Indications for direct measurement of the free phenytoin concentration:
(1) hospitalized patient, especially if critically ill
(2) concurrent administration of drugs that compete for protein binding sites
(3) moderate to severe hypoalbuminemia, especially when ill (burns, cachexia, hepatic cirrhosis, pregnancy, nephrotic syndrome, cystic fibrosis, etc.)
(4) moderate to severe renal dysfunction
(5) severe liver disease with jaundice
(6) increased serum levels of free fatty acids
(7) patient symptoms consistent with phenytoin toxicity
(8) failure of clinical efficacy despite adequate dose administration
Adverse effects of phenytoin may include central nervous system side effects:
(1)nystagmus
(2) ataxia
(3) decreased mentation
Drugs which may displace phenytoin from protein binding sites include:
(1) valproic acid
(2) phenylbutazone
(3) sulfisoxazole, sulfamethoxazole/trimethoprine
(4) salicylic acid
(5) omeprazole
(6) heparin
(7) ciprofloxacin
(8) carbamazepine
(9) warfarin
