86.
Aapro M, Bourke JP. Rapid intravenous administration of granisetron prior to chemotherapy is not arythmogenic: results of a pilot study. Eur J Cancer 2003; 39(7): 927-31.
Carmichael J, Harris AL. High-dose i.v. granisetron for the prevention of chemotherapy-induced emesis: cardiac safety and tolerability. Anticancer Drugs 2003; 14(9): 739-44.
Carmichael J, Harris AL. The cardiovascular safety of high-dose intravenous granisetron in cancer patients receiving highly emetogenic chemotherapy. Cancer Chemother Pharmacol 2004; 53(2): 123-8.
Boike SC, Ilson B, Zariffa N, Jorkasky DK. Cardiovascular effects of i.v. granisetron at two administration rates and ofondansetron in healthy adults. Am J Health Syst Pharm 1997; 54(10): 1172-6.
Bazett HR. An analysis of the time relations of electrocardiograms. Heart 1920; 7: 353-70.
Keefe DL. The cardiotoxic potential of the 5-HT(3) receptor antagonist antiemetics: is there cause for concern? Oncologist 2002; 7(1): 65-72.
Gray GW, McLellan TM, Ducharme MB. Granisetron shows no pro-arrhythmic effect in normal subjects during or after exercise in a hot environment. Aviat Space Environ Med 1996; 67(8): 759-61.
Benedict CR, Arbogast R, Martin L, Patton L, Morrill B, Hahne W. Single-blind study of the effects of intravenous dolasetron mesylate versus ondansetron on electrocardiographic parameters in normal volunteers. J Cardiovasc Pharmacol 1996; 28(1): 53-9.
Hesketh P, Navari R, Grote T, Gralla R, Hainsworth J, Kris M, et al. Double-blind, randomized comparison of the antiemetic efficacy of intravenous dolasetron mesylate and intravenous ondansetron in the prevention of acute cisplatininduced emesis in patients with cancer. Dolasetron Comparative Chemotherapy-induced Emesis Prevention Group. J Clin Oncol 1996; 14(8): 2242-9.
Aapro M, Rabaeus M. The effects of ondansetron and granisetron on electrocardiography in children receiving chemotherapy for acute leukemia. Am J Clin Oncol 2005; 28(2): 201-4.
Nishio H, Fujii A, Nakata Y. Re-examination for pharmacological properties of serotonin-induced tachycardia in isolated guinea-pig atrium. Behav Brain Res 1996; 73(1-2): 301-4.
Kuryshev YA, Brown AM, Wang L, Benedict CR, Rampe D. Interactions of the 5-hydroxytryptamine 3 antagonist class of antiemetic drugs with human cardiac ion channels. J Pharmacol Exp Ther 2000; 295(2): 614-20.
Tutar HE, Ocal B, Imamoglu A, Atalay S. Dispersion of QT and QTc interval in healthy children, and effects of sinus arrhythmia on QT dispersion. Heart 1998; 80(1): 77-9.
Files | ||
Issue | Vol 47, No 4 (2009) | |
Section | Original Article(s) | |
Keywords | ||
Electrocardiography Granisetron chemotherapy |
Rights and permissions | |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |