palonosetron (Rx)

1-10%

Prolonged QT interval (up to 5%)

Anxiety

Dizziness

Headache

Weakness

Constipation

Diarrhea

Prutitus

Hyperkalemia

LFT's increased

<1%

First degree atrioventricular block

Second degree atrioventricular block

Frequency Not Defined

Immune hypersensitivity reaction (very rare)

Seizure

Dyskinesia

Infusion site pain

Allergic dermatitis, skin disorder

Contraindications

Hypersensitivity to drug, other selective 5-HT3 receptor antagonists (eg, granisetron), or any other component

Coadministration with apomorphine; combination reported to cause profound hypotension and loss of consciousness

Cautions

Use caution in patients with congenital long QT syndrome or other factors that may prolong QT interval

Serotonin syndrome reported with 5-HT3 receptor antagonists alone but particularly with concomitant use of serotonergic drugs including SSRIs, SNRIs, MAO inhibitors, lithium, tramadol, methylene blue IV, and mirtazapine

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

For chemotherapy, the drug should follow a specific schedule, and not be administered as needed

Drug is not recommended in PONV if expectation for nausea or vomiting is very small; use only if the expectation is low or it is essential to avoid nausea and vomiting in the postoperative period

Pregnancy Category: B

Lactation: unknown, discontinue drug or do not nurse

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Selective 5-HT3 receptor antagonist; palonosetron binds to 5-HT3 receptors both in peripheral and central nervous system with primary effects in GI tract

Pharmacokinetics

Half-life: 40 hr

Peak plasma: 5.6±5.5 ng/mL (dose-proportional)

AUC: 35.8±20.9 ng.hr/mL (dose-proportional)

Protein bound: 62%

Vd: 8.3±2.5 L/kg

Metabolism: CYP2D6, CYP3A and CYP1A2

Metabolites: N-oxide-palonosetron and 6-S-hydroxy-palonosetron (<1% parent activity)

Excretion: Urine (80-93%); feces (5-8%)

Clearance: 160±35 mL/hr/kg (total)

Pediatric administration

For a dose of 0.25 mg use either the single-dose vial or pre-filled syringe; do not use pre-filled syringe to administer a dose other than 0.25 mg

IV Incompatibilities

Do not mix with other drugs

IV Administration

Flush IV line with NS before and after administration

CINV: give IVP evenly over 30 sec (adults) or 15 min (children)

PONV: IVP over 10 sec