Can Lyrica (pregabalin) cause Stevens-Johnson syndrome?

Can Lyrica (Pregabalin) Cause Stevens-Johnson Syndrome?

Yes, Lyrica (pregabalin) can potentially cause Stevens-Johnson syndrome (SJS), although it is a rare adverse effect that is not among the most common drugs associated with this serious condition.

Understanding Stevens-Johnson Syndrome

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe, potentially life-threatening mucocutaneous reactions characterized by:

• Widespread epidermal detachment
• Mucosal involvement (mouth, eyes, genitalia)
• Systemic symptoms
• Mortality rates of 1-5% for SJS and 25-35% for TEN 1

Common Medications Associated with SJS/TEN

According to the British Journal of Dermatology guidelines, the most common drugs causing SJS/TEN include:

• Allopurinol
• Carbamazepine
• Lamotrigine
• Nevirapine
• Oxicam NSAIDs
• Phenobarbital
• Phenytoin
• Sulfamethoxazole and other sulfonamide antibiotics
• Sulfasalazine 2

Among anticonvulsants, carbamazepine, phenytoin, and lamotrigine have been most strongly associated with SJS/TEN, with absolute risks of:

• Phenytoin: 45.86 cases/100,000 exposed
• Lamotrigine: 44.17 cases/100,000 exposed
• Carbamazepine: 20.38 cases/100,000 exposed 3

Pregabalin (Lyrica) and SJS Risk

While pregabalin is not listed among the highest-risk medications for SJS/TEN, the British Thoracic Society guidelines do mention Stevens-Johnson syndrome as a "serious" but "rare" adverse effect of moxifloxacin 2, and similar rare serious dermatological reactions can occur with other medications including anticonvulsants.

The 2017 study on antiepileptic drugs and SJS/TEN risk found increased odds ratios for several medications including pregabalin, but causality assessment using the ALDEN score (Algorithm of Drug Causality for Epidermal Necrolysis) did not confirm a causal association for pregabalin 3.

Cross-Reactivity Considerations

There is evidence of cross-reactivity between antiepileptic drugs in causing serious skin eruptions. A case report documented a patient who experienced severe SJS with phenytoin and carbamazepine, and subsequently developed a skin eruption (though less severe) with gabapentin, which is structurally similar to pregabalin 4. This suggests potential cross-reactivity risk among structurally related anticonvulsants.

Clinical Implications

If a patient develops any of the following symptoms while taking pregabalin, immediate medical attention should be sought:

• Skin rash
• Mucosal involvement
• Fever
• Flu-like symptoms preceding rash
• Blistering or peeling of skin

Management of Suspected SJS/TEN

1. Immediate discontinuation of the suspected causative drug
2. Referral to specialized care (dermatology, burn unit, or intensive care)
3. SCORTEN calculation to predict mortality risk
4. Supportive care including fluid management, wound care, and pain control
5. Consideration of immunomodulating agents in severe cases 2

Prevention

For patients with a history of severe drug reactions:

• Document the reaction thoroughly
• Consider testing for genetic susceptibility markers in specific populations (e.g., HLA-B*1502 in patients of Asian ancestry)
• Avoid structurally similar medications due to potential cross-reactivity

While pregabalin is not among the highest-risk medications for SJS/TEN, clinicians should remain vigilant for this rare but serious adverse effect with any medication, particularly anticonvulsants.