Citation

Thomas L, Pollak PT. J. Emerg. Med. 2003; 25(1): 61-66.

Copyright

(Copyright © 2003, Elsevier Publishing)

DOI

10.1016/S0736-4679(03)00130-6

PMID

unavailable

Abstract

Experience with managing overdoses of the atypical antipsychotic agent, clozapine, has been limited. A 20-year-old woman, who presented 6 h after ingesting 3500 mg of clozapine, had an unexpectedly prolonged duration of tachycardia and somnolence. Successful recovery followed management with supportive measures for several days in the intensive care unit. However, the duration of symptoms greatly exceeded that predicted by the published 12-h half-life of clozapine and was associated with an unexplained persistence of serum clozapine concentrations. Recovery with normalization of autonomic function occurred only after serum clozapine began to decline again after a 4-day plateau, as revealed by serum monitoring. Similar observations have been reported in two other cases. In overdose, clozapine may not behave as predicted by its published pharmacokinetics. Persistent serum drug concentrations may prolong the period of intensive care, suggesting that aggressive measures to remove clozapine from the gut at the time of overdose may be warranted. © 2003 Elsevier Inc.; FreeText:The patient was brought to the Emergency Department (ED) with a decreased level of consciousness. The initial history indicated that she had attempted suicide by overdose. Six years prior, she had been diagnosed as having a schizoaffective disorder with psychotic features and had previously attempted suicide with acetaminophen, with no permanent organ damage. Due to poor adherence to prescribed therapy, her medications were often changed. At the time of presentation, her medications included flupenthixol 22.5 mg imevery 10-12 days (last dose was missed), valproic acid 1500 mg daily, orally, clonazepam 0.5 mg, orally, bid, and lorazepam as needed for anxiety. Routine blood work (blood glucose, electrolytes, urea, creatinine, CBC) was within normal limits and an initial toxicology screen was negative except for a qualitative test confirming ingestion of benzodiazepines.; Indications:1 patient with schizoaffective disorder.; Patients:One 20-year-old woman (inpatient).; TypeofStudy:Delayed recovery associated with persistent serum concentrations after Leponex overdose was studied. Case report.; DosageDuration:3500 mg (100 mg/tablet, 35 tablets).; Results:Upon arrival to the hospital, noted were a heart rate (HR) of 124 beats/min, respiratory rate (RR) of 12 breaths/min, and an oxygen saturation of 82%. The Glasgow Coma Scale (GCS) score was 6 and deteriorated to 3. She had a HR of 110 beats/min, blood pressure (BP) of 156/73 mmHg, and the temperature was 33.1° C. The skin was warm and dry. The pupils were 4 mm, equal and sluggishly reactive. Respiratory and cardiac examinations were unremarkable aside from the rapid heart rate. Bowel sounds could not be detected. Deep tendon reflexes were absent bilaterally, but no focal neurological signs were found. The electrocardiogram (EKG) showed a sinus tachycardia. The patient remained intubated and 50 g of activated charcoal was instilled in her stomach via a nasogastric tube. Upon recovery, the patient confirmed that she collected about a 2-week supply, or 35 clozapine 100 mg tablets, for the purpose of overdose. She had taken a few clonazepam tablets, but denied ingesting any other medications, alcohol, or illicit drugs. Patient was placed in the Intensive Care Unit (ICU) for monitoring and supportive care. Prophylactic heparin 5000 units, sc, bid, and ranitidine 50 mg iv were initiated. Signs and symptoms exhibited by the patient that were consistent with those previously described in Leponex overdose included: sedation or coma, tachycardia, hypothermia, hypersalivation, areflexia, and mydriasis. Serial measurements of serum Leponex concentrations were made during her stay (highest 2183 ng/ml with heart rate of 124 beats/min. Bowel sounds were not audible until day 6 and the first bowel movement occurred on day 8. In addition to supportive care, the patient required antibiotic therapy for pneumonia. After extubation on day 4, she produced green-yellow sputum with high temperature. Ceftriaxone 1 gram daily, iv was administered, and after transfer out of the ICU on day 5, results of the endotracheal tube culture confirmed the presence of Staphylococcus aureus. Treatment of pneumonia was successfully treated completed with cefazolin 1 gram, iv, every 8 hours and gentamicin 300 mg daily, iv.; AdverseEffects:The patient experienced sedation or coma, tachycardia, hypothermia, hypersalivation, areflexia and mydriasis.; AuthorsConclusions:In conclusion, although unusual, clozapine overdose is going to be encountered in the ED. The possibility that it exhibits an unusual pharmacokinetic profile at large doses may affect the recovery time of the patient. Why some cases have sustained elevations of serum clozapine concentrations remains unclear, but one possibility is delayed drug absorption. Most patients will make a full recovery after single agent overdose with clozapine if serious complications such as aspiration pneumonia are avoided and autonomic function is supported.

Language: en

Keywords

Safety; Overdose; Clozapine; Pharmacokinetics; Therapeutics