Serious reactions to phenytoin are very rare but everyone who takes this medicine should at least be aware of them because a very small number of people have died because of them. A complete list of all reactions to phenytoin can be found in the package insert, but it is important to remember that most people who take phenytoin have none of these serious problems.

As with many other seizure medicines, there is a very small chance of developing a rash so serious that hospitalization may be required. (It has been estimated that this happens to 2 to 5 people out of each 10,000 who take phenytoin). Though the risk is small, call the doctor promptly if you notice a rash, since in a few cases these rashes are fatal.

In rare cases, allergic reactions to phenytoin can result in damage to the liver or bone marrow. The doctor may perform blood tests from time to time to look for early stages of this kind of damage.

Another rare reaction to phenytoin is disease of the lymph nodes. The doctor should be informed about fever, rash, and swollen, tender lymph glands. These usually are found in the neck, armpits, or groin.

Phenytoin (like other seizure medicines) should never be stopped without instructions from the doctor. Abruptly stopping phenytoin can lead to nonstop seizures (called status epilepticus), a life-threatening condition. The levels of other medicines in the body might go up or down too. Then their side effects may increase or they will be less effective. The doctor may be able to prescribe a different medicine if phenytoin is causing unpleasant side effects.

On July 10, 2008, an advisory panel was convened by the Food and Drug Administration (FDA) to review data that the FDA had previously collected from drug studies showing an association between many of the antiepileptic drugs (AEDs) and suicidal ideation and behavior, which together are called suicidality. According to the FDA’s Alert, among the patients with epilepsy in these drug studies, 1 out of 1000 people taking the placebo (inactive substance) showed suicidality compared to approximately 3.5 out of 1000 people who took an AED. The FDA advisory panel voted to accept the FDA's data at its meeting on July 10. The FDA has provided the following information for patients, family members, and caregivers at www.fda.gov/cder/drug/InfoSheets/HCP/antiepilepticsHCP.htm.

• Taking antiepileptic medicines may increase the risk of having suicidal thoughts or actions;
• Do not make any changes to the medication regimen without first talking with the responsible healthcare professional;
• Pay close attention to any day-to-day changes in mood, behavior and actions. These changes can happen very quickly so it is important to be mindful of any sudden differences.
• Be aware of common warning signs that might be a signal for risk of suicide. Some of these are:
  • Talking or thinking about wanting to hurt yourself or end your life
  • Withdrawing from friends and family
  • Becoming depressed or having your depression get worse
  • Becoming preoccupied with death and dying
  • Giving away prized possessions

We again urge patients and families to contact their doctor before stopping an epilepsy medication because this may possibly lead to seizures and worsening of mood.

Reviewed July 2008 by Steven C. Schachter, MD, epilepsy.com Editorial Board.