The FDA is warning that the antiseizure medicines, Keppra, Keppra XR,
Elepsia XR, Spritam (levetiracetam) and Onfi, Sympazan (clobazam), 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 (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, the FDA is
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.
Keppra, Keppra XR, Elepsia XR, Spritam (levetiracetam)
- Levetiracetam is an antiseizure medicine approved for use alone
or with other medicines to control certain types of seizures in adults
and children such as partial seizures, myoclonic seizures, or
- It has been FDA-approved for 24 years and is available in multiple
formulations under the brand names Keppra, Keppra XR, Elepsia XR, and
Spritam, and as generics.
- Common side effects of levetiracetam include unusual irritability
or aggression, confusion, loss of balance or coordination, and extreme
Onfi, Sympazan (clobazam)
- Clobazam is a benzodiazepine indicated for use in combination
with other medicines to control seizures in adults and children 2 years
and older who have a specific severe form of epilepsy called
- Benzodiazepines are a class of medicines that depress the central
nervous system. DRESS and other serious skin reactions reported with
clobazam have generally been associated only with clobazam and not with
- Clobazam has been FDA-approved for 12 years. It is available in
multiple formulations under the brand names Onfi and Sympazan, and as
- Common side effects of clobazam include difficulty speaking or
swallowing, tiredness, change in appetite, and problems with muscle
control or coordination.
Patients and Caregivers
- Do not stop taking levetiracetam or clobazam without talking
with your health care professional. Stopping these medicines suddenly
can lead to uncontrolled seizures.
- It is important to seek immediate medical attention for DRESS.
Patients who develop any unusual symptoms or reactions, including a
rash, at any time while taking levetiracetam or clobazam should go to an
emergency room immediately. Fever with a rash and swollen lymph nodes
or swelling in the face are common with DRESS, but some patients may not
develop a rash.
- Symptoms of DRESS generally start 2 weeks to 8 weeks after starting
on the medicine, but these symptoms may occur earlier or later. A
physical examination, laboratory blood tests, and other evaluations are
used to diagnose DRESS.
Health Care Professionals
- Health care professionals should be aware that prompt
recognition and early treatment is important for improving DRESS
outcomes and decreasing mortality. Diagnosis is often difficult because
early signs and symptoms such as fever and swollen lymph nodes may be
present without evidence of a rash.
- 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 (SJS) and Toxic Epidermal Necrolysis (TEN).
- 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.
Health professionals and patients are encouraged to report
adverse events or side effects related to the use of these products to
the FDA's MedWatch Safety Information and Adverse Event Reporting
- Complete and submit the report online.
- Download form
or call 1-800-332-1088 to request a reporting form, then complete and
return to the address on form, or submit by fax to 1-800-FDA-0178.
[11/28/2023 - Drug Safety Communication - FDA]
Source: News Release
US Food & Drug Administration
November 28, 2023