Dilantin Capsule Drug Interactions

Drug Interactions: Phenytoin is extensively bound to serum plasma proteins and is prone to competitive displacement. Phenytoin is metabolized by hepatic cytochrome (CYP) P450 enzymes CYP2C9 and CYP2C19, and is particularly susceptible to inhibitory drug interactions because it is subject to saturable metabolism. Inhibition of metabolism may produce significant increases in circulating phenytoin concentrations and enhance the risk of drug toxicity.
Phenytoin is a potent inducer of hepatic drug-metabolizing enzymes and may reduce the levels of drugs metabolized by these enzymes.
There are many drugs that may increase or decrease serum phenytoin levels or that 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 in Tables 1 to 4.
Drugs that may increase phenytoin serum levels: Table 1 summarizes the drug classes that may potentially increase phenytoin serum levels: (See Table 1.)

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Drugs that may decrease phenytoin serum levels: Table 2 summarizes the drug classes that may potentially decrease phenytoin serum levels: (See Table 2.)

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Molindone hydrochloride contains calcium ions, which interfere with the absorption of phenytoin. Ingestion times of phenytoin and calcium preparations, including antacid preparations containing calcium, should be staggered to prevent absorption problems.
Drugs that may either increase or decrease phenytoin serum levels: Table 3 summarizes the drug classes that may either increase or decrease phenytoin serum levels. (See Table 3.)

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Drugs whose serum levels and/or effects may be altered by phenytoin: Table 4 summarizes the drug classes whose serum levels and/or effects may be altered by phenytoin. (See Table 4).

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Although not a true drug interaction, tricyclic antidepressants may precipitate seizures in susceptible patients and phenytoin dosage may need to be adjusted.
Drug-Enteral Feeding/Nutritional Preparations Interaction: Literature reports suggest that patients who have received enteral feeding preparations and/or related nutritional supplements have lower than expected phenytoin plasma levels. It is therefore suggested that phenytoin not be administered concomitantly with an enteral feeding preparation. More frequent serum phenytoin level monitoring may be necessary in these patients.
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).
Phenytoin may affect blood calcium and blood sugar metabolism rates.