Which is more likely to cause skin reactions, Augmentin (amoxicillin/clavulanate) or Enzoflam (diclofenac) or Xarelto (rivaroxaban)?

Skin Reactions Associated with Augmentin, Enzoflam, and Xarelto

Augmentin (amoxicillin/clavulanate) is most likely to cause skin reactions compared to Enzoflam (diclofenac) and Xarelto (rivaroxaban).

Comparative Risk of Skin Reactions

Augmentin (Amoxicillin/Clavulanate)

• Beta-lactam antibiotics, including amoxicillin/clavulanate, are among the most common causes of drug allergies, with approximately 5-10% of patients reporting a penicillin allergy 1
• Skin reactions with Augmentin can include maculopapular exanthems, urticaria, and in rare cases, severe cutaneous adverse reactions like Stevens-Johnson syndrome and toxic epidermal necrolysis 1
• In clinical studies, rash was reported in approximately 3% of patients taking Augmentin 2
• The combination of amoxicillin with clavulanic acid may increase the risk of skin reactions compared to amoxicillin alone 3
• A veterinary study showed significantly higher incidence of adverse events with Augmentin (36%) compared to another antibiotic, with the majority involving cutaneous signs 4

Enzoflam (Diclofenac)

• NSAIDs like diclofenac can cause skin reactions, but at a lower frequency than beta-lactam antibiotics 5
• Oxicam NSAIDs (like meloxicam) have a higher association with skin reactions compared to other NSAID classes like diclofenac 6, 5
• Diclofenac can cause delayed hypersensitivity reactions that manifest as cutaneous reactions including pruritus, but these are less common than with beta-lactam antibiotics 5

Xarelto (Rivaroxaban)

• Rivaroxaban has a relatively low incidence of skin reactions compared to beta-lactam antibiotics and NSAIDs 1
• There are few reported cases of hypersensitivity reactions with rivaroxaban, suggesting this class of drugs may be safer from a dermatologic perspective 1

Risk Factors for Skin Reactions

Patient-Related Factors

• History of previous drug allergies increases risk of new drug allergies, particularly with beta-lactam antibiotics 1
• Children tend to have a lower risk of true beta-lactam allergy than adults 1
• The risk of allergy to beta-lactams decreases with older age (>60 years) 1
• More severe index reactions (e.g., anaphylaxis, angioedema) are strongly associated with true drug allergies 1

Medication-Related Factors

• Higher doses of medications may increase the risk of skin adverse events 5
• Longer duration of treatment increases risk of developing skin reactions 1
• Parenteral administration of beta-lactams may carry a higher risk of severe reactions compared to oral administration 1

Clinical Implications

When to Avoid These Medications

• Patients with a history of severe cutaneous adverse reactions (SCAR) like Stevens-Johnson syndrome or toxic epidermal necrolysis should avoid the culprit drug class 1, 6
• Patients with a history of anaphylaxis to any of these medications should strictly avoid the culprit drug 1
• Patients with aspirin-exacerbated respiratory disease should use NSAIDs like diclofenac with caution 6

Management of Skin Reactions

• For mild to moderate reactions: topical therapies, systemic antihistamines, or short courses of systemic steroids 5
• For severe reactions: immediate discontinuation of the culprit drug and appropriate supportive care 1
• Consider testing for beta-lactam allergy in patients with a history of reaction to Augmentin, as many reported allergies cannot be confirmed 1

Conclusion

Based on the available evidence, Augmentin (amoxicillin/clavulanate) has the highest likelihood of causing skin reactions among the three medications, followed by Enzoflam (diclofenac), with Xarelto (rivaroxaban) having the lowest risk. This ranking is consistent with the known safety profiles of these medication classes, with beta-lactam antibiotics being among the most common causes of drug-induced skin reactions.