A rare presentation of phenytoin toxicity triggered by isoniazid in reactivated pulmonary TB

Abstract

Phenytoin is a commonly used antiepileptic drug with a narrow therapeutic index and is susceptible to clinically significant drug–drug interactions. It is primarily metabolized by hepatic cytochrome P450 enzymes, particularly CYP2C9. Isoniazid, a first-line anti-tubercular agent, is a known inhibitor of this enzyme and may precipitate phenytoin toxicity when co-administered. We report a case of phenytoin toxicity in a patient with reactivated pulmonary tuberculosis following the initiation of isoniazid therapy. The patient experienced neurological features including dizziness, generalized weakness, involuntary movements, and MRI brain revealed multifactorial encephalopathy suggestive of phenytoin toxicity, supported by laboratory findings (serum phenytoin levels-35.2 μg/mL) and clinical evaluation. Phenytoin was discontinued and replaced with levetiracetam, along with appropriate supportive management. The patient showed gradual clinical improvement after withdrawal of phenytoin, and antitubercular therapy was continued under close monitoring.  This case highlights the importance of recognizing potential drug–drug interactions between phenytoin and isoniazid, early neuroimaging and therapeutic drug monitoring in tuberculosis patients receiving long -term antiepileptic therapy.