Palonosetron Hydrochloride

PALONOSETRON HYDROCHLORIDE- palonosetron hydrochloride injection
West-Ward Pharmaceuticals Corp

1 INDICATIONS AND USAGE

1.1 Chemotherapy-Induced Nausea and Vomiting in Adults

Palonosetron Hydrochloride (HCl) Injection is indicated for:

• Moderately emetogenic cancer chemotherapy – prevention of acute and delayed nausea and vomiting associated with initial and repeat courses

• Highly emetogenic cancer chemotherapy – prevention of acute nausea and vomiting associated with initial and repeat courses

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

C hemotherapy-Induced Nausea and Vomiting

The recommended adult dosage of Palonosetron HCl Injection is 0.25 mg administered as a single intravenous dose over 30 seconds. Dosing should occur approximately 30 minutes before the start of chemotherapy.

2.2 Instructions for Intravenous Administration

  • Palonosetron HCl Injection is intended for direct intravenous administration without further dilution.
  • Do not mix with other drugs.
  • When applicable, flush the line with normal saline before and after administration of Palonosetron HCl Injection to ensure complete dosing and to avoid drug incompatibilities.
  • Inspect Palonosetron HCl Injection visually for particulate matter and discoloration before administration.

3 DOSAGE FORMS AND STRENGTHS

Palonosetron Hydrochloride Injection is sterile, clear, and colorless:

• 0.25 mg palonosetron in 2 mL (0.125 mg/mL) in a single-dose vial

4 CONTRAINDICATIONS

Palonosetron HCl Injection is contraindicated in patients known to have hypersensitivity to the drug or any of its components [see Adverse Reactions (6.2)].

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity

Hypersensitivity reactions, including anaphylaxis, have been reported with or without known hypersensitivity to other 5-HT3 receptor antagonists.

5.2 Serotonin Syndrome

The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists. Most reports have been associated with concomitant use of serotonergic drugs (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and intravenous methylene blue). Some of the reported cases were fatal. Serotonin syndrome occurring with overdose of another 5-HT3 receptor antagonist alone has also been reported. The majority of reports of serotonin syndrome related to 5-HT3 receptor antagonist use occurred in a post-anesthesia care unit or an infusion center.

Symptoms associated with serotonin syndrome may include the following combination of signs and symptoms: mental status changes (e.g. agitation, hallucinations, delirium, and coma), autonomic instability (e.g. tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, with or without gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome, especially with concomitant use of Palonosetron HCl Injection and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue Palonosetron HCl Injection and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if Palonosetron HCl Injection is used concomitantly with other serotonergic drugs [see Drug Interactions (7.1)].

6 ADVERSE REACTIONS

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 reported in practice.

The safety of Palonosetron HCl Injection has been established from adequate and well-controlled studies of another intravenous formulation of palonosetron HCl [see Clinical Studies (14)]. Below is a display of the adverse reactions of palonosetron HCl in these adequate and well-controlled studies.

C hemotherapy-Induced Nausea and Vomiting

In clinical trials for the prevention of nausea and vomiting induced by moderately or highly emetogenic chemotherapy, 1374 adult patients received a single 0.25 mg dose of palonosetron HCl. Adverse reactions were similar in frequency and severity with intravenous palonosetron HCl and ondansetron or dolasetron.

The following is a listing of all adverse reactions reported by ≥ 2% of patients in these trials (Table 1).

T able 1: Adverse Reactions from Chemotherapy-Induced Nausea and Vomiting Studies 2% in any Treatment Group

A dverse Reaction

P a l onosetron HCl 0.25 mg Intravenous ( N= 633)

O ndansetron 32 mg Intraveneous ( N= 410)

D olasetron 100 mg Intraveneous ( N= 194)

Headache

60 (9%)

34 (8%)

32 (16%)

Constipation

29 (5%)

8 (2%)

12 (6%)

Diarrhea

8 (1%)

7 (2%)

4 (2%)

Dizziness

8 (1%)

9 (2%)

4 (2%)

Fatigue

3 (< 1%)

4 (1%)

4 (2%)

Abdominal Pain

1 (< 1%)

2 (1%)

3 (2%)

Insomnia

1 (< 1%)

3 (1%)

3 (2%)

In other studies, 2 patients experienced severe constipation following a single palonosetron HCl dose of approximately 0.75 mg, three times the recommended dose.

In clinical trials, the following infrequently reported adverse reactions, assessed by investigators as treatment-related or causality unknown, occurred following administration of palonosetron HCl to adult patients receiving concomitant cancer chemotherapy:

C ardiovascular: 1%: non-sustained tachycardia, bradycardia, hypotension, < 1%: hypertension, myocardial ischemia, extrasystoles, sinus tachycardia, sinus arrhythmia, supraventricular extrasystoles and QT prolongation. In many cases, the relationship to palonosetron was unclear.

D ermatological: < 1%: allergic dermatitis, rash.

Hearing and Vision: < 1%: motion sickness, tinnitus, eye irritation and amblyopia.

G astrointestinal System: 1%: diarrhea, < 1%: dyspepsia, abdominal pain, dry mouth, hiccups and flatulence.

G eneral: 1%: weakness, < 1%: fatigue, fever, hot flash, flu-like syndrome.

Liver: < 1%: transient, asymptomatic increases in AST and/or ALT and bilirubin. These changes occurred predominantly in patients receiving highly emetogenic chemotherapy.

M etabolic: 1%: hyperkalemia, < 1%: electrolyte fluctuations, hyperglycemia, metabolic acidosis, glycosuria, appetite decrease, anorexia.

M usculoskeletal: < 1%: arthralgia.

N ervous System: 1%: dizziness, < 1%: somnolence, insomnia, hypersomnia, paresthesia.

Psychiatric: 1%: anxiety, < 1%: euphoric mood.

U rinary System: < 1%: urinary retention.

Vascular: < 1%: vein discoloration, vein distention.

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