Time-to-onset Analysis of Rhabdomyolysis due to Different Proton Pump Inhibitors Using a Pharmacovigilance Database

Abstract

Background/aim: Recent research has increasingly demonstrated an association between proton pump inhibitors (PPIs) and serious adverse events. This study aimed to evaluate the association between PPI and rhabdomyolysis (RM), examining its time-to-onset profiles using the Japanese Adverse Drug Event Report (JADER) database.

Patients and methods: Data spanning from April 2004 to March 2022 were used. The association between PPIs and RM was evaluated using the reporting odds ratio (ROR), adjusted for sex and age. Subsequent analyses were conducted after excluding cases involving concomitant use of statins or fibrates. Furthermore, the onset time of RM and Weibull distribution parameters were calculated to evaluate the expression profile of RM, and the outcomes were examined.

Results: RM was associated with the use of esomeprazole, omeprazole, and rabeprazole, even in the absence of concomitant statin or fibrate use. The median time to RM onset varied among PPIs, ranging from 6.5 to 127 d. The Weibull distribution parameters indicated that the hazard types of nearly all orally administered PPIs were classified as early failure or close to random failure. Regarding outcomes, cases of death were reported for all PPIs except vonoprazan.

Conclusion: The findings suggest the need for vigilant monitoring of RM during PPI administration, particularly in the early stages, considering the varying onset times.

Keywords: Japanese Adverse Drug Event Report database; Rhabdomyolysis; Weibull distribution; adverse event profiles; disproportionality analysis; proton pump inhibitors.

Figure 1. Box plot illustrating the onset time of rhabdomyolysis after the administration of proton pump inhibitors. Lines within the boxes represent the median, the boxes depict the interquartile range, and the whiskers indicate the minimum and maximum values.