Adverse drug reaction related to drug shortage: A retrospective study on the French National Pharmacovigilance Database.

AIM: Drug shortages are a growing global health issue. The aim of the study was to evaluate the consequences of drug shortages on patient safety based on data recorded in the French National Pharmacovigilance Database. METHODS: All cases involving drug shortages reported from 1985 to the end of 2019 were extracted from the database. RESULTS: Following the selection process, 462 cases were included. The number of cases increased significantly from 2004 to 2019. Cases mainly involved drugs from the nervous system (22.1%, 95% confidence interval [CI] 17.5-27.0%), the cardiovascular system (16.4%, 95% CI 11.9-21.4%) and anti-infectives for systemic use (14.3%, 95% CI 9.7-19.2%) ATC classes. Most of the cases reported an adverse drug reaction (ADR) belonging to the SOC nervous system (21%, 95% CI 18-24%), skin and subcutaneous (14%, 95% CI 11-17%), general (13%, 95% CI 10-17%) and gastrointestinal (8%, 95% CI 5-11%) disorders. Disease worsening was observed in 15.9% of the cases, mostly related to a lack of efficacy of the replacement drug. Half of the cases were considered as serious. Evolution was favourable in 79.4% of the cases. Death and/or life-threatening situations were reported in 5.8% of the cases. Medication errors (MEs) were identified in 51 cases (11%), mostly occurring at the administration step and involving a human factor. CONCLUSION: This study emphasizes the clinical impact of drug shortage in terms of ADRs, ME and inefficiency. These observations underline the importance of a global health policy programme to limit the occurrence of drug shortages and to reinforce the information provided to patients and health care professionals in this context to limit risk.

Adverse drug effect in the context of drug shortage: the CIRUPT prospective study from the French pharmacovigilance network.

OBJECTIVES: Drug shortages are of increasing concern to worldwide public health. The consequences of drug shortages for patient safety have been little studied, especially from a pharmacovigilance point of view. In this context, the network of French pharmacovigilance centres conducted the CIRUPT study (Conséquences Iatrogènes des RUPTures de stock/iatrogenic consequences of drug shortages) based on a prospective campaign of adverse effects occurring in the context of drug shortage notifications. METHODS: All notifications involving a shortage drug submitted to the French pharmacovigilance centres between 1 January 2020 and 30 June 2021 were collected and registered in the French national pharmacovigilance database with the standardised high level term 'product supply and availability issues' and with predefined keywords in the narrative section. RESULTS: 224 cases were included, involving mainly adverse drug reactions (ADRs) (n=131/224, 59%) and medication errors (n=51/224, 23%); 29% of the cases were serious. The most represented classes of shortage drugs were: vaccines (n=78/224, 35%); drugs for acid-related disorders (H2-receptor antagonists) (n=27/224, 12%); antineoplastic agents (n=17/224, 8%); and antiepileptics (n=15/224, 7%). In 82% of cases, the involved shortage drug was the subject of information delivered to health professionals by the National Agency for the Safety of Medicines and Health Products. Drug shortages were associated with an ADR related to replacement drugs in 59% (n=131/224) of the cases, drug inefficacy in 18% (n=41/224), and/or an aggravation of the underlying disease in 11% (n=25/224). CONCLUSIONS: From a pharmacovigilance point of view, a large diversity of anatomical therapeutic classes is involved and the risk related to drug shortages is not limited to drugs registered on 'major therapeutic interest or essential drug' lists. Information from health agencies is not sufficient to avoid the risks, and further strategies should be developed.