title: Eosinophilic myocarditis during treatment with olanzapine - report of two possible cases.
abstract: BACKGROUND
  Drug-induced eosinophilic myocarditis is a life-threatening and frequently overlooked condition. The prevalence of myocarditis in clozapine-treated patients may be as high as 3 %. An association between olanzapine and myocarditis has not previously been described, but given the chemical similarity between olanzapine and clozapine, we hypothesized the existence of such an association. We searched the spontaneous adverse drug reports database of the Danish Health and Medicines Authority for olanzapine and myocarditis in the period from October 21, 1996 to - June 03, 2015. We identified two fatal cases of eosinophilic myocarditis associated with the use of olanzapine.
  
  
  METHODS
  Case 1 was a 39-year-old Caucasian man with known substance abuse and schizophrenia. He was found dead in his home. Olanzapine was prescribed at day -54, and dose at time of death was 40 mg/day. Post-mortem toxicological examination demonstrated presence of olanzapine, morphine, venlafaxine and oxazepam. Syringes indicating substance abuse were found in his home. Case 2 was a 36-year-old Caucasian man diagnosed with schizophrenia was found dead unexpectedly. There was no history of substance abuse. Current treatment was olanzapine 20 mg/day +5 mg as PRN (prescribed for almost 4 years), aripiprazole 30 mg/day (prescribed for 6 months) and mirtazapine 30 mg/day (prescribed for 6 months). Both cases of eosinophilic myocarditis were confirmed by autopsy findings and both patients received olanzapine in doses exceeding the recommendations.
  
  
  CONCLUSIONS
  Olanzapine may have contributed to and/or worsened the two reported fatal cases of myocarditis. Additional studies are required to establish a causal link between olanzapine and eosinophilic myocarditis.
authors.affiliation: Aalborg University Hospital, Psychiatry, Brandevej 5, 9220, Aalborg, Demmark.
authors.forename: Torkel
authors.initials: T
authors.lastname: Vang
authors.affiliation: Danish Health and Medicines Authority, Copenhagen, Denmark.
authors.forename: Mary
authors.initials: M
authors.lastname: Rosenzweig
authors.affiliation: Danish Health and Medicines Authority, Copenhagen, Denmark.
authors.forename: Christina Hedegaard
authors.initials: CH
authors.lastname: Bruhn
authors.affiliation: Aalborg University Hospital, Psychiatry, Brandevej 5, 9220, Aalborg, Demmark.|Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Polcwiartek
authors.affiliation: Laboratory of Experimental Cardiology, University of Copenhagen, Copenhagen, Denmark.|Department of Cardiology, Herlev University Hospital, Copenhagen, Denmark.
authors.forename: Jørgen Kim
authors.initials: JK
authors.lastname: Kanters
authors.affiliation: Aalborg University Hospital, Psychiatry, Brandevej 5, 9220, Aalborg, Demmark. jin@rn.dk.|Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. jin@rn.dk.
authors.forename: Jimmi
authors.initials: J
authors.lastname: Nielsen
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects* / Q000627:therapeutic use; D004802:Eosinophilia / Q000139:chemically induced*; D017809:Fatal Outcome; D006801:Humans; D008297:Male; D009205:Myocarditis / Q000139:chemically induced*; D000077152:Olanzapine; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine
keywords: ADR; Clozapine; Eosinophilic; Hypersensitivity; Myocarditis; Olanzapine