Palonosetron Hydrochloride

Pronunciation: (PAL-oh-NOE-se-tron HYE-droe-KLOR-ide)
Class: 5-HT ₃ receptor antagonist

Trade Names

Aloxi
- Injection, solution 0.05 mg/mL

Pharmacology

Selective antagonist for the 5-HT ₃ receptor with a strong binding affinity for this receptor.

Pharmacokinetics

Absorption

Following IV administration, the C _max and AUC are generally dose-proportional. After a single IV dose at 3 mcg/kg, mean C _max was approximately 5.6 ng/mL and AUC was 35.8 ng•h/mL.

Distribution

Vd is approximately 8.3 L/kg, and protein binding is about 62%.

Metabolism

Approximately 50% is metabolized to 2 metabolites that have less than 1% of the activity of palonosetron. The major isozyme responsible for metabolism appears to be CYP2D6 and, to a lesser degree, CYP1A2 and CYP3A are involved.

Elimination

Following IV administration, approximately 80% of the dose is recovered in the urine. The terminal half-life is approximately 40 h.

Special Populations

Renal Function Impairment

No dosage adjustments are needed with any degree of renal function impairment. However, pharmacokinetics have not been studied in patients with ESRD.

Hepatic Function Impairment

No dosage adjustments are needed with any degree of hepatic function impairment.

Elderly

No dosage adjustments or special monitoring are needed in elderly patients.

Race

Has not been adequately characterized.

Gender

Dosage adjustments are not necessary based on gender.

Indications and Usage

Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy; prevention of acute nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy; prevention of postoperative nausea and vomiting for up to 24 h following surgery.

Contraindications

Standard considerations.

Dosage and Administration

Chemotherapy-Induced Nausea and Vomiting
Adults

IV 0.25 mg administered over 30 sec approximately 30 min before the start of chemotherapy.

Postoperative Nausea and Vomiting
Adults

IV 0.075 mg administered over 10 sec immediately before the induction of anesthesia.

General Advice

• For IV administration only. Not for intradermal, subcutaneous, or IM administration.
• Do not administer if particulate matter, cloudiness, or discoloration is noted.
• Administer prescribed dose via 30-sec IV infusion.
• Discard any unused solution. Do not save unused solution for later administration.
• Do not mix with other medications.

Storage/Stability

Store at 59° to 86°F. Protect from light and protect injectable from freezing.

Drug Interactions

None well documented.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

ECG QT prolongation (5%); bradycardia (4%); hypotension, sinus bradycardia, tachycardia (1%).

CNS

Headache (9%); anxiety, dizziness, weakness (1%).

GI

Constipation (5%); diarrhea (1%).

Genitourinary

Urinary retention (1%).

Hepatic

Increased ALT, increased AST (1%).

Hypersensitivity

Hypersensitivity (postmarketing).

Local

Burning, discomfort, induration, pain (postmarketing).

Metabolic

Hyperkalemia (1%).

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Hypersensitivity

May occur in patients who have exhibited hypersensitivity to other selective 5-HT ₃ receptor antagonists.

CV effects

Although palonosetron has been safely administered to patients with preexisting cardiac impairment, administer with caution in patients who have or may develop prolongation of cardiac conduction intervals, particularly QTc.

Overdosage

Symptoms

No data available.

Patient Information

• Advise patient, family, or caregiver that IV formulation will be prepared and administered by health care provider in a medical facility.
• Advise patient, family, or caregiver that medication will greatly reduce likelihood of nausea or vomiting, but that these are still possible.
• Instruct patient to inform health care provider if medication does not prevent nausea or vomiting.
• Advise patient to report any of the following to health care provider: intolerable headache, persistent or intolerable constipation or diarrhea.

Copyright © 2009 Wolters Kluwer Health.