Zofran Injection

Clinical Pharmacology

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Clinical Pharmacology

Zofran Injection

Ondansetron was compared with metoclopramide in a single-blind trial in 307 patients receiving cisplatin ≥ 100 mg/m² with or without other chemotherapeutic agents. Patients received the first dose of ondansetron or metoclopramide 30 minutes before cisplatin. Two additional ondansetron doses were administered 4 and 8 hours later, or five additional metoclopramide doses were administered 2, 4, 7, 10, and 13 hours later. Cisplatin was administered over a period of 3 hours or less. Episodes of vomiting and retching were tabulated over the period of 24 hours after cisplatin. The results of this study are summarized in Table 5.

Table 5. Prevention of Vomiting Induced by Cisplatin ( ≥ 100 mg/m²) Single-Day Therapy* in Adults

	ZOFRAN Injection	Metoclopramide	P Value
Dose	0.15 mg/kg x 3	2 mg/kg x 6
Number of patients in efficacy population	136	138
Treatment response
0 Emetic episodes	54 (40%)	41 (30%)
1-2 Emetic episodes	34 (25%)	30 (22%)
3-5 Emetic episodes	19 (14%)	18 (13%)
More than 5 emetic episodes/rescued	29 (21%)	49 (36%)
Comparison of treatments with respect to 0 Emetic episodes	54/136	41/138	0.083
More than 5 emetic episodes/rescued	29/136	49/138	0.009
Median number of emetic episodes	1	2	0.005
Median time to first emetic episode (h)	20.5	4.3	< 0.001
Global satisfaction with control of nausea and vomiting (0-100)^†	85	63	0.001
Acute dystonic reactions	0	8	0.005
Akathisia	0	10	0.002
* In addition to cisplatin, 68% of patients received other chemotherapeutic agents, includingcyclophosphamide, etoposide, and fluorouracil. There was no difference between treatments in the types of chemotherapy that would account for differences in response. ^† Visual analog scale assessment: 0 = not at all satisfied, 100 = totally satisfied.

In a stratified, randomized, double-blind, parallel-group, multicenter study, a single 32-mg dose of ondansetron was compared with three 0.15-mg/kg doses in patients receiving cisplatin doses of either 50 to 70 mg/m² or ≥ 100 mg/m². Patients received the first ondansetron dose 30 minutes before cisplatin. Two additional ondansetron doses were administered 4 and 8 hours later to the group receiving three 0.15-mg/kg doses. In both strata, significantly fewer patients on the single 32-mg dose than those receiving the three-dose regimen failed.

Table 6. Prevention of Chemotherapy-Induced Nausea and Vomiting in Single-Dose Therapy in Adults

	0.15 mg/kg x 3	Ondansetron Dose 32 mg x 1	P Value
High-dose cisplatin ( ≥ 100 mg/m²)
Number of patients	100	102
Treatment response
0 Emetic episodes	41 (41%)	49 (48%)	0.315
1-2 Emetic episodes	19 (19%)	25 (25%)
3-5 Emetic episodes	4 (4%)	8 (8%)
More than 5 emetic episodes/rescued	36 (36%)	20 (20%)	0.009
Median time to first emetic episode (h)	21.7	23	0.173
Median nausea scores (0-100)*	28	13	0.004
Medium-dose cisplatin (50-70 mg/m²)
Number of patients	101	93
Treatment response
0 Emetic episodes	62 (61%)	68 (73%)	0.083
1-2 Emetic episodes	11 (11%)	14 (15%)
3-5 Emetic episodes	6 (6%)	3 (3%)
More than 5 emetic episodes/rescued	22 (22%)	8 (9%)	0.011
Median time to first emetic episode (h)	Undefined^†	Undefined
Median nausea scores (0-100)*	9	3	0.131
* Visual analog scale assessment: 0 = no nausea, 100 = nausea as bad as it can be. ^†Median undefined since at least 50% of patients did not have any emetic episodes.