Antiseizure medications have long been recognized as potential triggers for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), two rare but potentially life-threatening conditions. New research is providing a clearer picture of how frequently these medications appear in reported SJS/TEN cases and which drugs are most often involved.
A systematic review and meta-analysis published in JAMA Dermatology examined 50 studies involving 4,403 patients with SJS or TEN. Researchers found that antiseizure medications, referred to as antiepileptic drugs in the study, were implicated in approximately 23% of the cases included in the analysis.
Nearly all of the antiseizure medication-associated cases involved a group known as aromatic antiseizure drugs. Carbamazepine was implicated most often, followed by phenytoin and lamotrigine.
When I evaluate an SJS or TEN case, one of the first things I look at is which medication may have triggered the reaction. Sometimes the connection is fairly clear. Other times, a patient may have been taking several medications, started a new prescription weeks earlier, or received additional drugs after becoming sick. In those cases, the timeline can become especially important.
What Did the Study Find About Antiseizure Drugs and SJS?
Researchers analyzed studies from North America, Asia, Europe, Africa, and Australia. Across the 50 studies, antiseizure medications were associated with about 23% of all reported SJS/TEN cases; when researchers looked specifically at SJS/TEN attributed to antiseizure medications, approximately 96% involved aromatic drugs.
Three medications accounted for the largest proportions:
- Carbamazepine: 39%
- Phenytoin: 19%
- Lamotrigine: 15%
The researchers also found considerable geographic differences. Antiseizure medications accounted for a larger proportion of reported SJS/TEN cases in some regions than others. They noted that genetic differences among populations could be one factor, but prescribing patterns and medication availability may also contribute.
Children were another notable finding. The pooled proportion of SJS/TEN cases associated with antiseizure medications was 35% among children, compared with 23% among adults.
The authors concluded that aromatic antiseizure medications remain significant contributors to SJS/TEN worldwide and said the findings support considering nonaromatic alternatives when clinically appropriate.
Why Are Some Antiseizure Drugs Associated With SJS and TEN?
SJS and TEN are rare but severe conditions that most often develop as a reaction to medication. Early symptoms can resemble an infection or common illness before progressing to painful blistering and peeling of the skin, along with serious damage to the eyes, mouth, and other parts of the body.
Researchers have examined more than antiseizure drugs. Antibiotics, allopurinol, and certain nonsteroidal anti-inflammatory drugs have also been associated with SJS/TEN. An earlier JAMA Dermatology investigation found that antibiotics were associated with about 28% of reported cases.
The new research is useful because it examines antiseizure medications as a group. Carbamazepine, phenytoin, and lamotrigine have uses beyond epilepsy and seizure disorders. Depending on the medication, they may also be prescribed for conditions such as bipolar disorder or certain types of nerve pain. That means patients who develop SJS or TEN after taking one of these drugs may not necessarily think of themselves as having taken an "antiseizure medication."
How Do You Know Which Medication Caused SJS?
One important point can easily get lost when studies like this receive attention.
Finding that a particular medication has been associated with SJS/TEN doesn’t mean the manufacturer, prescribing physician, pharmacist, or another party is automatically legally responsible whenever a patient develops the condition.
It also doesn't necessarily establish that the medication caused SJS in an individual patient.
Answering that question usually starts with the patient's complete medication history. Which drugs were they taking? When was each medication started? Was a dosage recently increased? Had the patient stopped taking another medication? When did the first symptoms appear? What happened after the patient sought medical treatment?
Those questions become especially important when someone was taking several medications during the weeks before the reaction.
Medical records, pharmacy records, prescribing information, drug labeling, hospital records, and input from appropriate medical experts may all become relevant when reconstructing what happened. The timing between drug exposure and the onset of symptoms can be particularly important.
This is also why population-level research should be interpreted carefully. A study can tell researchers which medications appear most frequently across thousands of reported cases, but it can't tell us what caused one person's reaction.
Evaluating an SJS Case Involves More Than Identifying the Drug
Identifying a likely trigger is only one part of evaluating a potential Stevens-Johnson syndrome case. Depending on what happened, questions may also arise about how the medication was prescribed, whether known risk factors should have been considered, whether appropriate warnings accompanied the drug, and what happened once symptoms began.
In some cases, the issue may involve a pharmaceutical manufacturer and the adequacy of a drug's warnings. In others, questions may involve prescribing or dispensing errors or whether healthcare providers appropriately recognized a developing reaction and discontinued a suspected medication.
And sometimes, despite the severity of a patient's injuries, the available evidence does not support a viable legal claim. SJS and TEN are devastating medical conditions, but that outcome alone does not establish negligence or product liability.
What the New Research Means for Patients Taking Antiseizure Drugs
For patients, the takeaway isn't to stop taking an antiseizure medication because it appears in this study. These drugs can be essential for treating seizures and other serious conditions, and abruptly stopping some of them can create significant risks. Patients who have concerns about a medication should talk with their doctor about those concerns and any symptoms they are experiencing.
When someone has already developed SJS or TEN, figuring out what happened often means going back to the weeks before the diagnosis. What medications was the person taking? Was something new prescribed? Did the dosage change? When did the first symptoms appear? That history can help doctors determine which drugs to avoid in the future, and it can also matter when evaluating questions about how a medication was prescribed, dispensed, or labeled.
Those are some of the same issues we examine when we investigate an SJS or TEN case at Childers, Schlueter & Smith. We represent people with these conditions throughout the U.S. and review the medical and medication history to understand what happened and whether the evidence supports a legal claim.
If you or a family member developed SJS or TEN after taking a prescription or over-the-counter medication and have questions about what happened, you can contact Childers, Schlueter & Smith or call 1-800-641-0098.
