Major
Acetylsalicylic acid × Diclofenac
Antiplatelet agents (low dose) / NSAIDs (analgesic dose)×Non-steroidal anti-inflammatory drugs (NSAIDs)
Mechanism
Diclofenac competitively inhibits platelet cyclooxygenase-1 and blocks aspirin's access for COX-1 acetylation. Co-administration loses aspirin's cardioprotective effect. Additive ulcerogenic effect of two NSAIDs.
Symptoms
Black or tarry stools (melena), vomiting blood or coffee-ground material, epigastric pain. Risk multiplies in older patients and with prior peptic ulcer disease.
Management
If the patient takes aspirin for cardioprotection, give aspirin 30 minutes before or 8 hours after diclofenac. Alternative analgesic without this issue: paracetamol or a selective COX-2 inhibitor (celecoxib).