There are many drugs which may increase or decrease phenytoin levels or which phenytoin may affect. Serum level
determinations for phenytoin are especially helpful when possible drug interactions are suspected. The most commonly
occurring drug interactions are listed below:
1. Drugs which may increase phenytoin serum levels include: acute alcohol intake, amiodarone,
chloramphenicol, chlordiazepoxide, diazepam, dicumarol, disulfiram, estrogens, H2-antagonists, halothane,
isoniazid, methylphenidate, phenothiazines, phenylbutazone, salicylates, succinimides, sulfonamides, tolbutamide,
2. Drugs which may decrease phenytoin serum levels include: carbamazepine, chronic alcohol abuse,
reserpine, and sucralfate. Moban brand of Molindone Hydrochloride contains calcium ions which interfere with the
absorption of phenytoin. Ingestion times of phenytoin and antacid preparations containing calcium should be staggered
in patients with low serum phenytoin levels to prevent absorption problems.
3. Drugs which may either increase or decrease phenytoin serum levels include: phenobarbital, sodium
valproate, and valproic acid. Similarly, the effect of phenytoin on phenobarbital, valproic acid and sodium valproate
serum levels is unpredictable.
4. Although not a true drug interaction, tricyclic antidepressants may precipitate seizures in susceptible
patients and phenytoin dosage may need to be adjusted.
5. Drugs whose efficacy is impaired by phenytoin include: corticosteroids, coumarin anticoagulants,
digitoxin, doxycycline, estrogens, furosemide, oral contraceptives, quinidine, rifampin, theophylline, vitamin D.
Drug/Laboratory Test Interactions
Hidantal may cause decreased serum levels of protein-bound iodine (PBI). It may also produce lower than normal
values for dexamethasone or metyrapone tests. Hidantal may cause increased serum levels of glucose, alkaline
phosphatase, and gamma glutamyl transpeptidase (GGT).