Moderate
Acetylsalicylic acid × Valproic acid
Antiplatelet agents (low dose) / NSAIDs (analgesic dose)×Antiepileptics. Fatty acid derivatives
Mechanism
Aspirin displaces valproate from albumin binding and suppresses its metabolism. The free valproate fraction rises, raising neurotoxicity risk (tremor, sedation, hyperammonaemia).
Symptoms
Tremor, drowsiness, nausea, confusion. Severe cases: hyperammonaemic encephalopathy. Symptoms appear within 1–2 weeks at high aspirin doses.
Management
Cardioprotective aspirin doses (75–100 mg) are usually acceptable. At high doses, check valproate level at 1 week. For chronic analgesia on valproate: paracetamol.