Case Presentation:  A 55-year-old African-American male presented to the emergency department with brown urine, decreased urinary frequency, and acute on chronic back pain with bilateral leg soreness. He was intermittently bed-bound over the last 2 weeks due to pain. He stated that his chronic back pain is normally controlled with Acetaminophen/Hydrocodone, Pregabalin, and Tramadol. Recently, he doubled his daily dose of Pregabalin and was taking a total of 900 mg per day (max dose is 600 mg). He also noted a recent sexual encounter and concern for STDs. Neurological exam exhibited bilateral thigh tenderness and ⅘ strength bilaterally with no loss of sensory function. He had tenderness in bilateral paraspinal muscles adjacent to the lumbar spine. Laboratory results showed creatinine kinase level at 27,451 [IU]/L, thrombocytopenia, and elevated liver enzymes. HIV and STD testing were negative. Aggressive fluid resuscitation was provided. Atorvastatin and Pregabalin were discontinued. The patient responded well to IV Fluids. In 40 hours, his creatinine kinase dropped over 18000 [IU]/L. On discharge from the hospital, his urine color was clear and his back pain was back to baseline. Patient was advised to hold the Pregabalin until his primary care doctor (PCP) visit. At his PCP visit, patient’s creatinine kinase levels, liver enzymes, and platelet levels normalized. His statin has since been resumed with no issue. 

Discussion: In premarketing clinical trials, three Pregabalin treated subjects had reported rhabdomyolysis with less than 0.10% chance of rhabdomyolysis occurring all together. Rhabdomyolysis is known to result from sodium and calcium channel dysfunction. Na/K-ATPase and Calcium ATPase pump dysfunction leads to an increased cellular permeability to sodium ions due to decreased ATP production. An accumulation of intracellular sodium ions will in turn increase the intracellular calcium concentration. Excess calcium activates proteolytic enzymes that break down muscle. Additionally, Pregabalin’s mechanism of action is inhibition of the alpha2-delta subunit of calcium channels, which could contribute to the means of muscular damage seen in some patients. When looking at this patient’s medication list, it was easy to suspect Atorvastatin as the cause of rhabdomyolysis. However, this patient was taking statin at a stable dose for many years without an adverse reaction. The risk for adverse muscle events related to statin use is increased by drugs that inhibit the P-450 system. Pregabalin is eliminated renally without hepatic metabolism. This suggests that Pregabalin did not potentiate the effects of Atorvastatin. While immobility also contributed to this presentation, overdosing of Pregabalin is the most likely cause of rhabdomyolysis in this patient. 

Conclusions: Rhabdomyolysis is caused by breakdown of muscle fibers and release of their contents into the blood. In severe cases, the deposition of myoglobin in the renal tubules leads to kidney injury. The most common causes of rhabdomyolysis include extreme physical exercise, crush injury, prolonged immobilization, and medications, most commonly statins. Early recognition of the causative agent of rhabdomyolysis is important to ensure a favorable prognosis. This case highlights the importance of considering Pregabalin as a possible but rare culprit for rhabdomylosis when a patient is admitted to the hospital.