Increased Plasma Valproate Concentrations When Coadministered with Guanfacine

Abstract

A preliminary clinical observation suggests the possibility of changes in valproate level when coadministered with guanfacine. Two pediatric inpatients (8 and 9 years of age) were treated with valproic acid and guanfacine concurrently. In one child, when guanfacine was tapered and discontinued, the plasma valproate concentration decreased by 41% from 128 microg/mL to 76 microg/mL. In the other case, studied in an ABA design, the child exhibited a rapid increase in plasma valproate levels while guanfacine was administered. It is proposed that guanfacine may affect the pharmacokinetics of valproic acid and lead to a significant increase in valproate plasma levels when used concurrently with this agent. The mechanism of this proposed interaction may involve drug-drug competition at the level of hepatic glucuronidation (conjugation), although shifts in protein binding cannot be ruled out.

Concomitant Psychotropic Medication for Youths

“…Other safety concerns with use of concomitant psychotropic medication in youths include 1) the greater possibility of untoward drug interactions (106,107) and 2) the creation of drug-induced behavioral toxicity after the addition of another psychotropic medication-a consequence not often recognized as such, which can then lead to even more complex drug therapy to treat that side effect (100). Table 4 presents a brief list of reports of adverse drug events with the use of concomitant psychotropic medication in youths.…”

Valproate Induced Hypertensive Urgency

“…Though there has not been a prior reported association between valproate and hypertensive urgency, it has been shown to cause hypertension [ 2 ]. Studies have linked the significant effects guanfacine can have on valproate metabolism [ 7 ] and the addition of valproate to an already high dose (5 mg total daily dose) of guanfacine that likely led to a rapid increase in valproate levels. Another possible mechanism could be explained by a shared mechanism of action of valproate with carbamazepine, which has been implicated in inducing hypertension [ 8 ].…”

Profile of guanfacine extended release and its potential in the treatment of attention-deficit hyperactivity disorder

“… 45 In addition, when guanfacine and valproic acid are administered simultaneously, plasma valproate levels may rise significantly. 46 However, two small open-label studies conducted with healthy adults revealed that coadministration of GXR and MPH 47 or lisdexamfetamine 48 did not result in significant pharmacokinetic drug–drug interactions.…”