Background Irinotecan is chemotherapeutic agent often used in abdominal cancers such as colorectal and pancreatic cancers. While often associated with non-central nervous system (CNS) adverse effects, in rare cases it may present with paresthesias and dysarthrias. In one case, a patient received an irinotecan-containing regimen (fluorouracil, irinotecan, oxaliplatin) and experienced several neurotoxic effects, which was successfully managed. Case Report A female patient with newly-diagnosed pancreatic cancer was started on fluorouracil, irinotecan, and oxaliplatin (modified FOLFIRINOX). She developed dysarthrias early on in the course. Causality assessment was conducted via the Naranjo criteria, yielding a score of 6, indicating a probable adverse reaction. Management & Outcome Initially managed with steroids and lorazepam, she was eventually given a prophylactic strategy of atropine 0.4 mg and a longer infusion time of 3 h instead of 90 min with as needed lorazepam. This strategy alleviated the dysarthrias and the patient was able to complete 12 cycles of therapy, resulting in a partial response at the end of treatment. Discussion Prolonging the infusion and giving prophylactic atropine may help to prevent these rare adverse effects of irinotecan.