What medications can cause Stevens-Johnson Syndrome (SJS), a severe skin and mucous membrane disorder?

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Last updated: April 29, 2025View editorial policy

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From the Guidelines

Stevens-Johnson Syndrome (SJS) is most commonly triggered by medications such as sulfonamides, penicillins, cephalosporins, anticonvulsants, NSAIDs, allopurinol, and certain antipsychotic medications, with sulfonamides like sulfamethoxazole-trimethoprim/Bactrim being a well-documented culprit 1.

Medications Associated with SJS

The medications associated with SJS include:

  • Antibiotics like sulfonamides (such as sulfamethoxazole-trimethoprim/Bactrim), penicillins, and cephalosporins
  • Anticonvulsants including carbamazepine, lamotrigine, phenytoin, and phenobarbital
  • Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen
  • Allopurinol used for gout
  • Certain antipsychotic medications

Mechanism and Genetic Factors

The reaction typically occurs within the first 8 weeks of starting a medication and involves a painful rash that spreads and blisters, affecting the skin and mucous membranes. The mechanism behind SJS involves an immune-mediated hypersensitivity reaction where the body's immune system mistakenly attacks its own cells in response to the medication. Genetic factors can increase susceptibility, particularly HLA-B1502 and HLA-B5801 alleles in certain populations.

Clinical Presentation and Management

If you develop any unusual rash, fever, or mucosal involvement while taking these medications, seek immediate medical attention as SJS can be life-threatening and requires prompt discontinuation of the triggering medication and supportive care. The management of SJS involves a multidisciplinary approach, including dermatology, ophthalmology, and intensive care, with a focus on wound care, pain management, and prevention of complications 1.

From the FDA Drug Label

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 Published literature has suggested that there may be an increased, although still rare, risk of hypersensitivity reactions, including skin rash, SJS, TEN, hepatotoxicity, and Anticonvulsant Hypersensitivity Syndrome in black patients Limited evidence suggests that HLA-B*1502 may be a risk factor for the development of SJS/TEN in patients of Asian ancestry taking drugs associated with SJS/TEN, including phenytoin.

Medications that cause Stevens-Johnson Syndrome (SJS) include:

  • Phenytoin (Dilantin) 2 Key points:
  • The risk of SJS is increased in black patients and patients of Asian ancestry with the HLA-B*1502 allelic variant
  • Patients should be alert for signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity
  • If a patient is diagnosed with SJS, the medication should be discontinued and appropriate supportive measures should be provided

From the Research

Medications that Cause Stevens-Johnson Syndrome

The following medications have been identified as potential causes of Stevens-Johnson syndrome:

  • Allopurinol 3, 4, 5
  • Phenytoin 3, 6, 4
  • Carbamazepine 3, 6, 4, 5, 7
  • Sulfa antibiotics (e.g. trimethoprim-sulfamethoxazole) 4
  • Aminopenicillins 4
  • Quinolones 4
  • Cephalosporins 4
  • Chlormezanone 4
  • Oxicam nonsteroidal anti-inflammatory drugs (NSAIDs) 4
  • Corticosteroids 4
  • Valproic acid 4
  • Lamotrigine 6, 5
  • Sodium valproate 6, 5
  • Ibuprofen 5
  • Penicillins 5

Mechanism and Risk Factors

The exact mechanism of Stevens-Johnson syndrome is not fully understood, but it is believed to be an immune-complex-mediated hypersensitivity reaction 7. Genetic predispositions, such as the presence of the HLA-B*1502 allele, can increase the risk of developing Stevens-Johnson syndrome 6. The risk of Stevens-Johnson syndrome is also higher in the first two months of treatment with certain medications, such as carbamazepine, phenobarbital, and phenytoin 4.

Clinical Presentation and Treatment

Stevens-Johnson syndrome is characterized by mucocutaneous lesions, fever, and other systemic symptoms 6, 7. Treatment typically involves discontinuation of the offending medication, supportive care, and in some cases, systemic steroid therapy 7. In severe cases, hospitalization and close monitoring may be necessary to prevent complications and improve outcomes 6, 7.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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