ADVERSE REACTIONS
Chemotherapy-Induced Nausea and Vomiting
The following have been reported during controlled clinical trials or in the routine management of patients. The percentage figures are based on clinical trial experience only. Table 10 gives the comparative frequencies of the five most commonly reported adverse events (≥3%) in patients receiving KYTRIL Injection, in single-day chemotherapy trials. These patients received chemotherapy, primarily cisplatin, and intravenous fluids during the 24-hour period following KYTRIL Injection administration. Events were generally recorded over seven days post-KYTRIL Injection administration. In the absence of a placebo group, there is uncertainty as to how many of these events should be attributed to KYTRIL, except for headache, which was clearly more frequent than in comparison groups.
Table 10 Principal Adverse Events in Clinical Trials — Single-Day Chemotherapy | | Percent of Patients With Event |
|---|
| | KYTRIL Injection
40 mcg/kg
(n=1268) | ComparatorMetoclopramide/dexamethasone and phenothiazines/dexamethasone.
(n=422) |
|---|
| Headache | 14% | 6% |
| Asthenia | 5% | 6% |
| Somnolence | 4% | 15% |
| Diarrhea | 4% | 6% |
| Constipation | 3% | 3% |
In over 3,000 patients receiving KYTRIL Injection (2 to 160 mcg/kg) in single-day and multiple-day clinical trials with emetogenic cancer therapies, adverse events, other than those in Table 10, were observed; attribution of many of these events to KYTRIL is uncertain.
Hepatic: In comparative trials, mainly with cisplatin regimens, elevations of AST and ALT (>2 times the upper limit of normal) following administration of KYTRIL Injection occurred in 2.8% and 3.3% of patients, respectively. These frequencies were not significantly different from those seen with comparators (AST: 2.1%; ALT: 2.4%).
Cardiovascular: Hypertension (2%); hypotension, arrhythmias such as sinus bradycardia, atrial fibrillation, varying degrees of A-V block, ventricular ectopy including non-sustained tachycardia, and ECG abnormalities have been observed rarely.
Central Nervous System: Agitation, anxiety, CNS stimulation and insomnia were seen in less than 2% of patients. Extrapyramidal syndrome occurred rarely and only in the presence of other drugs associated with this syndrome.
Hypersensitivity: Rare cases of hypersensitivity reactions, sometimes severe (eg, anaphylaxis, shortness of breath, hypotension, urticaria) have been reported.
Other: Fever (3%), taste disorder (2%), skin rashes (1%). In multiple-day comparative studies, fever occurred more frequently with KYTRIL Injection (8.6%) than with comparative drugs (3.4%, P<0.014), which usually included dexamethasone.
Postoperative Nausea and Vomiting
The adverse events listed in Table 11 were reported in ≥2% of adults receiving KYTRIL Injection 1 mg during controlled clinical trials.
Table 11 Adverse Events ≥2% | | Percent of Patients With Event |
|---|
| | KYTRIL Injection
1 mg
(n=267) | Placebo
(n=266) |
|---|
| Pain | 10.1 | 8.3 |
| Constipation | 9.4 | 12.0 |
| Anemia | 9.4 | 10.2 |
| Headache | 8.6 | 7.1 |
| Fever | 7.9 | 4.5 |
| Abdominal Pain | 6.0 | 6.0 |
| Hepatic Enzymes Increased | 5.6 | 4.1 |
| Insomnia | 4.9 | 6.0 |
| Bradycardia | 4.5 | 5.3 |
| Dizziness | 4.1 | 3.4 |
| Leukocytosis | 3.7 | 4.1 |
| Anxiety | 3.4 | 3.8 |
| Hypotension | 3.4 | 3.8 |
| Diarrhea | 3.4 | 1.1 |
| Flatulence | 3.0 | 3.0 |
| Infection | 3.0 | 2.3 |
| Dyspepsia | 3.0 | 1.9 |
| Hypertension | 2.6 | 4.1 |
| Urinary Tract Infection | 2.6 | 3.4 |
| Oliguria | 2.2 | 1.5 |
| Coughing | 2.2 | 1.1 |
In a clinical study conducted in Japan, the types of adverse events differed notably from those reported above in Table 11. The adverse events in the Japanese study that occurred in ≥2% of patients and were more frequent with KYTRIL 1 mg than with placebo were: fever (56% to 50%), sputum increased (2.7% to 1.7%), and dermatitis (2.7% to 0%).
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