Clozapine-Related Appendicitis: UK Pharmacovigilance Data, 1992-2022

An association between appendicitis and clozapine has been reported, but not studied systematically.

To document records of clozapine-associated appendicitis/appendectomy, we audited UK MHRA Yellow Card reports classified as clozapine-related gastrointestinal disorders, from 1992 to the end of 2022.

There were 65 unique reports (48 males) where appendicitis/appendectomy were documented and confirmed as occurring while the patient was taking clozapine. There were no significant differences in median age (40/45 y), clozapine dose (362.5/325mg d -1 ), and in the duration of clozapine treatment before the index event (1296/780 d) between men/women, respectively. The reports were coded under 29 different adverse drug reaction terms, most commonly those mentioning abdominal pain (16), constipation (17), ileus paralytic (15), intestinal obstruction (11), and vomiting (13). "Appendix disorder" was only mentioned 4 times. Overall, the coded terms reflected those associated with harmful clozapine-induced gastrointestinal hypomotility (CIGH). The annual number of reports reached 10 in 2011, but have since fallen (no reports: 2022). Appendectomy was recorded 59 times. Peritonitis was mentioned in 10 reports (all 3 deaths), but may have featured in other cases. According to the data, clozapine was continued postoperatively in 27 instances, but stopped in 16.

The data suggest that appendicitis while taking clozapine is often a manifestation of harmful CIGH and can occur at any stage once treatment is established. Every effort must be made to monitor bowel function and ensure that laxative treatment is adhered to when prescribing clozapine.