Phenytoin toxicity caused by a drug-to-drug interaction between phenytoin and antitubercular therapy

Phenytoin is one of the most used antiepileptic drugs. Isoniazid, a first-line antitubercular drug, blocks the CYP2C19 enzyme, preventing phenytoin from being metabolised. Concomitant use of phenytoin and isoniazid predisposes to phenytoin toxicity. Here, we present the case of a female in her mid-30s with a known seizure disorder on phenytoin monotherapy. She was also started on antitubercular therapy, including isoniazid, after being diagnosed with pulmonary tuberculosis recently. This led to a catastrophic sequence of events including progressive loss of balance, psychosis, nystagmus, hyperreflexia and later, stupor. Her serum phenytoin level was found to exceed 40 mg/L. Her symptoms improved when phenytoin was switched to levetiracetam. Ours is the first case report of such an interaction in over 10 years and highlights the need to be extra-cautious while prescribing phenytoin and antitubercular therapy concomitantly, especially in a populations dominated by slow acetylators.