The common border between Bulgaria and North Macedonia, alongside the regulatory requirements stemming from Bulgaria’s membership in the European Union, provide grounds for comparing the legislative environment in both countries. This article presents a comparative case study of the regulatory frameworks governing community pharmacies in Bulgaria and North Macedonia. The aim of this study is to examine the specific features of current legislation related to the operation of community pharmacies, and to identify similarities, differences, and gaps in the organizational structure of pharmacy services, the population’s access to pharmaceutical care, and the qualification requirements for personnel working in community pharmacies. Bulgaria has been a member of the European Union since 2007, while the Republic of North Macedonia has had official EU candidate status since 2005. This provides a basis for comparing the regulatory frameworks of an EU and a non-EU system within the same regional context. In both countries, the overall pharmacy-to-population ratio exceeds the European average (3.3 pharmacies per 10,000 inhabitants), indicating sufficient availability. However, pharmacies are predominantly concentrated in major urban areas. In Bulgaria, challenges remain in ensuring access to pharmaceutical services in smaller and rural settlements, while in North Macedonia, the provision of such services is better ensured. The findings of this case study may be particularly relevant for countries undergoing health system reforms or EU harmonization processes.

Introduction: Antimicrobial resistance (AMR) is a pressing global health issue exacerbated by the overuse of antibiotics during the COVID-19 pandemic. Despite WHO guidelines against antibiotics for mild-to-moderate COVID-19 cases without bacterial co-infection, significant misuse has been reported globally. This study aimed to evaluate antibiotic consumption during the COVID-19 pandemic at a hospital in North Macedonia and to analyze adherence to WHO guidelines, with a focus on antimicrobial stewardship, using the ATC and WHO AWaRe classification systems. Objective: To analyze antibiotic utilization trends from January 2020 to December 2021 and assess adherence to WHO guidelines, focusing on the potential impact on AMR. Method: This retrospective observational study measured antibiotic consumption in defined daily doses (DDD) per 100 occupied bed-days (DDD/100 OBD) using ATC and WHO AWaRe classifications. Data were obtained only from ICU inpatients treated at the Clinical Hospital in Shtip, North Macedonia. Trends in annual consumption were analyzed, including rate-of-change calculations for individual antibiotics between 2020 and 2021. Result: Total antibiotic consumption decreased from 2902.6 DDD/100 OBD in 2020 to 2286.5 DDD/100 OBD in 2021. A third-generation cephalosporin, ceftriaxone, was the most consumed antibiotic, accounting for 57.62% of total consumption in 2020 and 48.55% in 2021. Tetracycline use slightly increased from 13.88% in 2020 to 15.83% in 2021. Fluoroquinolone use decreased significantly from 15.22% in 2020 to 6.5% in 2021. Carbapenem consumption rose sharply from 1.7% in 2020 to 14.37% in 2021, while azithromycin use declined threefold. Antibiotics in the Access group accounted for less than 20% of total usage, while those in the Watch group predominated. result: Total antibiotic consumption decreased from 2902.6 DDD/100 OBD in 2020 to 2286.5 DDD/100 OBD in 2021. Third-generation cephalosporin ceftriaxone was the most consumed antibiotic, representing 57.62% of total consumption in 2020 and 48.55% in 2021. Tetracycline use slightly increased from 13.88% in 2020 to 15.83% in 2021. Fluoroquinolone use decreased significantly from 15.22% in 2020 to 6.5% in 2021. Carbapenem consumption rose sharply from 1.7% in 2020 to 14.37% in 2021, while azithromycin use declined threefold. Antibiotics in the Access group accounted for less than 20% of total usage, while those in the Watch group predominated. Discussion: The study highlights a continued reliance on broad-spectrum antibiotics during the pandemic, diverging from WHO recommendations emphasizing Access to antibiotics. These trends suggest inadequate implementation of antimicrobial stewardship practices and raise concerns about their long-term impact on AMR. Limitations include the retrospective, single-center design, which may limit the generalizability of the findings. Conclusion: The findings underscore the high dependency on Watch category antibiotics and a limited focus on Access antibiotics, contrary to WHO recommendations. This highlights the urgent need for robust antimicrobial stewardship programs to control inappropriate antibiotic use and combat AMR.

The purpose of this study is to formulate and evaluate amphiphilic cream with meloxicam indicated for topical relief of pain, particularly because there are currently no available topical dosage forms on the market. Thus, the present research is focused on characterization of the capacity of the amphiphilic base, composed of glycerol monostearate, cetyl alcohol, Tagat^® S2, Myritol^® 318, propylene glycol, and white petrolatum, to be loaded with drug model meloxicam dissolved in propylene glycol. To enhance the solubility and penetration of meloxicam, menthol as a rubefacient was added to the meloxicam solution. The series of three formulations were prepared with variable content of added menthol. Obtained creams were characterized by drug content, pH, spreadability, viscosity, microbial purity, drug release, and stability. Results showed stable cream formulations with good spreadability and viscosity, suitable for topical application.

National legislative frameworks governing prescribing, pricing, reimbursement, and dispensing play a decisive role in shaping access to medicines. This study examines the financial availability of medicines in Bulgaria and North Macedonia through a comparative review of national pharmaceutical legislation, pricing mechanisms, reimbursement models, and digitalisation policies, assessed in relation to European Union standards. The findings indicate that access to medicines in both countries is shaped by the combined effects of multiple regulatory and financial instruments rather than by individual policy measures. Both systems apply strict control of prescribing and dispensing, external reference pricing, and positive reimbursement lists, reflecting alignment with international recommendations. However, significant differences in policy design lead to divergent access outcomes. Bulgaria’s more advanced digitalisation of prescribing and reimbursement, including mandatory electronic prescribing for selected therapeutic groups, enhances regulatory oversight and expenditure control but is associated with higher patient out-of-pocket expenditure, partly due to the application of the standard value-added tax on medicines. In contrast, North Macedonia combines lower taxation with capped patient co-payments, higher regulated pharmacy margins, and fixed pharmacy remuneration per prescription, contributing to improved financial affordability for patients while supporting pharmacy sustainability. Additional instruments, such as the Generics without Co-Payment List, further strengthen patient financial protection. The study provides comparative evidence relevant to pharmaceutical policy reforms and highlights the importance of balanced regulatory approaches that promote affordability, system sustainability, and equitable access to medicines.

Medication adherence is essential for achieving therapeutic outcomes. However, many patients do not follow their prescribed medication regimens. About 50% of patients do not adhere to their pharmacotherapy, making medication adherence a widespread issue. Accurately measuring adherence is essential for effective care planning and intervention. This paper reviews various methods for measuring medication adherence, highlighting the advantages and disadvantages of each approach. Many factors can affect medication adherence. This review focuses on practical ways to measure adherence and strategies to enhance it, underscoring its importance in achieving better healthcare results. Healthcare providers must prioritize medication adherence, as it directly impacts the effectiveness of treatment and overall public health outcomes.

Medicine registration refers to evaluating a medical product's safety, efficacy, and quality, leading to the granting of a Marketing Authorization. Given the intense globalization of the pharmaceutical industry, harmonizing regulatory procedures between the European Medicines Agency (EMA) and the United States's Food and Drug Administration (FDA) is critical for accelerating the availability of new medicines. The EMA oversees three different procedures for medicine registration: Centralized, Decentralized and Mutual Recognition Procedure. Conversely, the FDA offers three registration applications - Investigational New Drug Application, New Drug Application and Abbreviated New Drug Application. A comparison between the FDA and EMA reveals numerous discrepancies within each system and highlights opportunities for harmonization. While both agencies achieve high concordance in their final decisions, the FDA is faster and more streamlined, benefiting from a centralized authority and expedited pathways. The EMA's structured approach ensures thorough evaluations but can delay approvals. Efforts to harmonize procedures, such as the FDA-EMA Parallel Scientific Advice program and the Mutual Recognition Agreement, aim to enhance alignment and reduce development resources, creating a global regulatory environment to streamline the registration of new medicines.