Use of atropine-diphenoxylate compared with hyoscyamine to decrease rates of irinotecan-related cholinergic syndrome

Cholinergic syndrome is a well established acute adverse reaction associated with irinotecan. Cholinergic side effects can be ameliorated or prevented with anticholinergic agents. To date, no formal studies have compared atropine-diphenoxylate and hyoscyamine as premedications for prophylaxis of the cholinergic syndrome with irinotecan infusion.

To compare the incidence of cholinergic syndrome with irinotecan using atropine-diphenoxylate or hyoscyamine as premedication.

We conducted a retrospective, single-center, nonrandomized, cohort study of adult patients treated with atropine-diphenoxylate or hyoscyamine as premedication before receiving irinotecan. For all irinotecan infusions, intravenous atropine was administered for patients experiencing any cholinergic reaction.

A total of 532 irinotecan cycles (354 cycles for atropine-diphenoxylate group; 178 cycles for hyoscyamine group) were analyzed in 80 patients. Overall incidence of cholinergic syndrome did not differ between atropine-diphenoxylate (8.2%) and hyoscyamine (9.0%) groups (P = .76). The incidence of cholinergic syndrome after the £rst cycle of irinotecan was similar between the 2 arms, atropine-diphenoxylate (14.6%) and hyoscyamine (10.7%), with P = .74. The most common cholinergic symptoms documented were abdominal pain or cramping, and diarrhea.

This study was subjected to vulnerabilities to bias and random error because of its observational retrospective design and small number of participants.

Lack of difference in the incidence of cholinergic syndrome observed in irinotecan-treated patients suggests atropinediphenoxylate and hyoscyamine may both be effective prophylactic options. The findings support the need for a larger, randomized study to assess and compare these agents with other potential premedications such as scopolamine and atropine in prevention of irinotecan-related cholinergic syndrome.