Amantadine-Induced Hypoglycemia in a Patient Without a History of Diabetes Mellitus

Abstract Introduction: Hypoglycemia, a state of low blood glucose, has multiple etiologies with the most common being drug-induced hypoglycemia particularly in individuals with a history of diabetes with insulin, sulfonylureas, and metformin as the most frequent offenders. However, one underrecognized reason behind drug-induced hypoglycemia is Amantadine. This medication acts as a dopamine receptor antagonist, nicotinic receptor antagonist and non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist used to treat symptoms of Parkinson's disease, multiple sclerosis or as an adjunctive therapy in the setting of antipsychotic use. Review of current literature yielded limited results on Amantadine-associated hypoglycemia prompting a deeper dive into this case report of suspected amantadine-induced hypoglycemia in a 72-year-old man with no prior history of diabetes mellitus or insulin use. Case Report: A 72-year-old man a past medical history of hypothyroidism, schizophrenia, epilepsy, COPD, asthma, CKD, BPH, glaucoma, osteoporosis who presented to the emergency department (ED) due to concerns of changes in mental status and decreased oral intake. The patient is minimally verbal and non-ambulatory at baseline. Of note, the patient had prior admissions for hypoglycemia while on adjunctive amantadine therapy. In the ED, vital signs were stable and labs were notable for leukocytosis of 13 x103 K/uL, a positive urinalysis and blood glucose (BG) level was 63 mg/dL. Chest x-ray revealed some retrocardiac opacity concerning for pneumonia. Blood cultures were negative. Thyroid function tests, cortisol levels and cosyntropin stimulation tests were within normal limits. Endocrinology was consulted and work up for other instigating factors including labs for insulin level, proinsulin, insulin antibodies, beta hydroxybutyrate and c-peptide was negative. Amantadine was discontinued with notable stable improvement in blood glucose levels. Discussion: Amantadine has been demonstrated to decrease glucagon levels and increase insulin levels which could potentially lead to hypoglycemia.3 While the etiology of hypoglycemia in this case is possibly multifactorial given the recent decreased PO intake, infection and poor reserves, Amantadine as a possible culprit was highly likely given the negative work up for other instigating factors. In essence, this case highlights the importance of comprehensive history taking and medication reconciliation in hospitalized patients.