Incidence of Suspected Serious Adverse Drug Reactions in Corona Virus Disease-19 Patients Detected by a Pharmacovigilance Program by Laboratory Signals in a Tertiary Hospital in Spain: Cautionary Data

Abstract

BACKGROUND: From March to April 2020, Spain was the center of the SARS-CoV-2 pandemic, particularly Madrid with approximately 30% of the cases in Spain. The aim of this study is to report the suspected serious adverse drug reactions (SADRs) in COVID-19 patients vs. non-COVID-19 patients detected by the prospective pharmacovigilance program based on automatic laboratory signals (ALSs) in the hospital (PPLSH) during that period. We also compared the results with the suspected SADRs detected during the same period for 2019.METHODS: All ALSs that reflected potential SADRs including neutropenia, pancytopenia, thrombocytopenia, anemia, eosinophilia, leukocytes in cerebrospinal fluid, hepatitis, pancreatitis, acute kidney injury, rhabdomyolysis, and hyponatremia were prospectively monitored in hospitalized patients during the study periods. We analyzed the incidence and the distribution of causative drugs for the COVID-19 patients.RESULTS: The incidence rate of SADRs detected in the COVID-19 patients was 760.63 (95% CI 707.89–816.01) per 10,000 patients, 4.75-fold higher than the SADR rate for non-COVID-19 patients (160.15 per 10,000 patients, 95% CI 137.09–186.80), and 5.84-fold higher than the SADR rate detected for the same period in 2019 (130.19 per 10,000 patients, 95% CI 109.53–154.36). The most frequently related drugs were tocilizumab (59.84%), dexketoprofen (13.93%), azithromycin (8.43%), lopinavir-ritonavir (7.35%), dexamethasone (7.62%), and chloroquine/hydroxychloroquine (6.91%).CONCLUSIONS: The incidence rate of SADRs detected by the PPSLH in patients with COVID-19 was 4.75-fold higher than that of the non-COVID-19 patients. Caution is recommended when using medications for COVID-19 patients, especially drugs that are hepatotoxic, myotoxic, and those that induce thromboembolic events.

Adverse Drug Reactions in COVID-19 patients admitted to Intensive care unit: Analysis of individual case study reports

“…Presence of comorbidities was also an independent risk factor (OR: 32.6; 95% CI 7.7-138; P < 0.0001). These ndings are consistent with the results of other studies which have shown polypharmacy and co-morbidity to be important risk factors for ADRs [4,8,9]. This association has been observed in non-COVID patients also [13,14].…”

“…As a result, drug safety must be prioritized while maintaining e cacy. An increased incidence of ADRs has been reported in COVID patients as compared to non-COVID [4]. However, the prevalence of ADRs in critically ill COVID-19 patients is poorly understood, if precisely estimated, could help with the determination of the burden caused by multiple pharmacological therapies.…”

Impact of COVID-19 pandemic on liver, liver diseases, and liver transplantation programs in intensive care units

“…A multivariate analysis showed that the occurrence of ADRs has been associated with the length of stay (OR: 2.02, 95%CI: 1.03–3.96, P = 0.04), number of drugs used in hospital (OR: 3.12, 95%CI: 1.60–6.27, P = 0.001) and underlying diseases (OR: 2.07, 95%CI: 1.02–4.23, P = 0.045)[ 73 ]. In a prospective study using pharmacovigilance system in Spain, patients with COVID-19 had a higher incidence of hepatitis as a serious ADR than that in non-COVID-19 patients (45.1% vs 23.7%)[ 74 ]. In a meta-analysis of 10 studies, DILI in COVID-19 was reported in 25.4% of the total patients[ 5 ].…”

“…In a meta-analysis of 10 studies, DILI in COVID-19 was reported in 25.4% of the total patients[ 5 ]. Therapies that have been implicated in hepatotoxicity included remdesivir, lopinavir/ritonavir, oseltamivir, hydroxychloroquine, paracetamol[ 5 ], tocilizumab[ 74 ], in addition to antibiotics, non-steroidal anti-inflammatory drugs, herbal medications, and interferon[ 34 ]. In a retrospective, observational cohort study ( n = 1827), the use of lopinavir/ritonavir, hydroxychloroquine, remdesivir, and tocilizumab was associated with statistically significant abnormal ALT and AST levels ( i.e.…”

COVID-19 Management, Treatment and Vaccination Strategies as the Most Efficient Host Manipulation by SARS CoV-2: Reappraisal of a Serious Global Public Health Crisis

“…The variegatedness of symptoms exhibited makes it difficult to discern the true symptoms of COVID-19 from the offshoots or adverse drug reactions or after effects [15] . Such trials without proper appraisal of the efficacy of any of them singly or in combination has led to the deaths of millions of people the world over but the medical science fraternity is unrepentant as no responsibility can be fixed on either the healthcare professionals or the pharmaceutical companies or the allopathic healthcare system itself.…”