6 ADVERSE REACTIONS
Serious or otherwise clinically significant adverse reactions reported in other sections of labeling:
- Hypersensitivity Reactions [see Warnings and Precautions (5.1)]
- Serotonin Syndrome [see Warnings and Precautions (5.2)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Chemotherapy-Induced Nausea and Vomiting
Adults
In double-blind randomized clinical trials for the prevention of nausea and vomiting induced by MEC or HEC, 1374 adult patients received a single dose of palonosetron injection, ondansetron (Studies 1 and 3) or dolasetron (Study 2) administered 30 minutes prior to chemotherapy [see Clinical Studies (14.1)]. Adverse reactions were similar in frequency and severity in all 3 treatment groups. Common adverse reactions reported in at least 2% of patients in these trials are shown in Table 2.
| Adverse Reaction | Palonosetron HCl Injection 0.25 mg intravenously (N=633) | Ondansetron 32 mg intravenously (N=410) | Dolasetron 100 mg intravenously (N=194) |
|---|---|---|---|
| |||
| Headache | 9% | 8% | 16% |
| Constipation | 5% | 2% | 6% |
| Diarrhea | 1% | 2% | 2% |
| Dizziness | 1% | 2% | 2% |
| Fatigue | < 1% | 1% | 2% |
| Abdominal Pain | < 1% | < 1% | 2% |
| Insomnia | < 1% | 1% | 2% |
Less common adverse reactions, reported in 1% or less of patients, in Studies 1, 2 and 3 were:
- Cardiovascular: non-sustained tachycardia, bradycardia, hypotension, hypertension, myocardial ischemia, extrasystoles, sinus tachycardia, sinus arrhythmia, supraventricular extrasystoles and QT prolongation
- Dermatological: allergic dermatitis, rash
- Hearing and Vision: motion sickness, tinnitus, eye irritation and amblyopia
- Gastrointestinal System: diarrhea, dyspepsia, abdominal pain, dry mouth, hiccups and flatulence
- General: weakness, fatigue, fever, hot flash, flu-like syndrome
- Liver: transient, asymptomatic increases in AST and/or ALT and bilirubin. These changes occurred predominantly in patients receiving highly emetogenic chemotherapy
- Metabolic: hyperkalemia, electrolyte fluctuations, hyperglycemia, metabolic acidosis, glycosuria, appetite decrease, anorexia
- Musculoskeletal: arthralgia
- Nervous System: dizziness, somnolence, insomnia, hypersomnia, paresthesia
- Psychiatric: anxiety, euphoric mood
- Urinary System: urinary retention
- Vascular: vein discoloration, vein distention
In other studies, 2 subjects experienced severe constipation following a single Palonosetron HCl Injection dose of approximately 0.75 mg (three times the recommended dose).
Pediatrics Aged 2 Months to 17 Years
In a pediatric clinical trial, 163 pediatric cancer patients with a mean age of 8 years received a single 20 mcg/kg (maximum 1.5 mg) intravenous infusion of Palonosetron HCl Injection 30 minutes before beginning the first cycle of emetogenic chemotherapy [see Clinical Studies (14.2)]. Adverse reactions were evaluated in pediatric patients receiving Palonosetron HCl Injection for up to 4 chemotherapy cycles. The following adverse reactions were reported in less than 1% of patients:
- Nervous System: headache, dizziness, dyskinesia
- General: infusion site pain
- Dermatological: allergic dermatitis, skin disorder
Postoperative Nausea and Vomiting
The most common adverse reactions reported in at least 2% of adults receiving Palonosetron HCl Injection 0.075 mg intravenously immediately before induction of anesthesia in 3 randomized placebo-controlled trials [see Clinical Studies (14.3)] are shown in Table 3. Rates of adverse reactions between Palonosetron HCl Injection and placebo groups were similar. Some events are known to be associated with, or may be exacerbated by, concomitant perioperative and intraoperative medications administered in this surgical population. A thorough QT/QTc study demonstrated Palonosetron HCl Injection does not prolong the QT interval to any clinically relevant extent [see Clinical Pharmacology (12.2)].
| Adverse Reaction | Palonosetron HCl Injection 0.075 mg intravenously (N=336) | Placebo (N=369) |
|---|---|---|
| ||
| Electrocardiogram QT prolongation | 5% | 3% |
| Bradycardia | 4% | 4% |
| Headache | 3% | 4% |
| Constipation | 2% | 3% |
Less common adverse reactions, reported in 1% or less of patients, in these PONV clinical trials were:
Cardiovascular: QTc prolongation, sinus bradycardia, tachycardia, blood pressure decreased, hypotension, hypertension, arrhythmia, ventricular extrasystoles, generalized edema, ECG T wave amplitude decreased, platelet count decreased. The frequency of these adverse effects did not appear to be different from placebo.
Dermatological: pruritus
Gastrointestinal System: flatulence, dry mouth, upper abdominal pain, salivary hypersecretion, dyspepsia, diarrhea, intestinal hypomotility, anorexia
General: chills
Liver: increases in AST and/or ALT, hepatic enzyme increased
Metabolic: hypokalemia, anorexia
Nervous System: dizziness
Respiratory: hypoventilation, laryngospasm
Urinary System: urinary retention
6.2 Postmarketing Experience
The following adverse reactions have been identified during postapproval use of palonosetron HCl. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Hypersensitivity reactions: including dyspnea, bronchospasm, swelling/edema, erythema, pruritus, rash, urticaria, anaphylaxis and anaphylactic shock [see Warnings and Precautions (5.1)]
- Injection site reactions: including burning, induration, discomfort and pain