Metoclopramide and Risk of Pheochromocytoma Crisis: A Causality Assessment Using Literature and VigiBase Data

The association between metoclopramide and pheochromocytoma crisis has been documented in literature. However, evidence has primarily relied on case reports and small-scale experimental studies rather than rigorous causal assessments. Therefore, this study aimed to assess the causal relationship between metoclopramide use and the occurrence of pheochromocytoma crisis by analyzing data from the literature and World Health Organization (WHO) global pharmacovigilance database.

This study was a descriptive analysis and causality assessment of metoclopramide and pheochromocytoma crisis. Data were retrieved from published literature and the WHO global pharmacovigilance database (VigiBase) on February 13, 2025. In addition to the causality results extracted from VigiBase, causality assessment at the individual level for published case reports was conducted using the Naranjo Adverse Drug Reaction Probability Scale. Causality assessment at the population level was conducted using the Austin Bradford-Hill causality assessment framework.

A total of 62 de-duplicate cases were found in VigiBase and the literature. Almost all cases were classified as serious with 12 fatalities. In many instances, the drug-induced crisis served as the first clinical indication of an undiagnosed (occult) tumor. A causality assessment using the Naranjo algorithm conducted by the current authors classified the 18 published cases as "probable" (13) and "possible" (5). In VigiBase, causality assessment at the individual level was reported for 10 cases, with possible (6), probable (2), and reasonable possibilities (2). The results of the causality assessment at the population level using Hill's criteria revealed compelling evidence across all nine criteria.

A reasonable causal relationship exists between metoclopramide and pheochromocytoma crisis, supporting its contraindication in patients with known or suspected pheochromocytoma.Clinicians should monitor patients, consider underlying pheochromocytoma, and be aware of this risk. Further international case-control studies are recommended to confirm this causal association.