Objective: The purpose of this study was to investigate the threshold blood level of amantadine and risk factors for central nervous system (CNS) side effects by analyzing the amantadine blood concentrations of patients who developed CNS side effects.

Background: Amantadine is used as a treatment for Parkinson’s disease, particularly for levodopa-induced dyskinesia. Hallucination, delirium, impaired consciousness, and myoclonus have been reported as CNS side effects of amantadine. We previously reported that CNS symptoms occurred in patients with amantadine blood concentrations of 3000ng/ml or higher, but later experienced CNS side effects even at amantadine blood concentrations below 3000ng/ml. To date, the detailed relationship between blood levels of amantadine and CNS side effects has not been determined.

Method: Among the patients whose amantadine blood levels were measured in our laboratory by June 2020, data of 46 patients with Parkinson’s disease who presented CNS side effects were used. Data of 46 patients with Parkinson’s disease who did not present CNS side effects were also used as a control. Amantadine blood concentration was measured by gas chromatography. We explored potential risk factors for CNS side effects using multivariable logistic regression models in patients with Parkinson’s disease. To investigate the threshold blood concentration of amantadine associated with CNS side effects, we performed receiver operating characteristic (ROC) curve analysis and calculated the optimal cutoff value. This study was approved by the Clinical Research Ethics Review Committee of Ehime University Hospital.

Results: The patients over 75 years of age had a high odds ratio (OR) of 11.527 (95% confidence interval (CI), 3.660‐45.802) for the occurrence of CNS side effects compared to under 75 years of age. The OR for patients taking more than 150 mg of amantadine was 7.349 (95% CI, 2.230‐30.512). The OR for patients with a serum creatinine level of 0.85mg/dL or higher was 5.382 (95% CI, 1.793‐18.282). The cut-off value of amantadine blood concentration for CNS side effects estimated by ROC curve was 1562ng/ml.

Conclusion: The risk factors for amantadine CNS side effects were elderly patients, amantadine dosage, and reduced renal function. The threshold blood level of amantadine for CNS side effects was 1562ng/ml.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/risk-factors-for-central-nervous-system-side-effects-of-amantadine/