Pays: Canada
Langue: anglais
Source: Health Canada
DOLASETRON MESYLATE
SANOFI-AVENTIS CANADA INC
A04AA04
DOLASETRON
20MG
SOLUTION
DOLASETRON MESYLATE 20MG
INTRAVENOUS
5ML
Prescription
5-HT3 RECEPTOR ANTAGONISTS
Active ingredient group (AIG) number: 0132936003; AHFS:
CANCELLED POST MARKET
2011-08-15
PRODUCT MONOGRAPH PR ANZEMET ® (DOLASETRON MESYLATE) 20 MG/ML INTRAVENOUS INJECTION 50 AND 100 MG TABLETS ANTIEMETIC (5-HT 3 RECEPTOR ANTAGONIST) sanofi-aventis Canda Inc. Date of Revision: 2150 St. Elzéar Blvd. West October 12, 2006 Laval, Quebec H7L 4A8 Submission Control No. 107318 s-a Version 2.0 dated 2 PRODUCT MONOGRAPH PR ANZEMET ® (Dolasetron Mesylate) 20 mg/mL Intravenous Injection 50 and 100 mg Tablets Antiemetic (5-HT 3 receptor antagonist) ACTION AND CLINICAL PHARMACOLOGY Dolasetron and its active metabolite, hydrodolasetron (MDL 74156), are selective 5-HT 3 receptor antagonists shown not to have activity at other known serotonin receptors and with low affinity for dopamine receptors. The serotonin 5-HT 3 receptors are located on the nerve terminals of the vagus in the periphery and centrally in the chemoreceptor trigger zone of the area postrema. It is thought that chemotherapeutic agents produce nausea and vomiting by releasing serotonin from the enterochromaffin cells of the small intestine, and that serotonin then activates the 5-HT 3 receptors located on vagal afferents to initiate the vomiting reflex. Acute, reversible, ECG changes (PR and QTc; QRS widening), caused by dolasetron, have been observed in controlled clinical trials. Dolasetron appears to prolong both depolarization and, to a lesser extent, repolarization time. Although QTc prolongation is primarily due to QRS widening, JT prolongation has also been observed. The magnitude and frequency of the ECG changes increased with dose (related to the peak plasma concentration of hydrodolasetron but not the parent compound). These ECG changes usually returned to baseline within 6 to 8 hours, but in some patients have lasted 24 h or longer. Dolasetron mesylate administration has little or no effect on blood pressure. In healthy volunteers (N=4), dolasetron mesylate in single intravenous doses up to 5 mg/kg produced no effect on pupil size or meaningful changes in EEG tracings. Results from neuropsychiatric tests revealed that dolasetron mesy Lire le document complet