Ethosuximide - Warnings and Precautions

WARNINGS Blood Dyscrasias Blood dyscrasias, including some with fatal outcome, have been reported to be associated with the use of ethosuximide; therefore, periodic blood counts should be performed.

Should signs and/or symptoms of infection (e.g., sore throat, fever) develop, blood counts should be considered at that point.

Drug-Induced Immune Thrombocytopenia Drug-induced immune thrombocytopenia (DITP) has been reported with ethosuximide.

In the reported cases, the onset of symptoms occurred 1 to 3 weeks after initiation of ethosuximide; one patient had recurrence of symptoms within 1 day of a subsequent re-challenge with the drug.

In those cases in which the platelet count was specified, the nadir was 2,000 and 3,000/mm 3 .

When DITP is suspected, discontinue ethosuximide, monitor serial platelet counts, and treat as appropriate.

If possible, assess the presence of drug-dependent antiplatelet antibodies.

Avoid future use of ethosuximide in patients with history of ethosuximide-induced DITP.

Effects on Liver and Kidneys Ethosuximide is capable of producing morphological and functional changes in the animal liver.

In humans, abnormal liver and renal function studies have been reported.

Ethosuximide should be administered with extreme caution to patients with known liver or renal disease.

Periodic urinalysis and liver function studies are advised for all patients receiving the drug.

Systemic Lupus Erythematosus Cases of systemic lupus erythematosus have been reported with the use of ethosuximide.

The physician should be alert to this possibility.

Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including ethosuximide, 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 (5–100 years) in the clinical trials analyzed.

Table 1 shows absolute and relative risk by indication for all evaluated AEDs.