Antiepileptics Have Low Risk of Stevens-Johnson Syndrome

NEW YORK (Reuters Health) Apr 20 - New users of antiepileptic drugs have a low likelihood of hospitalization with Stevens-Johnson syndrome (SJS), a new study sponsored by GlaxoSmithKline shows.

The risk of developing SJS or toxic epidermal necrolysis (TEN) is between 1 and 10 per 10,000 new users of carbamazepine, lamotrigine, phenobarbital, phenytoin, and valproic acid, Dr. Maja Mockenhaupt of the University of Freiburg in Germany and colleagues report. More than 90% of cases occurred during the first 2 months of use.

"Fortunately, these serious reactions are rare and relatively predictable in occurring within the first 2 months of therapy. Clinicians prescribing these anti-epileptic drugs should communicate to their patients the signs and symptoms to watch for during this time period of highest risk," the researchers advise in their report, which is published in the April issue of Neurology.

SJS and TEN have been linked to more than 100 medications, the researchers note. But the difficulty of accurately diagnosing these conditions, as well as the challenge of estimating the number of new users of a drug, has made it difficult to correctly characterize the risk.

To investigate, Dr. Mockenhaupt and colleagues reviewed data from the German Registry for Serious Cutaneous Reactions for all patients hospitalized with SJS and TEN associated with carbamazepine, lamotrigine, phenobarbital, phenytoin, and valproic acid. The investigators developed an algorithm for estimating the fraction of these patients who were new users of the drugs.

Using different assumptions about the rate of incident use, as mentioned, the researchers found the risk of SJS and TEN was between 1 and 10 per 10,000 new users for all of the drugs, with a lower risk identified for valproic acid than for the other medications.

"Any one clinician is likely to see only one or two of these events in a lifetime, and the ability to identify a relatively narrow time window of high risk should facilitate the early detection of such events," they write.

The researchers advise prescribing physicians to tell patients about the symptoms that distinguish TEN and SJS from mild drug reactions, and to watch patients carefully for these symptoms for at least 6 weeks after prescribing the drugs.

Neurology 2005;64:1134-1138.