ABSTRACT
Introduction: Zolpidem and zopiclone are widely used for sleep disorders, yet their abuse and dependence potential has been underestimated. The electronic prescription of zolpidem/zopiclone became mandatory on 17.07.2019 in Greece. Objectives: To investigate descriptive characteristics of zolpidem/ zopiclone prescriptions and the impact of the mandatory electronic prescription mandate. Methods: Anonymized prescriptions of zopiclone (ATC: N05CF01) and/or zolpidem (ATC: NC05CF02) that were executed in pharmacies between 01.10.2018 and 01.10.2021 were obtained from the Greek nationwide prescription database. The database covers almost the entire Greek population and it is administrated by IDIKA of the Greek Ministry of Health. We investigated descriptive characteristics of prescriptions, and calculated themonthly number of prescriptions taking into consideration dates with potential impact, i.e., the date of the mandatory electronic prescription mandate (on 17.07.2019) and the date of the first case of COVID-19 in Greece (on 26.02.2020). Results and Conclusion: During the investigated period of three years, there were 1229842 executed prescriptions of zolpidem (89.4%), zopiclone (10.4%) or both (0.3%), considering 156554 unique patients. The patients weremainly elderly (73.1%were ≥ 65 years old) andwomen (64.5%). The majority of the prescription physicians (69.9%) were general practitioners or internists, followed by 17% psychiatrists or neurologists, 5.3% cardiologists, 4.5% physicians in specialty training, 1% nephrologists and 2.4% of physicians with another specialty. After the mandatory electronic prescription mandate and before COVID- 19 in Greece, i.e., between 08.2019 to 03.2020, there was a notable increase of prescriptions in comparison to the previous period from 10.2018 to 07.2019 (median 37267 vs median 34106;Mann-Whitney U=9, p-value=0.009). After COVID-19, the median monthly number of prescriptions was 36363, yet there were variations ranging from 16963 to 39956. In conclusion, the mandatory electronic prescription system could increase the surveillance of drugs with abuse potential such as zolpidem and zopiclone. Nevertheless, the large number of prescriptions in elderly patients and prescribed by primary care physicians is worrisome and warrants further investigation.
ABSTRACT
OBJECTIVE: The present study aims to identify potential safety signals of chloroquine (CQ) and hydroxychloroquine (HCQ), over the period preceding their repurpose as COVID-19 treatment options, through the analysis of safety data retrieved from the FDA Adverse Event Reporting System (FAERS) pharmacovigilance database. MATERIALS AND METHODS: We performed a disproportionality analysis of FAERS data between the first quarter of 2004 and December 2019 using the OpenVigil2.1-MedDRA software. Disproportionality was quantified using the reporting odds ratio (ROR) and its 95% confidence interval (CIs). The reported mortality of CQ and HCQ was also investigated. RESULTS: The dataset contained 6,635,356 reports. Comparison of the RORs revealed significant differences between CQ and HCQ for the following adverse events: cardiomyopathy, cardiac arrhythmias, retinal disorders, corneal disorders, hearing disorders, headache, hepatic disorders, severe cutaneous reactions, musculoskeletal disorders, and cytopenia. Only CQ was associated with psychotic disorders, suicide, self-injury, convulsions, peripheral neuropathy, and decreased appetite. In multivariable logistic regression, death was more frequently associated with CQ use, advanced age, male sex, co-reported suicide and self-injury, cardiomyopathy, cardiac arrhythmias, and decreased appetite. CONCLUSIONS: Our results confirm previously published evidence and suggest that HCQ has a safer clinical profile compared to CQ, and thus could serve as the drug of choice for future therapeutic purposes.