Outside any therapeutic trial prescription of hydroxychloroquine for hospitalized patients with covid-19 during the first wave of the pandemic: A national inquiry of prescription patterns among French hospitalists.

INTRODUCTION: During the first wave of the coronavirus-disease 2019 (covid-19) pandemic in early 2020, hydroxychloroquine (HCQ) was widely prescribed in light of in vitro activity against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Our objective was to evaluate in early 2020 the rate of French hospitalists declaring having prescribed HCQ to treat covid-19 patients outside any therapeutic trial, compare the reasons and the determinants for having prescribed HCQ or not. MATERIAL AND METHODS: A national inquiry submitted by email from May 7 to 25, 2020, to a sample of French hospitalists: doctors managing patients hospitalized for covid-19 in a French department of internal medicine or infectious diseases and identified in the directories of French hospitals or as a member of the French Infectious Diseases Society (SPILF). Primary outcome was the percentage of hospitalists declaring having prescribed HCQ to covid-19 patients. Secondary outcomes were reasons and determinants of HCQ prescription. RESULTS: Among 400 (22.8%) responding hospitalists, 45.3% (95% CI, 40.4 to 50.1%) declared having prescribed HCQ to covid-19 patients. Two main profiles were discerned: HCQ prescribers who did not raise its efficacy as a motive, and non-prescribers who based their decision on evidence-based medicine. Multivariate analysis retained the following prescription determinants (adjusted odds ratio; 95% confidence interval): a departmental procedure for HCQ prescription (8.25; 4.79 to 14.20), having prescribed other treatments outside a therapeutic trial (3.21; 1.81 to 5.71), prior HCQ prescription (2.75; 1.5 to 5.03) and HCQ prescribed within the framework of a therapeutic trial (0.56; 0.33 to 0.95). CONCLUSION: Almost half of the hospitalists prescribed HCQ. The physician's personality (questioning or not evidence-based-medicine principles in the context of the pandemic) and departmental therapeutic procedures were the main factors influencing HCQ prescription. Establishment of "therapeutic" procedures represents a potential means to improve the quality of therapeutic decision-making during a pandemic.

[Drug use during the covid-19 pandemic in Italy.] / L'uso dei farmaci durante la pandemia di covid-19 in Italia.

The Italian Medicines Agency has started, since the first months of 2020, a monitoring of drug use during the covid-19 pandemic. This made it possible to identify specific trends in hospital and local purchases, such as the extensive use of off-label drugs with little evidence of efficacy during the first weeks of the epidemic, and to progressively assess the degree of implementation of regulatory and ministerial recommendations.Fin dalle prime fasi dell'emergenza covid-19 è emersa per l'Agenzia Italiana del Farmaco (AIFA) la necessità di monitorare in modo specifico l'uso dei farmaci utilizzati nel corso dell'epidemia. È infatti fondamentale, in un contesto caratterizzato da grande incertezza e da continui aggiornamenti delle linee guida, disporre di informazioni utili a una corretta lettura e interpretazione dei dati. È stato quindi realizzato un primo rapporto dell'Osservatorio Nazionale sull'Impiego dei Medicinali (OsMed) sull'uso dei farmaci utilizzati, a livello ospedaliero e territoriale, nella fase iniziale dell'epidemia1. Questo metteva a confronto i consumi relativi al periodo compreso tra marzo a maggio del 2020 con quelli del trimestre immediatamente precedente, da dicembre 2019 a febbraio 2020. In seguito, il 4 marzo 2021, è stato pubblicato un aggiornamento dei dati in riferimento alle fasi successive dell'epidemia2. Il monitoraggio ha preso in considerazione diverse categorie di farmaci, andando a valutare le oscillazioni negli acquisti in riferimento al progressivo aggiornamento degli indirizzi regolatori. I volumi osservati per ciascun farmaco sono stati standardizzati per 10.000 abitanti/die, andando a valutare le differenze pre- e post-covid-19 in termini di differenza assoluta, differenza percentuale e di p-value (p).

Cardiac safety of off-label COVID-19 drug therapy: a review and proposed monitoring protocol.

More than 2,000,000 individuals worldwide have had coronavirus 2019 disease infection (COVID-19), yet there is no effective medical therapy. Multiple off-label and investigational drugs, such as chloroquine and hydroxychloroquine, have gained broad interest due to positive pre-clinical data and are currently used for treatment of COVID-19. However, some of these medications have potential cardiac adverse effects. This is important because up to one-third of patients with COVID-19 have cardiac injury, which can further increase the risk of cardiomyopathy and arrhythmias. Adverse effects of chloroquine and hydroxychloroquine on cardiac function and conduction are broad and can be fatal. Both drugs have an anti-arrhythmic property and are proarrhythmic. The American Heart Association has listed chloroquine and hydroxychloroquine as agents which can cause direct myocardial toxicity. Similarly, other investigational drugs such as favipiravir and lopinavir/ritonavir can prolong QT interval and cause Torsade de Pointes. Many antibiotics commonly used for the treatment of patients with COVID-19, for instance azithromycin, can also prolong QT interval. This review summarizes evidenced-based data regarding potential cardiac adverse effects due to off-label and investigational drugs including chloroquine and hydroxychloroquine, antiviral therapy, monoclonal antibodies, as well as common antibiotics used for the treatment of COVID-19. The article focuses on practical points and offers a point-of-care protocol for providers who are taking care of patients with COVID-19 in an inpatient and outpatient setting. The proposed protocol is taking into consideration that resources during the pandemic are limited.