Search

Introduction: The policy concerning drugs represents a concentrated effort to achieve better health outcomes for all, with a particular focus on people's access to and rational use of medications. On the basis of pharmacoeconomic analyses, it is possible to modify established prescribing habits, it is possible to influence the creation of guidelines, development strategy and long-term health care planning. Aim: The aim of the work was to determine drugs with the highest expenditure in the Republic of Serbia, and to compare the results obtained in three consecutive years 2016, 2017 and 2018. Also, to analyze which are the most expensive medications listed in the National Register of Medications and what is the trend of changing them. Material and methods: The drug expenditure was monitored using the ATC/DDD methodology. It implies the classification of medications according to the internationally accepted ATC classification of drugs, while DDD, i.e. defined daily dose, is used as a statistical unit for consumption monitoring. The number of DDD/1,000 inhabitants per day provides an insight into how many inhabitants (out of 1,000 of them) used the observed medication and were exposed to its effects during one day. Results: The trend of expenditure of these medications was growing exponentially from 2016 to 2018. The most expensive medications per box are from group J - anti-infective drugs for systemic use and L - antineoplastics and immunomodulators, but their expenditure in the Republic of Serbia is very low. The drugs with the highest price per 1 DDD are: enzymes imiglucerase, laronidase and the biological medication basiliximab in all three years, but considering the indications and rare prescribing, the total cost for these drugs is not high. The largest funds in the Republic of Serbia for the mentioned period were spent on drugs such as: acetylsalicylic acid, paracetamol in combinations, trastuzumab, pantoprazole, amlodipine and rosuvastatin. Comparing the spending on L group of drugs in 2017 compared to 2016, there was a significant increase. Conclusion: The medications with the highest expenditure in the Republic of Serbia are used very little compared to countries with good pharmacotherapy practice. The most expensive drugs are those that are used for special and rare indications, and large amounts of money are not allocated for them as for some cheaper, but more frequently prescribed drugs.

Introduction: According to the ATC system of drug classification, group R06 includes H1 antihistamines for systemic use, which are divided into drug groups of the 1st and 2nd generation. Aim: Since there are no national guidelines in Serbia, for treating most allergic diseases, our aim was to compare pharmaceutical products and treatment strategies of systemic antihistamines use in Serbia with that in the Nordic countries that have been recognized as countries with good pharmacoeconomic practice. Material and methods: Data on drug consumption in the Republic of Serbia, the Kingdom of Norway, the Republic of Finland, and the Kingdom of Denmark were collected from the publications of national drug regulatory agencies for the period from 2009 to 2019. Results: Loratadine was the most commonly consumed antihistamine in Serbia in 2009, making 72.32% of the total consumption of drugs in the R06 group. During observed period the consumption of cetirizine increased 21.8 times, levocetirizine increased 36.6 times, desloratadine increased 2.6 times. The most commonly used antihistamines in Serbia in 2016 were: loratadine with 34.86%, followed by desloratadine with 18.70%, and ketotifen with 14.52% of the total consumption of drugs in the R06 group. In 2019, the most commonly used antihistamines were levocetirizine, loratadine, desloratadine and cetirizine. In Norway as well as in Finland and Denmark, during all eleven years (2009-2019) cetirizine was the most consumed antihistamine with mild increase trend in consumption of 1.5-5.74-20.5%. The second most consumed antihistamine in Norway and in Finland was desloratadine and in Denmark, fexofenadine. A decrease in consumption was recorded in case of loratadine in all three Scandinavian countries. First generation antihistamines promethazine and dexchlorpheniramine showed a continuous but minimal downward trend. Conclusion: Unlike Norway, Sweden and Denmark, in Serbia in the last 11 years, the consumption trends of antihistamines have not been consistent and seem to depend on various factors such as price.

Introduction: According to current understanding of the role of excipient in medicines, they could not be considered as completely pharmacologically inert substances. Although excipients do not have the potential to cause adverse drug reactions (ADRs) in most patients, some of their negative effects have been established. Special caution regarding excipients intake is advised, especially in vulnerable populations such as pediatric one. Aim: The aim of this paper was to investigate the exposure of children on antibiotic therapy to excipients with known effects (EKE). Methods: During a one-month period antibiotic prescriptions data were taken from community pharmacies in Novi Sad, Serbia. Age, diagnosis and prescribed therapy were observed. Data about qualitative content of prescribed medicines were taken from Summaries of Product Characteristics (SmPC) available at the official website of Medicines and medical devices agency of Serbia (ALIMS). Excipients were considered to be potentially harmful if they were listed in European Medicines Agency (EMA) guidelines. Results: The most commonly observed diagnosis was a respiratory infection, which affected more than 88% of children prescribed with an antibiotic. Only 5 out of 33 prescribed antibiotic formulations did not contain at least one EKE. Prescribed medicines mostly contained sodium compounds (77.78%), sucrose (34.07%) and sodium benzoate (31.11%). In addition, the following EKE were detected: propylene glycol, aspartame, sorbitol, lactose, potassium, mannitol, benzalkonium chloride, azorubine, parabens, sodium metabisulfite and sunset yellow. Around 75% of prescribed antibiotic formulations contained inappropriately labeled EKE (sodium and potassium compounds, sodium benzoate and propylene glycol). Additionally, inappropriately labeled information leaflets did not include possible adverse effects caused by the EKE. Conclusions: This paper indicates high exposure of patients to EKE, where almost all children treated with antibiotics (96.3%) were simultaneously administered at least one EKE. We confirmed that approved medicines cannot meet the treatment needs of all patients, and that inappropriately labeled medicines carry a risk of ADRs, especially in newborns. Personalized treatment is especially important in children, as the appropriate dosage forms and diversity in formulation ingredients is lacking. Knowing the type and roles of each ingredient of the medicines it is possible to formulate a preparation that will meet all the individual children's needs.

Introduction: In addition to the active pharmaceutical ingredient (API), the composition of the medicines also includes excipients which are only ideally completely pharmacologically inactive. It has been shown that excipients in inhaled preparations can cause effects opposite to the pharmacological effect of the medicine. Aim: The Aim of the study was to identify potentially harmful excipients in inhaled medicines approved in the Republic of Serbia. Material and Methods: The academic study was conducted during April 2021 and included the analysis of medicines that received a marketing authorization from the Medicines and Medical Devices Agency of Serbia (ALIMS). Qualitative compositions of inhaled medicines available in Summaries of product characteristics (SmPC) on the ALIMS's official website were observed. Excipients considered potentially harmful if they are recognised as excipients with known effect (EKE) in Serbian and European regulations. Results: Total of 46 inhalation preparations that are approved in Serbia were analyzed. In their composition were found 17 different excipients. By comparing appropriate domestic and European regulations three excipients from examined preparations that represent potential causative agents of adverse drug reactions (ADRs) were identified: lactose-monohydrate, ethanol and benzalkonium chloride. It has been shown that disodium EDTA is also a potential causative agent of ADRs, but it is not classified as EKE. Conclusion: Neither domestic nor international regulations have classified EDTA and its salts as EKE and they should be given special attention in the future as potential causative agents of ADRs. It has been shown that benzalkonium chloride is the only excipient that can lead to bronchospasm and it was found in two inhaled medicines.

Introduction: Cardiovascular diseases are the leading cause of death both in Serbia and in the rest of the world. It has been shown that as many as 80% of them are preventable. Control of serum lipid levels is one of the most important tasks of cardiovascular diseases prevention. Aim: The aim of the study was to analyze the use of serum lipid-modifying drugs in Serbia, Norway and Finland in the period 2015-2017. Methods: Data on drugs use during 2015, 2016 and 2017 were taken from the official websites of national drug regulatory authorities: the Serbian Medicines and Medical Devices Agency, the Norwegian Institute of Public Health and the Finnish Medicines Agency. Use was expressed as DDD/1000 inhabitants/day according to the Anatomical Therapeutic Chemical classification. Results: The share of drugs used for treatment of cardiovascular diseases in total drugs use was the largest in all three countries during the observed period. The use of lipidmodifying agents was 3-4 times lower in Serbia than in Norway or Finland. Of all lipidmodifying drugs, statins are most commonly prescribed in all three countries. Atorvastatin and rosuvastatin are the most widely used in Serbia, and simvastatin and atorvastatin in Norway and Finland. Conclusions: Use of lipid-modifying drugs in Serbia is lower than in Norway and Finland, but it is constantly increasing. This use in Serbia still represents the smallest share of all drugs for the treatment of cardiovascular diseases.

Introduction: Hypertension is a condition which represents one of the main risk factors for the development of cardiovascular diseases. High sodium intake contributes to occurrence of hypertension, increasing the volume of extracellular fluid. Therefore, World Health Organization (WHO) and other associations involved with hypertension research advise to decrease intake of sodium. Effervescent dosage forms usually contain high levels of sodium which could lead to above mentioned health issues. Aim: The aim of this study was to evaluate the levels of sodium in the effervescent dosage forms available in the Serbian drug market. Methods: Data about sodium levels, and excipients was obtained from Summary of Product Characteristics from website of Medicines and Medical Devices Agency of Serbia (ALIMS). Maximum daily doses recommended by the manufacturer and approved by ALIMS were observed. Exposure to sodium through consumption of maximum daily doses was calculated as percentages of the adequate daily intake given by Food and Nutrition Board (Institute of Medicine, National Academies, Washington D.C., USA), and also as percentage of recommended daily intake of sodium given by WHO. Results: There are five formulations with exposure to sodium through consumption of maximum daily doses higher than 100% of the adequate daily intake (2 g), all of which are effervescent tablet formulations. The highest exposure to sodium was found in effervescent tablets containing acetylsalycic acid (500 mg) as active pharmaceutical ingredient: 250.62 % for people aged 51 to 70 years; 271.50 % for people aged 70 and older. Conclusion: In effervescent dosage forms available on Serbian market, level of sodium can be very high, even up to 271.50% of adequate daily intake when maximum daily doses are consumed. Major cause for concern is for vascular patients who use effervescents for chronic therapy. This data should be considered during prescribing and dispensing this category of medicines as well as during analyzing pharmacovigilance.

Introduction: Community-acquired pneumonia is one of the most common diseases in infancy but most of these diseases have relatively simple course. We are presenting a case of child who developed lung abscess as a complication of pneumonia. Case Report: The goal of our case report is to point out that lung abscess is a relatively rare entity whose development is not always typical, sudden and acute, but also hidden, inconspicuous and perfidious. Although clinical picture and laboratory findings indicated that the pneumonia was cured, a single control CT scan showed that there was inflammation (hotspot) in the organism. Discussion: Lung abscess is a rare state which is developed as a complication only at 1% of pneumonias. Complications are rare and depend on the previous immunological status of the child and the presence of comorbidity. The duration of antibiotic therapy depends on the clinical and radiographic response of the patient. The chosen antibiotics have to cover a wide specter of Gram-positive and Gram-negative bacteria. Conclusions: The key role in making a diagnosis played radiological methods which were crucial in monitoring the evolution of the change itself, from its creation to regression. The triple antibiotic therapy with meropenem, vancomycin and metronidazole enabled an (excellent) recovery outcome.

Introduction: Antibiotic resistance is a growing problem. Adherence to national guidelines is one of the key factors necessary for the rational use of antibiotics. Aim: The aim of the study was to examine characteristics of antibiotic prescribing practice in primary health care in Novi Sad. Method: The analysis was designed as a descriptive, cross-sectional study based on the data obtained from the health institution Cvejić Pharmacy. The guidelines available to physicians at the time of prescribing were used to assess the compliance of the prescribed antibiotics with the guidelines. Additionally, the most frequently dispensed antibiotics for all diagnoses were recorded and results were expressed as a percentage of frequency of analyzed antibiotic prescriptions. Results: The study has shown that antibiotic prescriptions make 5.48% of all prescriptions (719 out of 13115), 513 (71.35%) of which were established by national guidelines, and 206 (28.65%) for less frequent diagnoses which was not included in national guidelines. In the study sample, 297 (65.42%) terapeutical regimes had adequate terapeutical dosage. The most commonly prescribed antibiotic groups were: macrolides (35.18%), penicillins (28.68%) and cephalosporins (14.60%). Conclusions: Irrational prescribing and dispensing of antibiotics is both national and global problem. It is necessary to pay close attention to antibiotics prescribing and dispensing. The focus should be on national guidelines and their extension.

Introduction: In addition to the active pharmaceutical ingredient (API), excipients and the pharmaceutical dosage form can also affect the overall effect of pharmacotherapy. Knowledge about these effects is not important only from the aspect of drug efficacy, but also from the aspect of pharmacovigilance. Materials and Methods: This paper presents secondary academic study results. Data on the dosage form and content of excipients were taken from SmPC documents on the official website of Medicines and Medical Devices Agency of Serbia. The presence of excipients with known effect (EKE) and their labeling was considered in accordance with the national and European regulations regarding this area. Results: We analyzed a total of 50 medicines for topical administration that are registered in Serbia. These all contained corticosteroids as API. Thirty-five (70 %) of them had one or more EKE. Creams had the highest number of different EKE per drug (3.25). Five out of seven identified EKE have the preservative function in formulations, which could be avoided by extemporaneous drug production. The labeling of these compounds was in accordance with the regulations in most drugs. Conclusions: The cause of an adverse drug reaction should be considered in a wider context and all the drug ingredients should be taken into account. In case of topical corticosteroids, over two third of drugs have the potential to cause adverse drug reactions that are non-API-related.

Introduction: Although they represent an important mediator between patients and National Pharmacovigilance Centre, pharmacists still don't participate enough in system of reporting adverse drug reactions (ADR). By reporting ADR both quality of therapy and quality of patient's life are improving, and pharmaceutical industry is also encouraged to invent and produce new formulations which will be better beared and whose use will significantly improve risk-benefi t ratio. Aim: The aim of this work is that by collecting information about ADRs, based on direct contact of a pharmacist and patients, explain and improve the role of a pharmacist in pharmacovigilance system. Subjects and Methods: Information about adverse reactions were being collected in three private pharmacies in Inđija and in one private pharmacy in Sombor. In period from 20.12.2017.-10.01.2018. pharmacists collected data about adverse reactions of medicines. In period from 11.01.-01.02.2018. patients were additionally informed about unexpected and adverse drug reactions. The standard form for reporting an adverse reaction, which was taken from the site of Medicines and Medical Devices Agency of Serbia (ALIMS), was fi lled for each reported case and sent to National Pharmacovigilance Center (NPC). Suspect drugs were classified in categories according to Anatomical-Therapeutic-Chemical classification (ATC). Results: In first period, there were 19 reported reactions. After additional information given to patients, there were 33 reported adverse reactions. The most numerous adverse drug reactions were reported for the group of cardiovascular drugs (32.7%), the group of anti-infective drugs with systemic effects (15.4%) and for group of drugs which affect nervous system (13.5%). After analyzing reported reactions, according to NPC all of reactions were expected (52), but 3 of them fulfilled criteria of seriousness. Conclusions: Thanks to additional information and direct communication between a pharmacist and patients, reporting unexpected and adverse drug reactions is significantly improving.

Introduction: Paracetamol is analgesic and antipyretic, which is usually in the form of an immediate release tablet formulations. Therapeutic effects in terms of the speed and intensity of the analgesic effect is dependent on speed of liberation from formulation. Aim: The aim of this work was to determine and compare dissolution profiles of 4 paracetamol immediate release tablet formulations and to determine influence of excipients on kinetic of paracetamol dissolution. Materials and Methods: Dissolution profiles of paracetamol tablets were determined using method with paddles and phosphate buffer pH 6.8 as a medium. Release of paracetamol was followed 60 minutes (using 6 time points). Concentration of paracetamol was measured using UV/Vis spectrophotometric method (243 nm). Dissolution profiles were compared using model-independent method (difference factor and similarity factor), statistic method (ANOVA-based method and pair Student's T-test, p

Introduction: Paracetamol is analgesic and antipyretic, which is usually in the form of an immediate release tablet formulations. Therapeutic eff ects in terms of the speed and intensity of the analgesic eff ect is dependent on speed of liberation from formulation. Aim: The aim of this work was to determine and compare dissolution profiles of 4 paracetamol immediate release tablet formulations and to determine infl uence of excipients on kinetic of paracetamol dissolution. Materials and Methods: Dissolution profi les of paracetamol tablets were determined using method with paddles and phosphate buff er pH 6.8 as a medium. Release of paracetamol was followed 60 minutes (using 6 time points). Concentration of paracetamol was measured using UV/Vis spectrophotometric method (243 nm). Dissolution profi les were compared using model-independent method (difference factor and similarity factor), statistic method (ANOVA-based method and pair Student's T-test, p<0.05) and model dependent methods (to determinate the release kinetics of paracetamol). Results: All formulations in the fi rst 45 minutes liberated more than 85 % of the labled content. Formulation D, which contained superdesintegrator, released 90% of the content in the first 5 minutes. Though based on values of diff erence and similarity factors formulations are, not signifi cantly different, ANOVA-based method showed that formulation A and B, B and C, as well as formulation B and D do statistically diff er in all 6 time points, meaning they have parallel profi les. The release of paracetamol from formulations A and D is best described by the fi rst order kinetic model, while the release of formulations B and C by the logistic model. Conclusions: The release kinetic of paracetamol is mostly infl uenced by the type of superdisintegrants and lubricants. Formulation with superdisintegrant technology OptiZorb® demonstrated fastes release rate and thus it is expected to produce the fastest pharmacodynamic effect. [ABSTRACT FROM AUTHOR]