Moderate
Established
Description
Prednisone may increase salicylate clearance, reducing aspirin's anti-inflammatory efficacy, and combined GI toxicity is substantially increased.
Mechanism
Corticosteroids induce hepatic enzymes and increase renal salicylate excretion, reducing salicylate plasma levels; both independently damage gastric mucosa through complementary mechanisms.
Clinical Significance
Combined GI mucosal toxicity is synergistic; risk of peptic ulcer, GI hemorrhage, and perforation is substantially elevated with co-administration.
Management
Add gastroprotection (PPI or misoprostol); use the lowest effective doses; consider acetaminophen as analgesic alternative.