NOV 29, 2023

FDA Issues Warning on Antiseizure Medications

WRITTEN BY: Amielle Moreno

In a surprising development, the FDA has issued a stark warning concerning antiseizure medications levetiracetam (Keppra, Keppra XR, Elepsia XR, Spritam) and clobazam (Onfi, Sympazan). These drugs, taken by millions, are now under scrutiny for their potential to induce a rare and life-threatening reaction known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

Part of the reason this is surprising is that no one thought that these medicines shared mechanisms of action.

Composite Image by Amielle Moreno

DRESS is a serious sensitivity that triggers a profound immune system response, causing severe inflammation throughout the body and posing a risk of organ damage. The consequences can be dire, leading to hospitalization and, in some cases, organ failure or death.

Symptoms of DRESS, which may commence as a rash, can rapidly escalate, demanding urgent medical attention. There is variability of symptoms, with fever often accompanying a rash, swollen lymph nodes, or facial swelling, though not everyone will manifest a rash.

Disturbingly, estimates suggest that 12 million levetiracetam prescriptions and 779,000 clobazam prescriptions were dispensed from U.S. outpatient pharmacies in 2022. This staggering figure underscores the urgency of the FDA's directive to include explicit warnings in medication guides.

To compound the gravity of the situation, sudden discontinuation of these medications can trigger uncontrolled seizures. Patients are advised not to cease taking levetiracetam or clobazam without consulting their healthcare professional. The delicate balance between managing seizures and potentially life-threatening reactions poses a dilemma for both patients and physicians.

Clobazam, classified as a benzodiazepine, operates as an agonist of GABA receptors in the nervous system and reduces abnormal electrical activity in the brain. In contrast, levetiracetam's mechanism is less understood. Levetiracetam is thought to impact synaptic transmission through the synaptic vesicle protein 2A.

The fact that these medications, from different classes, induce similar adverse effects will spark intrigue in the scientific community. The overlap hints at a potential avenue for further investigation into mechanisms of action.

Patients are urged to remain vigilant for any unusual symptoms while taking these medications. Any unusual symptoms or reactions, notably rashes, while taking levetiracetam or clobazam warrant immediate attention, emphasizing the critical role of early detection in averting the potentially fatal consequences of DRESS.

Sources: FDA, Medline, Drug Bank (1) (2), NHS