Buspirone grapefruit juice

J. T., Lamberg, T. S., Neuvonen, P. J., Grapefruit juice substantially increases plasma concentrations of buspirone, Clin. Pharmacol. Ther. 1998, 64, 655— 660. 

Buspirone (BuSpar) [Anxiolytic] WARNING Closely monitor for worsening depression or emergence of suicidality Uses Short-term relief of anxiety Action Antianxiety antagonizes CNS serotonin receptors Dose Initial 7.5 mg PO bid T by 5 mg q2-3d to effect usual 20-30 mg/d max 60 mg/d Contra w/ MAOI Caution [B, /-] Avoid w/ severe hepatic/renal insuff Disp Tabs SE Drowsiness, dizziness, HA, N, EPS, serotonin synd, hostility, depression Notes No abuse potential or physical/psychologic d endence Interactions T Effects W/ erythromycin, clarithromycin, itraconazole, ketoconazole, diltiazem, verapamil, grapefruit juice effects W/ carbamazepine, rifampin, phenytoin, dexamethasone, phenobarbital, fluoxetine EMS T Sedation w/ concurrent EtOH use grapefruit juice may T risk of adverse effects OD May cause dizziness, miosis, N/V symptomatic and supportive... 

Verapamil, diltiazem, erythromycin, and itraconazole all increase the plasma concentration of buspirone. The plasma concentration is decreased almost 10-fold by rifampicin. Grapefruit juice increases the overall subjective effect of the drug (Mahmood and Saha-jwalla, 1999). 

Buspirone is rapidly absorbed orally but undergoes extensive first-pass metabolism via hydroxylation and dealkylation reactions to form several active metabolites. The major metabolite is l-(2-pyrimidyl)-piperazine (1-PP), which has K2-adrenoceptor-blocking actions and which enters the central nervous system to reach higher levels than the parent drug. It is not known what role (if any) 1-PP plays in the central actions of buspirone. The elimination half-life of buspirone is 2-4 hours, and liver dysfunction may slow its clearance. Rifampin, an inducer of cytochrome P450, decreases the half-life of buspirone inhibitors of CYP3A4 (eg, erythromycin, ketoconazole, grapefruit juice, nefazodone) can markedly increase its plasma levels. 

In a randomized, two-phase crossover study, the effects of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral buspirone were investigated in 10 healthy volunteers. Grapefruit juice increased the mean peak plasma concentration of buspirone 4.3-fold (26). Large amounts of grapefruit juice should be avoided in patients taking buspirone. 

BUSPIRONE-ORAL GRAPEFRUIT JUICE Possibly t efficacy and t adverse effects, e.g. sedation, CNS depression Possibly t bioavailability, 1 presystemic metabolism. Constituents of grapefruit juice irreversibly inhibit intestinal CYP3A4. Transport via P-gp and MRP-2 efflux pumps is also inhibited Avoid concomitant use. Be particularly vigilant in elderly patients or those with impaired liver function. Consider an alternative, e.g. temazepam... 

Grapefruit juice can significantly increase plasma levels of buspirone. 

There are isolated cases of apparent interactions between clozapine, and ampicillin, buspirone, caffeine, haloperidol, loperamide, modafinil, nefazodone, nicotinic acid, tryptophan, or vitamin C. Grapefruit juice, influenza vaccine mirtazapine, reboxetine, or venlafaxine do not appear to interact Cocaine levels may increase when taken with clozapine. 

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