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Drug Criteria & Outcomes: Palonosetron (Aloxi) Formulary Evaluation
Part 2: Clinical Trial Data, Adverse Effects, and Cost Analysis
By Brian Watkins,
Harrison School of Pharmacy
Auburn (AL) University
(Editor’s note: This second part of the palonosetron formulary evaluation addresses the available clinical trial, adverse effects, and cost analysis data. For information on mechanism of action, pharmacokinetics, indications, dosage, and administration of palonosetron, please consult the March issue of Drug Formulary Review's Drug Criteria & Outcomes.)
Moderately emetogenic chemotherapy
Trial 1: Palonosetron improves prevention of chemotherapy-induced nausea and vomiting (CINV) following moderately emetogenic chemotherapy: Results of a double-blind randomized Phase III trial comparing single doses of palonosetron with ondansetron.
Objective: To compare the efficacy and tolerability of single, fixed intravenous doses of palonosetron with a single intravenous dose of ondansetron in the prevention of acute and delayed CINV following administration of moderately emetogenic therapy.
Study Design: Multicenter, randomized, controlled, double-blind, double-dummy, stratified, Phase III study, noninferiority study.
Trial 2: Palonosetron is active in preventing acute and delayed emesis following moderately emetogenic chemotherapy: Results of a Phase III trial.
Objective: To assess the safety and efficacy of single intravenous doses of palonosetron vs. dolasetron for the prevention of moderately emetogenic CINV.
Study design: Multicenter, randomized, double-blind, parallel, stratified, noninferiority trial.
Highly emetogenic chemotherapy
Trial 3: The efficacy and safety profile of palonosetron in a Phase II study involving chemotherapy-naïve patients undergoing highly emetogenic chemotherapy.
Objective: To assess the safety and efficacy of palonosetron administered over a range of single intravenous doses for the prevention of highly emetic CINV.
Study design: Randomized, double-blind, multicenter, dose-ranging Phase II trial.
Authors’ conclusion: Palonosetron was safe and effective as a monotherapy in treating chemotherapy-induced emesis and warranted further study as an antiemetic in patients receiving highly emetogenic chemotherapy.
Trial 4: Palonosetron is effective in preventing acute and delayed CINV in patients receiving highly emetogenic chemotherapy.
Objective: To assess the efficacy and safety of single IV doses of palonosetron 0.25 mg or 0.75 mg vs. ondansetron 32 mg administered 30 minutes prior to highly emetogenic chemotherapy.
Study design: Multicenter, randomized, double-blind, stratified Phase III study.
Author’s conclusion: A single dose of palonosetron prior to highly emetogenic chemotherapy is as effective as a single dose of ondansetron 32 mg for prevention of acute CINV and maybe of greater benefit in preventing delayed CINV after highly emetogenic chemotherapy.
Adverse drug reactions
To date, palonosetron appears to have a side effect profile similar to other currently available setrons; however, post-marketing surveillance should reveal any side effects that recent clinical trials may not have demonstrated. Also, one potential limitation of palonosetron is its ability to prolong QT and QTc intervals, although the drug has been administered safely to 192 patients with pre-existing cardiac impairment.
Currently, palonosetron is the most expensive setron at Huntsville Hospital when comparing equivalent single doses; the formulary drug granisetron is the least expensive of the four available agents (ondansetron, dolasetron, granisetron, and palonosetron). The price difference per dose between granisetron and the other agents varies from $60 to $100 per dose.
Nausea and vomiting can be a strong predictor of a patient’s decision to continue an efficacious chemotherapy regimen. Palonosetron’s pharmacodynamics gives way to a binding affinity 100 times greater than that of any other setron. Kinetically, this drug has an elimination half-life of approximately 40 hours. Together, these properties yield efficacy in preventing both acute and delayed CINV. However, drugs in other classes are generally used first for delayed nausea and vomiting.
Palonosetron has not been compared to other regimens used for CINV, including oral and intravenous granisetron (the HH formulary drug). Benefits of palonosetron and other setron drugs include rapid and durable clinical effectiveness, ease of administration, single fixed dosing, and a favorable side effect profile. Additionally, palonosetron has no dosage adjustment in renal or hepatic impairment, and a low potential for drug interactions. Palonosetron is considerably more expensive than granisetron oral or IV in equivalent dosages (see cost summary section). As with other setrons, potential limitations of palonosetron include the ability to prolong the QT and QTc intervals.
Palonosetron should not be added to the formulary at this time. To date, palonosetron appears at least comparable to other setrons in the prevention of CINV, and shows positive results in preventing delayed symptoms.
However, greater experience with this drug through post-marketing surveillance will give a clearer picture with respect to the safety and efficacy of this new therapeutic option. Orders for palonosetron should be converted to granisetron according to the following dosage equivalents: palonosetron 0.25 mg IV for CINV be interchanged to either granisetron 1 mg IV or 2 mg oral tablet.