FDA warns of rare but serious drug reaction to the antiseizure medicines levetiracetam (Keppra, Keppra XR, Elepsia XR, Spritam) and clobazam (Onfi, Sympazan)
FDA Drug Safety Podcast
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Welcome to the FDA Drug Safety Podcast for health care professionals from the Division of Drug Information.
On November 28, 2023, FDA is warning that the antiseizure medicines levetiracetam (brand names Keppra, Keppra XR, Elepsia XR, and Spritam) and clobazam (brand names Onfi and Sympazan), can cause a rare but serious reaction that can be life-threatening if not diagnosed and treated quickly. This reaction is called Drug Reaction with Eosinophilia and Systemic Symptoms (or DRESS). It may start as a rash but can quickly progress, resulting in injury to internal organs, the need for hospitalization, and even death. As a result, we are requiring warnings about this risk to be added to the prescribing information and patient Medication Guides for these medicines.
This hypersensitivity reaction to these medicines is serious but rare. DRESS can include fever, rash, swollen lymph nodes, or injury to organs including the liver, kidneys, lungs, heart, or pancreas.
We are requiring manufacturers of these medicines to add new warnings about DRESS to the prescribing information and the Medication Guide for patients and caregivers. For levetiracetam, this involves adding a new warning in the Warnings and Precautions section of the prescribing information, which describes the most serious and significant potential safety issues. Currently the symptoms associated with this condition are described less prominently. For clobazam, we are requiring a new warning specifically about DRESS to be added to the prescribing information. Symptoms related to this risk are already described more generally in other sections of the clobazam prescribing information.
The warnings for both levetiracetam and clobazam medicines will include information that early symptoms of DRESS such as fever or swollen lymph nodes can be present even when a rash cannot be seen. This is different from other serious skin-related reactions that can happen with these medicines and where a rash is present early on, including Stevens-Johnson Syndrome and toxic epidermal necrolysis. We are also requiring information on this risk to be added to the Medication Guides to help inform patients and caregivers about this risk.
Health care professionals should be aware that prompt recognition and early treatment is important for improving DRESS outcomes and decreasing mortality. DRESS can develop 2 weeks to 8 weeks after starting the medicines, and symptoms and intensity can vary widely. DRESS can also be confused with other serious skin reactions such as Stevens-Johnson Syndrome and toxic epidermal necrolysis. Advise patients of the signs and symptoms of DRESS and to stop taking their medicine and seek immediate medical attention if DRESS is suspected during treatment with levetiracetam or clobazam.
FDA’s cumulative review found serious cases of DRESS in children and adults worldwide. Most patients in these cases required hospitalization and received medical treatments, and two patients treated with levetiracetam died. These numbers include only reports submitted to FDA and found in the medical literature, so there are likely additional cases about which we are unaware. We determined there was reasonable evidence that levetiracetam and clobazam were the cause of DRESS in these cases based on the timing of the onset of these events after receiving the medicines and the order in which they occurred. The majority of cases for which information about discontinuation was available reported that DRESS symptoms improved when the medicines were discontinued.
All medicines have side effects even when used correctly as prescribed. It is important to know that people respond differently to all medicines depending on their health, the diseases they have, genetic factors, other medicines they are taking, and many other factors. As a result, we cannot determine how likely it is that someone will experience DRESS, a rare but serious reaction, when taking levetiracetam or clobazam.
Side effects involving levetiracetam and clobazam should be reported to FDA’s MedWatch reporting program at www.fda.gov/medwatch.
A link to the full communication detailing specific information for health care professionals and the complete Data Summary can be found at www.fda.gov/DrugSafetyCommunications. If you have drug questions, you can reach us at druginfo@fda.hhs.gov. And follow us on X (formerly Twitter) @FDA_Drug_Info. Thank you for listening.