From the FDA Drug Label
Patients taking ethosuximide should be advised of the importance of adhering strictly to the prescribed dosage regimen Patients should be instructed to promptly contact their physician when they develop signs and/or symptoms suggesting an infection (e.g., sore throat, fever). Patients, their caregivers, and families should be counseled that AEDs, including Zarontin, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm Prior to initiation of treatment with Zarontin, the patient should be instructed that a rash may herald a serious medical event and that the patient should report any such occurrence to a physician immediately Ethosuximide may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a motor vehicle or other such activity requiring alertness; therefore, the patient should be cautioned accordingly.
The patient should be counseled about the following side effects when initiating Ethosuximide 500 mg bid:
- Infection: signs and symptoms such as sore throat, fever
- Suicidal thoughts and behavior: emergence or worsening of symptoms of depression, unusual changes in mood or behavior
- Rash: may herald a serious medical event
- Impaired mental and/or physical abilities: caution when performing hazardous tasks such as driving 1 1
From the Research
When initiating ethosuximide 500 mg twice daily, patients should be counseled about potential side effects including gastrointestinal disturbances, drowsiness, fatigue, dizziness, and headache, as well as less common side effects such as skin rashes and blood dyscrasias. The most common side effects of ethosuximide include gastrointestinal disturbances such as nausea, vomiting, stomach pain, and loss of appetite, which occur in approximately 20% of patients, as reported in a study published in 2007 2. Drowsiness, fatigue, dizziness, and headache are also frequently reported. Some patients may experience behavioral changes including irritability, nervousness, sleep disturbances, or mood changes. Less common but important side effects include:
- Skin rashes, which could indicate hypersensitivity
- Blood dyscrasias such as leukopenia or pancytopenia, which necessitate periodic blood count monitoring Rarely, patients may develop systemic lupus erythematosus-like syndrome or hiccups. These side effects typically appear within the first few weeks of treatment and often diminish with continued use as the body adjusts to the medication. A more recent study from 2016 3 reported anxiety, nervousness, headache, and dizziness as common side effects, causing some patients to stop the trial. However, the highest quality and most recent evidence comes from the 2016 study 3, which provides more specific information on the side effects of ethosuximide. Patients should be advised to report any persistent or severe side effects promptly to their healthcare provider, and not to discontinue the medication abruptly as this could precipitate seizures. It is also important to note that ethosuximide works by reducing abnormal electrical activity in the brain by inhibiting T-type calcium channels in thalamic neurons, which helps prevent absence seizures, as described in the 2007 study 2.