What medications are associated with Stevens-Johnson syndrome (SJS), a severe skin and mucous membrane disorder?

From the Guidelines

Medications most commonly associated with Stevens-Johnson syndrome (SJS) include sulfonamide antibiotics, anticonvulsants, non-steroidal anti-inflammatory drugs (NSAIDs), and allopurinol, with specific high-risk medications being sulfamethoxazole-trimethoprim, phenytoin, carbamazepine, lamotrigine, allopurinol, and certain NSAIDs like ibuprofen and naproxen, as reported in the most recent study 1.

Key Medications Associated with SJS

• Sulfonamide antibiotics
• Anticonvulsants (e.g., phenytoin, carbamazepine, lamotrigine)
• Non-steroidal anti-inflammatory drugs (NSAIDs), particularly oxicam and acetic acid derivatives
• Allopurinol
• Certain antibiotics (penicillins, cephalosporins, fluoroquinolones)
• Nevirapine (an HIV medication)
• Acetaminophen (with unclear association but potential for causing SJS)

Important Considerations

• Genetic factors can predispose individuals to SJS reactions, emphasizing the need for caution when starting high-risk medications, especially in populations with known genetic predispositions, such as HLA-B*1502 in South East Asia before treatment with carbamazepine 1.
• Infections, particularly those caused by HSV and Mycoplasma pneumoniae, are common triggers of SJS in the pediatric population, highlighting the importance of considering infectious causes and consulting with infectious disease teams when necessary 1.
• The use of algorithms like ALDEN can help in determining drug causality in SJS/TEN cases, and referral to specialist centers for diagnostic testing, including patch testing and T-cell proliferation/cytokine release assays, may be beneficial in severe or complex cases 1.

Clinical Approach

• Immediate withdrawal of suspected medications is crucial to decrease the risk of death in SJS/TEN cases, and any decision to stop or change medications should be made in consultation with a healthcare provider 1.
• Vigilance for prodromal symptoms of SJS/TEN, such as fever and mucosal involvement, is essential, especially when starting new medications known to have a higher risk of SJS, as reported in recent guidelines and studies 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 Severe dermatologic reactions such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and linear IgA bullous dermatosis (LABD) have been reported in association with the use of vancomycin

The medications associated with Stevens-Johnson syndrome (SJS) are:

• Phenytoin (Dilantin) 2
• Vancomycin 3

From the Research

Medications Associated with Stevens-Johnson Syndrome (SJS)

The following medications have been identified as potential triggers for SJS:

• Allopurinol 4, 5, 6, 7
• Carbamazepine 4, 5, 8, 6, 7
• Phenytoin 4, 5, 6
• Lamotrigine 5, 7
• Sodium valproate 5, 7
• Sulfa drugs 5, 7
• Penicillins 7
• Ibuprofen 7
• Non-steroidal anti-inflammatory drugs (NSAIDs) including piroxicam and tenoxicam 6
• Antibiotics including amoxicillin and cephalexin 6
• Phenobarbital 6
• Valproate 6

Signal Strength of Medications

The signal strength of medications associated with SJS has been analyzed using the Information Component (IC) method and Reporting odds ratio (ROR) 4. The top 3 strongest signals are:

• Allopurinol (IC025/ROR025=5.86/69.84)
• Phenytoin (IC025/ROR025=5.60/57.65)
• Carbamazepine (IC025/ROR025=5.25/43.88)

Combination Drug Use

Combination drug use has been identified as a potential risk factor for SJS 6. The use of certain medications in combination with allopurinol, carbamazepine, or phenytoin may increase the incidence of SJS. These medications include:

• Phenobarbital
• Valproate
• Non-steroidal anti-inflammatory drugs (NSAIDs) including piroxicam and tenoxicam
• Antibiotics including amoxicillin and cephalexin

Genetic Predisposition

Genetic predisposition, particularly the presence of the HLA-B*1502 allele, has been identified as a risk factor for SJS 5. Patients with this allele may be at increased risk of developing SJS when taking certain medications, such as carbamazepine.