Phenytoin Delayed Excretion because of Esomeprazole Co-administration

Background: Drug Interaction between Phenytoin and Esomeprazole is not commonly reported or widely recognized. A case of Phenytoin toxicity post prolonged administration of phenytoin and esomeprazole is reported. Case Summary: A 22 years old female diagnosed with MELAS (Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, stroke like symptoms). She was maintained on Phenytoin 100 mg suspension via nasogastric tube every 8 hours as anticonvulsant for 3 years and esomeprazole 40 mg via nasogastric tube every 24 hours for hyperacidity. After 7 months from co-administration of phenytoin and esomeprazole the patient developed bradycardia, hypotension with nystagmus so upon checking the phenytoin trough serum level it was found to be 163 μmole/L, phenytoin was suspended and serum level monitored daily but it was found to be increasing to 167 μmole/L and the patient laboratory results showed leukopenia, thrombocytopenia and elevated liver enzymes, upon suspending Esomeprazole it was noticed that the Phenytoin serum level decreased dramatically by 10-20 μmole/L/day so the toxicity symptoms and abnormal laboratory results resolved upon normalization the Phenytoin serum level. Conclusion: Esomeprazole may competitively inhibit the CYP2C19 mediated Phenytoin metabolism which leads to prolonged exposure to high serum level and toxicities.