Pharmacy & Therapeutics - October 2008 - (Page PP7)

PRODUCT PROFILER: Granisetron Transdermal Delivery System PHARMACOTHERAPY Pharmacological treatment options for CINV can be classified as follows:11 • • • • 5-HT3 receptor antagonists NK1 receptor antagonists corticosteroids dopamine receptor antagonists, such as butyrophenones (e.g., haloperidol), benzamides (e.g., metoclopramide), or phenothiazines (e.g., prochlorperazine, chlorpromazine), antihistamines (e.g., diphenhydramine), benzodiazepines (e.g., lorazepam), and cannabinoids (e.g., dronabinol) In light of all these options, the most commonly employed antiemetic agents for moderate-risk to highrisk emetic chemotherapy are the 5-HT 3 receptor antagonists, NK1 receptor antagonists, and corticosteroids. NK1 receptor antagonists, such as aprepitant and fosaprepitant, work by selectively blocking the binding of substance P at the NK1 receptor in the CNS.11 Unlike other antiemetic agents, these agents augment the antiemetic activity of 5-HT3 receptor antagonists and corticosteroids for the inhibition of acute and delayed chemotherapy-induced emesis.11 NK1 receptor antagonists are available in oral and intravenous (IV) formulations. The most frequently studied corticosteroids are dexamethasone and methylprednisolone.12 Their mechanism of action in CINV remains to be elucidated. At equivalent doses, these agents have equivalent safety and efficacy and can be used interchangeably.12 A key advance in the prevention of CINV has been the development of 5-HT3 receptor antagonists. These drugs prevent the serotonin-stimulated emetic re sponse by blocking the 5-HT3 receptors of the vagal afferent nerves in the GI tract and the CTZ.5 In the U.S., these agents include granisetron, ondansetron, dolasetron, and palonosetron; tropisetron is not available in the U.S. All agents are currently or soon to be available in both IV and oral formulations. Oral and IV formulations of granisetron have been marketed for more than 10 years and are licensed for the prevention of CINV that is associated with initial and repeated courses of emetogenic cancer therapy.15 The recommended adult dosage of oral granisetron (Kytril) is 2 mg once daily or 1 mg twice daily. In the 2-mg once-daily regimen, two 1-mg tablets or 10 mL of Kytril Oral Solution (2 teaspoonfuls, equivalent to 2 mg of granisetron) are given up to one hour before chemotherapy. In the 1-mg twice daily regimen, the first 1-mg tablet or one teaspoonful (5 mL) of Kytril Oral Solution is given up to one hour before chemotherapy, and the second tablet or second teaspoonful (5 mL) of Kytril Oral Solution is given 12 hours after the first. Either regimen is administered only on the day(s) of chemotherapy. Continued treatment, while patients are not on chemotherapy, has not been found to be useful.16 The recommended dosage for Kytril Injection is 10 mcg/kg, administered intravenously within 30 minutes before the initiation of chemotherapy and only on the day(s) of chemotherapy.17 Many clinical trials have demonstrated that all of the agents in this class are generally equally effective and have mild, infrequent AEs.5,11 At equivalent doses for the prevention of acute emesis, these agents have equivalent antiemetic activity and safety and are therefore interchangeable.12 IV and oral formulations are considered to be equally effective and safe.12 These agents are administered for preventing acute emesis on days of chemotherapy, and they are given once or twice daily. TREATMENT GUIDELINES Acute Chemotherapy-Induced Nausea and Vomiting Current guidelines recommend using a multidrug regimen for preventing acute CINV in high-risk patients that consists of a 5-HT3 receptor antagonist, an NK1 receptor antagonist, and dexamethasone.11,12 The combination of dexamethasone plus a 5-HT 3 receptor antagonist is recommended for preventing acute CINV in moderate-risk patients. An NK1 receptor antagonist can be added to the regimen for patients receiving an anthracycline and cyclophosphamide.11,12 Delayed Chemotherapy-Induced Nausea And Vomiting In patients receiving anthracycline and cyclophosphamide, monotherapy with aprepitant is recommended. For all other chemotherapies of moderate emetic risk only, monotherapy with dexamethasone or a 5-HT3 receptor antagonist is suggested for preventing delayed emesis.12 Dexamethasone and aprepitant are recommended in patients receiving cisplatin and all other agents of high emetic risk for preventing delayed emesis.12 RATIONALE FOR TRANSDERMAL DELIVERY Strakan Pharmaceuticals Ltd. has developed a new granisetron formulation, the granisetron transdermal delivery system (GTDS, Sancuso®), for preventing CINV that can be used for up to seven days. It is anticipated that a single patch application will replace the current 5-HT3-receptor antagonist dose regimens, obviating the need for repeated injections and repeated oral dosing while providing antiemetic protection during the entire period of multiday chemotherapy for patients at risk of CINV. The system consists of a stable matrix of granisetron base (6% weight/weight) in a commercially available 7

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Pharmacy & Therapeutics - October 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/ New Medical Devices Drug Forecast Medical Management of Parkinson’s Disease Why Is Health Care Regulation So Complex? The Next President’s Prescription for Action on Drugs Trends in Managing Multiple Sclerosis Product Profiler: Sancuso®

Pharmacy & Therapeutics - October 2008

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