Effect of Rifampin on the Plasma Concentration and the Clinical Effect of Haloperidol Concomitantly Administered to Schizophrenic Patients

Abstract

We assessed the changes of plasma haloperidol concentrations and clinical responses repeatedly up to 4 weeks after coadministration or discontinuation of rifampin in 12 schizophrenic patients taking haloperidol alone (group I) and 5 patients taking haloperidol and antituberculotic drugs (group II). After coadministration of rifampin in group I, daily trough haloperidol concentrations rapidly decreased and reached 63% of baseline level by day 3, 41.3% by day 7, and 30% by day 28. On the other hand, after discontinuation of rifampin in group II, plasma haloperidol concentration increased to 140.7% of baseline level by day 3, 228.7% by day 7, and 329% by day 28. In this study, a 30% or greater change in the clinical rating scale was considered a positive clinical response of the drug interaction. Using this criterion, 50% of the group I subjects responded according to the Brief Psychiatric Rating Scale (BPRS) total score, and 25% responded according to the BPRS subscale for psychiatric symptoms. No positive responses were observed in group II patients. These results strongly suggest that rifampin interacts with the clinical effects as well as the plasma concentrations of coadministered haloperidol, and careful monitoring should be considered when coadministration or discontinuation of rifampin is needed in a schizophrenic patient taking haloperidol.

Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

“…Haloperidol and RIF co-administration led to a decrease in haloperidol AUC to 30% of baseline by day 28, whereas cessation of RIF in patients receiving haloperidol and RIF resulted in higher haloperidol AUCs up to 329% at day 28 [122]. In a two-phase open-label cross-over study, RIF decreased risperidone AUC by 72% and C max by 50%, possibly through CYP3A4 induction [123].…”

Probable Case of Neuroleptic Malignant Syndrome Following Administration of Antituberculotic Drugs in a Chlorpromazine-Treated Patient

“…Accordingly, the plasma concentrations and therapeutic effects of antipsychotics can be reduced by the administration of rifampin. Kim et al (8) reported that a decrease in the plasma haloperidol concentration due to rifampin administration developed rapidly and that the extent was large in several patients. Gorski et al (7) demonstrated that there is a large interindividual variability in the extent of CYP 3A induction by rifampin.…”

Drug Metabolism

“…An aspect worth stressing is that phenelzine is not only an MAO substrate, but also an inactivator of the enzyme; it facilitates the breakdown of diazene to N 2 and the phenylethyl radical, which is capable of forming covalent adducts with the enzyme at the specific position C 4 of the flavin. Under these circumstances, the enzyme will be inactivated by alkylation ("suicide substrate" behaviour) [147] (Figure 2.57). …”

“…(decreased metabolism) [140] anti-coagulants, oral decreased anticoagulant effect with nafcillin (increased metabolism) [141] cephalosporins possible cefotaxime toxicity with mezlocillin in patients with renal impairment (decreased excretion) [142] lithium hypernatremia with ticarcillin (decreased renal excretion) [143] neuromuscular blocking agents recurrent neuromuscular blockade with IV piperacillin (mechanism not established) [144] barbiturates decreased barbiturate effect (increased metabolism) [145] corticosteroids marked decrease in corticosteroid effect (increased metabolism) [146] haloperidol decreased haloperidol effect (increased metabolism) [147] isoniazid hepatotoxicity (possibly increased toxic metabolites) [148] Rifampin trimethoprimsulfamethoxazole possible rifampin toxicity (possibly decreased metabolism) [149] barbiturates increased thiopental effect (decreased albumin binding) [150] cyclosporins decreased cyclosporin effect with sulphadiazine (possibly increased metabolism) [151] Sulphonamides hypoglycaemics increased hypoglycaemic effect (mechanism not established) [152] Drug interactions and adverse reactions 323…”