Phenytoin Intoxication in a Patient Receiving a Therapeutic Dose for Postoperative Seizure Prophylaxis: A Case Study.

OBJECTIVE: Phenytoin is commonly prescribed to prevent postoperative seizures. Despite the rarity of the CYP2C9 genetic polymorphism, which may result in poor phenytoin metabolism, in the Thai population, the authors report a case of phenytoin toxicity in a patient with poor metabolism administered with a standard dose of phenytoin. CASE REPORT: A 58-year-old Thai woman presented to the outpatient clinic with a 2-day history of nausea, vomiting, and dizziness. She underwent craniotomy for tumor removal 2 weeks after being diagnosed with tuberculum sellae meningioma. After the surgery, she was prescribed 300 mg of phenytoin daily to prevent seizures. During the physical examination, ataxia, horizontal nystagmus, and cerebellar abnormalities were observed, with an initial serum phenytoin concentration of 58.85 mg/L. The brain imaging results were unremarkable. Omeprazole was the only recognized drug interaction; however, it is highly unlikely to account for this condition. Pharmacogenetic investigation of CYP2C9 revealed a homozygous CYP2C9*3/*3 mutation, which is indicative of suboptimal drug metabolism and can reduce phenytoin metabolism by 50%. This patient was administered repeated dosages of activated charcoal over the course of 2 days. Her symptoms eventually subsided, with the phenytoin levels dropping to 29.51 mg/L. CONCLUSIONS: In the absence of an overdose history or drug-drug interaction, CYP2C9 polymorphism should be suspected in patients with phenytoin toxicity. In such situations, the phenytoin dosage must be decreased and monitored closely.

Sensitivity of dose-estimations for acute acetaminophen overdose in predicting hepatotoxicity risk using the Rumack-Matthew Nomogram.

Timely assessment of acetaminophen concentration in overdose situations is not always available in resource-poor settings. The 150 mg/kg dose-estimate for acetaminophen is widely considered as criterion for acetaminophen overdose. Its sensitivity and specificity when compared to the 150 mg/L treatment line on the Rumack-Matthew Nomogram (150-treatment line) has rarely been evaluated. This is a retrospective chart review of acute acetaminophen overdose patients. We evaluated the sensitivity and specificity of the 150, 200 mg/kg and 8- and 10-g dose-estimates by plotting the serum acetaminophen levels and using 150-treatment line on the Nomogram as the treatment cut-off. A comparison of medical care costs was performed. We enrolled 784 cases for analysis. Median (IQR) age was 23 (20-28) years (81.9% female). There were 545 cases (69.5%) where the estimated ingested acetaminophen dose were ≥150 mg/kg and 406 cases (51.8%) with concentrations ≥150-treatment line. Hepatotoxicity and acute liver injury (ALI) occurred in 7.3% and 23.9%, respectively. The sensitivity and specificity of 150 mg/kg dose-estimate for the 150-treatment line were 92.6% (95% CI 89.6, 94.8) and 55.3% (95% CI 50.3, 60.2). Among patients with dose-estimate below150 mg/kg, none developed hepatotoxicity and 17 (7.1%) develop ALI. The administration of activated charcoal significantly decreased the risk of being above the 150-treatment line by half. In resource-poor setings, the use of 150 mg/kg dose-estimate as a stand-alone criteria for initiation of N-acetylcysteine therapy is satisfactory, especially when combined with decontamination with activated charcoal and follow up of aminotransferase at 24 h.