New drug
Palonosetron hydrochloride
- Aust Prescr 2011;34:119-23
- 1 August 2011
- DOI: 10.18773/austprescr.2011.064
ISSUE 4 AUGUST
Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Aloxi (Specialised Therapeutics)
vials containing 250 microgram/5 mL
Approved indication: prevention of nausea and vomiting
Australian Medicines Handbook section 12.3.2
Patients having cytotoxic chemotherapy are likely to develop severe nausea and vomiting. To try and prevent these adverse reactions patients are given antiemetic drugs. These include the serotonin (5HT3) receptor antagonists dolasetron, granisetron, ondansetron and tropisetron.
Like the other members of the class palonosetron has a high affinity for the 5HT3 receptor. Blocking this receptor reduces the response to the emetogenic stimulus induced by cytotoxic drugs.
To prevent the nausea and vomiting, palonosetron is given intravenously 30 minutes before chemotherapy. Plasma concentrations decline rapidly, but there is a long elimination half-life (mean 40 hours). Palonosetron is metabolised by several enzymes including cytochrome P450 2D6, but 40% of the dose is excreted unchanged in the urine. No dosage reductions are recommended for patients with hepatic or renal impairment.
The approved indication for palonosetron was mainly supported by two trials in patients having moderately emetogenic chemotherapy1,2 and one trial in patients having highly emetogenic chemotherapy.3
In the highly emetogenic study, 673 patients were randomised to receive different doses of palonosetron or a single dose of ondansetron. After 24 hours, 57% of the patients given ondansetron had experienced no vomiting or had not needed rescue medication. Among the patients given 250 microgram of palonosetron, 59% had a complete response.3
Ondansetron was also included in a study of moderately emetogenic chemotherapy involving 570 patients. There was a complete response in 69% of the patients given ondansetron and in 81% of those given 250 microgram of palonosetron. This difference was statistically significant.1
The other study of moderately emetogenic chemotherapy randomised 592 patients to take dolasetron or one of two doses of palonosetron. There was a complete response in 53% of the patients given dolasetron and in 63% of those given 250 microgram of palonosetron.2
The pattern and frequency of adverse reactions to palonosetron was similar to that of ondansetron and dolasetron. Headache and gastrointestinal symptoms, such as constipation, were the most frequently reported problems. Although palonosetron did not cause extensive QT prolongation in the trials, caution is advised when giving the drug to patients who are at risk of QT prolongation.
The trials show that palonosetron is not inferior to other 5HT3 antagonists for the prevention of acute vomiting. The longer half-life may help in reducing the incidence of delayed nausea and vomiting,4 but the safety and efficacy of repeated dosing has not been evaluated.
manufacturer provided the product information
The Transparency Score () is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
Notes on references
At the time the comment was prepared, information about this drug was available on the web site of the Food and Drug Administration in the USA (www.fda.gov).
At the time the comment was prepared, a scientific discussion about this drug was available on the website of the European Medicines Agency (www.emea.europa.eu).
References
- Gralla R, Lichinitser M, Van der Vegt S, Sleeboom H, Mezger J, \r\nPeschel C, et al. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol 2003;14:1570-7.
- Eisenberg P, Figueroa-Vadillo J, Zamora R, Charu V, Hajdenberg J, Cartmell A, et al. Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron. Cancer 2003;98:2473-82.
- Aapro MS, Grunberg SM, Manikhas GM, Olivares G, \r\nSuarez T, Tjulandin SA, et al. A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy. Ann Oncol 2006;17:1441-9.
- Mattiuzzi GN, Cortes JE, Blamble DA, Bekele N, Xiao L, \r\nCabanillas M, et al. Daily palonosetron is superior to ondansetron in the prevention of delayed chemotherapy-induced nausea and vomiting in patients with acute myelogenous leukemia. Cancer 2010;116:5659-66.
