Global Safety Database Summary of COVID-19-Related Drug Utilization-Safety Surveillance: A Sponsor’s Perspective

Abstract

Introduction Evidence-based clinical data on coronavirus disease 2019 (COVID-19) pharmacotherapies are scarce . Objective This study documented and characterized COVID-19 cases reported in individuals receiving treatment with Pfizer pharmaceutical products and cases that reported use of Pfizer pharmaceutical products for COVID-19 treatment. Methods This retrospective observational review leveraged the Pfizer safety database containing adverse event data collected in association with use of Pfizer products between 1 October, 2019, and 25 June, 2020; the database includes worldwide adverse event data from various sources. Selected Medical Dictionary for Drug Regulatory Activities (MedDRA ® ) Preferred Terms and subsequent clinical review were used to characterize COVID-19 cases. Results Over 1500 relevant cases were identified over an 8-month period. In cases that reported COVID-19, immunosuppressant/immunomodulating agents, followed by anticoagulant/antithrombic agents and corticosteroids, were the most frequently reported agents. The frequent reporting of immunosuppressant/immunomodulating agents among cases of COVID-19 suggests increased vulnerability to infection among treated patients, either because of immunosuppressive effects of certain agents or the nature of the underlying treated condition. In cases involving off-label pharmacotherapy use for the treatment of COVID-19-related conditions, the most frequently reported therapeutic classes included antibiotics, antimalarial agents, antivirals/antiretroviral agents, immunosuppressant/immunomodulating agents, corticosteroids, anticoagulants, and immunoglobulin/interferons. The most frequently reported pharmacotherapeutic agents were azithromycin and chloroquine/hydroxychloroquine, followed by lopinavir-ritonavir, ceftriaxone, and tofacitinib. The most frequently reported clinical adverse events associated with azithromycin (as sole therapy or combined with chloroquine/hydroxychloroquine) include electrocardiogram QT prolonged, drug interaction, hepatitis, diarrhea, and hepatitis acute. Regarding cardiac-related events, 19% (120/645) of azithromycin cases reported events associated with QT prolongation/torsade de pointes (which included seven fatal cardiac events). The most frequently reported clinical adverse events associated with other commonly used agents are also presented. Conclusions This pharmacovigilance surveillance study provides a unique characterization of cases in which a broad range of pharmaceutical products was reported in relation to COVID-19.

Safety Consequences of Off-Label Drugs Used for COVID-19

“…During a global emergency, making clever use of existing resources is a fundamental human impulse. The cavalier repurposing of hydroxychloroquine, chloroquine, and azithromycin during the coronavirus disease 2019 (COVID- 19) pandemic may have consequences [1], and not only have clinical trials decisively shown that these particular drugs lack effectiveness in this disease [2,3] but Beyzarov et al [4] have also provided empirical evidence of safety-related harms. Therefore, we would be wise to read this study in the context of a well-intentioned but tragically flawed global scramble for cures for COVID-19.…”

“…The study by Beyzarov et al [4] evaluates two questions of considerable importance to public health. The first is, "What are the consequences of off-label use of drugs such as hydroxychloroquine and azithromycin when treating COVID-19?…”

“…The second question is, "Can medications predispose one to an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or full-blown disease?" Beyzarov et al [4] presented a compelling hypothesis that some immunosuppressive treatments may increase the risk of developing fulminant COVID-19. Among the 353 cases of emergent COVID-19, the most common were patients undergoing therapy for rheumatoid arthritis.…”

“…A narrow view from pharmacology might suggest that answers to both of these questions were anticipated based solely on molecular mechanisms: the side effects are known, and immunosuppression is predictable [1]. Yet, real-world data are imperative, and Beyzarov et al [4] provide muchneeded empirical evidence. They do not overstate their data, and in the discussion they lay out careful logic supporting their hypotheses.…”

“…General interest and prescribing frequency both strongly influenced reporting volume during the pandemic, as demonstrated in Fig. 1 in Beyzarov et al [4]. Each report was medically assessed to establish the strength of the causal connection between the medication and the reported side effect.…”