Off-label use of nicardipine as tocolytic and acute pulmonary oedema: A post-marketing analysis of adverse drug reaction reports in EudraVigilance

Purpose: 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 96hours. 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.