Diclofenac and the Risk of Rhabdomyolysis: Analysis of Publications and the WHO Global Pharmacovigilance Database

Background: Diclofenac, a nonsteroidal anti-inflammatory drug, is not a documented cause of rhabdomyolysis in the Summaries of Product Characteristics held by major regulators. There are, however, eight published single case reports that associate rhabdomyolysis with diclofenac. Objective: Triggered by a serious local case report, this study was conducted to evaluate the evidence for a causal association between diclofenac and rhabdomyolysis. Patients and Methods: A descriptive analysis of rhabdomyolysis associated with diclofenac was conducted by mining data from the WHO Global Database of Individual Case Safety Reports, VigiBase, and published case reports. Results: 70 eligible cases were retrieved from VigiBase. The median age was 56.5 years (range 1–90). Where reported precisely (26 reports), the median time to onset of rhabdomyolysis following administration of diclofenac was 3 days. In 20 cases, diclofenac was reported as a sole suspect and was solely administered in 14 of these. In 30 cases, rhabdomyolysis abated following withdrawal of diclofenac. Seven of these cases fulfilled the WHO-UMC case-causality assessment criteria for ‘probable’. Diclofenac was probably an indirect cause in another five reports where rhabdomyolysis ensued from injection-site necrosis. There were eight fatalities and intramuscular administration was over-represented in this group. In 27 patients taking lipid-lowering agents, the incidence of acute kidney injury with rhabdomyolysis was 62.9% compared with 37.1% for the whole cohort. Off-label use of diclofenac for minor or undiagnosed conditions was reported. Conclusion: Currently available data suggests a causal link between diclofenac and rhabdomyolysis either directly or indirectly.