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Drug Interaction Between Sevelamer and Levetiracetam: The First Clinical Experience.

To the Editor: Sevelamer is a potent phosphate binder used in prevention and treatment of hyperphosphatemia in patients with chronic kidney disease. Generally, this drug demonstrates favorable safety and tolerability profiles.1 Based on pharmacokinetic reports, drug interactions of sevelamer are exceedingly rare. The published medical literature contains anecdotal clinical evidence regarding major interactions between sevelamer and drugs such as furosemide, cyclosporine, tacrolimus, levothyroxine, and mycophenolate mofetil.2,3 However, to the best of our knowledge, drug interaction between sevelamer and levetiracetam has never been reported. This report delineates the first clinical case study of a drug interaction that ensued on the simultaneous administration of sevelamer and levetiracetam. Physicians should be cognizant of this novel interaction in patients adhering to a stringent sevelamer regimen requiring initiation of anticonvulsant therapy. A 42-year-old man with a history of chronic glomerulopathy secondary to diabetes mellitus was receiving thrice weekly hemodialysis for 9 months. He was started on sevelamer carbonate 800 mg thrice daily with meals for persistent hyperphosphatemia (7.6 mg/dL). The patient reportedly developed a new-onset state of confusion starting a few hours after the administration of the first dose of sevelamer that gradually worsened with subsequent doses. One day after the commencement of sevelamer therapy, he experienced 17 seizure episodes in a 2-hour span. Each episode lasted for around 2 minutes, after which he immediately recuperated and was able to verbalize and speak coherently. At presentation, he was hemodynamically stable with normal body temperature. Physical examination revealed a body mass index of 36.8. Neurological examination of sensory and motor responses was unremarkable. His medical history included seizure-like episodes, coronary artery disease status after coronary artery bypass grafting, end stage renal disease, diabetes mellitus, hypertension, dyslipidemia, migraine, nephrolithiasis, obesity, chronic obstructive pulmonary disease, appendectomy, and cholecystectomy. His daily home medications included sevelamer carbonate 800 mg thrice daily, levetiracetam 1000 mg twice daily, insulin glargine, carvedilol 12.5 mg twice daily, lisinopril 40 mg, topiramate 100 mg, montelukast 10 mg, cholecalciferol 2000 IU, diphenhydramine 25 mg twice daily, subcutaneous dulaglutide 1.5 mg/0.5 mL once weekly, ezetimibe 10 mg, pantoprazole 40 mg, famotidine 20 mg, ferrous sulfate 325 mg, fluticasone propionate 50 mg/actuation nasal spray, rosuvastatin 40 mg, sertraline 25 mg, and renal multivitamins. His recent levetiracetam level was 45.6 mg/mL (12–46 mg/mL), topiramate 9.0 mg/mL (5– 20 mg/mL), and acetaminophen ,2 mg/mL. Magnetic resonance imaging brain before these new seizure episodes revealed chronic microvascular ischemic changes. Basal ganglia and thalamic lacunar infarcts were also noted. Differential considerations included vasculitis or demyelinating processes. The patient had been completely stable on levetiracetam 1000 mg twice daily regimen with no seizure episode over the past 3 years until his current admission. The workup for the seizure recurrence was started but his health care proxy refused further imaging. Because there were no focal deficits or findings suspected of intracranial pathology, immediate brain imaging was deferred after discussion with the attending neurologist. The patient’s random blood glucose was 176 mg/dL, whereas the HbA1c was noted to be 7.7%. Serum electrolyte levels, liver panel, and renal function tests were within normal limits. Laboratory evaluation was inconclusive for potential metabolic or infective causes underlying his seizure episode. Based on the temporal association between initiation of sevelamer and the timing of seizure recurrence, sevelamer–levetiracetam drug interaction was considered plausible. The Naranjo Nomogram for Adverse Drug Reaction Assessment (Naranjo score) resulted in 8. Sevelamer was thus immediately discontinued. He was then initiated on calcium acetate 667 mg thrice daily with meals for his hyperphosphatemia. Rest of his medication regimens were left unaltered. Subsequently, he was discharged home in a stable condition. At the 1week follow-up visit, the patient remained seizure free. His serum phosphate levels trended down to normal. At the subsequent follow-ups, he did not report another American Journal of Therapeutics 0, 1–2 (2020)