title: Assessing drug-drug interactions through therapeutic drug monitoring when administering oral second-generation antipsychotics.
abstract: BACKGROUND
  Second-generation antipsychotics (SGAs) are frequently co-prescribed with drug metabolic inducers and inhibitors. SGA pharmacokinetic drug-drug interactions (DDIs) with inducers and inhibitors have not received enough attention in the literature but can be studied in by using therapeutic drug monitoring (TDM).
  
  
  METHODS
  The limited information available on oral SGA pharmacokinetic DDIs is reviewed. A systematic literature search on the available oral SGA TDM studies is completed. By integrating TDM studies with the information on in vitro metabolism studies, case report/series and prospective studies, a table is provided to manage average SGA patients taking inducers or inhibitors by using TDM and/or dose SGA changes. Adding an inhibitor or discontinuing an inducer may increase plasma concentrations and cause adverse drug reactions (ADRs) on clozapine or risperidone. Quetiapine and lurasidone, which are very sensitive to decreases of plasma concentrations by induction, should not be administered with potent inducers. Prescribing sertindole with TDM may make its use safer.
  
  
  CONCLUSIONS
  Reading our article may encourage: 1) clinicians using these combinations to publish TDM case reports/series to demonstrate whether our dose indications are correct or not, in their patients with DDIs; and 2) pharmacokinetic researchers to study these DDIs in prospective and retrospective ways using large TDM databases.
authors.affiliation: a Department of Clinical and Experimental Medicine , University of Messina , Messina , Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Spina
authors.affiliation: b Department of Psychiatry and Psychotherapy , University Medical Center of Mainz , Mainz , Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hiemke
authors.affiliation: c University of Kentucky Mental Health Research Center at Eastern State Hospital , Lexington , KY , USA.|d Psychiatry and Neurosciences Research Group (CTS-549) , Institute of Neurosciences, University of Granada , Granada , Spain.|e Biomedical Research Centre in Mental Health Net (CIBERSAM) , Santiago Apostol Hospital, University of the Basque Country , Vitoria , Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: de Leon
mesh_terms: D000284:Administration, Oral; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring; D064420:Drug-Related Side Effects and Adverse Reactions / Q000097:blood / Q000517:prevention & control; D006801:Humans
chemical_list: D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents
keywords: Drug interactions; inducers; inhibitors; pharmacokinetics; second-generation antipsychotics; therapeutic drug monitoring