Phenytoin is much more commonly used in American nursing homes than any other antiepileptic drug (AED). Some of these doses of AEDs are prescribed for conditions other than epilepsy, and some are prescribed for elderly patients who have experienced only one seizure.

Older people metabolize phenytoin more slowly than younger adults and they are often more susceptible to side effects. Lower initial doses and caution in titration are required. A total daily dose of 3 mg/kg is appropriate for many elderly patients.

Reduced elimination also extends the half-life of phenytoin for elderly patients, so that many do well taking phenytoin just once a day.

Declining serum albumin levels in many elderly people mean that the unbound phenytoin concentration may be higher than expected in relationship to the total drug concentration, The total drug level thus may be poorly correlated with clinical response. An appropriate therapeutic range may be 5–15 mcg/mL rather than the 10–20 mcg/mL suggested for young adults.

Variations in gastrointestinal function may affect absorption and mean that blood levels may fluctuate even if the patient is taking a steady dosage of the same formulation.

Another difficulty with the use of phenytoin in seniors is its large number of interactions with other medications, including many commonly used by elderly patients. Changes in dosages of both medications are often required.

Some common side effects of phenytoin, such as imbalance, may exacerbate pre-existing problems of seniors, and their greater risk of injury from falls or other accidents makes this an area of concern. Phenytoin also may affect cognitive functioning at higher levels.