FDA Issues Warning of Potential Adverse Events Associated With Antiseizure Drugs

The FDA has issued a warning regarding the risk of drug reaction with eosinophilia and systemic symptoms (DRESS) among patients taking antiseizure medications. Included in the FDA warning were levetiracetam, under the brand names Keppra and Keppra XR (GlaxoSmithKline); Elepsia XR (Sun Pharmaceutical Industries Ltd); Spritam (Prasco; Aprecia Pharmaceuticals); and clobazam, under the brand names Onfi (Lundbeck) and Sympazan (Otter Pharmaceuticals).

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DRESS, a rare but serious and potentially fatal reaction, may initially appear as a rash before rapidly progressing to impact internal organs, leading to hospitalization. Patients who develop DRESS may experience fever, rash, and swollen lymph nodes, as well as damage to the liver, kidneys, lungs, heart, or pancreas. Early signs of DRESS can include fever and swollen lymph nodes even without the presence of a rash. DRESS can manifest two to eight weeks following the start of treatment with variable symptoms and intensity on a case-by-case basis, according to the FDA.

The agency also stated that it will require warnings to be listed on prescribing information and on patient guides for the affected medications. FDA recommendations for healthcare professionals include awareness of the symptoms of DRESS, which is vital because initiating early treatment may improve outcomes and lower the risk of mortality. According to the FDA, DRESS may be confused with other adverse skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis. As such, the agency emphasized the importance of healthcare professionals recognizing and understanding the differences among these conditions to reduce the risk of adverse outcomes.

Additionally, healthcare providers are urged to educate patients regarding the signs and symptoms of DRESS, to cease use of their medications if symptoms develop, and to seek medical care if DRESS is suspected during treatment with levetiracetam or clobazam. The FDA emphasized that patients should not stop taking medications without first discussing it with their healthcare provider because this can lead to uncontrolled seizures. DRESS can be diagnosed with physical exams, laboratory blood tests, and additional clinical evaluations.

The FDA said that patients and healthcare professionals should report any adverse events (AEs) related to the use of levetiracetam or clobazam to its MedWatch Safety Information and Adverse Event Reporting Program, either via an online report or by downloading and mailing the form or submitting it via fax at 800-FDA-0178, according to the press release.

Levetiracetam has been approved by the FDA for use alone or combined with other drugs for seizure control in adults and children, including partial seizures, myoclonic seizures, or tonic-clonic seizures. Common AEs associated with these medications include irritability, aggression, confusion, loss of balance or coordination, and extreme drowsiness.

Clobazam is a benzodiazepine indicated in combination with other drugs that control seizures in individuals two years of age and older with Lennox-Gastaut syndrome. Commonly reported AEs among patients administered clobazam include difficulty speaking or swallowing, fatigue, changes in appetite, and challenges with muscle control or coordination, according to the FDA release. Although benzodiazepines affect the central nervous system, DRESS has not been associated with any other medications in this class, and has only been associated with use of clobazam, according to the FDA.

Reference

Antiseizure medicines Keppra, Keppra XR, Elepsia XR, Spritam (levetiracetam) and Onfi, Sympazan (clobazam): drug safety communication - FDA warns of rare but serious drug reaction. News release. FDA. November 28, 2023. Accessed November 30, 2023. https://www.fda.gov/safety/medical-product-safety-information/antiseizure-medicines-keppra-keppra-xr-elepsia-xr-spritam-levetiracetam-and-onfi-sympazan-clobazam