THE QUESTION OF EFFECTIVENESS AND SAFETY OF DIRECT ANTIVIRAL DRUGS IN THE TREATMENT OF CHRONIC HEPATITIS IN THE UNDERGRADUATE EDUCATION OF STUDENTS OF MEDICAL AND PHARMACY FACULTIES

Abstract

Relevance. Modern pharmaceutical agents, particularly nucleoside analogs, have become the cornerstone of therapeutic regimens aimed at improving clinical outcomes in patients by suppressing HBV replication and reducing the progression of liver fibrosis. However, issues such as drug resistance and adverse reactions – including those arising from the concomitant administration of antibacterial agents – underscore the need for individualized treatment strategies for chronic hepatitis B (CHB). Objective. To evaluate the utility of the internet databases “HEP Drug Interaction” and “DrugBank” in assessing the safety of co-administering direct-acting antiviral agents in CHB with beta-lactam antibiotics and beta-lactamase inhibitors, as well as to determine the appropriateness of integrating this information into the educational curricula for future physicians and pharmacists.Method. An information-analytical approach was employed, incorporating the authors’ personal experience in utilizing the pharmacological databases “Hep Drug Interactions” and “DrugBank” within the postgraduate education of students from both pharmaceutical and medical faculties.Results and Discussion. In CHB patients, when comparing clinical and laboratory efficacy regarding viral suppression, the capacity to slow liver fibrosis progression, and the development of secondary complications, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) demonstrated superior effectiveness compared to entecavir (ETV). Our analysis of the potential risks associated with the simultaneous administration of ETV and TDF alongside antibacterial agents and beta-lactamase inhibitors revealed that the combination of these antiviral agents with cephalexin and tazobactam poses the greatest hazard. Cephalexin and tazobactam are predominantly excreted unchanged via the kidneys through glomerular filtration and tubular secretion mediated by OAT1, OAT3, and MATE1. In contrast, ETV and TDF are primarily eliminated through urinary excretion via glomerular filtration and tubular secretion facilitated by OAT1. This suggests a potential competition for renal transporters, which may lead to elevated concentrations of both the antiviral agents and the antibiotics, thereby increasing the risk of adverse reactions.Conclusions. Analysis of the clinical and laboratory efficacy of two tenofovir variants – TDF and TAF – in recent clinical studies has demonstrated that TAF is a more effective and safer option in patients with chronic HBV infection. From a safety perspective, TAF is preferable due to its compatibility with all antibiotics from the penicillin and cephalosporin classes, as well as with beta-lactamase inhibitors, in contrast to TDF and ETV, which exhibit potentially hazardous renal interactions with cephalexin and tazobactam. The results obtained and the prognostic capabilities of the HEP Drug Interaction database regarding drug adverse reactions support the incorporation of this information into the educational programs for medical and pharmaceutical students.