Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIUOGR5J4)
Drug Name			Valproic acid		Drug Info		Guanfacine		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Anticonvulsants				Antiadrenergic Agents
Structure

Mechanism of Valproic acid-Guanfacine Interaction (Severity Level: Moderate)
Competitive inhibition of metabolic enzyme Click to Show/Hide Mechanism Graph

Drug Name		Valproic acid				Guanfacine
Mechanism		UGT substrate				UGT substrate
Key Mechanism Factor 1
		Factor Name		UDP-glucuronosyltransferase				Structure Sequence
		Protein Family		UDP-glycosyltransferase family
		Protein Function		[Isoform 1]: UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15472229, PubMed:18004206, PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004206, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:15472229, PubMed:18719240, PubMed:23288867). Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (PubMed:17187418, PubMed:18004206, PubMed:19830808). Also catalyzes the glucuronidation the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:18004212, PubMed:20610558). Click to Show/Hide
Mechanism Description		Increased plasma concentrations of Valproic acid and Guanfacine due to competitive inhibition of the same metabolic pathway

Recommended Action
Management		Caution is advised if valproic acid is used with guanfacine. Dosage adjustment as well as clinical and laboratory monitoring of valproic acid should be considered. Patients should be advised to notify their health care professional if they experience increased CNS effects, including dizziness, drowsiness, lightheadedness, confusion, or fainting.

References
1	Cerner Multum, Inc. "UK Summary of Product Characteristics.".