Gabapentinoids-Induced Rhabdomyolysis/Myopathy: Clinical Characteristics, Management, Outcomes, and Critical Safety Alerts.

BACKGROUND

Gabapentinoids, increasingly prescribed for neuropathic pain, demonstrate undercharacterized muscular toxicity risks despite perceived safety advantages over opioids, this includes the potential to induce rhabdomyolysis-a critical condition characterized by rapid release of intracellular contents into the systemic circulation due to muscle cell injury, ultimately leading to systemic complications.

METHODS

A systematic global review (inception-2024) identified 19 gabapentinoid-induced rhabdomyolysis cases across 15 databases, analyzed via standardized protocols for clinical patterns, management, and outcomes.

RESULTS

Cases (median age 63; 52.6% male) manifested rapid symptom onset (≤7 days in 52.9%), severe creatine phosphokinase(CPK) elevation (median 3,095 U/L), and renal impairment (78.9%). All patients discontinued gabapentinoids, with 57.9% receiving hydration/alkalinization and 31.6% requiring dialysis. Biochemical resolution occurred in 78.9% (median 14 days), though one mortality resulted from comorbid complications. Naranjo assessments confirmed probable causality in 84.2% of cases. Of note, a significant majority of patients (89.5%) presented with multiple comorbidities (such as hypertension, diabetes, and hyperlipidemia) and received polypharmacy. Particularly when co-administered with statins (as observed in 7 cases where symptom onset occurred following combination therapy), drug-drug interactions may lead to accumulation of medicinal products, thereby significantly increasing the risk of rhabdomyolysis.

CONCLUSION

This study provides the first evidence-based framework for gabapentinoid myotoxicity monitoring, emphasizing renal function-guided dosing, early CPK surveillance, and drug interaction vigilance. Clinicians should consider gabapentinoid cessation in unexplained myalgia with CK >3×ULN, particularly in high-risk populations.