A Study on the Effect of Changing the Dose on the Package Insert of Distigmine on Cholinergic Syndrome Onset Using the Japanese Adverse Drug Event Report (JADER) Database

Abstract

Distigmine has reversible and persistent cholinesterase (ChE) antagonism, and is used for the dysuria due to low activity bladders such as the neurogenic bladder dysfunction widely postoperatively, but fatal cases were reported by cholinergic syndrome. Therefore a dose was limited to 5mg only for adaptation of “the dysuria due to hypotonic bladder such as after surgery and the neurogenic bladder dysfunction” in March, 2010. In the current study, we examined a ministerial policy in the package insert revision using Japanese Adverse Drug Event Report database (JADER). Using a side effect report registered with JADER from January, 2004 to June, 2016, we calculated Reporting Odds Ratio (ROR) which was the index of the safe signal of the medical supplies adverse event and we compared number of reports and ROR of the cholinergic syndrome by the distigmine in approximately the measure in March, 2010 and evaluated it. The number of reports of the cholinergic syndrome by the distigmine was 138 cases before March 2010 and 65 cases after March 2010. After a measure, the number of reports decreased. The possibility that the package insert revision of the distigmine contributed to a decrease in cholinergic syndrome onset was suggested. Whereas monitoring careful sequentially needs the onset of the cholinergic syndrome in constant frequency to be found.