Cardiac safety concerns for ondansetron, an antiemetic commonly used for nausea linked to cancer treatment and following anaesthesia

Bibliography

• Seynaeve C, Verweij J, deMulder PH. 5-HT3 receptor antagonists, a new approach in emesis: a review of ondansetron, granisetron and tropisetron. Anticancer Drugs 1991;2(4):343-55
   PubMed Web of Science ®Google Scholar
• Aapro M. 5-HT3 receptor antagonists in the management of nausea and vomiting in cancer and cancer treatment. Oncology 2005;69(2):97-109
   PubMed Web of Science ®Google Scholar
• Hsu ES. A review of granisetron, 5-hydroxytryptamine3 receptor antagonists, and other antiemetics. Am J Ther 2010;17(5):476-86
   PubMed Web of Science ®Google Scholar
• Kris MG, Tonato M, Bria E, Consensus recommendations for the prevention of vomiting and nausea following high-emetic-risk chemotherapy. Support Care Cancer 2011;19(Suppl 1):S25-32
   PubMedGoogle Scholar
• FDA Drug Safety Communication: abnormal heart rhythms may be associated with the use of Zofran (ondansetron). Available from: http://www.fda.gov/Drugs/DrugSafety/ucm271913.htm#data [Accessed 13/12/2012]
   Google Scholar
• FDA Drug Safety Communication: updated information on 32 mg intravenous ondansetron (Zofran) dose and pre-mixed ondansetron products. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm330049.htm [Accessed 13/12/2012]
   Google Scholar
• FDA Drug Safety Communication: new information regarding QT prolongation with ondansetron (Zofran). Available from: http://www.fda.gov/Drugs/DrugSafety/ucm310190.htm [Accessed 13/12/2012]
   Google Scholar
• AZCERT Drugs with possible risk of torsades de points. Available from: http://www.azcert.org/medical-pros/drug-lists/list-02.cfm [Accessed 11/2/2012]
   Google Scholar
• Tyers MB. Pharmacology and preclinical antiemetic properties of ondansetron. Semin Oncol 1992;19(4 Suppl 10):1-8
   PubMed Web of Science ®Google Scholar
• Gan TJ. Selective 5-HT3 receptor antagonists for postoperative nausea and vomiting: are they all the same. CNS Drugs 2005;19(3):225-38
   PubMed Web of Science ®Google Scholar
• Grunberg SM, Groshen S, Robinson DC, Correlation of anti-emetic efficacy and plasma levels of ondansetron. Eur J Cancer 1990;26(8):879-82
   PubMed Web of Science ®Google Scholar
• Khosjasteh A, Sartiano G, Tapazoglou E, Ondansetron for the prevention of emesis induced by high-dose cisplatin – a multi-center dose-response study. Cancer 1990;66:1101-5
   PubMed Web of Science ®Google Scholar
• Hainsworth JD, Hesketh PJ. Single-dose ondansetron for the prevention of cisplatin-induced emesis: efficacy results. Semin Oncol 1992;19(6 Suppl 15):14-19
   Web of Science ®Google Scholar
• Tsavaris N, Fountzilas G, Mylonakis N. A randomized comparative study of antiemetic prophylaxis with ondansetron in a single 32-mg loading dose versus 8 mg every 6 h in patients undergoing cisplatin-based chemotherapy. Oncology 1998;55(6):513-16
   PubMed Web of Science ®Google Scholar
• Beck TM, York M, Chang A, Oral ondansetron 8 mg twice daily is as effective as 8 mg three times daily in the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy. S3A-376 Study Group. Cancer Invest 1997;15(4):297-303
   PubMed Web of Science ®Google Scholar
• Hesketh PJ, Beck T, Uhlenhopp M, Adjusting the dose of intravenous ondansetron plus dexamethasone to the emetogenic potential of the chemotherapy regimen. J Clin Oncol 1995;13(8):2117-22
   PubMed Web of Science ®Google Scholar
• Gralla RJ, de Wit R, Herrstedt J, Antiemetic efficacy of the neurokinin-1 antagonist, aprepitant, plus a 5HT3 antagonist and a corticosteroid in patients receiving anthracylines or cyclophosphamide in addition to high-dose cisplatin: analysis of combined data from two Phase III randomized clinical trials. Cancer 2005;104(4):864-8
   PubMed Web of Science ®Google Scholar
• Franzén L, Nyman J, Hagberg H, A randomised placebo controlled study with ondansetron in patients undergoing fractionated radiotherapy. Ann Oncol 1996;7:587-92
   PubMed Web of Science ®Google Scholar
• Sykes AJ, Kiltie AE, Stewart AI. Ondansetron versus chlorpromazine and dexamethasone combination for the prevention of nausea and vomiting: a prospective, randomised study to assess efficacy, cost effectiveness and quality of life following single-fraction radiotherapy. Support Care Cancer 1997;5:500-3
   PubMed Web of Science ®Google Scholar
• Figueredo ED, Canosa LG. Ondansetron in the prophylaxis of postoperative vomiting: a meta-analysis. J Clin Anesth 1998;10(3):211-21
   PubMed Web of Science ®Google Scholar
• Apfel CC, Korttila K, Abdalla M, A factorial trial of six interventions of postoperative nausea and vomiting. N Engl J Med 2004;350(24):2441-51
   PubMed Web of Science ®Google Scholar
• Pritchard JF. Ondansetron metabolism and pharmacokinetics. Semin Oncol 1992;4(Suppl 10):9-15
   Google Scholar
• Blum RA, Majumdar A, McCrea J, Effects of aprepitant on the pharmacokinetics of ondansetron and granisetron in healthy subjects. Clin Ther 2003;25(5):1407-19
   PubMed Web of Science ®Google Scholar
• Colthup PV, Felgate CC, Palmer JL, Scully NL. Determination of ondansetron in plasma and its pharmacokinetics in the young and elderly. J Pharm Sci 1991;80(9):868-71
   PubMed Web of Science ®Google Scholar
• Hsyu PH, Pritchard JF, Bozigian HP, Oral ondansetron pharmacokinetics: the effect of chemotherapy. J Clin Pharmacol 1994;34(7):767-73
   PubMed Web of Science ®Google Scholar
• Saynor DA, Dixon CM. The metabolism of ondansetron. Eur J Cancer Clin Oncol 1989;25(Suppl 1):S75-7
   PubMedGoogle Scholar
• Blake JC, Palmer JL, Minton NA, Burroughs AK. The pharmacokinetics of intravenous ondansetron in patients with hepatic impairment. Br J Clin Pharmacol 1993;35(4):441-3
   PubMed Web of Science ®Google Scholar
• Stamer UM, Lee EH, Rauers NI, CYP2D6- and CYP3A-dependent enantioselective plasma concentrations of ondansetron in postanaesthesia care. Anesth Anal 2011;113(1):48-54
   PubMed Web of Science ®Google Scholar
• Williams PD, Cohen ML, Turk JA. Electrocardiographic effects of zatosetron and ondansetron, two 5HT3 receptor antagonists, in anesthetized dogs. Drug Dev Res 1991;24:277-84
   Web of Science ®Google Scholar
• De Lorenzi FG, Bridal TR, Spinelli W. Block of the delayed rectifier current (IK) by the 5-HT3 antagonists ondansetron and granisetron in feline ventricular myocytes. Br J Pharmacol 1994;113(2):527-35
   PubMed Web of Science ®Google Scholar
• Kuryshev YA, Brown AM, Wang L, 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; 99
   PubMed Web of Science ®Google Scholar
• Sanguinetti MC, Jiang C, Curran ME, Keating MT. A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel Cell. 1995;81(2):299-307
   Google Scholar
• Trudeau MC, Warmke JW, Ganetzky B, Robertson GA. HERG, a human inward rectifier in the voltage-gated potassium channel family. Science 1995;269(5220):92-5
   PubMed Web of Science ®Google Scholar
• Hancox JC, McPate MJ, El Harchi A, Zhang YH. The hERG potassium channel and hERG screening for drug-induced torsades de pointes. Pharmacol Ther 2008;119(2):118-32
   PubMed Web of Science ®Google Scholar
• Gintant GA. Preclinical torsades-de-pointes screens: advantages and limitations of surrogate and direct approaches in evaluating proarrhythmic risk. Pharmacol Ther 2008;119(2):199-209
   PubMed Web of Science ®Google Scholar
• Weissenburger J, Funck-Brentano C, Jaillon P, Charbit B. Droperidol and ondansetron in vitro electrophysiology drug interaction study. Fundam Clin Pharmacol 2009;23(6):719-26
   PubMed Web of Science ®Google Scholar
• Rouet R, Worou ME, Puddu PE, Nifedipine blocks ondansetron electrophysiological effects in rabbit purkinje fibers and decreases early after depolarization incidence. Curr Clin Pharmacol 2012;7(1):41-8
   PubMedGoogle Scholar
• Heyman JS, Young ML, Bagshaw RJ, Cardiovascular stability with rapid intravenous infusion of ondansetron. Can J Anaesth 1993;40(5 Pt 1):448-52
   PubMed Web of Science ®Google Scholar
• Rose JB, McCloskey JJ. Rapid intravenous administration of ondansetron or metoclopramide is not associated with cardiovascular compromise in children. Paediatr Anaesth 1995;5(2):121-4
   PubMedGoogle Scholar
• Benedict CR, Arbogast R, Lorene M, 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
   PubMed Web of Science ®Google Scholar
• Hesketh P, Navari R, Grote T, Double-blind, randomized comparison of the antiemetic efficacy of intravenous dolasetron mesylate and intravenous ondansetron in the prevention of acute cisplatin-induced emesis in patients with cancer. Dolasetron Comparative Chemotherapy-induced Emesis Prevention Group. J Clin Oncol 1996;14(8):2242-9
   PubMed Web of Science ®Google Scholar
• Keefe DL. The cardiotoxic potential of the 5-HT3 receptor antagonist antiemetics: is there cause for concern? Oncologist 2002;7(1):65-72
   PubMed Web of Science ®Google Scholar
• Boike SC, Ilson B, Zariffa N, Jorkasky DK. Cardiovascular effects of i.v. granisetron in two administration rates and of ondansetron in healthy adults. Am J Health Syst Pharm 1997;54:1172-6
   PubMed Web of Science ®Google Scholar
• Lofters WS, Pater JL, Zee B, Phase III double-blind comparison of dolasetron mesylate and ondansetron and an evaluation of the additiverole of dexamethasone in the prevention of acute and delayed nausea and vomiting due to moderately emetogenic chemotherapy. J Clin Oncol 1997;15(8):2966-73
   PubMed Web of Science ®Google Scholar
• Charbit B, Albaladejo P, Funck-Brentano C, Prolongation of QTc interval after postoperative nausea and vomiting treatment by droperidol or ondansetron. Anesthesiology 2005;102(6):1094-100
   PubMed Web of Science ®Google Scholar
• Charbit B, Alvarez JC, Dasque E, Droperidol and ondansetron-induced QT interval prolongation: a clinical drug interaction study. Anesthesiology 2008;109(2):206-12
   PubMed Web of Science ®Google Scholar
• Gupta SD, Pal R, Sarkar A, Evaluation of ondansetron-induced QT interval prolongation in the prophylaxis of postoperative emesis. J Nat Sci Biol Med 2011;2:119-24
   PubMedGoogle Scholar
• Hafermann MJ, Namdar R, Seibold GE, Page RL. Effect of intravenous ondansetron on QT interval prolongation in patients with cardiovascular disease and additional risk factors for torsades: a prospective, observational study. Drug Healthc Patient Saf 2011;3:53-8
   PubMedGoogle Scholar
• The FDA Safety Information and Adverse Event Reporting Program Safety Information. Safety Iapsine (droperidol). Available from: http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm172364.htm [Accessed 17th December, 2012]
   Google Scholar
• Chan MTV, Choi KC, Gin T, The additive interactions between ondansetron and droperidol for preventing postoperative nausea and vomiting. Anesth Analg 2006;103(5):1155-62
   PubMed Web of Science ®Google Scholar
• Charbit B, Alvarez JC, Dasque E, Droperidol and ondansetron-induced QT interval prolongation: a clinical drug interaction study. Anesthiology 2008;109(2):206-12
   PubMed Web of Science ®Google Scholar
• Buyukavci M, Olgun H, Cevic N. The effects of ondansetron and granisetron on electrocardiography in children receiving chemotherapy for acute leukemia. Am J Clin Oncol 2005;28(2):201-4
   PubMed Web of Science ®Google Scholar
• Pinarli FG, Elli M, Dagdemir A, Electrocardiographic findings after 5-HT3 antagonists and chemotherapy in children with cancer. Pediatr Blood Cancer 2006;47(5):567-71
   PubMed Web of Science ®Google Scholar
• Mehta D, Sanatani S, Whyte SD. The effects of droperidol and ondansetron on dispersion of myocardial repolarisation in children. Pediatric Anesthesia 2010;20:905-12
   PubMed Web of Science ®Google Scholar
• McKechnie K, Froese A. Ventricular tachycardia after ondansetron administration in a child with undiagnosed long QT syndrome. Can J Anaesth 2010;57(5):453-7
   PubMed Web of Science ®Google Scholar
• Nathan AT, Berkowitz DH, Montenegro LM, Implications of anesthesia in children with long QT syndrome. Anesth Analg 2011;112(5):1163-8
   PubMed Web of Science ®Google Scholar
• Ballard HS, Bottino G, Bottino J. Ondansetron and chest pain. Lancet 1992;340:1107
   PubMed Web of Science ®Google Scholar
• Bosek V, Hu P, Robinson LA. Acute myocardial ischemia after administration of ondansetron hydrochloride. Anesthesiology 2000;92(3):885-7
   PubMed Web of Science ®Google Scholar
• Guigui N, Luyt CE, Vincent F. Coronary artery spasm after injection of ondansetron: case report and review of the literature. Int J Cardiol 2008;123:341-2
   PubMed Web of Science ®Google Scholar
• Baguley WA, Hey WT, Mackie KP, Cardiac dysrhythmias associates with the intravenous administration of ondansetron and metoclopramide. Anesth Analg 1997;84(6):1380-1
   PubMed Web of Science ®Google Scholar
• Bevacqua BK. Supraventricular tachycardia associated with postpartum metoclopramide administration. Anesthesiology 1988;68(1):124-5
   PubMed Web of Science ®Google Scholar
• Schwartz BG. Metoclopramide and digoxin cause 22 episodes of bradyarrhythmias. Am J Med 2010;123(6):e5-6
   PubMed Web of Science ®Google Scholar
• Chandrakala R, Vijayashankara CN, Kumar KK, Sarala N. Ondansetron induced fatal tachycardia. Indian J Pharmacol 2008;40(4):186-7
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Havrilla PL, Kane-Gill SL, Verrico MM, Coronary vasospasm and atrial fibrillation with ondansetron therapy. Ann Pharmacother 2009;43(3):532-6
   PubMed Web of Science ®Google Scholar
• Moazzam MS, Nasreen F, Bano S, Amir SH. Symptomatic sinus bradycardia: a rare adverse effect of intravenous ondansetron. Saudi J Anaesth 2011;5(1):96-7
   PubMedGoogle Scholar
• International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. ICH harmonised tripartite guideline. The non-clinical evaluation of the potential for delayed ventricular repolarisation (QT interval prolongation) by human pharmaceuticals S7B. Available from: http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Safety/S7B/Step4/S7B_Guideline.pdf [Accessed 28th December, 2012]
   Google Scholar
• International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. ICH harmonised tripartite guideline. The clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs E14. Available from: http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E14/E14_Guideline.pdf [Accessed 28th December, 2012]
   Google Scholar
• Darpo B, Nebout T, Sager PT. Clinical evaluation of QT/QTc prolongation and proarrhythmic potential for nonantiarrhythmic drugs: the International Conference on Harmonization of technical requirements for registration of pharmaceuticals for human use E14 guideline. J Clin Pharmacol 2006;46(5):498-507
   PubMed Web of Science ®Google Scholar
• FDA Safety Inapsine (droperidol). Available from: http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm172364.htm [Accessed 28th December, 2012]
   Google Scholar
• Jackson CW, Sheehan AH, Reddan JG. Evidence-based review of the black-box warning for droperidol. Am J Health Syst Pharm 2007;64(11):1174-86
   PubMed Web of Science ®Google Scholar
• Habib AS, Gan TJ. Pro: the Food and Drug Administration Black box warning on droperidol is not justified. Anesth Analg 2008;106(5):1414-17
   PubMed Web of Science ®Google Scholar
• Ludwin DB, Shafer SL. Con: the black box warning on droperidol should not be removed (but should be clarified!). Anesth Analg 2008;106(5):1418-20
   PubMed Web of Science ®Google Scholar
• Halloran K, Barash PG. Inside the black box: current policies and concerns with the Unites States Food and Drug Administration's highest drug safety warning system. Curr Opin Anaesthesiol 2010;23(3):423-7
   PubMed Web of Science ®Google Scholar
• Faine B, Hogrefe C. News flash. Old Mother Hubbard reports the cupboard is bare…time for the FDA to let droperidol out of the (black) box. Ann Pharmacother 2012;46(9):1259-61
   PubMed Web of Science ®Google Scholar
• Yap YG, Camm AJ. Drug induced QT prolongation and torsades de pointes. Heart 2003;89(11):1363-72
   PubMed Web of Science ®Google Scholar
• Redfern WS, Carlsson L, Davis AS, Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development. Cardiovasc Res 2003;58(1):32-45
   PubMed Web of Science ®Google Scholar
• Blum K. Is QT prolongation a valid reason to abandon zofran. Available from: http://www.anesthesiologynews.com/ViewArticle.aspx?d=Clinical+Anesthesiology&d_id=1&i=December+2011&i_id=793&a_id=19824 [Accessed 11/2/2013]
   Google Scholar
• Saxena PR, Villalón CM. 5-Hydroxytryptamine: a chameleon in the heart. Trends Pharmacol Sci 1991;12(6):223-7
   PubMed Web of Science ®Google Scholar
• Methods for treating apnea and apnea disorders using optinally pure R(+) ondansetron. Available from: http://www.patentgenius.com/patent/6548082.html [Accessed 31st December, 2012]
   Google Scholar
• Swami OC. Can we prevent ondansetron induced fatal ventricular tachycardia? Indian J Pharmacol 2009.41:91-2. Available from: http://www.ijp-online.com/text.asp?2009/41/2/91/51352 Cited 2012 Dec 30] [Accessed 31st December, 2012]
   Google Scholar
• Quraishi SA, Schuler GH, Janicki PK. 5-HT3-receptor antagonists and cardiac repolarisation time in patients expressing a novel genetic target associated with baseline QTc interval abnormalities. J Clin Anesth 2011;23(4):297-302
   PubMed Web of Science ®Google Scholar
• Mattiuzzi GN, Cortes JE, Blamble DA, Daily palonosetron is superior to ondansetron in the prevention of delayed chemotherapy-induced nausea and vomiting in patients with acute myelogenous leukemia. Cancer 2010;116(24):5659-66
   PubMed Web of Science ®Google Scholar
• Feinberg B, Gilmore J, Haislip S, Impact of initiating antiemetic prophylaxis with palonosetron versus ondansetron on risk of uncontrolled chemotherapy-induced nausea and vomiting in patients with lung cancer receiving multi-day chemotherapy. Support Card Cancer 2012;20(3):615-23
   PubMed Web of Science ®Google Scholar
• Dogan U, Yavas G, Tekinalp M, Evaluation of the acute effect of palonosetron on transmural dispersion of myocardial repolarisation. Eur Rev Med Pharmacol Sci 2012;16(4):462-8
   PubMed Web of Science ®Google Scholar
• Gonullu G, Demircan S, Demirag MK, Electrophysiological findings of palonosetron in cancer patients. Support Care Cancer 2012;20(7):1435-9
   PubMed Web of Science ®Google Scholar
• Yavas C, Dogan U, Yavas G, Acute effect of palonosetron on electrocardiographic parameters in cancer patients: a prospective study. Support Care Cancer 2012;20(10):2343-7
   PubMed Web of Science ®Google Scholar
• Wickham R. Evolving treatment paradigms for chemotherapy-induced nausea and vomiting. Cancer Contr 2012;19(2 Suppl):3-9
   PubMed Web of Science ®Google Scholar