Risk of Stevens-Johnson Syndrome with Co-amoxiclav
Co-amoxiclav (amoxicillin-clavulanate) can cause Stevens-Johnson syndrome and toxic epidermal necrolysis, though it carries a lower risk compared to the highest-risk medications such as sulfonamide antibiotics, anticonvulsants, allopurinol, and oxicam NSAIDs. 1, 2
Documented Risk Profile
The FDA drug label for amoxicillin-clavulanate explicitly lists erythema multiforme (rarely Stevens-Johnson syndrome) and toxic epidermal necrolysis as reported hypersensitivity reactions, though these occur as "occasional" cases. 1
When SJS/TEN does occur with co-amoxiclav, it represents a serious and potentially fatal hypersensitivity reaction that requires immediate drug discontinuation. 1
Comparative Risk Assessment
Large-scale epidemiological data from the EuroSCAR study (379 validated SJS/TEN cases across Europe) identified the highest-risk medications as: 2
- Anti-infective sulfonamides (strong association)
- Allopurinol (strong association)
- Anticonvulsants: carbamazepine, phenobarbital, phenytoin, lamotrigine (strong associations)
- Oxicam NSAIDs (strong association)
- Nevirapine (relative risk >22)
Co-amoxiclav was not among the medications demonstrating strong statistical associations in this comprehensive European surveillance study, suggesting it carries lower risk than these notorious agents. 2
Clinical Evidence in Pediatric Populations
A case report documents co-amoxiclav as the sole causative agent of SJS in an 18-month-old child, confirming that while rare, the drug can independently trigger this syndrome even in pediatric patients. 3 This is particularly notable because antibiotics (mainly sulfonamides) are the most commonly implicated drugs in pediatric SJS. 4
Critical Timing Considerations
The risk window for drug-induced SJS/TEN is restricted to the first few weeks of drug intake, typically occurring 5-28 days following drug initiation. 5, 2 Patients should be monitored most closely during the first month of therapy. 5
Cross-Reactivity Warning
Patients with documented history of SJS/TEN to any beta-lactam antibiotic (including penicillins) should avoid all beta-lactams, including co-amoxiclav, due to potential type IV delayed cell-mediated cross-reactivity. 6 A case report demonstrates meropenem-induced SJS in a patient with prior amoxicillin-induced SJS, establishing that cross-reactivity between beta-lactams can result in life-threatening reactions. 6
Clinical Recognition and Management
The FDA label specifies that when hypersensitivity reactions occur with co-amoxiclav, "the drug should be discontinued, unless the opinion of the physician dictates otherwise." 1 However, in the context of suspected SJS/TEN, there is no clinical scenario where continuing the drug is appropriate—immediate discontinuation is mandatory and decreases mortality risk. 4
Early clinical features to recognize include: 1, 7
- Macular exanthema with atypical target lesions
- Prominent mucosal involvement (eyes, mouth, nose, genitalia)
- Rapid confluence of lesions
- Positive Nikolsky's sign
- Widespread epidermal detachment
Risk-Benefit Considerations in Prescribing
The use of drugs with known SJS/TEN risk as first-line therapies should be considered carefully, especially when safer alternative treatments exist. 2 For co-amoxiclav specifically, this means weighing the infection severity and antibiotic alternatives against the patient's individual risk factors, including: 8, 2
- Prior history of drug hypersensitivity reactions
- Prior SJS/TEN to any medication
- Genetic predisposition (though no specific testing exists for co-amoxiclav)
Prognosis When SJS/TEN Occurs
When SJS/TEN develops from any medication including co-amoxiclav, mortality ranges from 3.2% (SCORTEN 0-1) to 90% (SCORTEN ≥5), with significant long-term morbidity including blindness, anogenital strictures, and chronic respiratory complications in survivors. 9, 7 Recovery typically requires 3-6 weeks. 7