Anticonvulsants can cause life-threatening reactions

Molecular tests and other screening tools can reduce the risk of potentially fatal reactions to antiseizure drugs taken by millions of Americans to treat epilepsy and other conditions, but skin rashes still require prompt medical attention, according to a Rutgers Health study.

Rashes are a common side effect of antiseizure medications, occurring in 2% to 16% of patients depending on which of the 26 Food and Drug Administration (FDA)-approved drugs they use.

While most rashes do not indicate serious problems, about 5% signal life-threatening reactions. The FDA recently issued a warning about serious reactions to two anti-seizure drugs: levetiracetam and clobazam.

“Dangerous reactions are rare, but patients and their caregivers need to understand the risk and know how to respond if something happens,” said Ram Mani, chief of adult epilepsy at Rutgers Robert Wood Johnson Medical School and lead author of the study published in the journal Current Treatment Options in Neurology.

“Patients should seek medical attention if they develop a rash rather than wait for it to go away,” Money said. “If symptoms are mild, they can contact their neurologist or primary care physician, but severe symptoms such as a high fever require a trip to the emergency room or an ambulance.”

The right anticonvulsant medication can eliminate epilepsy symptoms in 70% of patients and relieve them in most others. Such medications also help many patients with bipolar disorder, anxiety, migraines, and neuropathic pain.

A new study summarizes published data on each individual anticonvulsant drug, distinguishes between the different types of rashes these drugs can cause, and explains how to treat each.

Factors that increase the risk of severe reactions include the use of aromatic anticonvulsants, rapid dose escalation, a genetic predisposition to the reaction, and the concomitant use of other medications that affect drug metabolism. Women under 50 and boys under 10 are also more likely to experience reactions, as are people with conditions such as HIV or lupus, or those undergoing treatments that increase or decrease the activity of the immune system, such as radiation therapy.

"Patients who respond to one drug are more likely to respond to others, especially drugs in the same class, but with 26 FDA-approved options, we can find an effective treatment for every patient with minimal side effects," Mani said.

Anticonvulsant drugs can cause at least 10 different types of rashes. Reactions such as fixed drug eruption, which is characterized by a small number of rashes, can begin within hours of the first injection, while other skin rashes, such as lichenoid drug reactions, can occur after years of drug use.

The most common reaction is called morbilliform exanthematous eruption. These rashes usually occur within the first two weeks of treatment and cover the trunk (and often the extremities) with small lesions. Symptoms usually resolve without treatment within a few weeks after stopping the drug, but may worsen for a few days before improving.

Severe conditions, on the other hand, often require urgent treatment. A reaction known as Stevens-Johnson syndrome or toxic epidermal necrolysis, which causes fever, eye pain, and peeling skin, usually requires hospitalization in a burn unit.

Money estimated that several thousand patients suffer severe reactions to anticonvulsants each year, but added that those numbers could be significantly reduced if neurologists routinely prescribed low-risk drugs to high-risk patients.

“I gave a talk on this at the American Epilepsy Society conference last year and asked the 200 or so doctors in the room how often they do the recommended [genetic] tests for patients of South Asian descent [the only group prone to the genes involved], and only a few people raised their hands,” Rami said. “So there is certainly room for improvement in patient safety.”