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Benefits and Risks of Newer Treatments for Chemotherapy-Induced and Postoperative Nausea and Vomiting

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Abstract

Nausea and vomiting are common adverse effects of chemotherapy, radiation therapy, anaesthesia and surgery. The incidence of chemotherapy-induced nausea and vomiting (CINV) is estimated to vary from 30 to 90%, depending on the type of chemotherapeutic agent used. Radiation-induced emesis varies with anatomical site radiated but is estimated to have an overall incidence of approximately 40%. The incidence of postoperative nausea and vomiting (PONV) depends on the type of anaesthesia and surgery, but overall is estimated to be 20–30%. Evidence-based medicine and meta-analysis have been used to direct medical therapy to help determine equivalence, optimal dose, timing, safety and efficacy of antiemetic medications. Concepts such as the number needed to treat and number needed to harm are helpful to guide the clinician regarding the benefits and risks of a particular treatment.

The serotonin 5-HT3 receptor antagonists ondansetron, granisetron, tropisetron and dolasetron have been important additions to the antiemetic armamentarium. The 5-HT3 receptor antagonists are similar in chemical structure, efficacy and adverse effect profile. They appear to have no important differences among themselves in clinical outcomes for CINV and PONV. Headache, dizziness, constipation and diarrhoea are their most common adverse effects, and when they occur they are usually mild and easily managed. Haemodynamic changes and extrapyramidal adverse effects are uncommon. ECG changes such as prolonged corrected QT (QTc) interval are infrequent, dose-related and overall judged to be clinically insignificant. As most studies with the 5-HT3 antagonists have been conducted on relatively healthy patients, caution should be exercised when these drugs are used in susceptible patients with co-morbidities. The clinician must weigh the benefit of administering an antiemetic for CINV or PONV against the risk of occurrence of an adverse event.

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References

  1. Jamrozik K. Why evidence-based medicine. Best Pract Res Clin Anaesthesiol 2001; 15(4): 505–18

    Article  Google Scholar 

  2. Sackett DL, Rosenberg WMC, Gray JA, et al. Evidence-based medicine: what it is and what it isn’t. BMJ 1996; 312: 71–2

    Article  PubMed  CAS  Google Scholar 

  3. Jones B, Jarvis P, Lewis JA, et al. Trials to assess equivalence: the importance of rigorous methods. BMJ 1996; 313: 36–9

    Article  PubMed  CAS  Google Scholar 

  4. Laupacis A, Sackett DL, Roberts RS. An assessment of clinically useful measures of the consequences of treatment. N Engl J Med 1988; 318: 1728–33

    Article  PubMed  CAS  Google Scholar 

  5. Cook RJ, Sackett DL. The number needed to treat: a clinically useful measure of treatment effect. BMJ 1995; 310: 452–4

    Article  PubMed  CAS  Google Scholar 

  6. Tramèr MR. A rational approach to the control of postoperative nausea and vomiting: evidence from systematic reviews. Part I. Efficacy and harm of antiemetic interventions, and methodological issues. Acta Anesthesiol Scand 2001; 45: 4–13

    Article  Google Scholar 

  7. Tramèr MR. A rational approach to the control of postoperative nausea and vomiting: evidence from systematic reviews. Part II. Recommendations for prevention and treatment, and research agenda. Acta Anesthesiol Scand 2001; 45: 14–9

    Article  Google Scholar 

  8. Tramèr MR, editor. Evidence-based resource in anaesthesia and analgesia. London; BMJ Books, 2000

    Google Scholar 

  9. ASHP Commission on Therapeutics. ASHP therapeutic guidelines on the pharmacologic management of nausea and vomiting in adult and pediatric patients receiving chemotherapy or radiation therapy or undergoing surgery. Am J Health Syst Pharm 1999; 56: 729–64

    Google Scholar 

  10. Hesketh P. Comparative review of 5-HT3 receptor antagonists in the treatment of acute chemotherapy-induced nausea and vomiting. Cancer Invest 2000; 18: 163–73

    Article  PubMed  CAS  Google Scholar 

  11. Aapro MS. 5-HT3 receptor antagonists: an overview of their present status and future potential in cancer therapy-induced emesis. Drugs 1991; 42(4): 551–68

    Article  PubMed  CAS  Google Scholar 

  12. Gregory RE, Ettinger DS. 5-HT3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting: a comparison of their pharmacology and clinical efficacy. Drugs 1998; 55(2): 173–89

    Article  PubMed  CAS  Google Scholar 

  13. Veyrat-Follet C, Farinotti R, Palmer JL. Physiology of chemotherapy-induced emesis and antiemetic therapy: predictive models for evaluation of new compounds. Drugs 1997; 53(2): 206–34

    Article  PubMed  CAS  Google Scholar 

  14. Merrifield KR, Chaffee BJ. Recent advances in the management of nausea and vomiting caused by antineoplastic agents. Clin Pharm 1989; 8: 187–99

    PubMed  CAS  Google Scholar 

  15. Bunce KT, Tyers MB. The role of 5-HT in postoperative nausea and vomiting. Br J Anaesth 1992; 69Suppl. 1: 60S–2S

    Article  PubMed  CAS  Google Scholar 

  16. Hesketh PJ, Kris MG, Grunberg SM, et al. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol 1997; 15: 103–9

    PubMed  CAS  Google Scholar 

  17. Eberhart LH, Hogel J, Seeling W, et al. Evaluation of three risk scores to predict postoperative nausea and vomiting. Acta Anaesthesiol Scand 2000; 44(4): 480–8

    Article  PubMed  CAS  Google Scholar 

  18. Watcha MF, White PF. Postoperative nausea and vomiting: its etiology, treatment and prevention. Anesthesiology 1992; 77: 162–84

    Article  PubMed  CAS  Google Scholar 

  19. Koivuranta M, Laara E, Snare L, et al. A survey of postoperative nausea and vomiting. Anaesthesia 1997; 52: 443–9

    Article  PubMed  CAS  Google Scholar 

  20. Apfel C, Laara E, Koivuranta M, et al. A simplified risk score for predicting post-anesthetic nausea and vomiting. Anesthesiology 1999; 91: 693–700

    Article  PubMed  CAS  Google Scholar 

  21. Sinclair DR, Chung F, Mezei G. Can postoperative nausea and vomiting be predicted? Anesthesiology 1999; 91: 109–18

    Article  PubMed  CAS  Google Scholar 

  22. Rose JB, Watcha MF. Postoperative nausea and vomiting in paediatric patients. Br J Anaesth 1999; 83: 104–17

    Article  PubMed  CAS  Google Scholar 

  23. Gold BS, Kitz DS, Lecky HJ, et al. Unanticipated admission to the hospital following ambulatory surgery. JAMA 1989; 262: 3003–10

    Article  Google Scholar 

  24. Fancourt-Smith PF, Hornstein J, Jenkins LC. Hospital admissions from the Surgical Day Care Centre of Vancouver General Hospital 1977-1987. Can J Anaesth 1990; 37(6): 699–704

    Article  PubMed  CAS  Google Scholar 

  25. Tramèr MR, Reynolds DJ, Moore RA, et al. When placebo controlled trials are essential and equivalence trials are inadequate. BMJ 1998; 317(7162): 875–80

    Article  PubMed  Google Scholar 

  26. Henzi I, Walder B, Tramèr MR. Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review. Anesth Analg 2000; 90(1): 186–94

    Article  PubMed  CAS  Google Scholar 

  27. Fortney JT, Gan TJ, Graczyk S, et al. A comparison of the efficacy, safety and patient satisfaction of ondansetron versus droperidol as antiemetics for elective outpatient surgical procedures. Anesth Analg 1998; 86: 731–8

    PubMed  CAS  Google Scholar 

  28. Milne RJ, Hell RC. Ondansetron: therapeutic use as an antiemetic. Drugs 1991; 41: 574–95

    Article  PubMed  CAS  Google Scholar 

  29. Wilde MI, Markham A. Ondansetron: a review of its pharmacology and preliminary clinical findings in novel applications. Drugs 1996; 52: 773–94

    Article  PubMed  CAS  Google Scholar 

  30. Zofran (ondansetron HCl): prescribing information. Research Triangle Park (NC): GlaxoSmithKline, 2001

  31. Frazer NM, Palmer JL. Tolerability and pharmacokinetics of intra-muscular ondansetron 4mg [abstract]. Anesthesiology 1992; 77(3A): A439

    Article  Google Scholar 

  32. Jarosinski PF, Hirschfeld S. Precipitation of ondansetron in alkaline solution. N Engl J Med 1991; 325(18): 1315–6

    PubMed  CAS  Google Scholar 

  33. Grunberg SM, Groshen S, Robinson D, et al. Correlation of anti-emetic efficacy and plasma levels of ondansetron. Eur J Cancer 1990; 26: 879–82

    Article  PubMed  CAS  Google Scholar 

  34. Dixon CM, Colthup PV, Serabjit-Singh CJ, et al. Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. Drug Metab Dispos 1995; 23: 1225–30

    PubMed  CAS  Google Scholar 

  35. Kaiser R, Sezen O, Papies A, et al. Patient-tailored antiemetic treatment with 5-hydroxytryptamine type 3 receptor antagonists according to cytochrome P-450 2D6 genotype. J Clin Oncol 2002; 20: 2805–11

    Article  PubMed  CAS  Google Scholar 

  36. Figg WD, Dukes GE, Pritchard JF. Pharmacokinetics of ondansetron in patients with hepatic insufficiency. J Clin Pharmacol 1996; 36: 206–15

    PubMed  CAS  Google Scholar 

  37. Kovac A. Prevention and treatment of postoperative nausea and vomiting. Drugs 2000; 59(2): 213–43

    Article  PubMed  CAS  Google Scholar 

  38. Gyermek L. Pharmacology of serotonin as related to anesthesia. J Clin Anesth 1996; 8: 402–25

    Article  PubMed  CAS  Google Scholar 

  39. Talley NJ, Phillips SF, Haddad A, et al. GR 38032F (ondansetron), a selective 5-HT3 receptor antagonist, slows colonic transit in healthy man. Dig Dis Sci 1990; 35: 477–80

    Article  PubMed  CAS  Google Scholar 

  40. Talley NJ, Phillips SF, Haddad A, et al. Effect of selective 5-HT3 antagonist (Gr 38032F) on small intestinal transit and release of gastrointestinal peptides. Dig Dis Sci 1989; 34: 1511–5

    Article  PubMed  CAS  Google Scholar 

  41. Gore S, Gilmore IT, Haigh CG, et al. Colonic transit in man is slowed by ondansetron (GR38032F), a selective 5-hydroxytryptamine receptor (type 3) antagonist. Aliment Pharmacol Ther 1990; 4: 139–44

    Article  PubMed  CAS  Google Scholar 

  42. Figg WD, Graham CL, Hak LJ, et al. Ondansetron: a novel antiemetic agent. South Med J 1993; 86: 497–501

    Article  PubMed  CAS  Google Scholar 

  43. Heyman JS, Young ML, Bagshaw RJ, et al. Cardiovascular stability with rapid intravenous infusion of ondansetron. Can J Anaesth 1993; 40: 448–52

    Article  PubMed  CAS  Google Scholar 

  44. Tramèr MR, Reynolds DJM, Moore RA, et al. Efficacy, dose-response, and safety of ondansetron in prevention of postoperative nausea and vomiting. Anesthesiology 1997; 87: 1277–89

    Article  PubMed  Google Scholar 

  45. Dershwitz M, diBiase PM, Rosow CE, et al. Ondansetron does not affect alfentanil-induced ventilatory depression or sedation. Anesthesiology 1992; 77(3): 447–52

    Article  PubMed  CAS  Google Scholar 

  46. Kovac A, Steer P, Hutchison M, et al. Effect of ondansetron on recovery time, sedation level and discharge from ambulatory surgery [abstract]. Anesthesiology 1991; 75(3A): A7

    Article  Google Scholar 

  47. Pearson KS, From RP, Ostman LP, et al. Psychomotor effects of intravenous ondansetron in female outpatients [abstract]. Anesthesiology 1991; 75(3A): A8

    Article  Google Scholar 

  48. Beck TM, Hesketh PJ, Madajewica S, et al. Stratified, randomized, double-blind comparison of intravenous ondansetron administered as a multiple-dose regiment versus two single-dose regimens in the prevention of cisplatin-induced nausea and vomiting. J Clin Oncol 1992; 10: 1969–75

    PubMed  CAS  Google Scholar 

  49. Pearman MH. Single dose intravenous ondansetron in the prevention of postoperative nausea and vomiting. Anaesthesia 1994; 49: 11–5

    Article  PubMed  Google Scholar 

  50. Rung GW, Claybon L, Hord A, et al. Intravenous ondansetron for postsurgical opioid-induced nausea and vomiting. Anesth Analg 1997; 84: 832–8

    PubMed  CAS  Google Scholar 

  51. Smith RN. Safety of ondansetron. Eur J Cancer Clin Oncol 1989; 25Suppl. 1: S47–50

    PubMed  Google Scholar 

  52. McKenzie R, Kovac A, O’Connor T, et al. Comparison of ondansetron versus placebo to prevent postoperative nausea and vomiting in women undergoing ambulatory gynecologic surgery. Anesthesiology 1993; 78: 21–8

    Article  PubMed  CAS  Google Scholar 

  53. Scuderi P, Wetchler B, Sung YF, et al. Treatment of postoperative nausea and vomiting after outpatient surgery with the 5-HT3 antagonist ondansetron. Anesthesiology 1993; 78: 15–20

    Article  PubMed  CAS  Google Scholar 

  54. Claybon L. Single dose intravenous ondansetron for the 24-hour treatment of postoperative nausea and vomiting. Anaesthesia 1994; 49: 24–9

    Article  PubMed  Google Scholar 

  55. Kovac AL, Pearman MH, Khalil SN, et al. Ondansetron prevents postoperative emesis in male outpatients. J Clin Anesth 1996; 8: 644–51

    Article  PubMed  CAS  Google Scholar 

  56. Kovac AL, O’Connor TA, Pearman MH, et al. Efficacy of repeat intravenous dosing of ondansetron in controlling postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled multicenter trial. J Clin Anesth 1999; 11: 453–9

    Article  PubMed  CAS  Google Scholar 

  57. Khalil S, Rodarte A, Weldon C, et al. Intravenous ondansetron in established postoperative emesis in children. Anesthesiology 1996; 85: 270–6

    Article  PubMed  CAS  Google Scholar 

  58. Furst SR, Rodarte A. Prophylactic antiemetic treatment with ondansetron in children undergoing tonsillectomy. Anesthesiology 1994; 81: 799–803

    Article  PubMed  CAS  Google Scholar 

  59. Rose JB, Brenn BR, Corddry DH, et al. Preoperative oral ondansetron for pediatric tonsillectomy. Anesth Analg 1996; 83: 558–62

    Google Scholar 

  60. Plosker GL, Goa KL. Granisetron: a review of its pharmacological properties and therapeutic use as an antiemetic. Drugs 1991; 42: 805–24

    Article  PubMed  CAS  Google Scholar 

  61. Hunter AE, Prentice HG, Pothecary K, et al. Granisetron, a selective 5-HT3 receptor antagonist, for the prevention of radiation induced emesis during total body irradiation. Bone Marrow Transplant 1991; 7: 439–41

    PubMed  CAS  Google Scholar 

  62. Yarker YE, McTavish D. Granisetron: an update of its therapeutic use in nausea and vomiting induced by antineoplastic therapy. Drugs 1994; 48(5): 761–93

    Article  PubMed  CAS  Google Scholar 

  63. Addelman M, Erlichman C, Fine S, et al. Phase I/II trial of granisetron: a novel 5-hydroxytryptamine antagonist for the prevention of chemotherapy-induced nausea and vomiting. J Clin Oncol 1990; 8: 337–41

    PubMed  CAS  Google Scholar 

  64. Chevallier B. Efficacy and safety of granisetron compared with high-dose metoclopramide plus dexamethasone in patients receiving high-dose cisplatin in a single-blind study. Eur J Cancer 1990; 26: S33–6

    Article  PubMed  Google Scholar 

  65. Marty M. A comparative study of the use of granisetron, a selective 5-HT3 antagonist, versus a standard anti-emetic regimen of chlorpromazine plus dexamethasone in the treatment of cytostatic-induced emesis. Eur J Cancer 1990; 26: S28–32

    PubMed  Google Scholar 

  66. Kytril injection (granisetron HCl): package insert. Nutley, NJ: Roche Laboratories, 2000

  67. Bloomer JC, Baldwin SJ, Smith GJ, et al. Characteristics of the cytochrome P450 enzymes involved in the in vitro metabolism of granisetron. Br J Clin Pharmacol 1994; 38: 557–66

    Article  PubMed  CAS  Google Scholar 

  68. Pintens H. Granisetron (BRL43694) in the treatment of cytostatic drug-induced emesis: a summary. Cancer Treat Rev 1990; 17: 307–10

    Article  PubMed  CAS  Google Scholar 

  69. Wilson AJ, Diemunsch P, Lindeque BG, et al. Single-dose iv granisetron in the prevention of postoperative nausea and vomiting. Br J Anaesth 1996; 76: 515–8

    Article  PubMed  CAS  Google Scholar 

  70. Fujii Y, Tanaka H, Toyooka H. Optimal antiemetic dose of granisetron for preventing postoperative nausea and vomiting. Can J Anaesth 1994; 51: 794–7

    Google Scholar 

  71. Fujii Y, Tanaka H, Toyooka H. Reduction of postoperative nausea and vomiting with granisetron. Can J Anaesth 1994; 41: 291–4

    Article  PubMed  CAS  Google Scholar 

  72. Fujii Y, Tanaka H, Toyooka H. Granisetron: dexamethasone combination reduces postoperative nausea and vomiting. Can J Anaesth 1995; 42: 387–90

    Article  PubMed  CAS  Google Scholar 

  73. Cieslak GD, Watcha MF, Phillips MB, et al. The dose-response relationship of granisetron for the prophylaxis of pediatric postoperative emesis. Anesthesiology 1996; 85: 1076–85

    Article  PubMed  CAS  Google Scholar 

  74. Taylor AM, Rosen M, Diemunsch PA, et al. A double-blind, parallel-group, placebo-controlled, dose-ranging, multicenter study of intravenous granisetron in the treatment of postoperative nausea and vomiting in patients undergoing surgery with general anesthesia. J Clin Anesth 1997; 9(8): 658–63

    Article  PubMed  CAS  Google Scholar 

  75. Mikawa K, Takao Y, Nichina K, et al. Optimal dose of granisetron for prophylaxis against postoperative emesis after gynecological surgery. Anesth Analg 1997; 85: 652–6

    PubMed  CAS  Google Scholar 

  76. Watanabe H, Hasegawa A, Shinozaki T, et al. 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: 278–82

    Article  PubMed  CAS  Google Scholar 

  77. Diemunsch P, Wilson J, Chitour K, et al. A double blind, parallel group, placebo controlled dose ranging study of intravenous granisetron in the prevention of postoperative nausea and vomiting (PONV) [abstract]. Anesthesiology 1994; 81: A1280

    Article  Google Scholar 

  78. de Bruijn KM. Tropisetron: a review of the clinical experience. Drugs 1992; 43: 11–22

    Article  PubMed  Google Scholar 

  79. Lee CR, Plosker GL, McTavish D. Tropisetron: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential as an antiemetic. Drugs 1993; 46: 925–43

    Article  PubMed  CAS  Google Scholar 

  80. Simpson K, Spencer CM, McClellan KJ. Tropisetron: an update of its use in the prevention of chemotherapy-induced nausea and vomiting. Drugs 2000; 59: 1297–316

    Article  PubMed  CAS  Google Scholar 

  81. Seinen H, Zonnenberg BA, Tija P, et al. The effect of three dose levels of ICS 205-930 (a selective 5HT-3 antagonist) on cisplatin-induced nausea and vomiting. Eur J Cancer Clin Oncol 1989; 25: 1333–5

    Article  PubMed  CAS  Google Scholar 

  82. Bleiberg H, Van Belle S, Paridaens R, et al. Compassionate use of a 5-HT3 receptor antagonist, tropisetron, in patients refractory to standard antiemetic treatment. Drugs 1992; 43: 27–32

    Article  PubMed  Google Scholar 

  83. Sorbe B, Berglind A-M. Tropisetron, a new 5-HT3 receptor antagonist, in the prevention of radiation-induced nausea, vomiting and diarrhoea. Drugs 1992; 43: 33–9

    Article  PubMed  Google Scholar 

  84. Alon E, Kocian R, Nett PC, et al. Tropisetron for the prevention of postoperative nausea and vomiting in women undergoing gynecologic surgery. Anesth analg 1966; 82: 338–41

    Google Scholar 

  85. Alon E, Buchser E, Herrera E, et al. Tropisetron for treating established postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled study. Anesth Analg 1998; 86: 617–23

    PubMed  CAS  Google Scholar 

  86. Lee CR, Plosker GL, McTavish D. Tropisetron: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential as an antiemetic. Drugs 1993; 46: 925–43

    Article  PubMed  CAS  Google Scholar 

  87. Bruntsch U, Drechsler S, Eggert J, et al. Prevention of chemotherapy-induced nausea and vomiting by tropisetron (Novoban) alone or in combination with other antiemetic agents. Semin Oncol 1994 Oct; 21(5 Suppl. 9): 7–11

    PubMed  CAS  Google Scholar 

  88. de Bruijn KM. The development of tropisetron in its clinical perspective. Ann Oncol 1993; 4Suppl. 3: S19–23

    Article  Google Scholar 

  89. Bruntsch U, Rüfenacht E, Parker I, et al. Tropisetron in the prevention of chemotherapy-induced nausea and vomiting in patients responding poorly to previous conventional antiemetic therapy. Ann Oncol 1993; 4Suppl. 3: S25–9

    Article  Google Scholar 

  90. Balfour JA, Goa KL. Dolasetron: a review of its pharmacology and therapeutic potential in the management of nausea and vomiting induced by chemotherapy, radiotherapy or surgery. Drugs 1997; 54: 273–98

    Article  PubMed  CAS  Google Scholar 

  91. Hui YF, Ignoffo RJ. Dolasetron: a new 5-hydroxytryptamine3 receptor antagonist. Cancer Pract 1997; 5: 324–8

    PubMed  CAS  Google Scholar 

  92. Anzemet (dolasetron mesylate): prescribing information. Kansas City (MO): Aventis Pharmaceuticals, 2002

  93. Reith MK, Sproles GD, Cheng LK. Human metabolism of dolasetron mesylate, a 5-HT3 receptor antagonist. Drug Metab Dispos 1995; 23: 806–8

    PubMed  CAS  Google Scholar 

  94. Dow J, Berg C. Steroselectivity of the carbonyl reduction of dolasetron in rats, dogs and humans. Chirality 1995; 7: 342–8

    Article  PubMed  CAS  Google Scholar 

  95. Boxenbaum H, Gillespie T, Heck K, et al. Human dolasetron pharmacokinetics: I. disposition following single-dose intravenous administration to normal male subjects. Biopharm Drug Dispos 1992; 13: 693–701

    Article  PubMed  CAS  Google Scholar 

  96. Boxenbaum H, Gillespie T, Heck K, et al. Human dolasetron pharmacokinetics: II. disposition following single-dose oral administration to normal male subjects. Biopharm Drug Dispos 1993; 14: 131–41

    Article  PubMed  CAS  Google Scholar 

  97. Shah A, Lanman R, Bhargava V, et al. Pharmacokinetics of dolasetron following single- and multiple-dose intravenous administration to normal male subjects. Biopharm Drug Dispos 1995; 16: 177–89

    Article  PubMed  CAS  Google Scholar 

  98. Dimmitt DC, Shah AK, Arumughan T, et al. Pharmacokinetics of oral and intravenous dolasetron mesylate in patients with renal impairment. J Clin Pharmacol 1998; 38: 798–806

    PubMed  CAS  Google Scholar 

  99. McDermott S, Songer S, Benedict C, et al. Safety profile of dolasetron. Eur Hosp Pharm 1996; 2Suppl. 1: S25–31

    Google Scholar 

  100. Dixon RM, Cramer M, Shah AK, et al. Single-dose, placebo-controlled, phase I study of oral dolasetron. Pharmacotherapy 1996; 16(2): 245–52

    PubMed  CAS  Google Scholar 

  101. Hunt TL, Cramer M, Shah A, et al. A double-blind, placebo-controlled, dose-ranging safety evaluation of single-dose intravenous dolasetron in healthy male volunteers. J Clin Pharmacol 1995 Jul; 35(7): 705–12

    PubMed  CAS  Google Scholar 

  102. Hunt TL, Cramer M, Christy-Bittel J, et al. Multiple-dose, placebo-controlled, phase I study of oral dolasetron. Pharmacotherapy 1996; 16: 253–60

    PubMed  CAS  Google Scholar 

  103. Lerman J, Sims C, Sikich N, et al. Pharmacokinetics of the active metabolite (MDL 74,156) of dolasetron mesylate after oral or intravenous administration to anesthetized children. Clin Pharmacol Ther 1996; 60: 485–92

    Article  PubMed  CAS  Google Scholar 

  104. Hesketh P, Navari R, Grote T, et al. 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. J Clin Oncol 1996; 14: 2242–9

    PubMed  CAS  Google Scholar 

  105. Chevallier B, Bleiberg H, Fauser AA, et al. Dolasetron in the control of chemotherapy-induced nausea and vomiting. Eur Hosp Pharm 1996; 2Suppl. 1: S38–42

    Google Scholar 

  106. Audhuy B, Cappelaer EP, Martin M, et al. A double-blind randomized comparison of the antiemetic efficacy of two intravenous doses of dolasetron mesylate and granisetron in patients receiving dose cisplatin therapy. Eur J Cancer 1996; 32A(5): 807–13

    PubMed  CAS  Google Scholar 

  107. Diemunsch P, d’Hollander A, Feiss P, et al. The prevention and treatment of postoperative nausea and vomiting with dolasetron. Eur Hosp Pharm 1996; 21Suppl. 1: S34–7

    Google Scholar 

  108. Warriner CB, Knox D, Belo S, et al. Prophylactic oral dolasetron mesylate reduces nausea and vomiting after abdominal hysterectomy. Can J Anaesth 1997; 44: 1167–73

    Article  PubMed  CAS  Google Scholar 

  109. Graczyk SG, McKenzie R, Kallar S. Intravenous dolasetron for the prevention of postoperative nausea and vomiting after outpatient laparoscopic gynecologic surgery. Anesth Analg 1997; 84: 325–30

    PubMed  CAS  Google Scholar 

  110. Diemunsch P, Leeser J, Feiss P, et al. Intravenous dolasetron mesilate ameliorates postoperative nausea and vomiting. Can J Anaesth 1997; 44: 173–81

    Article  PubMed  CAS  Google Scholar 

  111. Kovac AL, Scuderi PE, Boerner TF, et al. Treatment of postoperative nausea and vomiting with single intravenous doses of dolasetron mesylate: multicenter trial. Dolasetron Mesylate PONV Treatment Study Group. Anesth Analg 1997; 84: 546–52

    Google Scholar 

  112. Whitmore JB, Kris MG, Hesketh PJ, et al. Rationale for the use of a single fixed intravenous dolasetron dose for the prevention of cisplatin-induced nausea and vomiting. Pooled analysis of 14 clinical trials. Support Care Cancer 1998; 6(5): 473–8

    Article  PubMed  CAS  Google Scholar 

  113. Chevallier B, Cappelaere P, Splinter T, et al. A double-blind, multicentre comparison of intravenous dolasetron mesilate and metoclopramide in the prevention of nausea and vomiting in cancer patients receiving high-dose cisplatin chemotherapy. Support Care Cancer 1997; 5(1): 22–30

    Article  PubMed  CAS  Google Scholar 

  114. Graczyk SG, McKenzie R, Kallar S, et al. Intravenous dolasetron for the prevention of nausea and vomiting after outpatient laparoscopic gynecologic surgery. Anesth Analg 1997; 84: 325–330

    PubMed  CAS  Google Scholar 

  115. Diemunsch P, D’Hollander A, Paxton L, et al. Intravenous dolasetron mesylate in the prevention of postoperative nausea and vomiting in females undergoing gynecological surgery. J Clin Anesth 1997; 9(5): 365–73

    Article  PubMed  CAS  Google Scholar 

  116. Diemunsch P, Lesser J, Feiss P, et al. Intravenous dolasetron mesilate ameliorates postoperative nausea and vomiting. Can J Anaesth 1997; 44(2): 173–81

    Article  PubMed  CAS  Google Scholar 

  117. Keefe DL. The cardiotoxic potential of the 5-HT3 receptor antagonist antiemetics: Is there cause for concern? Oncologist 2002; 7: 65–72

    Article  PubMed  CAS  Google Scholar 

  118. Hesketh P, Navari R, Grote T, et al. 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  CAS  Google Scholar 

  119. Jantunen IT, Kataja VV, Muhonen TT, et al. Effects of granisetron with doxorubicin or epirubicin on ECG intervals. Cancer Chemother Pharmacol 1996; 37: 502–4

    Article  PubMed  CAS  Google Scholar 

  120. Lofters WS, Pater JL, Zee B, et al. Phase III double-blind comparison of dolasetron mesylate and ondansetron and an evaluation of the additive role 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  CAS  Google Scholar 

  121. Ballard HS, Bottino G, Bottino J. Ondansetron and chest pain [letter]. Lancet 1992; 340: 1107

    Article  PubMed  CAS  Google Scholar 

  122. Baltzer L, Kris MG, Hinkley L, et al. Reversible electrocardiographic interval prolongations following the specific serotonin antagonists ondansetron (OND) and dolasetron mesylate (DM): a possible drug class effect without sequelae? [abstract 1489]. Proc Am Soc Clin Oncol 1994; 13: 544

    Google Scholar 

  123. Benedict CR, Arbogast R, Martin L, et al. Single-blind study of the effects of intravenous dolasetron mesylate versus ondansetron on electrocardiographic parameters in normal volunteers. J Cardiovasc Pharmacol 1996; 28: 53–9

    Article  PubMed  CAS  Google Scholar 

  124. Kuryshev YA, Brown AM, Wang L, et al. Interactions of the 5-hydroxytryptamine 3 antagonist class of antiemetic drugs with human cardiac ion channels. J Pharmacol Ther 2000; 295: 614–20

    CAS  Google Scholar 

  125. Yancik R. Cancer burden in the aged: an epidemiologic and demographic overview. Cancer 1997; 80: 1273–83

    Article  PubMed  CAS  Google Scholar 

  126. Lindsey AM, Larson PJ, Dodd MJ, et al. Comorbidity, nutrition intake, social support, weight and functional status over time in older cancer patients receiving radiotherapy. Cancer Nurs 1994; 17: 113–24

    Article  PubMed  CAS  Google Scholar 

  127. Wei JY. Cardiovascular comorbidity in the older cancer patient. Semin Oncol 1995; 22: 9–10

    PubMed  CAS  Google Scholar 

  128. Kamataki T, Yokoi T, Fujita K, et al. Preclinical approach for identifying drug interactions. Cancer Chemother Pharmacol 1998; 42Suppl: S50–3

    Article  PubMed  CAS  Google Scholar 

  129. Bertz RJ, Granneman GR. Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Clin Pharmacokinet 1997; 32(3): 210–58

    Article  PubMed  CAS  Google Scholar 

  130. Woosley RL. Drugs that prolong QTc and/or induce torsades de pointes [online]. Available from URL: http://www.torsades.org [Accessed 2002 Dec 26]

  131. Moss AJ, Schwartz PJ, Crampton RS, et al. The long QT syndrome: prospective longitudinal study of 328 families. Circulation 1991; 84: 1136–44

    Article  PubMed  CAS  Google Scholar 

  132. Keating M, Atkinson D, Dunn C, et al. Linkage of a cardiac arrhythmia the long-QT syndrome and the Harvey-ras-1 gene. Science 1991; 252: 704–6

    Article  PubMed  CAS  Google Scholar 

  133. Vincent MG, Timothy KW, Leppert M, et al. The spectrum of symptoms and QT intervals in carriers of the gene for the long QT syndrome. N Engl J Med 1992; 327: 846–52

    Article  PubMed  CAS  Google Scholar 

  134. Schwartz PT, Locati EH, Moss AJ, et al. Left cardiac sympathetic denervation in the therapy of congenital long QT syndrome: a worldwide report. Circulation 1991; 84: 503–11

    Article  PubMed  CAS  Google Scholar 

  135. Lowenthal RM, Eaton K. Toxicity of chemotherapy. Hematol Oncol Clin North Am 1996; 10: 967–90

    Article  PubMed  CAS  Google Scholar 

  136. Eberhart LHJ, Morin AM, Seeling W, et al. Meta-analysis of controlled randomized studies on droperidol for prevention of postoperative phas nausea and vomiting. Anasthesiol Intensivmed Notfallmed Schmerzther 1999; 34: 528–36

    Article  PubMed  CAS  Google Scholar 

  137. Tang J, Watcha MF, White PF. A comparison of costs and efficacy of ondansetron and droperidol as prophylactic antiemetic therapy for elective outpatient gynecologic procedures. Anesth Analg 1996; 83: 304–13

    PubMed  CAS  Google Scholar 

  138. Henzi I, Sonderegger J, Tramèr MR. Efficacy, dose-response and adverse effects of droperidol for prevention of postoperative nausea and vomiting. Can J Anaesth 2000; 47: 537–51

    Article  PubMed  CAS  Google Scholar 

  139. Lischke V, Behne M, Doelken P, et al. Droperidol causes a dose-dependent prolongation of the QT interval. Anesth Analg 1994; 79: 983–6

    Article  PubMed  CAS  Google Scholar 

  140. Food and Drug Administration. FDA strengthens warnings for droperidol [online]. Available from URL: http://www.fda.gov/bbs/topics/ANSWERS/2001/ANS01123.html [Accessed 2002 Dec 26]

  141. McCormick CG. FDA alert: current FDA report on droperidol status and basis for black box warning. Am Soc Anesthesiologists Newsletter 2002; 66(4): 19–20

    Google Scholar 

  142. Lopez-Olaondo L, Carrascosa F, Pueyo FJ. Advances in antiemetic pharmacology. Review Course Lectures, European Society of Anesthesiologists 8th Annual Meeting; 2000 Apr; Vienna, Austria: 251–8

  143. Chang N, Rappaport B. FDA alert: update on droperidol and the FDA. Am Soc Anesth Newsletter 2002; 66(12): 25.

    Google Scholar 

  144. Hochhaus G, Barth J, al Fayoumi S, et al. Pharmacokinetics and pharmacodynamics of dexamethasone sodium-m-sulfobenzoate (DS) after intravenous and intramuscular administration: a comparison with dexamethasone phosphate (DP). J Clin Pharmacol 2001; 41(4): 425–34

    Article  PubMed  CAS  Google Scholar 

  145. Henzi I, Walder B, Tramèr MR. Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review. Anesth Analg 2000; 90(1): 186–94

    Article  PubMed  CAS  Google Scholar 

  146. Aouad MT, Siddik SS, Rizk LB, et al. The effect of dexamethasone on postoperative vomiting after tonsillectomy. Anesth Analg 2001; 92(3): 636–40

    Article  PubMed  CAS  Google Scholar 

  147. Wang JJ, Ho ST, Tzeng JI, et al. The effect of timing of dexamethasone administration on its efficacy as a prophylactic antiemetic for postoperative nausea and vomiting. Anesth Analg 2000; 91: 136–9

    PubMed  CAS  Google Scholar 

  148. McKenzie R, Tantisira B, Karambelkar DJ, et al. A recent revolution in patient symptom control. Cancer Treat Rev 1991; 18: 95–135

    Article  Google Scholar 

  149. McKenzie R, Tantisira B, Karambelkar DJ, et al. Comparison of ondansetron with ondansetron plus dexamethasone in the prevention of postoperative nausea and vomiting. Anesth Analg 1994; 79: 961–4

    Article  PubMed  CAS  Google Scholar 

  150. McKenzie R, Riley TJ, Tantisira B, et al. Effect of propofol for induction and ondansetron with or without dexamethasone for the prevention of nausea and vomiting after major gynecologic surgery. J Clin Anesth 1997; 9: 15–20

    Article  PubMed  CAS  Google Scholar 

  151. Fujii Y, Toyooka H, Tanaka H. Prevention of postoperative nausea and vomiting with a combination of granisetron and droperidol. Anesth Analg 1998; 86: 613–6

    PubMed  CAS  Google Scholar 

  152. Fujii Y, Tanaka H, Toyooka H. The effects of dexamethasone on antiemetics in female patients undergoing gynecologic surgery. Anesth Analg 1997; 85(4): 913–7

    PubMed  CAS  Google Scholar 

  153. Fujii Y, Toyooka H, Tanaka H. Prophylactic antiemetic therapy with granisetron-dexamethasone combination in women undergoing breast surgery. Acta Anaesthesiol Scand 1998; 42: 1038–42

    Article  PubMed  CAS  Google Scholar 

  154. Fujii Y, Toyooka H, Tanaka H. Prophylactic antiemetic therapy with a combination of granisetron and dexamethasone in patients undergoing middle ear surgery. Br J Anaesth 1998; 81: 754–6

    Article  PubMed  CAS  Google Scholar 

  155. Fujii Y, Saitoh Y, Tanaka Y, et al. Granisetron/dexamethasone combination for preventing postoperative nausea and vomiting after laparoscopic cholecystectomy. Eur J Anaesthesiol 2000; 17: 64–8

    PubMed  CAS  Google Scholar 

  156. Fujii Y, Tanaka H, Kobayashi N. Granisetron/dexamethasone combination for the prevention of postoperative nausea and vomiting after thyroidectomy. Aneasth Intensive Care 2000; 28: 266–9

    CAS  Google Scholar 

  157. Fujii Y, Saitoh Y, Tanaka H, et al. Granisetron/dexamethasone combination for reducing nausea and vomiting during spinal anesthesia for cesarean section. Anesth Analg 1999; 88: 1346–50

    PubMed  CAS  Google Scholar 

  158. Lopez-Olaondo L, Carrascosa F, Pueyo FJ, et al. Combination of ondansetron and dexamethasone in the prophylaxis of postoperative nausea and vomiting. Br J Anaesth 1996; 76: 835–40

    Article  PubMed  CAS  Google Scholar 

  159. Coloma M, White PF, Markowitz SD, et al. Dexamethasone in combination with dolasetron for prophylaxis in the ambulatory setting. Anesthesiology 2002; 96: 1346–50

    Article  PubMed  CAS  Google Scholar 

  160. McKenzie R, Uy NT, Riley TJ, et al. Droperidol/ondansetron combination controls nausea and vomiting after tubal banding. Anesth Analg 1996; 83: 1218–22

    PubMed  CAS  Google Scholar 

  161. Fujii Y, Saitoh Y, Tanaka H, et al. Prevention of PONV with granisetron, droperidol or metoclopramide in patients with postoperative emesis. Can J Anaesth 1998; 45(2): 153–6

    Article  PubMed  CAS  Google Scholar 

  162. Fujii Y, Toyooka H, Tanaka H, et al. Prevention of PONV with granisetron, droperidol and metoclopramide in female patients with history of motion sickness. Can J Anaesth 1997; 44: 820–4

    Article  PubMed  CAS  Google Scholar 

  163. Fujii Y, Toyooka H, Tanaka H. Prevention of postoperative nausea and vomiting in female patients during menstruation: comparison of droperidol, metoclopramide and granisetron. Br J Anaesth 1998; 80(2): 248–9

    Article  PubMed  CAS  Google Scholar 

  164. Koivuranta M, Jokela R, Kiviluomak K, et al. The antiemetic efficacy of a combination of ondansetron and droperidol. Anaesthesia 1997; 52(9): 863–8

    Article  PubMed  CAS  Google Scholar 

  165. Pueyo FJ, Carrascosa F, Lopez L, et al. Combination of ondansetron and droperidol in the prophylaxis of postoperative nausea and vomiting. Anesth Analg 1996; 83: 117–22

    PubMed  CAS  Google Scholar 

  166. Steinbrook RA, Freiberger D, Gosnell JL, et al. Prophylactic antiemetics for laparoscopic cholecystectomy: ondansetron versus droperidol plus metoclopramide. Anesth Analg 1996; 83: 1081–3

    PubMed  CAS  Google Scholar 

  167. Sanchez-Ledesma MJ, Lopez-Olaondo L, Pueyo FJ, et al. A comparison of three antiemetic combinations for the prevention of postoperative nausea and vomiting. Anesth Analg 2002

    Google Scholar 

  168. Eberhart LH, Morin AM, Georgieff M. Dexamethasone for prophylaxis of postoperative nausea and vomiting: a meta-analysis of randomized controlled studies. Anaesthetist 2000; 49: 713–20

    Article  CAS  Google Scholar 

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Acknowledgments

Dr Kovac has disclosed that in the past he has received grant support from GlaxoWellcome (now GlaxoSmithKline), Roche Pharmaceuticals and Hoechst Marion Roussel (now Aventis Pharmaceuticals) and participated on the Speakers Bureau for GlaxoWellcome, Roche Pharmaceuticals and Abbott Laboratories. There were no sources of funding for the preparation of this manuscript.

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Kovac, A.L. Benefits and Risks of Newer Treatments for Chemotherapy-Induced and Postoperative Nausea and Vomiting. Drug-Safety 26, 227–259 (2003). https://doi.org/10.2165/00002018-200326040-00003

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