Drug General Information (ID: DDI0SFKDYW)
Drug Name			Valproic acid		Drug Info		Bismuth subsalicylate		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Anticonvulsants				Antidiarrheals
Structure

Mechanism of Valproic acid-Bismuth subsalicylate Interaction (Severity Level: Moderate)
Competitive binding of plasma proteins Click to Show/Hide Mechanism Graph
Drug Name		Valproic acid				Bismuth subsalicylate
Mechanism		Competition for plasma protein binding sites				Competition for plasma protein binding sites
Key Mechanism Factor 1
		Factor Name		Plasma protein binding
		Factor Description		Plasma protein binding refers to the degree of binding of a drug to proteins in the blood, and the lower the degree of binding, the more efficiently the drug can cross cell membranes or diffuse. Plasma protein binding alters the distribution and therapeutic characteristics of the drugs.
Mechanism Description		Increased plasma concentration of Bismuth subsalicylate and Valproic acid due to competitive binding of plasma proteins

Recommended Action
Management		Small single doses of salicylates are unlikely to cause significant effects. However, patients who take large doses of salicylates or over a prolonged period of time should be closely monitored for clinical and laboratory evidence of valproate toxicity and hepatotoxicity. Free fraction of valproate may be particularly helpful in detecting this interaction. Patients should be advised to notify their physician if they experience possible symptoms of toxicity (e.g., malaise, weakness, lethargy, drowsiness, nausea, vomiting, or abdominal pain).

References
1	Abbott FS, Kassam J, Orr JM, Farrell K "The effect of aspirin on valproic acid metabolism." Clin Pharmacol Ther 40 (1986): 94-100. [PMID: 3087680]
2	Dasgupta A, Jacques M "Reduced in vitro displacement of valproic acid from protein binding by salicylate in uremic sera compared with normal sera - role of uremic compounds." Am J Clin Pathol 101 (1994): 349-53. [PMID: 8135194]
3	Farrell K, Orr JM, Abbott FS, et al "The effect of acetylsalicylic acid on serum free valproate concentrations and valproate clearance in children." J Pediatr 101 (1982): 142-4. [PMID: 6806458]
4	Orr JM, Abbott FS, Farrell K, Ferguson S, Sheppard I, Godolphin W "Interaction between valproic acid and aspirin in epileptic children: serum protein binding and metabolic effects." Clin Pharmacol Ther 31 (1982): 642-9. [PMID: 6804150]