title: Midazolam-related drug interactions: detection of risk situations to the patient safety in a brazilian teaching hospital.
abstract: OBJECTIVE
  To identify clinically significant drug interactions and potentially related adverse drug events associated with the use of midazolam.
  
  
  METHODS
  Retrospective data analysis was performed at a single tertiary Brazilian Teaching Hospital from an electronic database derived from the Hospital's computerized physician order entry system over 1 year. Records from patients who received injectable midazolam within a period of 24 hours before flumazenil use were selected. Patients' orders were checked for the presence of clinically significant drug interactions and for the inclusion and discontinuation of potential trigger medications for adverse drug events related to midazolam.
  
  
  RESULTS
  A total of 7431 patients were exposed to midazolam, representing 28% of all patients admitted to the hospital. Twenty-six (0.35%) patients received flumazenil within 24 hours after midazolam, corresponding to more than one third of the orders for flumazenil. Clinically significant drug interactions were observed in prescriptions of drugs preceding the use of flumazenil for 23 (88%) of these patients. The most prevalent group of drug interactions were related to the prescription of central nervous system depressants (22 cases), mainly opiate agonists. Analysis of inclusion and discontinuation of drugs demonstrated that the first order for opiates preceded the use of flumazenil in 31% of the cases and, except for tramadol, all opiates were discontinued after its administration, highlighting the potential of these drugs to act as triggers for adverse drug events.
  
  
  CONCLUSIONS
  Midazolam-related drug interactions are not infrequent and may conduce to serious adverse drug events, including hypotension, respiratory depression, and arrest. Efforts directed toward monitoring interactions and preventing injuries from midazolam use are expected to have a substantial impact on patient safety concerning the use of midazolam.
authors.affiliation: Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Brazil.
authors.forename: Daniel Fábio
authors.initials: DF
authors.lastname: Kawano
authors.forename: Julieta
authors.initials: J
authors.lastname: Ueta
authors.forename: Ajith Kumar
authors.initials: AK
authors.lastname: Sankarankutty
authors.forename: Leonardo Régis Leira
authors.initials: LR
authors.lastname: Pereira
authors.forename: Osvaldo
authors.initials: O
authors.lastname: de Freitas
mesh_terms: D000959:Antihypertensive Agents / Q000009:adverse effects; D002492:Central Nervous System Depressants / Q000009:adverse effects; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004347:Drug Interactions; D005442:Flumazenil / Q000627:therapeutic use; D018757:GABA Modulators / Q000627:therapeutic use; D006801:Humans; D050316:Medical Order Entry Systems; D008874:Midazolam / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000959:Antihypertensive Agents; D002492:Central Nervous System Depressants; D018757:GABA Modulators; D005442:Flumazenil; D051544:Cytochrome P-450 CYP3A; D008874:Midazolam