Palonosetron

Palonosetron is a medication that is used for the treatment of nausea and vomiting. The Food and Drug Administration (FDA) initially approved its use for nausea and vomiting caused by cancer chemotherapy on July 25, 2004. In March 2008, the FDA extended its approval to the prevention of postoperative nausea and vomiting. Palonosetron is given shortly before chemotherapy or surgery, and its protection against sickness can last for more than 24 hours. It is marketed under the brand name Aloxi by Eisai, Inc.

Uses/Indications

Palonosetron is used to prevent nausea (antinauseant) and vomiting (antiemetic) caused by cancer chemotherapy. It is given shortly before the chemotherapy. Chemotherapy can cause vomiting for more than 24 hours after the treatment. No other drug is approved by the FDA to prevent this late-onset sickness. Palonosetron has only been studied in adults (18 years of age or older). Palonosetron is also used to prevent postoperative nausea and vomiting.

How Palonosetron Is Taken

Palonosetron is administered as a single 30-second intravenous infusion. It is administered 30 minutes before chemotherapy on day 1 of each cycle. It should not be used more than once a week. To prevent postoperative nausea or vomiting, physicians inject 0.075 mg palonosetron just before anesthesia.

How Palonosetron Works

Nausea and vomiting during chemotherapy are caused by release of the neurotransmitter serotonin (5-HT) from the small intestine. Palonosetron blocks the receptors to which serotonin binds in the brain and spinal cord. Palonosetron specifically blocks the 5-HT3 subtype serotonin receptor.^[1]

How the Body Affects Palonosetron

Approximately 50% of palonosetron is metabolized (broken down) in the liver primarily by an enzyme called CYP2D6. The CYP3A4 and CYP1A2 enzymes also contribute to a lesser extent. Most of a palonosetron dose is excreted in the urine. Palonosetron is effective for treating nausea and vomiting for more than 24 hours after chemotherapy because the time needed to reduce the amount of palonosetron in the circulation by half is approximately 40 hours. This long half-life suggests that, after 24 hours, enough palonosetron remains in the body to still have an effect.

Side Effects

Below are some common side effects of treatment with palonosetron:

• Diarrhea
• Constipation
• Headache
• Fatigue
• Pain in the stomach area
• Dizziness
• Trouble sleeping

Risks and Precautions

Palonosetron should not be taken by patients who are allergic to any 5-HT receptor blockers, including palonosetron. Other blockers include ondansetron (Zofran), dolasetron (Anzemet), tropisetron, or granesetron (Kytril).

Palonosetron may affect the heartbeat. Certain people are more likely to develop these problems:

• Those who have an irregular heartbeat or heart problems (especially a condition called QT prolongation)
• Those being treated with diuretics (“water pills”)
• Those with low levels of magnesium and potassium in the blood
• Those receiving treatment for heartbeat problems
• Those receiving treatment with antiarrhythmic drugs or other drugs that might prolong the QT interval (a heart measurement)
• Those receiving cumulative high-dose anthracycline (a chemotherapy drug)

The effects of palonosetron on pregnancy are not known. A physician should be notified if a patient is planning a pregnancy or is breast-feeding.

Drug Interactions

• Palonosetron is not expected to have many drug interactions, but a physician should be aware of all the medicines and supplements the patient takes.

• Co-administration of palonosetron with apomorphine (Apokyn) has been reported to cause hypotension (low blood pressure) and altered consciousness. These drugs should not be taken together.

Alternatives

The key drugs for reducing nausea and vomiting are dexamethasone, neurokinin 1 receptor inhibitors, and antagonists of the 5-HT3 serotonin receptor (of which palonosetron is the newest).

Clinical Trials

Palonosetron prevents nausea and vomiting due to chemotherapeutic agents that provoke a moderate or strong vomiting response. The effectiveness of palonosetron in preventing nausea and vomiting after chemotherapy was determined with a range of palonosetron doses in 161 patients with cancer.^[2] The chemotherapy consisted of either cisplatin or cyclophosphamide. Within 24 hours of chemotherapy, palonosetron had prevented vomiting in 40%-50% of patients, depending on dose. Palonosetron prevented vomiting in approximately one-third of patients for one week after chemotherapy. Clinical trials have also shown that palonosetron is more effective than some other 5-HT blockers for the treatment of chemotherapy-induced vomiting and nausea.^[3]

References

1. ↑ Rubenstein EB. Palonosetron: a unique 5-HT3 receptor antagonist indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. Clin Adv Hematol Oncol. 2004 May;2(5):284-9. Abstract
2. ↑ Eisenberg P, MacKintosh FR, Ritch P, et al. Efficacy, safety and pharmacokinetics of palonosetron in patients receiving highly emetogenic cisplatin-based chemotherapy: a dose-ranging clinical study. Ann Oncol 2004;15:330-7. Full Text
3. ↑ De Leon A. Palonosetron (Aloxi): a second-generation 5-HT(3) receptor antagonist for chemotherapy-induced nausea and vomiting. Proc (Bayl Univ Med Cent). 2006;19:413-6. Full Text

External Links

Antiemetic guidelines from the Multinational Association of Supportive Care in Cancer

Helsinn Healthcare: Aloxi Main Page

Drugs.com: Aloxi Official FDA Information: Side Effects and Uses

MedicineNet: Palonosetron Injection

American Cancer Society: Palonosetron Hydrochloride

FDA: Aloxi Consumer Information