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PRESCRIBING INFORMATIONONDANSETRON INJECTION USP


DESCRIPTION

The active ingredient in Ondansetron Injection is ondansetron hydrochloride (HCl), the racemic form of ondansetron and a selective blocking agent of the serotonin 5-HT3 receptor type. Chemically it is (±) 1, 2, 3, 9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one, monohydrochloride, dihydrate. It has the following structural formula:

The empirical formula is C18H19N3O•HCl•2H2O, representing a molecular weight of 365.9. Ondansetron HCl is a white to off-white powder that is soluble in water and normal saline. Sterile Injection for Intravenous (I.V.) or Intramuscular (I.M.) Administration: Each 1 mL of aqueous solution in the 2-mL single-dose vial contains 2 mg of ondansetron as the hydrochloride dihydrate; 9 mg of sodium chloride, USP; and 0.5 mg of citric acid monohydrate, USP and 0.25 mg of sodium citrate dihydrate, USP as buffers in Water for Injection, USP.Each 1 mL of aqueous solution in the 20-mL multidose vial contains 2 mg of ondansetron as the hydrochloride dihydrate; 8.3 mg of sodium chloride, USP; 0.5 mg of citric acid monohydrate, USP and 0.25 mg of sodium citrate dihydrate, USP as buffers; and 1.2 mg of methylparaben, NF and 0.15 mg of propylparaben, NF as preservatives in Water for Injection, USP.Ondansetron Injection is a clear, colorless, nonpyrogenic, sterile solution. The pH of the injection solution is 3.3 to 4.0.


CLINICAL PHARMACOLOGY

Age-group (years)nPeak PlasmaConcentration(ng/mL)Mean EliminationHalf-life (h)Plasma Clearance(L/h/kg)
19-40111023.50.381
61-74121064.70.319
≥75111705.50.262
 Subjects and Age Group NCL(L/h/kg)Vdss(L/kg)T½(h)
Geometric MeanMean
Pediatric Cancer Patients4 to 18 years of ageN = 210.5991.92.8
Population PK Patientsa1 month to 48 months of ageN = 1150.5823.654.9
Subjects and Age GroupNCL(L/h/kg)Vdss(L/kg)T½(h)
Geometric MeanMean
Pediatric Surgery Patients3 to 12 years of AgeN = 210.4391.652.9
Pediatric Surgery Patients5 to 24 months of AgeN = 220.5812.32.9
Pediatric Surgery Patients1 month to 4 months of AgeN = 190.4013.56.7

CLINICAL TRIALS

Ondansetron InjectionPlaceboP Value†
Number of patients1414
Treatment response
     0 Emetic episodes2 (14%)0 (0%)
     1-2 Emetic episodes8 (57%)0 (0%)
     3-5 Emetic episodes2 (14%)1 (7%)
     More than 5 emetic episodes/rescued2 (14%)13 (93%)0.001
Median number of emetic episodes1.5Undefined‡
Median time to first emetic episode (h)11.62.80.001
Median nausea scores (0-100)§3590.034
Global satisfaction with control of nausea and vomiting (0-100)II9610.50.009
  Ondansetron InjectionMetoclopramideP Value
Dose0.15 mg/kg x 32 mg/kg x 6 
Number of patients in efficacy population136138
Treatment response
     0 Emetic episodes54 (40%)41 (30%)
     1-2 Emetic episodes34 (25%)30 (22%)
     3-5 Emetic episodes19 (14%)18 (13%)
     More than 5 emetic episodes/rescued29 (21%)49 (36%)
Comparison of treatments with respect to
     0 Emetic episodes54/13641/1380.083
     More than 5 emetic episodes/rescued29/13649/1380.009
Median number of emetic episodes120.005
Median time to first emetic episode (h)20.54.3<0.001
Global satisfaction with control of nausea and vomiting (0-100)†85630.001
Acute dystonic reactions080.005
Akathisia0100.002
  Ondansetron Dose 
0.15 mg/kg x 332 mg x 1P Value
High-dose cisplatin (≥100 mg/m2)
Number of patients100102
Treatment response
     0 Emetic episodes41 (41%)49 (48%)0.315
     1-2 Emetic episodes19 (19%)25 (25%)
     3-5 Emetic episodes4 (4%)8 (8%)
     More than 5 emetic episodes/rescued36 (36%)20 (20%)0.009
Median time to first emetic episode (h)21.7230.173
Median nausea scores (0-100)*28130.004
Medium-dose cisplatin (50-70 mg/m2)
Number of patients10193
Treatment response
     0 Emetic episodes62 (61%)68 (73%)0.083
     1-2 Emetic episodes11 (11%)14 (15%)
     3-5 Emetic episodes6 (6%)3 (3%)
     More than 5 emetic episodes/rescued22 (22%)8 (9%)0.011
Median time to first emetic episode (h)Undefined†Undefined
Median nausea scores (0-100)*930.131
  Ondansetron InjectionPlaceboP Value†
Number of patients 1010
Treatment response
      0 Emetic episodes7 (70%)0 (0%)0.001
      1-2 Emetic episodes 0 (0%)2 (20%)
      3-5 Emetic episodes 2 (20%)4 (40%)
     More than 5 emetic episodes/rescued1 (10%)4 (40%)0.131
Median number of emetic episodes040.008
Median time to first emetic episode (h)Undefined‡8.79
Median nausea scores (0-100)§0600.001
Global satisfaction with control of nausea and vomiting (0-100)II100520.008
 Ondansetron 4 mg I.V.PlaceboP Value
Study 1
Emetic episodes:
Number of patients136139
Treatment response over 24-h postoperative period
      0 Emetic episodes103 (76%)64 (46%)<0.001
      1 Emetic episode13 (10%)17 (12%)
      More than 1 emetic episode/rescued20 (15%)58 (42%)
Nausea assessments:
Number of patients134136
No nausea over 24-h postoperative period56 (42%)39 (29%)
Study 2
Emetic episodes:
Number of patients136143
Treatment response over 24-h postoperative period
      0 Emetic episodes85 (63%)63 (44%)0.002
     1 Emetic episode 16 (12%)29 (20%)
      More than 1 emetic episode/rescued35 (26%)51 (36%)
Nausea assessments:
Number of patients125133
No nausea over 24-h postoperative period48 (38%)42 (32%)
Treatment ResponseOver 24 HoursOndansetronn (%) Placebon (%) P Value
Study 1
Number of patients 205210
0 Emetic episodes 140 (68%)82 (39%)≤0.001
Failure*65 (32%) 128 (61%)
Study 2
Number of patients 112110
0 Emetic episodes 68 (61%) 38 (35%) ≤0.001
Failure*44 (39%)72 (65%)
Study 3
Number of patients206206
0 Emetic episodes123 (60%)96 (47%)≤0.01
Failure*83 (40%)110 (53%)
Nausea assessments†:
Number of patients185191
None119 (64%)99 (52%)≤0.01
 Ondansetron 4 mg I.V.PlaceboP Value
Study 1
Emetic episodes:
Number of patients104117
Treatment response 24 h after study drug
      0 Emetic episodes49 (47%)19 (16%)<0.001
      1 Emetic episode12 (12%)9 (8%)
      More than 1 emetic episode/rescued43 (41%)89 (76%)
Median time to first emetic episode (min)*55.043.0
Nausea assessments:
Number of patients98102
Mean nausea score over 24-hpostoperative period†1.73.1
Study 2
Emetic episodes:
Number of patients112108
Treatment response 24 h after study drug
      0 Emetic episodes49 (44%)28 (26%)0.006
      1 Emetic episode14 (13%)3 (3%)
      More than 1 emetic episode/rescued49 (44%)77 (71%)
Median time to first emetic episode (min)*60.534.0
Nausea assessments:
Number of patients10585
Mean nausea score over 24-hpostoperative period†1.92.9
Treatment ResponseOver 24 Hours Ondansetron n (%) Placebon (%) P Value
Number of patients180171
0 Emetic episodes96 (53%)29 (17%)≤0.001
Failure*84 (47%)142 (83%)

INDICATIONS AND USAGE

  • Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including high-dose cisplatin. Efficacy of the 32-mg single dose beyond 24 hours in these patients has not been established.
  • 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, ondansetron injection is recommended even where the incidence of postoperative nausea and/or vomiting is low. For patients who do not receive prophylactic ondansetron injection and experience nausea and/or vomiting postoperatively, ondansetron injection may be given to prevent further episodes (see CLINICAL TRIALS).

CONTRAINDICATIONS


WARNINGS


PRECAUTIONS


ADVERSE REACTIONS

Number of Adult Patients With Event
Ondansetron Injection0.15 mg/kg x 3n = 419Ondansetron Injection32 mg x 1n = 220 Metoclopramiden = 156 Placebon = 34
Diarrhea16%8%44%18%
Headache17%25%7%15%
Fever8%7%5%3%
Akathisia0%0%6%0%
Acute dystonic reactions*0%0%5%0%
Ondansetron Injection4 mg I.V.n = 547 patients Placebon = 547 patients
Headache92 (17%)77 (14%)
Dizziness67 (12%)88 (16%)
Musculoskeletal pain57 (10%)59 (11%)
Drowsiness/sedation44 (8%)37 (7%)
Shivers38 (7%)39 (7%)
Malaise/fatigue25 (5%)30 (5%)
Injection site reaction21 (4%)18 (3%)
Urinary retention17 (3%)15 (3%)
Postoperative CO2-related pain*12 (2%)16 (3%)
Chest pain (unspecified)12 (2%)15 (3%)
Anxiety/agitation11 (2%)16 (3%)
Dysuria11 (2%)9 (2%)
Hypotension10 (2%)12 (2%)
Fever10 (2%)6 (1%)
Cold sensation9 (2%)8 (1%)
Pruritus9 (2%)3 (<1%)
Paresthesia9 (2%)2 (<1%)
 Adverse EventOndansetronn = 755 PatientsPlacebon = 731 Patients
Wound problem80 (11%)86 (12%)
Anxiety/agitation49 (6%)47 (6%)
Headache44 (6%)43 (6%)
Drowsiness/sedation41 (5%)56 (8%)
Pyrexia32 (4%)41 (6%)
 Adverse EventOndansetronn = 336 PatientsPlacebon = 334 Patients
Pyrexia14 (4%)14 (4%)
Bronchospasm2 (< 1%)6 (2%)
Post-procedural pain4 (1%)6 (2%)
Diarrhea6 (2%)3 (< 1%)

DRUG ABUSE AND DEPENDENCE


OVERDOSAGE


DOSAGE AND ADMINISTRATION


HOW SUPPLIED

  • Britto MR, Hussey EK, Mydlow P, et al. Effect of enzyme inducers on ondansetron (OND) metabolism in humans. Clin Pharmacol Ther. 1997;61:228.
  • Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Brit J Surg. 1973;60:646-649.
  • Villikka K, Kivisto KT, Neuvonen PJ. The effect of rifampin on the pharmacokinetics of oral and intravenous ondansetron. Clin Pharmacol Ther. 1999;65:377-381.
  • De Witte JL, Schoenmaekers B, Sessler DI, et al. Anesth Analg. 2001;92:1319-1321.
  • Arcioni R, della Rocca M, Romanò R, et al. Anesth Analg. 2002;94:1553-1557.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL