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Overview of CAS 103639-04-9

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4H-Carbazol-4-one, 1,2,3,9-tetrahydro-9-methyl-3-[(2- methyl-1H-imidazol-1-yl)methyl]-, monohydrochloride, (+/-)-, dihydrate
PharmaCompass
  • Chemistry
4H-Carbazol-4-one, 1,2,3,9-tetrahydro-9-methyl-3-[(2- methyl-1H-imidazol-1-yl)methyl]-, monohydrochloride, (+/-)-, dihydrate
Also known as: Ondansetron hydrochloride dihydrate, 103639-04-9, Zofran, 99614-01-4, Gr 38032f, Ondansetron (hydrochloride dihydrate)
Molecular Formula
C18H24ClN3O3
Molecular Weight
365.858  g/mol
InChI Key
VRSLTNZJOUZKLX-UHFFFAOYSA-N

A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and has reported anxiolytic and neuroleptic properties.
1 2D Structure

4H-Carbazol-4-one, 1,2,3,9-tetrahydro-9-methyl-3-[(2- methyl-1H-imidazol-1-yl)methyl]-, monohydrochloride, (+/-)-, dihydrate

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1H-carbazol-4-one;dihydrate;hydrochloride
2.1.2 InChI
InChI=1S/C18H19N3O.ClH.2H2O/c1-12-19-9-10-21(12)11-13-7-8-16-17(18(13)22)14-5-3-4-6-15(14)20(16)2;;;/h3-6,9-10,13H,7-8,11H2,1-2H3;1H;2*1H2
2.1.3 InChI Key
VRSLTNZJOUZKLX-UHFFFAOYSA-N
2.1.4 Canonical SMILES
CC1=NC=CN1CC2CCC3=C(C2=O)C4=CC=CC=C4N3C.O.O.Cl
2.2 Synonyms
2.2.1 Depositor-Supplied Synonyms

1. Ondansetron Hydrochloride Dihydrate

2. 103639-04-9

3. Zofran

4. 99614-01-4

5. Gr 38032f

6. Ondansetron (hydrochloride Dihydrate)

7. St024023

8. Zofran (tn)

9. (+-)-2,3-dihydro-9-methyl-3-((2-methylimidazol-1-yl)methyl)carbazol-4(1h)-one Monohydrochloride Dihydrate

10. C18h19n3o.hcl.2h2o

11. 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1h-imidazol-1-yl)methyl]-4h-carbazol-4-one Hydrochloride

12. 4h-carbazol-4-one, 1,2,3,9-tetrahydro-9-methyl-3-((2-methyl-1h-imidazol-1-yl)methyl)-, Monohydrochloride, (+-)-, Dihydrate

13. 9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1h-carbazol-4-one Dihydrate Hydrochloride

14. 99614-02-5 (parent)

15. Setofilm

16. Setrodon

17. Zensana

18. Zofrene

19. Yatrox

20. Zofran Zydis

21. Ks-1091

22. 9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1h-carbazol-4-one;dihydrate;hydrochloride

23. Ondansetron Hydrochloride [usan:jan]

24. Ondansetron Hydrochloride [usan:usp:jan]

25. Ncgc00016968-01

26. Ac1l1rx8

27. Dsstox_cid_28783

28. Dsstox_rid_83052

29. Cas-103639-04-9

30. Dsstox_gsid_48857

31. Chebi:7774

32. Chembl3186492

33. Dtxsid9048857

34. Ctk8g2185

35. Hy-b0002a

36. Ks-00000xjx

37. Rhb-102

38. Molport-002-322-292

39. Vrsltnzjouzklx-uhfffaoysa-n

40. Mfcd00764297 (anhy.)

41. Eur-1025

42. Tox21_113345

43. Ac-667

44. Gg-032

45. Mfcd00374371

46. S4748

47. Akos015994673

48. Ondansetron Monohydrochloride Dihydrate

49. Bcp9001026

50. Cs-1716

51. Gr-c505/75

52. To-2061

53. W39o049

54. An-15657

55. An-34134

56. Bc226780

57. K786

58. Sc-21358

59. Ab0004573

60. Ls-171880

61. Ft-0631028

62. Ondansetron Hydrochloride Hydrate (jan/usp)

63. D00678

64. J10349

65. Gr 38032;sn 307;nsc 665799

66. Ondansetron Hydrochloride Dihydrate, >=98% (hplc), Powder

67. Ondansetron For Lc System Suitability, European Pharmacopoeia (ep) Reference Standard

68. Ondansetron For Tlc System Suitability, European Pharmacopoeia (ep) Reference Standard

69. Ondansetron Hydrochloride Dihydrate, European Pharmacopoeia (ep) Reference Standard

70. Ondansetron Hydrochloride, Pharmaceutical Secondary Standard; Certified Reference Material

71. Ondansetron Hydrochloride, United States Pharmacopeia (usp) Reference Standard

72. (+/-)-2,3-dihydro-9-methyl-3-[(2-methylimidazol-1- Yl)methyl]carbazol-4(1h)-one Monohydrochloride Dihydrate

73. 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1h-imidazol-1-yl)methyl]-4h-carbazol-4-one Hydrochloride Dihydrate

74. 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1h-imidazole-1-yl)methyl]-4h-carbazol-4-one Hydrochloride Dihydrate

75. 4h-carbazol-4-one, 1,2,3,9-tetrahydro-9-methyl-3-[(2- Methyl-1h-imidazol-1-yl)methyl]-, Monohydrochloride, (+/-)-, Dihydrate

76. 9-methyl-3-[(2-methyl-1h-imidazol-1-yl)methyl]-2,3,4,9-tetrahydro-1h-carbazol-4-one Dihydrate Hydrochloride

77. 9-methyl-3-[(2-methylimidazolyl)methyl]-1,2,3,9-tetrahydro-4ah-carbazol-4-one, Chloride, Hydrate, Hydrate

2.3 Create Date
2005-06-24
3 Chemical and Physical Properties
Molecular Weight 365.858 g/mol
Molecular Formula C18H24ClN3O3
Hydrogen Bond Donor Count3
Hydrogen Bond Acceptor Count4
Rotatable Bond Count2
Exact Mass365.151 g/mol
Monoisotopic Mass365.151 g/mol
Topological Polar Surface Area41.8 A^2
Heavy Atom Count25
Formal Charge0
Complexity440
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count1
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count4
4 Drug and Medication Information
4.1 Drug Information
1 of 1  
Drug NameZOFRAN
Active IngredientONDANSETRON HYDROCHLORIDE
CompanyNOVARTIS PHARMS CORP (Application Number: N020103); NOVARTIS PHARMS CORP (Application Number: N020605)

4.2 Therapeutic Uses

/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Ondansetron is included in the database.

NIH/NLM; ClinicalTrials.Gov. Available from, as of March 17, 2016: https://clinicaltrials.gov/ct2/results?term=Ondansetron&Search=Search


Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin ... . /Included in US product label/

NIH; DailyMed. Current Medication Information for Zofran (Ondansetron Hydrochloride) Solution; Zofran ODT (Ondansetron) Table, Orally Disintegrating; Zofran (Ondansetron Hydrochloride) Tablet, Film Coated (Updated: October 2014). Available from, as of January 20, 2016: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7d61d98-fe86-4340-9b86-47eb92acaa0e


Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy. /Included in US product label/

NIH; DailyMed. Current Medication Information for Zofran (Ondansetron Hydrochloride) Solution; Zofran ODT (Ondansetron) Table, Orally Disintegrating; Zofran (Ondansetron Hydrochloride) Tablet, Film Coated (Updated: October 2014). Available from, as of January 20, 2016: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7d61d98-fe86-4340-9b86-47eb92acaa0e


Prevention of nausea and vomiting associated with radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen. /Included in US product label/

NIH; DailyMed. Current Medication Information for Zofran (Ondansetron Hydrochloride) Solution; Zofran ODT (Ondansetron) Table, Orally Disintegrating; Zofran (Ondansetron Hydrochloride) Tablet, Film Coated (Updated: October 2014). Available from, as of January 20, 2016: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7d61d98-fe86-4340-9b86-47eb92acaa0e


Prevention of postoperative nausea and/or vomiting. As with other antiemetics, routine prophylaxis is not recommended for patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively. In patients where nausea and/or vomiting must be avoided postoperatively, Zofran Tablets, Zofran ODT Orally Disintegrating Tablets, and Zofran Oral Solution are recommended even where the incidence of postoperative nausea and/or vomiting is low. /Included in US product label/

NIH; DailyMed. Current Medication Information for Zofran (Ondansetron Hydrochloride) Solution; Zofran ODT (Ondansetron) Table, Orally Disintegrating; Zofran (Ondansetron Hydrochloride) Tablet, Film Coated (Updated: October 2014). Available from, as of January 20, 2016: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7d61d98-fe86-4340-9b86-47eb92acaa0e


MEDICATION (VET): Ondansetron is an antiemetic used for severe vomiting in dogs and cats. It can be particularly effective for treating chemotherapy associated-vomiting.

Plumb D.C. Veterinary Drug Handbook. 8th ed. (pocket). Ames, IA: Wiley-Blackwell, 2015., p. 1071


MEDICATION (VET): In dogs with canine parvovirus (CPV) enteritis ... ondansetron ... appears to be ... effective at controlling vomiting ... .

Kahn, C.M (ed.).; The Merck Veterinary Manual 10th Edition. Merck & Co. Whitehouse Station NJ. 2010, p. 347


4.3 Drug Warning

Because of the risk of QT-interval prolongation, ondansetron should be avoided in patients with congenital long QT syndrome. ECG monitoring is recommended in patients with electrolyte abnormalities such as hypokalemia or hypomagnesemia, congestive heart failure, or bradyarrhythmias and in those receiving other drugs known to prolong the QT interval. Electrolyte abnormalities should be corrected prior to IV administration of ondansetron. Because effects of ondansetron on the QT interval are dose related, use of single IV doses exceeding 16 mg should be avoided. Patients receiving ondansetron should be advised to seek immediate medical care if feelings of faintness, lightheadedness, irregular heartbeat, shortness of breath, or dizziness occur.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2910


Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron, concomitant use of apomorphine with ondansetron is contraindicated

NIH; DailyMed. Current Medication Information for Zofran (Ondansetron Hydrochloride) Solution; Zofran ODT (Ondansetron) Table, Orally Disintegrating; Zofran (Ondansetron Hydrochloride) Tablet, Film Coated (Updated: October 2014). Available from, as of January 21, 2016: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7d61d98-fe86-4340-9b86-47eb92acaa0e


Advise patients of the possibility of serotonin syndrome with concomitant use of Zofran and another serotonergic agent such as medications to treat depression and migraines. Advise patients to seek immediate medical attention if the following symptoms occur: changes in mental status, autonomic instability, neuromuscular symptoms with or without gastrointestinal symptoms.

NIH; DailyMed. Current Medication Information for Zofran (Ondansetron Hydrochloride) Solution; Zofran ODT (Ondansetron) Table, Orally Disintegrating; Zofran (Ondansetron Hydrochloride) Tablet, Film Coated (Updated: October 2014). Available from, as of January 21, 2016: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7d61d98-fe86-4340-9b86-47eb92acaa0e


Seizures (including tonic-clonic seizures) have been reported rarely in patients receiving ondansetron.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2909


Restlessness, akathisia, ataxia, lightheadedness, and insomnia have been reported rarely with IV ondansetron. Lightheadedness was reported mainly during IV infusion of ondansetron and resolved rapidly. Panic attacks also have been reported rarely.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2909


Although extrapyramidal reactions were not reported with ondansetron in clinical trials comparing the drug with metoclopramide, manifestations consistent with, but not necessarily diagnostic of, such reactions have been reported rarely in patients receiving ondansetron. Oculogyric crisis, appearing alone, as well as other dystonic reactions, have been reported during postmarketing experience in patients receiving IV ondansetron.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2909


Dizziness has been reported in 7% of patients receiving ondansetron orally in recommended dosages for prevention of postoperative nausea and vomiting in controlled clinical trials. Dizziness has occurred occasionally in patients receiving the drug IV (mainly during or shortly after IV infusion) and in 4-5% of patients receiving ondansetron orally for prevention of chemotherapy-induced nausea and vomiting; however, a direct causal relationship to the drug has not been established. Although not directly attributed to the drug, other adverse nervous system effects reported include drowsiness or sedation, which occurred in 8%,1 and paresthesia, which occurred in 2%, of patients receiving the drug IV in the recommended dosage for prevention of postoperative nausea and vomiting; these effects also occurred occasionally in patients receiving the drug orally or IV for prevention of chemotherapy-induced nausea and vomiting. Drowsiness/sedation occurred in 20%, and anxiety/agitation in 6%, of patients receiving oral ondansetron for prevention of postoperative nausea and vomiting in clinical trials. Anxiety or agitation also has occurred in patients receiving the drug IV for prevention of postoperative nausea and vomiting.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2909


Headache is the most common adverse nervous system effect of ondansetron, occurring in 11-24% of patients receiving the drug orally or IV in recommended dosages for prevention of chemotherapy-induced nausea and vomiting and in 9-17% of those receiving the drug for postoperative nausea and vomiting in controlled clinical trials; headache occurred in 5% of patients receiving ondansetron for radiation-induced nausea and vomiting. Preliminary observations in a small number of patients suggest that headache occurs more frequently when ondansetron orally disintegrating tablets are taken with water as compared to ingestion without water. Headache generally is mild to moderate in severity and generally responds to mild analgesics. While some evidence suggests that the incidence of headache may be dose related, other evidence failed to establish a clear relationship, particularly regarding severity. Migraine headache has been reported rarely with oral or IV ondansetron.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2909


In clinical trials in patients receiving ondansetron for the prevention of postoperative nausea and vomiting, the incidences of adverse effects associated with ondansetron, with the exception of headache, did not differ substantially from those associated with placebo. Most such patients were receiving concomitantly multiple preoperative and postoperative drugs. Studies of oral ondansetron for the prevention of postoperative nausea and vomiting to date have included only women undergoing inpatient surgical procedures; no studies have been performed in males.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2909


The adverse effect profile of ondansetron in patients receiving the drug for the prevention of radiation-induced nausea and vomiting is similar to that in patients receiving the drug for the prevention of chemotherapy-induced nausea and vomiting, although specific incidences of effects may vary; the most common adverse effects of the drug in patients undergoing radiation were headache, constipation, and diarrhea.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2909


Diarrhea is the most common adverse GI effect of ondansetron, occurring in 16% of patients receiving the drug IV in recommended dosages for prevention of chemotherapy-induced nausea and vomiting in controlled clinical trials and in 4-6% of patients receiving the drug orally in recommended dosages. Because most patients receiving ondansetron IV for chemotherapy-induced nausea and vomiting were receiving cisplatin concomitantly, which can cause diarrhea, a causal relationship to ondansetron has not been established. Constipation occurred in 3% of ondansetron-treated patients receiving single-day IV therapy, but is more common in patients receiving multiple-day therapy, occurring in 11% of patients receiving multiple-day IV therapy and in 6-9% of patients receiving multiple-day oral therapy in the recommended dosage for chemotherapy-induced nausea and vomiting. The incidence of constipation may be dose related. Dyspepsia or heartburn, thirst, flatulence, abdominal cramps, abdominal pain, abnormal taste, anorexia, xerostomia, and intestinal obstruction also have been reported with oral or IV ondansetron for prevention of chemotherapy-induced nausea and vomiting.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2909


Ondansetron generally is well tolerated. Most adverse effects reported in clinical trials have been mild to moderate in severity. Adverse effects rarely have resulted in discontinuance of the drug. The most frequent adverse effects of ondansetron in patients receiving the drug for the prevention of chemotherapy-induced nausea and vomiting involve the nervous system (e.g., headache) and GI tract (e.g., diarrhea, constipation). Because most patients receiving ondansetron in clinical trials for chemotherapy-induced nausea and vomiting had serious underlying disease (e.g., cancer) and were receiving toxic drugs (e.g., cisplatin), diuretics, and IV fluids concomitantly, it may be difficult to attribute various adverse effects to ondansetron. In trials comparing ondansetron and metoclopramide, adverse effects occurring substantially more frequently for one drug compared with the other included headache and constipation for ondansetron and diarrhea and extrapyramidal/dystonic manifestations for metoclopramide; adverse effects resulting in drug discontinuance were less common with ondansetron.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2909


Increased serum concentrations of ALT (SGPT) and AST (SGOT) exceeding twice the upper limit of normal have been reported in approximately 1-2% of patients receiving ondansetron orally for prevention of chemotherapy-induced nausea and vomiting, in approximately 5% of patients receiving the drug IV for prevention of chemotherapy-induced nausea and vomiting, and in approximately 1% of patients receiving the drug IV for prevention of postoperative nausea and vomiting. The increases were transient and appeared to be unrelated to dose or duration of ondansetron therapy; however, similar transient increases recurred in some courses of therapy with repeat exposure to the drug, but symptomatic hepatic disease did not occur. In patients with cancer, the role of cancer chemotherapy in these increases cannot be clearly determined. Hepatosplenomegaly, jaundice, and increased serum concentrations of bilirubin and gammaglutamyltransferase (GGT, gamma-glutamyltranspeptidase, GGTP) also have been reported rarely.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2909


Liver failure and death have been reported rarely in patients with cancer receiving ondansetron concomitantly with other drugs, including potentially hepatotoxic cytotoxic chemotherapy and antibiotics; the etiology of the liver failure is unclear.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2909


Although a definite causal relationship to ondansetron has not been established, hypokalemia has been reported rarely in patients receiving the drug orally or IV for prevention of cancer chemotherapy-induced nausea and vomiting.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2910


Cold sensation occurred in 2% of patients receiving ondansetron IV for prevention of postoperative nausea and vomiting in controlled clinical trials, although a causal relationship has not been established. Urinary retention has occurred in 5%, and gynecologic disorder in 7%, of patients receiving oral ondansetron for prevention of postoperative nausea and vomiting. Sensation of cold has been reported in patients receiving ondansetron IV for prevention of chemotherapy-induced nausea and vomiting; sensation of warmth also has been reported rarely with IV ondansetron therapy. Musculoskeletal pain has been reported in patients receiving IV ondansetron. Hypoxia has been reported in 9% of those receiving the drug orally for postoperative nausea and vomiting. Dyspnea, hypoxia, and hiccups also have been reported with ondansetron.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2910


Injection site reactions (including pain, erythema, swelling, and burning) occurred in 4% of patients receiving ondansetron IV for prevention of postoperative nausea and vomiting and occasionally in patients receiving the drug IV for prevention of chemotherapy-induced nausea and vomiting in controlled clinical trials. Wound problems were reported in 28% of patients receiving ondansetron orally for postoperative nausea and vomiting in controlled trials. Throat problems and hemorrhage also have been reported in patients receiving ondansetron orally or IV for prevention of postoperative nausea and vomiting.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2910


Fever occurred in 8% of patients receiving ondansetron IV for prevention of chemotherapy-induced nausea and vomiting and in 2% of patients receiving the drug IV for prevention of postoperative nausea and vomiting in controlled clinical trials. Malaise or fatigue was reported in 9-13% and weakness was reported in up to 2% of patients receiving ondansetron orally for prevention of chemotherapy-induced nausea and vomiting. Pyrexia was reported in 8% of patients receiving oral ondansetron for prevention of postoperative nausea and vomiting in controlled trials. Shivers have been reported in 5% of patients receiving ondansetron orally for prevention of postoperative nausea and vomiting in controlled clinical trials, and occasionally in patients receiving the drug orally for prevention of chemotherapy-induced nausea and vomiting. However, these effects have not been directly attributed to the drug. Sweating also has been reported rarely with IV ondansetron.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2910


Transient blurred vision, occasionally associated with abnormalities of accommodation, has been reported rarely in patients during or shortly after IV infusion of ondansetron. This adverse effect may be ameliorated with a slower infusion rate or following discontinuance of the infusion. Transient blindness, which resolved within a few minutes to 48 hours, also has been reported, generally during IV administration of the drug.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2910


Angina (chest pain), hypotension, flushing, tachycardia, ECG alterations (including arrhythmias34 and prolongation of PR, QRS, and QT intervals), and vascular occlusive events (e.g., myocardial infarction, cerebrovascular accident, pulmonary embolism, deep-vein thrombosis) have been reported rarely during clinical trials or postmarketing experience in patients receiving ondansetron orally or IV for prevention of chemotherapy-induced nausea and vomiting; a definite causal relationship to the drug has not been established. Arrhythmias (including ventricular and supraventricular tachycardia, premature ventricular complexes, and atrial fibrillation), bradycardia, ECG alterations (including second-degree heart block and ST-segment depression), hypertension, syncope, and palpitations have been reported in patients receiving IV ondansetron, although these effects have not been directly attributed to the drug. Transient ECG alterations including QT-interval prolongation have been reported rarely, mainly in patients receiving the drug IV; cases of torsades de pointes have been reported during postmarketing experience in patients receiving ondansetron. Bradycardia also was reported in 6% of patients receiving oral ondansetron in clinical trials for prevention of postoperative nausea and vomiting.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2909-10


Hypotension has occurred in 5% of patients receiving oral ondansetron for prevention of postoperative nausea and vomiting. Unspecified chest pain and hypotension have been reported in patients receiving ondansetron IV for prevention of postoperative nausea and vomiting in controlled clinical trials, but these effects have not been directly attributed to the drug.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2909


Prolongation of the QT interval and cases of torsades de pointes have been reported in patients receiving ondansetron. Preliminary results of a randomized, double-blind, placebo- and active-controlled crossover study conducted in healthy adults to assess the drug's effects on the QT interval indicate that ondansetron prolongs the QT interval in a dose-dependent manner. Following IV infusion of ondansetron 8 or 32 mg over 15 minutes, the maximum mean baseline-corrected increase in the QTc interval (QT interval corrected for heart rate using Fridericia's formula) relative to placebo was 5.8 or 19.6 milliseconds, respectively. Other studies in postoperative patients or healthy individuals also suggest that ondansetron can prolong the QT interval. Based on these findings, an antiemetic regimen consisting of a single IV ondansetron dose of 32 mg given prior to emetogenic cancer chemotherapy no longer is recommended. Individual IV doses of the drug should not exceed 16 mg.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2909


Serious hypersensitivity reactions have occurred in patients receiving ondansetron orally or IV. In patients with cancer, these reactions have been reported to occur mainly following the first dose during the second or third course of cancer chemotherapy. These reactions may include anaphylaxis/anaphylactoid reactions, angioedema, bronchospasm, cardiopulmonary arrest, hypotension, laryngeal edema, laryngospasm, shock, shortness of breath, stridor, wheezing, facial edema, and urticaria. Sensitivity reactions also have been reported in patients who have exhibited sensitivity to other selective 5-HT3-receptor antagonists. If a hypersensitivity reaction occurs during ondansetron therapy, the drug should be discontinued, and severe acute hypersensitivity reactions should be treated with appropriate therapy (e.g., epinephrine, corticosteroids, maintenance of an adequate airway, oxygen, IV fluids, antihistamines, maintenance of blood pressure) as indicated.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2909


Pruritus has been reported in 2% of patients receiving ondansetron IV and in 5% of those receiving the drug orally for prevention of postoperative nausea and vomiting in controlled clinical trials. Rash, which may be maculopapular and/or accompanied by pruritus, has occurred in approximately 1% of patients receiving the drug orally or IV for prevention of chemotherapy-induced nausea and vomiting in controlled clinical trials. Rarely, rash may be followed by desquamation and hyperpigmentation.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2909


Because clearance of ondansetron is decreased and apparent volume of distribution and plasma half-life are increased in patients with severe hepatic impairment, the drug should be used with caution and at reduced dosage in such patients.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2910


The manufacturer states that little information is available on IV use of ondansetron for the prevention of postoperative nausea and vomiting in pediatric patients younger than 1 month of age or for the prevention of cancer chemotherapy-induced nausea and vomiting in pediatric patients younger than 6 months of age. Little information is available on oral dosage of ondansetron in pediatric patients 4 years of age or younger. Efficacy of the single 24-mg oral dose of ondansetron for the prevention of nausea and vomiting induced by highly emetogenic cancer chemotherapy in pediatric patients younger than 18 years of age has not been established. Efficacy of oral ondansetron for prevention of radiation-induced and postoperative nausea and vomiting in pediatric patients younger than 18 years of age has not been established. In prevention of cancer chemotherapy-induced emesis, safety and efficacy of the drug orally and IV generally are comparable to that observed in older children and adults. In placebo-controlled trials evaluating IV ondansetron for prevention of postoperative nausea and vomiting in pediatric patients, adverse effects occurred at similar frequencies in pediatric patients receiving recommended dosages of ondansetron and those receiving placebo; however, among pediatric patients 1-24 months of age, diarrhea occurred more frequently in those receiving ondansetron compared with those receiving placebo (2 versus less than 1%). Pediatric cancer or surgical patients younger than 18 years of age generally tend to have higher clearances and shorter half-lives of ondansetron compared with adults. However, in infants 1-4 months of age, clearance of the drug is reduced and half-life is prolonged (by approximately 2.5-fold relative to values in infants older than 4 months up to 24 months of age); thus, the manufacturer recommends that infants younger than 4 months of age receiving ondansetron therapy be closely monitored.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2910


While safety and efficacy of ondansetron have not been established specifically in geriatric patients, a large proportion of patients treated with the drug for chemotherapy-induced nausea and vomiting and prevention of postoperative nausea and/or vomiting have been 65 years of age or older. Plasma clearance of ondansetron may be decreased and elimination half-life increased in patients older than 75 years of age. In clinical studies with ondansetron that included patients 65 years of age and older, no overall differences in efficacy or safety were observed between patients in this age group and younger patients. However, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2910


It is not known whether ondansetron is distributed into human milk; however, the drug is distributed into the milk of lactating rats. Because many drugs are distributed in human milk, ondansetron should be used with caution in nursing women.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2910


There are no adequate and controlled studies to date using ondansetron in pregnant women, and the drug should be used during pregnancy only when clearly needed.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2910


Individuals with phenylketonuria (i.e., homozygous genetic deficiency of phenylalanine hydroxylase) and other individuals who must restrict their intake of phenylalanine should be warned that each 4- and 8-mg Zofran ODT orally disintegrating tablet contains aspartame, which is metabolized in the GI tract to provide less than 0.03 mg of phenylalanine following oral administration.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2910


Because ondansetron does not stimulate gastric or intestinal peristalsis, it should not be used as a substitute for nasogastric suction.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2910


Like other antiemetics, ondansetron may mask a progressive ileus and/or gastric distention in patients undergoing abdominal surgery or in patients with chemotherapy-induced nausea and vomiting.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2910


5 Pharmacology and Biochemistry
5.1 MeSH Pharmacological Classification

Serotonin Antagonists

Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.


Antipsychotic Agents

Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus.


Anti-Anxiety Agents

Agents that alleviate ANXIETY, tension, and ANXIETY DISORDERS, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. ADRENERGIC BETA-ANTAGONISTS are commonly used in the symptomatic treatment of anxiety but are not included here.


Antiemetics

Drugs used to prevent NAUSEA or VOMITING.


Antipruritics

Agents, usually topical, that relieve itching (pruritus).


5.2 Absorption, Distribution and Excretion

Ondansetron is a 5-HT3 receptor antagonist that is an effective anti-emetic in cats. The purpose of this study was to evaluate the pharmacokinetics of ondansetron in healthy cats. Six cats with normal complete blood count, serum biochemistry, and urinalysis received 2 mg oral (mean 0.43 mg/kg), subcutaneous (mean 0.4 mg/kg), and intravenous (mean 0.4 mg/kg) ondansetron in a cross-over manner with a 5-day wash out. Serum was collected prior to, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18, and 24 hr after administration of ondansetron. Ondansetron concentrations were measured using liquid chromatography coupled to tandem mass spectrometry. Noncompartmental pharmacokinetic modeling and dose interval modeling were performed. Repeated measures anova was used to compare parameters between administration routes. Bioavailability of ondansetron was 32% (oral) and 75% (subcutaneous). Calculated elimination half-life of ondansetron was 1.84 + or - 0.58 hr (intravenous), 1.18 + or - 0.27 hr (oral) and 3.17 + or - 0.53 hr (subcutaneous). The calculated elimination half-life of subcutaneous ondansetron was significantly longer (P < 0.05) than oral or intravenous administration. Subcutaneous administration of ondansetron to healthy cats is more bioavailable and results in a more prolonged exposure than oral administration. This information will aid management of emesis in feline patients.[Quimby JM et al; J Vet Pharmacol Ther 37 (4): 348-53 (2014)] Full text: PMC4059788


Nausea and vomiting are some of the major side effects caused by certain drug therapies, e.g. chemotherapy, radiotherapy and general anesthesia. Because of the nature of the symptoms, oral delivery is inappropriate, while intravenous administration may be unpractical. The aim of the present study was to develop a transdermal gel (2% Klucel) for ondansetron, a first line 5-HT3-receptor-antagonist antiemetic. The effects of the penetration enhancer camphor and isopropyl-myristate (IPM) were first investigated in-vitro using modified Franz diffusion-cells and then tested in-vivo in a rabbit model by measuring skin and plasma concentrations. Since a disadvantage of transdermal delivery is a prolonged lag-time, the effect of skin treatment with a micro-needle roller was tested. The in-vitro permeation studies through excised porcine ear skin showed that the presence of 2.5% camphor or IPM increased steady state flux by 1.2- and 2.5-fold, respectively, compared to the control gel. Ondansetron was not detectable in either skin or plasma following in-vivo application of the base-gel, whereas the camphor gel and IPM gel delivered 20 and 81 ug/sq cm of ondansetron, respectively. Microporation led to an increase in plasma Cmax and AUC by 10.47 + or - 1.68-fold and 9.31 + or - 4.91-fold, respectively, for the camphor gel, and by 2.31 + or -0.53-fold and 1.59 + or - 0.38-fold, respectively for the IPM gel. In conclusion, the 2.5% IPM gel demonstrated optimal in-vivo transdermal flux. Skin pretreatment with a micro-needle roller slightly improved the delivery of the IPM gel, whereas dramatically increased the transdermal delivery of the camphor gel.

Patel DR et al; Drug Dev Ind Pharm 41 (6): 1030-6 (2015)


Ondansetron is a potent antiemetic drug that has been commonly used to treat acute and chemotherapy-induced nausea and vomiting (CINV) in dogs. The aim of this study was to perform a pharmacokinetic analysis of ondansetron in dogs following oral administration of a single dose. A single 8-mg oral dose of ondansetron was administered to beagles (n = 18), and the plasma concentrations of ondansetron were measured by liquid chromatography-tandem mass spectrometry. The data were analyzed by modeling approaches using ADAPT5, and model discrimination was determined by the likelihood-ratio test. The peak plasma concentration (Cmax ) was 11.5 +/- 10.0 ng/mL at 1.1 +/- 0.8 hr. The area under the plasma concentration vs. time curve from time zero to the last measurable concentration was 15.9 +/- 14.7 ng hr/mL, and the half-life calculated from the terminal phase was 1.3 +/- 0.7 hr. The interindividual variability of the pharmacokinetic parameters was high (coefficient of variation > 44.1%), and the one-compartment model described the pharmacokinetics of ondansetron well. The estimated plasma concentration range of the usual empirical dose from the Monte Carlo simulation was 0.1-13.2 ng/mL. These findings will facilitate determination of the optimal dose regimen for dogs with CINV.

Baek IH et al; J Vet Pharmacol Ther 38 (2): 199-202 (2015)


Ondansetron is the drug of choice to prevent nausea in women undergoing cesarean surgery and can be used to prevent neonatal abstinence syndrome (NAS). The pharmacokinetics of ondansetron have not been characterized in pregnant women or in newborns. A nonlinear mixed-effects modeling approach was used to analyze plasma samples obtained from 20 nonpregnant and 40 pregnant women following a single administration of 4 or 8 mg ondansetron, from umbilical cord blood at delivery, and from neonates after birth. The analysis indicates that: ondansetron disposition is not affected by pregnancy (P > 0.05), but influenced by dose (P < 0.05), and is characterized by rapid transplacental transfer and longer elimination half-life in neonates compared to their mother. A dosing regimen for prevention of NAS was designed based on the model. The regimen involves IV administration of 4 mg to the mothers shortly before cord clamping, or oral administration of 0.07 mg/kg (or equivalently 0.04 mg/kg IV) to neonates.[Elkomy MH et al; Clin Pharmacol Ther 97 (2): 167-76 (2015)] Full text: PMC4325425


Ondansetron, a 5-HT3 receptor antagonist, is an effective anti-emetic in cats. The purpose of this study was to compare pharmacokinetics of subcutaneous (SQ) ondansetron in healthy geriatric cats to cats with chronic kidney disease (CKD) or liver disease using a limited sampling strategy. 60 cats participated; 20 per group. Blood was drawn 30 and 120 min following one 2 mg (mean 0.49 mg/kg, range 0.27-1.05 mg/kg) SQ dose of ondansetron. Ondansetron concentrations were measured by liquid chromatography coupled to tandem mass spectrometry. Drug exposure represented as area under the curve (AUC) was predicted using a limited sampling approach based on multiple linear regression analysis from previous full sampling studies, and clearance (CL/F) estimated using noncompartmental methods. Kruskal-Wallis anova was used to compare parameters between groups. Mean AUC (ng/mL hr) of subcutaneous ondansetron was 301.4 (geriatric), 415.2 (CKD), and 587.0 (liver). CL/F (L/hr/kg) of SQ ondansetron was 1.157 (geriatric), 0.967 (CKD), and 0.795 (liver). AUC was significantly higher in liver and CKD cats when compared to geriatric cats (P < 0.05). CL/F in liver cats was significantly decreased (P < 0.05) compared to geriatric cats. In age-matched subset analysis, AUC and CL/F in liver cats remained significantly different from geriatric cats.[Fitzpatrick RL et al; J Vet Pharmacol Ther. 2015 Dec 14. doi: 10.1111/jvp.12286.

Epub ahead of print]


/MILK/ It is not known whether ondansetron is distributed into human milk; however, the drug is distributed into the milk of lactating rats.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2910


Ondansetron is well absorbed from the gastrointestinal tract and undergoes some first-pass metabolism. Mean bioavailability in healthy subjects, following administration of a single 8-mg tablet, is approximately 56%.

NIH; DailyMed. Current Medication Information for Zofran (Ondansetron Hydrochloride) Solution; Zofran ODT (Ondansetron) Table, Orally Disintegrating; Zofran (Ondansetron Hydrochloride) Tablet, Film Coated (Updated: October 2014). Available from, as of January 26, 2016: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7d61d98-fe86-4340-9b86-47eb92acaa0e


Nausea and vomiting are common conditions that occur during early pregnancy and can be disabling. Ondansetron had been used in pregnant women when treatment with conventional antiemetics has failed; however, the safety and tolerability of this relatively new antiemetic drug during pregnancy is still uncertain. The objective of this study was to quantify the placental transfer of ondansetron in the first trimester of human pregnancy. This was a prospective, observational study. Forty-one patients who requested surgical termination of pregnancy at the first trimester were administered three doses of ondansetron 8 mg before surgery. Maternal venous blood, coelomic fluid, amniotic fluid and fetal tissue were collected from each patient for analysis of ondansetron by liquid chromatography-mass spectometry. Ondansetron was found in all samples. Drug concentration in fetal tissue was significantly higher than that in the amniotic fluid and similar to that in the coelomic fluid. The median (interquartile range) fetal/maternal ratio was 0.41 (0.31-0.52) and there were no significant correlations between ondansetron concentrations in each compartment and gestational age. A significant amount of ondansetron was present in all embryonic compartments. The developmental significance of this drug exposure requires further investigation, i.e. whole embryo culture.

Siu SS et al; Clin Pharmacokinet 45 (4): 419-23 (2006)


5.3 Metabolism/Metabolites

Ondansetron is extensively metabolized in humans, with approximately 5% of a radiolabeled dose recovered as the parent compound from the urine. The primary metabolic pathway is hydroxylation on the indole ring followed by subsequent glucuronide or sulfate conjugation. Although some nonconjugated metabolites have pharmacologic activity, these are not found in plasma at concentrations likely to significantly contribute to the biological activity of ondansetron.

NIH; DailyMed. Current Medication Information for Zofran (Ondansetron Hydrochloride) Solution; Zofran ODT (Ondansetron) Table, Orally Disintegrating; Zofran (Ondansetron Hydrochloride) Tablet, Film Coated (Updated: October 2014). Available from, as of January 26, 2016: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7d61d98-fe86-4340-9b86-47eb92acaa0e


5.4 Biological Half-Life

In humans ... elimination half lives are approximately 3-4 hours, but are prolonged in elderly patients.

Plumb D.C. Veterinary Drug Handbook. 8th ed. (pocket). Ames, IA: Wiley-Blackwell, 2015., p. 1071


... Six cats with normal complete blood count, serum biochemistry, and urinalysis received 2 mg oral (mean 0.43 mg/kg), subcutaneous (mean 0.4 mg/kg), and intravenous (mean 0.4 mg/kg) ondansetron in a cross-over manner with a 5-day wash out. Serum was collected prior to, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18, and 24 hr after administration of ondansetron. ... Calculated elimination half-life of ondansetron was 1.84 + or - 0.58 hr (intravenous), 1.18 + or - 0.27 hr (oral) and 3.17 + or - 0.53 hr (subcutaneous). The calculated elimination half-life of subcutaneous ondansetron was significantly longer (P < 0.05) than oral or intravenous administration. ...[Quimby JM et al; J Vet Pharmacol Ther 37 (4): 348-53 (2014)] Full text: PMC4059788


... A single 8-mg oral dose of ondansetron was administered to beagles (n = 18), ... and the half-life calculated from the terminal phase was 1.3 +/- 0.7 hr. ...

Baek IH et al; J Vet Pharmacol Ther 38 (2): 199-202 (2015)


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