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Different classes of medication have been reported in the literature to be associated with an increased risk of gastrointestinal perforation. However, little is known about the risk of drug-induced perforated appendicitis. We analyzed the Food and Drug Administration Adverse Event Reporting System (FAERS), a large national database of reported adverse events associated with post-market FDA-approved medications from January 2011 to October 2021. Patients of any age group with appendiceal perforation were included. Duplicated reports and other anatomical areas of gastrointestinal tract perforation outside the appendix were excluded. During the study period, 474 event cases met inclusion criteria, of which 284 were females. Most reports of perforation occurred in patients 40–49 years ( n  = 110) and 50–59 years ( n  = 144). Cases of perforated appendicitis occurred in patients being treated for multiple sclerosis (31.5%) and rheumatoid arthritis (17.1%). Perforation occurred in patients receiving interferon beta 1a (23.6%), adalimumab (17.9%), etanercept (14.1%), natalizumab (12.2%), clozapine (10.1%), infliximab (9.9%), bevacizumab (7.2%), and calcium chloride (4.9%). Sixteen fatal outcomes were reported. Findings from the FAERS database highlight the risk of appendiceal perforation in the context of different classes of drugs. Larger pharmacovigilance studies are needed to confirm these observations.

Medications and the risk of perforated appendicitis: an adverse event report system (FAERS) database analysis