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Side Effects & Drug Interactions
ADVERSE REACTIONS
Central Nervous System 
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Drug Interactions: 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: 1. Drugs which may increase phenytoin serum levels include: acute alcohol intake,
amiodarone,
chloramphenicol,
chlordiazepoxide,
diazepam,
dicumarol,
disulfiram,
estrogens,
ethosuximide,
fluoxetine,
H2-antagonists,
halothane,
isoniazid,
methylphenidate,
phenothiazines,
phenylbutazone,
salicylates,
succinimides,
sulfonamides,
tolbutamide,
trazodone. 2. Drugs which may decrease phenytoin levels include: carbamazepine,
chronic alcohol abuse,
reserpine,
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,
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: Phenytoin may cause decreased serum levels of protein-bound iodine (PBI). It may also produce lower than normal values for dexamethasone or metyrapone tests. Phenytoin may cause increased serum levels of glucose, alkaline phosphatase, and gamma glutamyl transpeptidase (GGT). Carcinogenesis: See WARNINGS section for information on carcinogenesis.
Pregnancy: See WARNINGS section. Nursing Mothers: Infant breast feeding is not recommended for women taking this drug because phenytoin appears to be secreted in low concentrations in human milk. Pediatric Use: See DOSAGE AND ADMINISTRATION section.
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