País: Canadà
Idioma: anglès
Font: Health Canada
DOLASETRON MESYLATE
SANOFI-AVENTIS CANADA INC
A04AA04
DOLASETRON
100MG
TABLET
DOLASETRON MESYLATE 100MG
ORAL
15
Prescription
5-HT3 RECEPTOR ANTAGONISTS
Active ingredient group (AIG) number: 0132936002; AHFS:
CANCELLED POST MARKET
2014-04-21
PRODUCT MONOGRAPH PR ANZEMET ® (DOLASETRON MESYLATE) 100 MG TABLET ANTIEMETIC (5-HT 3 RECEPTOR ANTAGONIST) sanofi-aventis Canada Inc. 2150 St. Elzéar Blvd. West Laval, Quebec H7L 4A8 Date of Revision: July 5, 2012 SUBMISSION CONTROL NO.: 155815 s-a Version dated Page 2 of 25 _ _ PRODUCT MONOGRAPH PR ANZEMET ® (Dolasetron Mesylate) 100 mg Tablet _ _ 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. 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 mesylate does not alter mood or concentration. Multiple daily doses of dolasetron have no effect on colonic transit in humans. Dolasetron has no effect on plasma prolactin concentrations. EFFECTS ON ELECTROCARDIOGRAM 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 repolarization time. 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 Llegiu el document complet