title: Off-label use of nicardipine as tocolytic and acute pulmonary oedema: a post-marketing analysis of adverse drug reaction reports in EudraVigilance.
abstract: OBJECTIVE
  To evaluate a signal of acute pulmonary oedema (APO) due to nicardipine used off-label as tocolytic in pregnant women.
  
  
  METHODS
  All the suspected cases of APO recorded in EudraVigilance database up to 31/01/2013 and associated with nicardipine containing medicinal products were retrieved. The Proportional Reporting Ratio was considered as measure of disproportionality. Individual cases evaluation was conducted.
  
  
  RESULTS
  Thirty-four spontaneous cases regarding pregnancy women who experienced APO following nicardipine treatment as tocolytic were collected. The detected proportional reporting ratio was 50.96 (95% confidence interval lower bound equal to 36.75). The analysis focused on 10 serious cases. Most women, aged between 27 and 39 years, were treated with intravenous nicardipine. The most of the suspected adverse reactions occurred between 24 and 96 hours.
  
  
  CONCLUSIONS
  A potentially causal association between APO and off-label use of nicardipine as tocolytic has been detected during a periodic signal detection activity. The Pharmacovigilance Risk Assessment Committee confirmed our findings, recommending an update of the summary of the product characteristics for medicines containing nicardipine for both intravenous and oral formulations. Then European Medicines Agency reaffirmed that nicardipine use in other indications is no longer recommended.
authors.affiliation: Department of Medical and Surgical Sciences - Unit of Pharmacology, University of Bologna, Bologna, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Melis
authors.affiliation: Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA)Pharmacovigilance Office, Rome, Italy.
authors.forename: Amelia
authors.initials: A
authors.lastname: Cupelli
authors.affiliation: Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA)Pharmacovigilance Office, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Sottosanti
authors.affiliation: Department of Medical and Surgical Sciences - Unit of Pharmacology, University of Bologna, Bologna, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Buccellato
authors.affiliation: Department of Medical and Surgical Sciences - Unit of Pharmacology, University of Bologna, Bologna, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Biagi
authors.affiliation: Department of Medical and Surgical Sciences - Unit of Pharmacology, University of Bologna, Bologna, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Vaccheri
authors.affiliation: Department of Medical and Surgical Sciences - Unit of Pharmacology, University of Bologna, Bologna, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Motola
mesh_terms: D000208:Acute Disease; D061605:Administration, Intravenous; D000284:Administration, Oral; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D016208:Databases, Factual; D005260:Female; D006801:Humans; D009529:Nicardipine / Q000009:adverse effects* / Q000627:therapeutic use; D056687:Off-Label Use; D060735:Pharmacovigilance; D011247:Pregnancy; D011358:Product Surveillance, Postmarketing; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000453:epidemiology; D013997:Time Factors; D015149:Tocolytic Agents / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D015149:Tocolytic Agents; D009529:Nicardipine
keywords: Eudra Vigilance; acute pulmonary oedema; nicardipine; pharmacoepidemiology; signal detection