What Are the Different Phenytoin Interactions?

Phenytoin is a common anticonvulsant medication used to control seizure disorders. The medication is structurally similar to major tranquilizers that may account for its commonly reported side effects of drowsiness and sedation. While phenytoin works primarily on the brain — reducing the excitability of the area that controls motor function — side effects from long-term use demonstrate a wide variety of effects on many body systems. Adding to the complexity of understanding this drug is the fact that phenytoin is strongly bound to serum protein, however, only the fraction that is "free" or unbound is pharmacologically active. Phenytoin interactions can occur anywhere within the drug's huge sphere of influence and include interactions with almost 1,000 other medications, foods and other diseases.

The most commonly reported phenytoin interactions are those with other medications. Almost 1,000 drugs reportedly have documented interactions with this anticonvulsant, including both over-the-counter and prescription drugs. Some common over-the-counter drugs that interaction with this drug include aspirin — which can increase drug levels in the body — and antacids which can have the opposite effect. Common prescription drugs with phenytoin interactions include diazepam, Lexapro® and furosemide.

Phenytoin interactions can be caused by interferences with absorption, contradictory actions, additive actions or even interruptions to serum protein levels. Indeed, reaching a therapeutic dosage for phenytoin is a balancing act that requires re-evaluation whenever a drug is added to, or removed from, a patient's usual regimen. Treatment recommendations for patients with an active seizure disorder include laboratory blood work testing for both total phenytoin levels and free phenytoin levels before the addition of a new medication. Follow-up testing is also recommended until therapeutic levels of phenytoin have stabilized. The same approximate procedure is recommended when a long-term drug is removed from a patient's medication regimen.

Foods are also indicated in some phenytoin interactions. Enteral feedings administered at the same time as phenytoin dosing can reduce the drug level in the system. Spicy foods that warrant over-the-counter antacids can also decrease phenytoin levels. Alcohol intake also has significant phenytoin interactions, causing increased or decreased levels depending upon whether the alcohol intake is acute or chronic.

Phenytoin interactions with other drugs, foods or compounds can be markedly increased by concomitant diseases. Anticonvulsants administration has been linked to onset of depression with suicidal tendencies or exacerbation of a preexisting depression. Patients suffering from diabetes mellitus can experience higher blood glucose levels with administration of phenytoin. Phenytoin's interference with vitamin D processing can cause conditions or injuries related to decreased skeletal density.