What are the most common medications to cause Stevens-Johnson Syndrome (SJS)?

From the Guidelines

Stevens-Johnson Syndrome (SJS) is most commonly caused by medications such as allopurinol, carbamazepine, lamotrigine, nevirapine, oxicam NSAIDs, phenobarbital, phenytoin, sulfamethoxazole, and sulfasalazine, as identified in the UK guidelines for the management of SJS/toxic epidermal necrolysis in adults 2016 1. The most frequently implicated medications in SJS include:

• Allopurinol
• Carbamazepine
• Lamotrigine
• Nevirapine
• Oxicam NSAIDs
• Phenobarbital
• Phenytoin
• Sulfamethoxazole and other sulfur antibiotics
• Sulfasalazine These medications can cause a rare but serious immune-mediated reaction that typically begins within the first 8 weeks of starting a new medication, leading to severe blistering and peeling of the skin and mucous membranes, often accompanied by fever and other systemic symptoms 1. It is essential to immediately discontinue the offending medication and seek urgent medical attention if SJS is suspected, as this condition can be life-threatening with mortality rates of 5-10% 1. Genetic factors can increase susceptibility, particularly HLA-B1502 and HLA-B5801 alleles in certain populations, which is why some medications carry genetic testing recommendations before initiation 1. The UK guidelines for the management of SJS/toxic epidermal necrolysis in adults 2016 provide recommendations for the management of SJS, including the use of analgesia, supportive therapeutic measures, and treatment of eye, mouth, urogenital, and airway involvement 1. However, the primary concern is to identify and avoid the culprit medication to prevent further reactions, as emphasized in the guidelines 1.

From the FDA Drug Label

Increased frequencies of major malformations ... Skin reactions Dilantin can cause rare, serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal In deciding which patients to screen, the rates provided above for the prevalence of HLA-B1502 may offer a rough guide, keeping in mind the limitations of these figures due to wide variability in rates even within ethnic groups, the difficulty in ascertaining ethnic ancestry, and the likelihood of mixed ancestry Carbamazepine should not be used in patients positive for HLA-B1502 unless the benefits clearly outweigh the risks. Limited evidence suggests that HLA-B*1502 may be a risk factor for the development of SJS/TEN in patients of Chinese ancestry taking other antiepileptic drugs associated with SJS/TEN, including phenytoin. The most common meds to cause Stevens-Johnson Syndrome (SJS) are:

• Carbamazepine
• Phenytoin as supported by 2 and 3.

From the Research

Most Common Medications to Cause Stevens-Johnson Syndrome (SJS)

The following medications have been identified as common causes of SJS:

• Anticonvulsants, such as:
  • Carbamazepine 4, 5, 6, 7, 8
  • Phenytoin 4, 5, 6, 8
  • Lamotrigine 4
  • Sodium Valproate 4, 7
• Allopurinol 4, 5, 8
• Sulphonamides, such as:
  • Cotrimoxazole 4
  • Sulfasalazine 4
• Non-steroidal anti-inflammatory drugs (NSAIDs), such as:
  • Ibuprofen 6
  • Piroxicam 8
  • Tenoxicam 8
• Antibiotics, such as:
  • Amoxicillin 8
  • Cephalexin 8

Key Findings

• A study found that Allopurinol, Phenytoin, and Carbamazepine were the top 3 strongest signals for SJS 5.
• Another study reported that Carbamazepine was the most common causative drug of SJS and TEN in children 7.
• Combination drug use, particularly with Carbamazepine or Phenytoin, may increase the incidence of SJS 8.