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.