Potential Polymorphic CYP1A2 and CYP2D6-mediated Pharmacokinetic Interactions between Risperidone or Olanzapine and Selected Drugs Intended to Treat COVID-19

Abstract

Risperidone/olanzapine are antipsychotics used in Peru to control symptoms of psychosis. The objective was to review the available evidence on potential pharmacokinetic interactions mediated by CYP1A2 and CYP2D6 polymorphic genes between risperidone or olanzapine and selected drugs for the treatment of COVID-19. A bibliographic search was conducted in SciELO and PubMed/Medline. The selection criteria included all types of articles in English and Spanish languages. In this review, the CYP1A2/CYP2D6/CYP3A4 genes that encode their respective enzymes have been described. The olanzapine/risperidone association increases the risk of prolonging the QT interval; chloroquine/hydroxychloroquine decreases metabolism and increases plasma concentration of risperidone; ritonavir decreases metabolism and increases plasma levels of hydroxychloroquine and lopinavir with the risk of prolonging the QT interval of the cardiac cycle and with a tendency to progression towards Torsades de Pointes. Ritonavir increases metabolism and decreases plasma levels of olanzapine. A low incidence of adverse effect was found between risperidone/azithromycin and olanzapine with azithromycin and hydroxychloroquine. Regarding the association of genes: CYP1A2*1D increases and CYP1A2*1F decreases the plasma concentration of olanzapine. Risperidone plasma levels are increased in CYP2D6 intermediate and poor metabolizers compared with normal metabolizers. Other studies indicate no significant association between poor metabolizers of CYP1A2 and CYP2D6 with increased pharmacokinetic parameters. It is concluded that there are potential risks of prolonging the QT interval due to pharmacokinetic interactions mediated by polymorphic genes CYP1A2 and CYP2D6 between risperidone or olanzapine and the drugs selected for the treatment of COVID-19.

Effects of Aripiprazole on Olanzapine Population Pharmacokinetics and Initial Dosage Optimization in Schizophrenia Patients

“…At the same weight, the olanzapine clearance rates were 0.608:1 in patients with or without aripiprazole, respectively. As is known to all, cytochrome P450 (CYP) 2D6 is one of the metabolic enzymes of olanzapine, 21,22 meanwhile CYP2D6 also metabolizes aripiprazole. [23][24][25] Namely, olanzapine and aripiprazole both are CYP2D6 substrates, there be competing interactions.…”

“…15 Therapeutic drug monitoring (TDM) technique is often used to monitor the blood concentration of olanzapine in clinical practice to evaluate the drug efficacy and adverse reactions, and the therapeutic range of olanzapine in schizophrenia patients was 20-80 ng/mL, 16 where lower drug concentrations lead to poor efficacy and higher drug concentrations are associated with adverse reactions. [17][18][19][20] As is known to all, cytochrome P450 (CYP) 2D6 is one of the metabolic enzymes of olanzapine, 21,22 meanwhile CYP2D6 also metabolizes aripiprazole. [23][24][25] Namely, olanzapine and aripiprazole both are CYP2D6 substrates, there may be competing interactions, influencing olanzapine concentration and clinical treatment outcome such as efficacy and adverse reactions.…”