Moderate toxic effects following acute zonisamide overdose

Abstract

Zonisamide is an antiepileptic drug that acts on voltage-sensitive sodium and calcium channels, with a modulatory effect on GABA-mediated neuronal inhibition and an inhibitory effect on carbonic anhydrase. It is used mainly for the treatment of partial seizures, and is generally well tolerated at therapeutic doses. The most common reported adverse effects are somnolence, anorexia, dizziness, and headache. There are limited data on zonisamide overdose in the literature, and no case of zonisamide mono-intoxication has been published to date. We describe the first case of zonisamide mono-intoxication in a 25-year-old woman who ingested 12.6 g of this substance with suicidal intent. Despite a plasma zonisamide concentration of 182 mg/L on admission, the patient exhibited a benign clinical course with vomiting and central nervous system depression, requiring brief intubation. Somnolence persisted for 50 hours, and normal-anion-gap metabolic acidosis and polyuria for several days. Complete recovery may be expected with supportive care, even after ingestion of large zonisamide overdoses.

Zonisamide-induced distal renal tubular acidosis and critical hypokalaemia

“…A direct relationship between serum drug concentration and clinical response has not been established, making routine therapeutic drug level monitoring of uncertain value; similarly, the development of metabolic acidosis is not related to either zonisamide dosage level or treatment duration 30–32. Even in cases of zonisamide overdose, measurement of serum drug levels is not mandated due to poor correlation with clinical features 33 34…”

Toxicological screening of human plasma by on‐line SPE‐HPLC‐DAD: identification and quantification of acidic and neutral drugs

“…The following toxic effects have been documented for these analytes in cases of acute intoxication: NSAIDS in lower doses – tinnitus, nausea, vomiting, hyperventilation, somnolence and ataxia. In cases of severe intoxication, ulceration, and perforation of the stomach or intestines (Broussard et al ., ), hypotension, hypothermia, respiratory depression, shock, coma and renal failure (Smolinske et al ., ). Barbiturates – central nervous system depression, painful stimuli, apnea, respiratory failure, cardiovascular collapse, coma and death (Gossel and Bricker, ). Anticoagulants – several extensive hematomas, massive clotting abnormality (prothrombin ratio < 10%) and bleeding events (Riesselmann et al ., ; Levine et al ., ). Anticonvulsants – coma, spontaneous horizontal nystagmus, myoclonus, bradycardia, hypotension and respiratory depression (Naito et al ., ) as well as somnolence, vomiting, central nervous system depression, metabolic acidosis and polyuria (Hofer et al ., ). Diuretics – dehydration, hypokalemia, hypovolemia, excessive urination, metabolic alkalosis and renal failure (Losse et al ., ; Schrier, ). …”

“…(4) Anticonvulsantscoma, spontaneous horizontal nystagmus, myoclonus, bradycardia, hypotension and respiratory depression (Naito et al, 1988) as well as somnolence, vomiting, central nervous system depression, metabolic acidosis and polyuria (Hofer et al, 2011). (5) Diureticsdehydration, hypokalemia, hypovolemia, excessive urination, metabolic alkalosis and renal failure (Losse et al, 1983;Schrier, 2007).…”