Drug General Information (ID: DDI9XBW5VM)
Drug Name			Lorazepam		Drug Info		Valproic acid		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antianxiety Agents				Anticonvulsants
Structure

Mechanism of Lorazepam-Valproic acid Interaction (Severity Level: Moderate)
Competitive binding of plasma proteins Click to Show/Hide Mechanism Graph
Drug Name		Lorazepam				Valproic acid
Mechanism 1		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 Valproic acid and Lorazepam due to competitive binding of plasma proteins
Increased risk of other adverse reactions (Unspecific) Click to Show/Hide Mechanism Graph
Drug Name		Lorazepam				Valproic acid
Mechanism 2		Teratogenic effects				Teratogenic effects
Key Mechanism Factor 2
		Factor Name		Adverse reactions
		Factor Description		An adverse reaction is an unexpected negative reaction to a medication or treatment that happens even when it's used correctly.
Mechanism Description		Increased risk of adverse reactions by the combination of Lorazepam and Valproic acid

Recommended Action
Management		Both valproate and benzodiazepines should be avoided during pregnancy unless the potential benefits outweigh the risks to the fetus. In other patients, close observation for clinical evidence of benzodiazepine toxicity (excessive sedation) is recommended if valproate and a benzodiazepine must be used together.

References
1	Kupferschmidt HHT, Ha HR, Ziegler WH, Meier PJ, Krahenbuhl S "Interaction between grapefruit juice and midazolam in humans." Clin Pharmacol Ther 58 (1995): 20-8. [PMID: 7628179]
2	Dhillon S, Richens A "Valproic acid and diazepam interaction in vivo." Br J Clin Pharmacol 13 (1982): 553-60
3	Laegreid L, Kyllerman M, Hedner T, Hagberg B, Viggedahl G "Benzodiazepine amplification of valproate teratogenic effects in children of mothers with absence epilepsy." Neuropediatrics 24 (1993): 88-92