Safety of Pharmacotherapy in COVID-19 Patients: A Literature Review

The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disor ders; gastrointestinal disorders, neurological disorders, and allergic reactions; and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia; neutropenia is also characteristic of a number of interleukin inhibitors. Haemo static adverse reactions to anticoagulants depend on the patient’s dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions

The rs11385942 and rs657152 variants are not associated with COVID-19 severity and outcomes in patients treated with favipiravir and remdesivir

Background. There is a mounting evidence in the scientific literature that susceptibility to SARS-CoV-2 infection could vary. The severity of COVID-19 symptoms can  range from asymptomatic to severe respiratory failure, requiring prolonged artificial ventilation. The underlying causes of this range of clinical manifestations remain unclear. Identification of the risk factors that may cause this variation in clinical symptoms is important for identifying the most susceptible populations at highest risk. This should help improve prevention measures, reduce hospitalizations, and decrease the mortality rate of the disease. Previously, an association has been found between the severity of COVID-19 and the genetic markers rs11385942 G>GA and rs657152 A>C.The aim. To assess the impact of carrying polymorphic markers rs11385942 G>GA and rs657152 A>C on the severity of COVID-19 in patients undergoing specific therapy. Materials and methods. A total of 240 patients hospitalized with a coronavirus infection were included in the study. All patients received therapy with favipiravir or remdesivir. The presence of the rs11385942 G>GA and rs657152 A>C variants was determined in all patients. The study compared the length of hospital stays, frequency of patient transfers to the intensive care unit (ICU), and frequency of clinical outcomes (recovery or death) among carriers of allelic variants of the markers under investigation.Results. There were no significant associations between the carriage of variants rs11385942 G>GA and rs657152 A>C and the duration of patients’ hospitalization, frequency of patient transfers to the ICU, and patient outcomes.Conclusion. The carriage of rs11385942 G>GA and rs657152 A>C variants did not affect the severity or type of clinical outcomes in patients with COVID-19

Effect of polymorphisms in CYP3A4*22 (rs35599367) C>T, CYP3A5*3 (rs776746) A>G, ABCB1 (rs4148738) C>T and ABCB1 (rs1045642) C>T genes on apixaban anticoagulation: pilot study results

Introduction. Apixaban is a direct oral anticoagulant prescribed for treatment and prevention of venous thromboembolism (VTE) and for prevention of stroke in patients with nonvalvular atrial fibrillation. Direct oral anticoagulants (DOACs) such as apixaban are rapidly replacing warfarin therapy due to improved efficacy and safety profile shown in clinical trials. However, anticoagulants can cause serious and adverse drug reactions (ADRs).Aim. Study of the effect of carriage of polymorphisms in CYP3A4*22 (rs35599367) C>T, CYP3A5*3 (rs776746) A>G, ABCB1 (rs4148738) C>T and ABCB1 (rs1045642) C>T genes on the change in prothrombin time (PT) and activated partial thromboplastin time (aPTT) in patients using apixaban.Materials and methods. A total of 36 patients were enrolled onto this prospective observational study. All patients received apixaban at doses in accordance with instructions on how to administer the drug. Atrial fibrillation was diagnosed in 26 patients, and secondary thrombotic complications in 23 patients. To perform pharmacogenetic tests and measure aPTT and PT parameters, venous blood samples from each patient were drawn on Days 4-5 after prescription of apixaban. The PharmGKB database was used to select candidate genes for the study. Genotyping was performed using the real-time polymerase chain reaction technique. Statistical analysis: data were analyzed by using IBM SPSS Statistics program, Version 23.0.Results. In our study, we assessed the effect of polymorphisms in ABCB1 (rs1045738) C>T, ABCB1 (rs4148642) C>T genes on the aPTT and PT parameters. No statistically significant associations were found.Conclusion. The differences between PT and APTT values in patients using apixaban in the groups with different polymorphisms in ABCB1 (rs1045738) C>T, ABCB1 (rs4148642) C>T gene were not statistically significant. Further studies are necessary to assess the effect of pharmacogenetics on the safety and efficacy profile of apixaban