Two cases of pregabalin neurotoxicity in chronic kidney disease patients

Sir We report two cases of newly presenting pregabalinneurotoxicity in chronic kidney disease (CKD) patients. A 67-year-old man was referred to our nephrology department for consultation. He had been admitted to the department of orthopedics because of spinal stenosisand had undergone surgery 5 weeks earlier. He had started hemodialysis 3 months previously. Upon presentation, he was in a deep drowsy mental state. He was also suffering from generalized myoclonic jerk, aphasia and dysarthriaof several days duration. We did not detect a brain lesion on magnetic resonance imaging or computed tomography. No medications were being given that could have induced his neurologic symptoms and signs. No laboratory abnormalities were detected that would explain his neurologic deficits. However, pregabalinhad been started at a dosage of 300 mg/day 2 weeks before presentation, and the dosage had been increased to 450 mg/day 7 days previously. We concluded that his neurologic deficits were the result of pregabalintoxicity. Pregabalinwas immediately withdrawn and an additional three hemodialysis sessions were performed, after which the patient became mentally alert and the generalized myoclonus, aphasia and dysarthriacompletely disappeared. The second case is that of a 43-year-old man who was admitted for evaluation of nausea, vomiting and general weakness. He was diagnosed with diabetes mellitus and CKD Stage 4. Three days after admission, he complained of pain around the posterior neck region and in both shoulders. He was diagnosed with fibromyalgiaand commenced therapy with pregabalin. After receiving a 75 mg/day dose of pregabalinfor 2 days, he developed a drowsy mental state and myoclonusof both upper extremities was detected. His calculated creatinine clearance (CCr) by Cockcroft–Gault formulawas 25.7 mL/min. We suspected pregabalintoxicity and immediately withdrew it. Thereafter, he fully recovered from the drowsiness, disorientation and myoclonus. Pregabalinis well absorbed orally and has a bioavailability of >90%. It is completely excreted into the urine without hepatic metabolism. It is usually suggested that pregabalindoses be decreased by ∼50% for each 50% decline in CCr to achieve similar plasma drug concentrations in patients with impaired renal function[1]. Pregabalintoxicity in CKD patients has very rarely been reported [2–4]. Two cases have occurred in hemodialysis patients, whereas one case occurred in a patient undergoing peritoneal dialysis. Our first patient was also undergoing hemodialysis, whereas the second one was a CKD Stage 4 patient. To the best of our knowledge, there have been no reports of pregabalintoxicity in a Stage 4 CKD patient. In our first patient, although the initial dosage of pregabalinwas high, there were no severe symptoms and signs before the increase in dosage. This might have been the result of drug removal by regular hemodialysis. Although we reduced the dosage of pregabalinin accordance with his renal function in the other patient, pregabalinneurotoxicity did occur. We think that a 75 mg/day dosage might not increase the serum level of pregabalinenough to induce neurologic impairment, although we did not measure the drug level in the serum. One should exercise prudencewhen prescribing this drug in a CKD patient and adjust the dosage in accordance with renal function. The drug should be immediately withdrawn if neurologic symptoms and signs appear.