Palonosetron Hydrochloride

PALONOSETRON HYDROCHLORIDE- palonosetron hydrochloride injection, solution
Teva Parenteral Medicines, Inc.

1 INDICATIONS AND USAGE

Palonosetron hydrochloride injection is indicated in adults for prevention of:

  • acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC).
  • acute nausea and vomiting associated with initial and repeat courses highly emetogenic cancer chemotherapy (HEC).
  • postoperative nausea and vomiting (PONV) for up to 24 hours following surgery. Efficacy beyond 24 hours has not been demonstrated.

As with other antiemetics, routine prophylaxis is not recommended in patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively. In patients where nausea and vomiting must be avoided during the postoperative period, palonosetron hydrochloride injection is recommended even where the incidence of postoperative nausea and/or vomiting is low.

Palonosetron hydrochloride injection is indicated in pediatric patients 1 month to less than 17 years of age for prevention of:

  • acute nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including highly emetogenic cancer chemotherapy.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

Prevention of Chemotherapy-Induced Nausea and Vomiting

The recommended dosage of palonosetron hydrochloride injection for prevention of nausea and vomiting associated with HEC and MEC in adults and associated with emetogenic chemotherapy, including HEC in pediatric patients 1 month to less than 17 years of age is shown in Table 1.

Table 1: Recommended Dosage of Palonosetron Hydrochloride Injection for the Prevention of Nausea and Vomiting Associated with Chemotherapy in Adults and Pediatric Patients 1 Month to Less than 17 Years

Age

Dose*

Infusion Time

Adults

0.25 mg as a single dose

Infuse over 30 seconds beginning approximately 30 minutes before the start of chemotherapy

Pediatrics (1 month to less than 17 years)

20 micrograms per

kilogram (max 1.5 mg) as a single dose

Infuse over 15 minutes beginning approximately 30 minutes before the start of chemotherapy

*Note different dosing units in pediatrics

Postoperative Nausea and Vomiting

The recommended dosage of palonosetron hydrochloride injection in adults for PONV is 0.075 mg administered as a single intravenous dose over 10 seconds immediately before the induction of anesthesia.

2.2 Instructions for Intravenous Administration

  • Palonosetron hydrochloride injection is supplied ready for intravenous administration at a concentration of 0.05 mg/mL (50 mcg/mL).
  • Do not mix palonosetron hydrochloride injection with other drugs.
  • Flush the infusion line with normal saline before and after administration of palonosetron hydrochloride injection.
  • Inspect palonosetron hydrochloride injection visually for particulate matter and discoloration before administration.
  • Discard unused portion.

3 DOSAGE FORM AND STRENGTHS

Palonosetron hydrochloride injection is supplied as a single-dose sterile, clear, colorless solution in glass vials that provide:

  • 0.25 mg (free base) per 5 mL (concentration: 0.05 mg/mL, 50 mcg/mL)

4 CONTRAINDICATIONS

Palonosetron hydrochloride injection is contraindicated in patients known to have hypersensitivity to palonosetron [see Warnings and Precautions (5.1)].

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis and anaphylactic shock, have been reported with administration of palonosetron hydrochloride injection [see Adverse Reactions (6.2)]. These reactions occurred in patients with or without known hypersensitivity to other 5-HT3 receptor antagonists. If hypersensitivity reactions occur, discontinue palonosetron hydrochloride injection and initiate appropriate medical treatment. Do not reinitiate palonosetron hydrochloride injection in patients who have previously experienced symptoms of hypersensitivity [see Contraindications (4)].

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 hydrochloride injection and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue palonosetron hydrochloride injection and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if palonosetron hydrochloride injection is used concomitantly with other serotonergic drugs [see Drug Interactions (7.1)].

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 hydrochloride 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.

Table 2: Common Adverse Reactions* in Adults with Receiving MEC (Studies 1 and 2) or HEC (Study 3)

Adverse Reaction

Palonosetron Hydrochloride 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%

* Reported in at least 2% of patients in any treatment group

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 hydrochloride 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 hydrochloride 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 hydrochloride 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 hydrochloride 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 hydrochloride 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 hydrochloride injection does not prolong the QT interval to any clinically relevant extent [see Clinical Pharmacology (12.2)].

Table 3: Common Adverse Reactions* in Trials of Adults with Postoperative Nausea and Vomiting

Adverse Reaction

Palonosetron Hydrochloride Injection 0.075 mg intravenously

(N=336)

Placebo (N=369)

Electrocardiogram QT prolongation

5%

3%

Bradycardia

4%

4%

Headache

3%

4%

Constipation

2%

3%

* Reported in at least 2% of patients in any treatment group

Less common adverse reactions, reported in 1% of 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

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2022. All Rights Reserved.