ONDANSETRON HYDROCHLORIDE (Page 4 of 6)

ADVERSE REACTIONS

The following have been reported as adverse events in clinical trials of patients treated with ondansetron. A causal relationship to therapy with ondansetron has been unclear in many cases.

Chemotherapy-Induced Nausea and Vomiting

The adverse events in Table 5 have been reported in ≥ 5% of adult patients receiving a single 24 mg ondansetron hydrochloride tablet in 2 trials. These patients were receiving concurrent highly emetogenic cisplatin-based chemotherapy regimens (cisplatin dose ≥ 50 mg/m²).

Table 5: Principal Adverse Events in US Trials: Single Day Therapy with 24 mg Ondansetron Hydrochloride Tablets (Highly Emetogenic Chemotherapy)

Event	Ondansetron 24 mg q.d. n = 300	Ondansetron 8 mg b.i.d. n = 124	Ondansetron 32 mg q.d. n = 117
Headache	33 (11%)	16 (13%)	17 (15%)
Diarrhea	13 (4%)	9 (7%)	3 (3%)

The adverse events in Table 6 have been reported in ≥ 5% of adults receiving either 8 mg of ondansetron tablets two or three times a day for 3 days or placebo in four trials. These patients were receiving concurrent moderately emetogenic chemotherapy, primarily cyclophosphamide-based regimens.

Table 6: Principal Adverse Events in US Trials: 3 Days of Therapy With 8 mg Ondansetron Tablets (Moderately Emetogenic Chemotherapy)

Event	Ondansetron 8 mg b.i.d. n = 242	Ondansetron 8 mg t.i.d. n = 415	Placebo n = 262
Headache	58 (24%)	113 (27%)	34 (13%)
Malaise/fatigue	32 (13%)	37 (9%)	6 (2%)
Constipation	22 (9%)	26 (6%)	1 (<1%)
Diarrhea	15 (6%)	16 (4%)	10 (4%)
Dizziness	13 (5%)	18 (4%)	12 (5%)

Central Nervous System: There have been rare reports consistent with, but not diagnostic of, extrapyramidal reactions in patients receiving ondansetron.

Hepatic: In 723 patients receiving cyclophosphamide-based chemotherapy in US clinical trials, AST and/or ALT values have been reported to exceed twice the upper limit of normal in approximately 1% to 2% of patients receiving ondansetron tablets. The increases were transient and did not appear to be related to dose or duration of therapy. On repeat exposure, similar transient elevations in transaminase values occurred in some courses, but symptomatic hepatic disease did not occur. The role of cancer chemotherapy in these biochemical changes cannot be clearly determined.

There have been reports of liver failure and death in patients with cancer receiving concurrent medications including potentially hepatotoxic cytotoxic chemotherapy and antibiotics. The etiology of the liver failure is unclear.

Integumentary: Rash has occurred in approximately 1% of patients receiving ondansetron.

Other: Rare cases of anaphylaxis, bronchospasm, tachycardia, angina (chest pain), hypokalemia, electrocardiographic alterations, vascular occlusive events, and grand mal seizures have been reported. Except for bronchospasm and anaphylaxis, the relationship to ondansetron was unclear.

Radiation-Induced Nausea and Vomiting

The adverse events reported in patients receiving ondansetron tablets and concurrent radiotherapy were similar to those reported in patients receiving ondansetron tablets and concurrent chemotherapy. The most frequently reported adverse events were headache, constipation, and diarrhea.

Postoperative Nausea and Vomiting

The adverse events in Table 7 have been reported in ≥ 5% of patients receiving ondansetron tablets at a dosage of 16 mg orally in clinical trials. With the exception of headache, rates of these events were not significantly different in the ondansetron and placebo groups. These patients were receiving multiple concomitant perioperative and postoperative medications.

Table 7: Frequency of Adverse Events From Controlled Studies With Ondansetron Tablets (Postoperative Nausea and Vomiting)

Adverse Event	Ondansetron 16 mg (n = 550)	Placebo (n = 531)
Wound problem	152 (28%)	162 (31%)
Drowsiness/sedation	112 (20%)	122 (23%)
Headache	49 (9%)	27 (5%)
Hypoxia	49 (9%)	35 (7%)
Pyrexia	45 (8%)	34 (6%)
Dizziness	36 (7%)	34 (6%)
Gynecological disorder	36 (7%)	33 (6%)
Anxiety/agitation	33 (6%)	29 (5%)
Bradycardia	32 (6%)	30 (6%)
Shiver(s)	28 (5%)	30 (6%)
Urinary retention	28 (5%)	18 (3%)
Hypotension	27 (5%)	32 (6%)
Pruritus	27 (5%)	20 (4%)