Pediatric Patients: Pharmacokinetic samples were collected from 74 cancer patients aged 6 to 48 months, who received a dose of 0.15 mg/kg of intravenous ondansetron every 4 hours for 3 doses during a safety and efficacy trial. These data were combined with sequential pharmacokinetics data from 41 surgery patients aged 1 month to 24 months, who received a single dose of 0.1 mg/kg of intravenous ondansetron prior to surgery with general anesthesia, and a population pharmacokinetic analysis was performed on the combined data set. The results of this analysis are included in Table 5 and are compared with the pharmacokinetic results in cancer patients aged 4 to 18 years.
Table 5. Pharmacokinetics in Pediatric Cancer Patients Aged 1 Month to 18 YearsSubjects and Age-group | N | CL (L/h/kg) | Vdss (L/kg) | t½ (h) |
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Geometric Mean | Mean |
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Pediatric Cancer Patients 4 to 18 years | N = 21 | 0.599 | 1.9 | 2.8 |
Population PK Patients* 1 month to 48 months | N = 115 | 0.582 | 3.65 | 4.9 |
Based on the population pharmacokinetic analysis, cancer patients aged 6 to 48 months who receive a dose of 0.15 mg/kg of intravenous ondansetron every 4 hours for 3 doses would be expected to achieve a systemic exposure (AUC) consistent with the exposure achieved in previous pediatric trials in cancer patients (4 to 18 years) at similar doses.
In a trial of 21 pediatric patients (3 to 12 years) who were undergoing surgery requiring anesthesia for a duration of 45 minutes to 2 hours, a single intravenous dose of ondansetron, 2 mg (3 to 7 years) or 4 mg (8 to 12 years), was administered immediately prior to anesthesia induction. Mean weight-normalized clearance and volume of distribution values in these pediatric surgical patients were similar to those previously reported for young adults. Mean terminal half-life was slightly reduced in pediatric patients (range, 2.5 to 3 hours) in comparison with adults (range, 3 to 3.5 hours).
In a trial of 51 pediatric patients (aged 1 month to 24 months) who were undergoing surgery requiring general anesthesia, a single intravenous dose of ondansetron, 0.1 or 0.2 mg/kg, was administered prior to surgery. As shown in Table 6, the 41 patients with pharmacokinetic data were divided into 2 groups, patients aged 1 month to 4 months and patients aged 5 to 24 months, and are compared with pediatric patients aged 3 to 12 years.
Table 6. Pharmacokinetics in Pediatric Surgery Patients Aged 1 Month to 12 YearsSubjects and Age-group | N | CL (L/h/kg) | Vdss (L/kg) | t½ (h) |
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Geometric Mean | Mean |
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Pediatric Surgery Patients 3 to 12 years | N = 21 | 0.439 | 1.65 | 2.9 |
Pediatric Surgery Patients 5 to 24 months | N = 22 | 0.581 | 2.3 | 2.9 |
Pediatric Surgery Patients 1 month to 4 months | N = 19 | 0.401 | 3.5 | 6.7 |
In general, surgical and cancer pediatric patients younger than 18 years tend to have a higher ondansetron clearance compared with adults leading to a shorter half-life in most pediatric patients. In patients aged 1 month to 4 months, a longer half-life was observed due to the higher volume of distribution in this age-group.
In a trial of 21 pediatric cancer patients (aged 4 to 18 years) who received three intravenous doses of 0.15 mg/kg of ondansetron at 4-hour intervals, patients older than 15 years exhibited ondansetron pharmacokinetic parameters similar to those of adults.
Patients with Renal Impairment: Due to the very small contribution (5%) of renal clearance to the overall clearance, renal impairment was not expected to significantly influence the total clearance of ondansetron. However, ondansetron mean plasma clearance was reduced by about 41% in patients with severe renal impairment (creatinine clearance < 30 mL/min). This reduction in clearance is variable and was not consistent with an increase in half-life [see Use in Specific Populations (8.7)].
Patients with Hepatic Impairment: In patients with mild-to-moderate hepatic impairment, clearance is reduced 2-fold and mean half-life is increased to 11.6 hours compared with 5.7 hours in those without hepatic impairment. In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), clearance is reduced 2-fold to 3-fold and apparent volume of distribution is increased with a resultant increase in half-life to 20 hours [see Dosage and Administration (2.3), Use in Specific Populations (8.6)].