Phenytoin - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Withdrawal Precipitated Seizure: May precipitate status epilepticus.

Dose reductions or discontinuation should be done gradually.

Suicidal Behavior and Ideation: Monitor patients for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Serious Dermatologic Reactions: Discontinue extended phenytoin sodium capsules at the first sign of a rash, unless the rash is clearly not drug-related.

If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed and alternative therapy should be considered.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity: If signs or symptoms of hypersensitivity are present, evaluate the patient immediately.

Discontinue if an alternative etiology cannot be established.

Cardiac Effects: Bradycardia and cardiac arrest have been reported.

Angioedema: Discontinue immediately if symptoms of angioedema such as facial, perioral, or upper airway swelling occur.

Hepatic Injury: Cases of acute hepatotoxicity have been reported with extended phenytoin sodium capsules.

If this occurs, immediately discontinue. ( 4 , 5.8 ) Hematopoietic Complications: If occurs, follow-up observation is indicated and an alternative antiepileptic treatment should be used.

5.1 Withdrawal Precipitated Seizure, Status Epilepticus Abrupt withdrawal of phenytoin in epileptic patients may precipitate status epilepticus.

When, in the judgment of the clinician, the need for dosage reduction, discontinuation, or substitution of alternative anticonvulsant medication arises, this should be done gradually.

However, in the event of an allergic or hypersensitivity reaction, more rapid substitution of alternative therapy may be necessary.

In this case, alternative therapy should be an anticonvulsant drug not belonging to the hydantoin chemical class.

5.2 Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including extended phenytoin sodium capsules, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication.

Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo.

In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated.

There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.

The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed.

Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.

The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed.

The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication.

The risk did not vary substantially by age (5 years to 100 years) in the clinical trials analyzed.