When does Stevens-Johnson Syndrome (SJS) typically occur when taking Lamictal (lamotrigine)?

Stevens-Johnson Syndrome Timing with Lamotrigine

Stevens-Johnson Syndrome (SJS) from lamotrigine typically occurs within 5-28 days after starting the medication, with over 90% of cases developing within the first 63 days of treatment. 1, 2

Critical Timing Window

• The highest risk period is 5-28 days following drug initiation, which represents the typical latency period for drug-induced SJS/TEN 1

• More than 90% of all SJS/TEN cases with antiepileptic drugs occur within the first 63 days (approximately 9 weeks) of use 2

• The onset can be as early as within the first week of starting lamotrigine, particularly if dose escalation is rapid 3

• Recent case reports confirm this pattern, with patients developing SJS following dose escalation of lamotrigine within the initial weeks of treatment 3

Important Clinical Context

• A latent period between initial drug intake and onset of SJS/TEN always occurs—there is no immediate reaction 1

• If a patient has had a previous reaction to the same drug, the latency period may be shorter than the typical 5-28 day window 1

• The risk is particularly elevated during dose escalation phases, not just initial exposure 3

Risk Magnitude

• The absolute risk of hospitalization for SJS/TEN in new lamotrigine users ranges between 1 and 10 per 10,000 new users across various assumptions 2

• Lamotrigine is one of the antiepileptic drugs most commonly associated with SJS, along with carbamazepine, phenytoin, and phenobarbital 4, 5

Critical Pitfalls to Avoid

• Do not assume safety after the first few days—the risk window extends through at least the first 2 months of therapy 1, 2

• Rapid dose escalation increases risk—manufacturers have developed strict dosing regimens specifically to prevent SJS 4

• Genetic screening for HLA-B*15:02 should be considered, particularly in patients of Chinese or Southeast Asian descent, as this genotype significantly increases susceptibility to lamotrigine-induced SJS 4

• Patients of Japanese origin with HLA-B31:01 and Koreans with HLA-B44:03 are also at increased risk 4

Immediate Action Required

• Any rash developing within the first 8 weeks of lamotrigine therapy should be considered potentially serious and warrants immediate evaluation 1

• Discontinue lamotrigine immediately if SJS is suspected—this is the single most important intervention to reduce mortality 1, 3

• Early recognition is crucial: look for fever, painful skin lesions, targetoid lesions, and particularly mucosal involvement of eyes, mouth, nose, and genitalia, which distinguishes SJS/TEN from other conditions 6, 7