Miljković, Branislava

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Authority KeyName Variants
orcid::0000-0001-5088-5976
  • Miljković, Branislava (190)
Projects
Basic and Clinical Pharmacological research of mechanisms of action and drug interactions in nervous and cardiovascular system Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 451-03-68/2020-14/200161 (University of Belgrade, Faculty of Pharmacy)
Eksperimentalna i kliničko-farmakološka istraživanja mehanizma dejstva i interakcija lekova u nervnom i kardiovaskularnom sistemu COST Action CA 15105
Modelling of different chromatographic systems with chemometrical approach in pharmaceutical analysis COST Action CA 15105 [European Medicines Shortages Research Network
COST (European Cooperation in Science and Technology) Erasmus Medical Center
Erasmus Mundus-Western Balkans grant (ERAWEB) - 2011-2586/001-001-EMA2 Faculty of Pharmacy, University of Sarajevo, Bosnia and Herzegovina
In 2022 research grant support was approved for this study by the Zoll foundation. Biomarkers for kidney diseases: diagnostic and prognostic significance
Motor and non-motor symptoms and signs in parkinsonism: clinical, morphological and molecular-genetic correlates Razvoj i primena in vitro i in silico metoda u biofarmaceutskoj karakterizaciji lekova BSK grupe 2 i 3
Institute of Mental Health in Belgrade Medicines and Medical Devices Agency of Serbia
Ministry of Defence of the Republic of Serbia (Grant number: MF VMA 05/20-22) Ministry of Education, Science and Technological Development, Republic of Serbia
The project was coordinated and supported financially by the Council of Europe’s European Directorate for the Quality of Medicines and HealthCare (EDQM), Strasbourg (France).

Author's Bibliography

Hepatotoxicity of newer antiseizure medications in children: an overview and disproportionality analysis of VigiBase

Petrović, Sanja; Kovačević, Milena; Vezmar-Kovačević, Sandra; Miljković, Branislava

(Taylor & Francis, 2024)

TY  - JOUR
AU  - Petrović, Sanja
AU  - Kovačević, Milena
AU  - Vezmar-Kovačević, Sandra
AU  - Miljković, Branislava
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5597
AB  - Background: We aimed to characterize newer antiseizure medications (ASMs)-induced hepatotoxicity
in children and identify signals of disproportionate reporting of hepatotoxicity-related adverse drug
events (ADEs).
Research Design and Methods: Case reports reported to VigiBase were accessed using Empirica™
Signal software. To summarize characteristics of the retrieved cases, descriptive statistics were used.
A disproportionality analysis was conducted using the Multi-item Gamma Poisson Shrinker algorithm,
which calculates Empirical Bayesian Geometric Mean value and its lower and upper 95% confidence
limits (EB05 and EB95, respectively). EB05 > 2, N > 0 was considered a signal.
Results: Based on 870 analyzed cases, a higher proportion of cases was reported in girls than in boys
and in patients aged 2–11 years than in other age groups. Most cases were serious. In 25 cases,
hepatotoxicity resulted in death. A high proportion of patients (n = 275, 31.61%) experienced hyper-
sensitivity reactions, mostly due to lamotrigine. The disproportionality analysis yielded 17 signals
concerning felbamate, lamotrigine, levetiracetam, oxcarbazepine, stiripentol, and topiramate. Four
signals were for severe liver injury and concerned felbamate, lamotrigine, levetiracetam, and topira-
mate. Gender-biased reporting frequency was detected for four ASM-ADE combinations.
Conclusion: Our results should serve to raise clinicians’ awareness about the potential association
between several newer ASMs and drug-induced liver injury in children.
PB  - Taylor & Francis
T2  - Expert Opinion on Drug Metabolism & Toxicology
T1  - Hepatotoxicity of newer antiseizure medications in children: an overview and disproportionality analysis of VigiBase
VL  - 20
IS  - 3
SP  - 165
EP  - 173
DO  - 10.1080/17425255.2024.2322114
ER  - 
@article{
author = "Petrović, Sanja and Kovačević, Milena and Vezmar-Kovačević, Sandra and Miljković, Branislava",
year = "2024",
abstract = "Background: We aimed to characterize newer antiseizure medications (ASMs)-induced hepatotoxicity
in children and identify signals of disproportionate reporting of hepatotoxicity-related adverse drug
events (ADEs).
Research Design and Methods: Case reports reported to VigiBase were accessed using Empirica™
Signal software. To summarize characteristics of the retrieved cases, descriptive statistics were used.
A disproportionality analysis was conducted using the Multi-item Gamma Poisson Shrinker algorithm,
which calculates Empirical Bayesian Geometric Mean value and its lower and upper 95% confidence
limits (EB05 and EB95, respectively). EB05 > 2, N > 0 was considered a signal.
Results: Based on 870 analyzed cases, a higher proportion of cases was reported in girls than in boys
and in patients aged 2–11 years than in other age groups. Most cases were serious. In 25 cases,
hepatotoxicity resulted in death. A high proportion of patients (n = 275, 31.61%) experienced hyper-
sensitivity reactions, mostly due to lamotrigine. The disproportionality analysis yielded 17 signals
concerning felbamate, lamotrigine, levetiracetam, oxcarbazepine, stiripentol, and topiramate. Four
signals were for severe liver injury and concerned felbamate, lamotrigine, levetiracetam, and topira-
mate. Gender-biased reporting frequency was detected for four ASM-ADE combinations.
Conclusion: Our results should serve to raise clinicians’ awareness about the potential association
between several newer ASMs and drug-induced liver injury in children.",
publisher = "Taylor & Francis",
journal = "Expert Opinion on Drug Metabolism & Toxicology",
title = "Hepatotoxicity of newer antiseizure medications in children: an overview and disproportionality analysis of VigiBase",
volume = "20",
number = "3",
pages = "165-173",
doi = "10.1080/17425255.2024.2322114"
}
Petrović, S., Kovačević, M., Vezmar-Kovačević, S.,& Miljković, B.. (2024). Hepatotoxicity of newer antiseizure medications in children: an overview and disproportionality analysis of VigiBase. in Expert Opinion on Drug Metabolism & Toxicology
Taylor & Francis., 20(3), 165-173.
https://doi.org/10.1080/17425255.2024.2322114
Petrović S, Kovačević M, Vezmar-Kovačević S, Miljković B. Hepatotoxicity of newer antiseizure medications in children: an overview and disproportionality analysis of VigiBase. in Expert Opinion on Drug Metabolism & Toxicology. 2024;20(3):165-173.
doi:10.1080/17425255.2024.2322114 .
Petrović, Sanja, Kovačević, Milena, Vezmar-Kovačević, Sandra, Miljković, Branislava, "Hepatotoxicity of newer antiseizure medications in children: an overview and disproportionality analysis of VigiBase" in Expert Opinion on Drug Metabolism & Toxicology, 20, no. 3 (2024):165-173,
https://doi.org/10.1080/17425255.2024.2322114 . .

Population Pharmacokinetic Model of Linezolid and Probability of Target Attainment in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation—A Step toward Correct Dosing

Milaković, Dragana; Kovačević, Tijana; Kovačević, Peđa; Barišić, Vedrana; Avram, Sanja; Dragić, Saša; Zlojutro, Biljana; Momčičević, Danica; Miljković, Branislava; Vučićević, Katarina

(MDPI, 2024)

TY  - JOUR
AU  - Milaković, Dragana
AU  - Kovačević, Tijana
AU  - Kovačević, Peđa
AU  - Barišić, Vedrana
AU  - Avram, Sanja
AU  - Dragić, Saša
AU  - Zlojutro, Biljana
AU  - Momčičević, Danica
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5557
AB  - During veno-venous extracorporeal membrane oxygenation (vv ECMO) therapy, antimicrobial drugs are frequently used, and appropriate dosing is challenging due to there being limited data to support the dosage. Linezolid is effective against multidrug-resistant Gram-positive pathogens frequently isolated in ECMO patients. In total, 53 steady-state linezolid levels were obtained following 600 mg intravenous (IV) injections every 8 h, and these were used to develop a population pharmacokinetic (PopPK) model in patients with COVID-19-associated acute respiratory distress syndrome (CARDS) on vv ECMO. The data were analyzed using a nonlinear mixed-effects modelling approach. Monte Carlo simulation generated 5000 patients’ individual PK parameters and corresponding concentration–time profiles using the PopPK model, following the administration of 600 mg/8 h (a higher-than-standard dosing) and 600 mg/12 h (standard). The probabilities of pharmacokinetic/pharmacodynamic (PK/PD) target attainment (PTA) and the cumulative fraction of responses (CFR) for three pathogens were calculated and compared between the two dosing scenarios. Linezolid 600 mg/8 h was predicted to achieve greater than or equal to 85%Tf>MIC in at least 90% of the patients with CARDS on vv ECMO compared to only approximately two thirds of the patients after dosing every 12 h at a minimal inhibitory concentration (MIC) of 2 mg/L. In addition, for the same MIC, fAUC24/MIC ≥ 80 was achieved in almost three times the number of patients following an 8-h versus a 12-h interval. PopPK simulation predicted that a significantly higher proportion of the patients with CARDS on vv ECMO would achieve the PK/PD targets following the 8-h dosing interval compared to standard linezolid dosing. Nevertheless, the safety concern, in particular, for thrombocytopenia, with higher-than-standard linezolid dosage is reasonable, and consequently, monitoring is essential.
PB  - MDPI
T2  - Pharmaceutics
T1  - Population Pharmacokinetic Model of Linezolid and Probability of Target Attainment in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation—A Step toward Correct Dosing
VL  - 16
IS  - 2
DO  - 10.3390/pharmaceutics16020253
ER  - 
@article{
author = "Milaković, Dragana and Kovačević, Tijana and Kovačević, Peđa and Barišić, Vedrana and Avram, Sanja and Dragić, Saša and Zlojutro, Biljana and Momčičević, Danica and Miljković, Branislava and Vučićević, Katarina",
year = "2024",
abstract = "During veno-venous extracorporeal membrane oxygenation (vv ECMO) therapy, antimicrobial drugs are frequently used, and appropriate dosing is challenging due to there being limited data to support the dosage. Linezolid is effective against multidrug-resistant Gram-positive pathogens frequently isolated in ECMO patients. In total, 53 steady-state linezolid levels were obtained following 600 mg intravenous (IV) injections every 8 h, and these were used to develop a population pharmacokinetic (PopPK) model in patients with COVID-19-associated acute respiratory distress syndrome (CARDS) on vv ECMO. The data were analyzed using a nonlinear mixed-effects modelling approach. Monte Carlo simulation generated 5000 patients’ individual PK parameters and corresponding concentration–time profiles using the PopPK model, following the administration of 600 mg/8 h (a higher-than-standard dosing) and 600 mg/12 h (standard). The probabilities of pharmacokinetic/pharmacodynamic (PK/PD) target attainment (PTA) and the cumulative fraction of responses (CFR) for three pathogens were calculated and compared between the two dosing scenarios. Linezolid 600 mg/8 h was predicted to achieve greater than or equal to 85%Tf>MIC in at least 90% of the patients with CARDS on vv ECMO compared to only approximately two thirds of the patients after dosing every 12 h at a minimal inhibitory concentration (MIC) of 2 mg/L. In addition, for the same MIC, fAUC24/MIC ≥ 80 was achieved in almost three times the number of patients following an 8-h versus a 12-h interval. PopPK simulation predicted that a significantly higher proportion of the patients with CARDS on vv ECMO would achieve the PK/PD targets following the 8-h dosing interval compared to standard linezolid dosing. Nevertheless, the safety concern, in particular, for thrombocytopenia, with higher-than-standard linezolid dosage is reasonable, and consequently, monitoring is essential.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Population Pharmacokinetic Model of Linezolid and Probability of Target Attainment in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation—A Step toward Correct Dosing",
volume = "16",
number = "2",
doi = "10.3390/pharmaceutics16020253"
}
Milaković, D., Kovačević, T., Kovačević, P., Barišić, V., Avram, S., Dragić, S., Zlojutro, B., Momčičević, D., Miljković, B.,& Vučićević, K.. (2024). Population Pharmacokinetic Model of Linezolid and Probability of Target Attainment in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation—A Step toward Correct Dosing. in Pharmaceutics
MDPI., 16(2).
https://doi.org/10.3390/pharmaceutics16020253
Milaković D, Kovačević T, Kovačević P, Barišić V, Avram S, Dragić S, Zlojutro B, Momčičević D, Miljković B, Vučićević K. Population Pharmacokinetic Model of Linezolid and Probability of Target Attainment in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation—A Step toward Correct Dosing. in Pharmaceutics. 2024;16(2).
doi:10.3390/pharmaceutics16020253 .
Milaković, Dragana, Kovačević, Tijana, Kovačević, Peđa, Barišić, Vedrana, Avram, Sanja, Dragić, Saša, Zlojutro, Biljana, Momčičević, Danica, Miljković, Branislava, Vučićević, Katarina, "Population Pharmacokinetic Model of Linezolid and Probability of Target Attainment in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation—A Step toward Correct Dosing" in Pharmaceutics, 16, no. 2 (2024),
https://doi.org/10.3390/pharmaceutics16020253 . .

Drug-Related Problems Prior to Hospitalization on Internal Medicine Wards

Draganov, Ivana; Drndarević, Aneta; Kovačević, Milena; Miljković, Branislava; Vuksanović, Miljanka; Janković, Aleksandar; Kalaba, Ana; Vezmar-Kovačević, Sandra

(Polish Pharmaceutical Society, 2024)

TY  - JOUR
AU  - Draganov, Ivana
AU  - Drndarević, Aneta
AU  - Kovačević, Milena
AU  - Miljković, Branislava
AU  - Vuksanović, Miljanka
AU  - Janković, Aleksandar
AU  - Kalaba, Ana
AU  - Vezmar-Kovačević, Sandra
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5604
AB  - Drug-related hospitalizations pose a significant burden to the health-care system. The aim
was to investigate the prevalence of drug-related problems (DRPs) and their association with hospital
admissions in five internal medicine wards. The study included patients admitted to the nephrology,
cardiology, gastroenterology, endocrinology, and geriatric wards. The Pharmaceutical Care Network
Europe classification V9.1 was used for identifying DRPs. In total, 535 patients participated in the study.
We identified 954 DRPs (range 1-7) in 80.7% of patients. Most DRPs were identified on the endocrinology,
cardiology, and geriatric wards, and they were associated with the efficacy of treatment (71.4%), adverse
drug events (10.2%), and unnecessary drug treatment (18.4%). DRPs were associated with the cause of
hospitalization in 74.4% of patients on the nephrology ward, 60.1% and 60.6% of patients on the cardiology
and endocrinology wards, respectively, whereas this number was lower on the geriatric and gastroenterology
wards (26.9% and 8.9%, respectively). Suboptimal drug treatment due to medication omissions was often
associated with the potential cause of hospital admission. Focusing on patients with specific diseases and
DRPs, rather than reducing the number of medications in primary care, may be potentially rational in an
attempt to reduce drug-related hospitalizations.
PB  - Polish Pharmaceutical Society
T2  - Acta Poloniae Pharmaceutica - Drug Research
T1  - Drug-Related Problems Prior to Hospitalization on Internal Medicine Wards
VL  - 81
IS  - 1
SP  - 145
EP  - 154
DO  - 10.32383/appdr/182840
ER  - 
@article{
author = "Draganov, Ivana and Drndarević, Aneta and Kovačević, Milena and Miljković, Branislava and Vuksanović, Miljanka and Janković, Aleksandar and Kalaba, Ana and Vezmar-Kovačević, Sandra",
year = "2024",
abstract = "Drug-related hospitalizations pose a significant burden to the health-care system. The aim
was to investigate the prevalence of drug-related problems (DRPs) and their association with hospital
admissions in five internal medicine wards. The study included patients admitted to the nephrology,
cardiology, gastroenterology, endocrinology, and geriatric wards. The Pharmaceutical Care Network
Europe classification V9.1 was used for identifying DRPs. In total, 535 patients participated in the study.
We identified 954 DRPs (range 1-7) in 80.7% of patients. Most DRPs were identified on the endocrinology,
cardiology, and geriatric wards, and they were associated with the efficacy of treatment (71.4%), adverse
drug events (10.2%), and unnecessary drug treatment (18.4%). DRPs were associated with the cause of
hospitalization in 74.4% of patients on the nephrology ward, 60.1% and 60.6% of patients on the cardiology
and endocrinology wards, respectively, whereas this number was lower on the geriatric and gastroenterology
wards (26.9% and 8.9%, respectively). Suboptimal drug treatment due to medication omissions was often
associated with the potential cause of hospital admission. Focusing on patients with specific diseases and
DRPs, rather than reducing the number of medications in primary care, may be potentially rational in an
attempt to reduce drug-related hospitalizations.",
publisher = "Polish Pharmaceutical Society",
journal = "Acta Poloniae Pharmaceutica - Drug Research",
title = "Drug-Related Problems Prior to Hospitalization on Internal Medicine Wards",
volume = "81",
number = "1",
pages = "145-154",
doi = "10.32383/appdr/182840"
}
Draganov, I., Drndarević, A., Kovačević, M., Miljković, B., Vuksanović, M., Janković, A., Kalaba, A.,& Vezmar-Kovačević, S.. (2024). Drug-Related Problems Prior to Hospitalization on Internal Medicine Wards. in Acta Poloniae Pharmaceutica - Drug Research
Polish Pharmaceutical Society., 81(1), 145-154.
https://doi.org/10.32383/appdr/182840
Draganov I, Drndarević A, Kovačević M, Miljković B, Vuksanović M, Janković A, Kalaba A, Vezmar-Kovačević S. Drug-Related Problems Prior to Hospitalization on Internal Medicine Wards. in Acta Poloniae Pharmaceutica - Drug Research. 2024;81(1):145-154.
doi:10.32383/appdr/182840 .
Draganov, Ivana, Drndarević, Aneta, Kovačević, Milena, Miljković, Branislava, Vuksanović, Miljanka, Janković, Aleksandar, Kalaba, Ana, Vezmar-Kovačević, Sandra, "Drug-Related Problems Prior to Hospitalization on Internal Medicine Wards" in Acta Poloniae Pharmaceutica - Drug Research, 81, no. 1 (2024):145-154,
https://doi.org/10.32383/appdr/182840 . .

Understanding hemoglobin contribution to high-dose methotrexate disposition—population pharmacokinetics in pediatric patients with hematological malignancies

Škorić, Biljana; Jovanović, Marija; Kuzmanović, Miloš; Miljković, Branislava; Vučićević, Katarina

(Springer Science and Business Media Deutschland GmbH, 2024)

TY  - JOUR
AU  - Škorić, Biljana
AU  - Jovanović, Marija
AU  - Kuzmanović, Miloš
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5583
AB  - Purpose: The aim of the present study was to develop a population pharmacokinetic model for methotrexate (MTX) during high-dose treatment (HDMTX) in pediatric patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL) and to describe the influence of variability factors. Methods: The study included 50 patients of both sexes (aged 1–18 years) who received 3 or 5 g/m2 of HDMTX. A nonlinear mixed effect modeling approach was applied for data analysis. Parameter estimation was performed by first-order conditional estimation method with interaction (FOCEI), whereas stepwise covariate modeling was used to assess variability factors. Results: The final model is a two-compartment model that incorporates the effect of body surface area and the influence of hemoglobin and serum creatinine on MTX clearance (CL). Population pharmacokinetic values for a typical subject were estimated at 5.75 L/h/m2 for clearance (CL), 21.3 L/m2 for volume of the central compartment (V1), 8.2 L/m2 for volume of the peripheral compartment (V2), and 0.087 L/h/m2 for intercompartmental clearance (Q). According to the final model, MTX CL decreases with increasing serum creatinine, whereas a positive effect was captured for hemoglobin. A difference of almost 32% in MTX CL was observed among patients’ hemoglobin values reported in the study. Conclusion: The developed population pharmacokinetic model can contribute to the therapy optimization during HDMTX in pediatric patients with ALL and NHL. In addition to renal function and body weight, it describes the influence of hemoglobin on CL, allowing better understanding of its contribution to the disposition of HDMTX.
PB  - Springer Science and Business Media Deutschland GmbH
T2  - European Journal of Clinical Pharmacology
T1  - Understanding hemoglobin contribution to high-dose methotrexate disposition—population pharmacokinetics in pediatric patients with hematological malignancies
DO  - 10.1007/s00228-024-03642-4
ER  - 
@article{
author = "Škorić, Biljana and Jovanović, Marija and Kuzmanović, Miloš and Miljković, Branislava and Vučićević, Katarina",
year = "2024",
abstract = "Purpose: The aim of the present study was to develop a population pharmacokinetic model for methotrexate (MTX) during high-dose treatment (HDMTX) in pediatric patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL) and to describe the influence of variability factors. Methods: The study included 50 patients of both sexes (aged 1–18 years) who received 3 or 5 g/m2 of HDMTX. A nonlinear mixed effect modeling approach was applied for data analysis. Parameter estimation was performed by first-order conditional estimation method with interaction (FOCEI), whereas stepwise covariate modeling was used to assess variability factors. Results: The final model is a two-compartment model that incorporates the effect of body surface area and the influence of hemoglobin and serum creatinine on MTX clearance (CL). Population pharmacokinetic values for a typical subject were estimated at 5.75 L/h/m2 for clearance (CL), 21.3 L/m2 for volume of the central compartment (V1), 8.2 L/m2 for volume of the peripheral compartment (V2), and 0.087 L/h/m2 for intercompartmental clearance (Q). According to the final model, MTX CL decreases with increasing serum creatinine, whereas a positive effect was captured for hemoglobin. A difference of almost 32% in MTX CL was observed among patients’ hemoglobin values reported in the study. Conclusion: The developed population pharmacokinetic model can contribute to the therapy optimization during HDMTX in pediatric patients with ALL and NHL. In addition to renal function and body weight, it describes the influence of hemoglobin on CL, allowing better understanding of its contribution to the disposition of HDMTX.",
publisher = "Springer Science and Business Media Deutschland GmbH",
journal = "European Journal of Clinical Pharmacology",
title = "Understanding hemoglobin contribution to high-dose methotrexate disposition—population pharmacokinetics in pediatric patients with hematological malignancies",
doi = "10.1007/s00228-024-03642-4"
}
Škorić, B., Jovanović, M., Kuzmanović, M., Miljković, B.,& Vučićević, K.. (2024). Understanding hemoglobin contribution to high-dose methotrexate disposition—population pharmacokinetics in pediatric patients with hematological malignancies. in European Journal of Clinical Pharmacology
Springer Science and Business Media Deutschland GmbH..
https://doi.org/10.1007/s00228-024-03642-4
Škorić B, Jovanović M, Kuzmanović M, Miljković B, Vučićević K. Understanding hemoglobin contribution to high-dose methotrexate disposition—population pharmacokinetics in pediatric patients with hematological malignancies. in European Journal of Clinical Pharmacology. 2024;.
doi:10.1007/s00228-024-03642-4 .
Škorić, Biljana, Jovanović, Marija, Kuzmanović, Miloš, Miljković, Branislava, Vučićević, Katarina, "Understanding hemoglobin contribution to high-dose methotrexate disposition—population pharmacokinetics in pediatric patients with hematological malignancies" in European Journal of Clinical Pharmacology (2024),
https://doi.org/10.1007/s00228-024-03642-4 . .

Recommendations for wider adoption of clinical pharmacy in Central and Eastern Europe in order to optimise pharmacotherapy and improve patient outcomes

Guntschnig, Sonja; Antoniadis, Vasilis; Falamic, Slaven; Kovačević, Tijana; Kurczewska-Michalak, Marta; Miljković, Branislava; Olearova, Anna; Sviestina, Inese; Szucs, Attila; Bampali, Konstantina; Tiszai, Zita; Volmer, Daisy; Wiela-Hojeńska, Anna; Fialova, Daniela; Vlcek, Jiri; Stuhec, Matej; Hogg, Anita; Scott, Michael; Stewart, Derek; Mair, Alpana; Ravera, Silvia; Lery, François-Xavier; Kardas, Przemysław

(Frontiers Media SA, 2023)

TY  - JOUR
AU  - Guntschnig, Sonja
AU  - Antoniadis, Vasilis
AU  - Falamic, Slaven
AU  - Kovačević, Tijana
AU  - Kurczewska-Michalak, Marta
AU  - Miljković, Branislava
AU  - Olearova, Anna
AU  - Sviestina, Inese
AU  - Szucs, Attila
AU  - Bampali, Konstantina
AU  - Tiszai, Zita
AU  - Volmer, Daisy
AU  - Wiela-Hojeńska, Anna
AU  - Fialova, Daniela
AU  - Vlcek, Jiri
AU  - Stuhec, Matej
AU  - Hogg, Anita
AU  - Scott, Michael
AU  - Stewart, Derek
AU  - Mair, Alpana
AU  - Ravera, Silvia
AU  - Lery, François-Xavier
AU  - Kardas, Przemysław
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4984
AB  - Clinical pharmacy as an area of practice, education and research started developing around the 1960s when pharmacists across the globe gradually identified the need to focus more on ensuring the appropriate use of medicines to improve patient outcomes rather than being engaged in manufacturing and supply. Since that time numerous studies have shown the positive impact of clinical pharmacy services (CPS). The need for wider adoption of CPS worldwide becomes urgent, as the global population ages, and the prevalence of polypharmacy as well as shortage of healthcare professionals is rising. At the same time, there is great pressure to provide both high-quality and cost-effective health services. All these challenges urgently require the adoption of a new paradigm of healthcare system architecture. One of the most appropriate answers to these challenges is to increase the utilization of the potential of highly educated and skilled professionals widely available in these countries, i.e., pharmacists, who are well positioned to prevent and manage drug-related problems together with ensuring safe and effective use of medications with further care relating to medication adherence. Unfortunately, CPS are still underdeveloped and underutilized in some parts of Europe, namely, in most of the Central and Eastern European (CEE) countries. This paper reviews current situation of CPS development in CEE countries and the prospects for the future of CPS in that region.
PB  - Frontiers Media SA
T2  - Frontiers in Pharmacology
T1  - Recommendations for wider adoption of clinical pharmacy in Central and Eastern Europe in order to optimise pharmacotherapy and improve patient outcomes
VL  - 14
DO  - 10.3389/fphar.2023.1244151
ER  - 
@article{
author = "Guntschnig, Sonja and Antoniadis, Vasilis and Falamic, Slaven and Kovačević, Tijana and Kurczewska-Michalak, Marta and Miljković, Branislava and Olearova, Anna and Sviestina, Inese and Szucs, Attila and Bampali, Konstantina and Tiszai, Zita and Volmer, Daisy and Wiela-Hojeńska, Anna and Fialova, Daniela and Vlcek, Jiri and Stuhec, Matej and Hogg, Anita and Scott, Michael and Stewart, Derek and Mair, Alpana and Ravera, Silvia and Lery, François-Xavier and Kardas, Przemysław",
year = "2023",
abstract = "Clinical pharmacy as an area of practice, education and research started developing around the 1960s when pharmacists across the globe gradually identified the need to focus more on ensuring the appropriate use of medicines to improve patient outcomes rather than being engaged in manufacturing and supply. Since that time numerous studies have shown the positive impact of clinical pharmacy services (CPS). The need for wider adoption of CPS worldwide becomes urgent, as the global population ages, and the prevalence of polypharmacy as well as shortage of healthcare professionals is rising. At the same time, there is great pressure to provide both high-quality and cost-effective health services. All these challenges urgently require the adoption of a new paradigm of healthcare system architecture. One of the most appropriate answers to these challenges is to increase the utilization of the potential of highly educated and skilled professionals widely available in these countries, i.e., pharmacists, who are well positioned to prevent and manage drug-related problems together with ensuring safe and effective use of medications with further care relating to medication adherence. Unfortunately, CPS are still underdeveloped and underutilized in some parts of Europe, namely, in most of the Central and Eastern European (CEE) countries. This paper reviews current situation of CPS development in CEE countries and the prospects for the future of CPS in that region.",
publisher = "Frontiers Media SA",
journal = "Frontiers in Pharmacology",
title = "Recommendations for wider adoption of clinical pharmacy in Central and Eastern Europe in order to optimise pharmacotherapy and improve patient outcomes",
volume = "14",
doi = "10.3389/fphar.2023.1244151"
}
Guntschnig, S., Antoniadis, V., Falamic, S., Kovačević, T., Kurczewska-Michalak, M., Miljković, B., Olearova, A., Sviestina, I., Szucs, A., Bampali, K., Tiszai, Z., Volmer, D., Wiela-Hojeńska, A., Fialova, D., Vlcek, J., Stuhec, M., Hogg, A., Scott, M., Stewart, D., Mair, A., Ravera, S., Lery, F.,& Kardas, P.. (2023). Recommendations for wider adoption of clinical pharmacy in Central and Eastern Europe in order to optimise pharmacotherapy and improve patient outcomes. in Frontiers in Pharmacology
Frontiers Media SA., 14.
https://doi.org/10.3389/fphar.2023.1244151
Guntschnig S, Antoniadis V, Falamic S, Kovačević T, Kurczewska-Michalak M, Miljković B, Olearova A, Sviestina I, Szucs A, Bampali K, Tiszai Z, Volmer D, Wiela-Hojeńska A, Fialova D, Vlcek J, Stuhec M, Hogg A, Scott M, Stewart D, Mair A, Ravera S, Lery F, Kardas P. Recommendations for wider adoption of clinical pharmacy in Central and Eastern Europe in order to optimise pharmacotherapy and improve patient outcomes. in Frontiers in Pharmacology. 2023;14.
doi:10.3389/fphar.2023.1244151 .
Guntschnig, Sonja, Antoniadis, Vasilis, Falamic, Slaven, Kovačević, Tijana, Kurczewska-Michalak, Marta, Miljković, Branislava, Olearova, Anna, Sviestina, Inese, Szucs, Attila, Bampali, Konstantina, Tiszai, Zita, Volmer, Daisy, Wiela-Hojeńska, Anna, Fialova, Daniela, Vlcek, Jiri, Stuhec, Matej, Hogg, Anita, Scott, Michael, Stewart, Derek, Mair, Alpana, Ravera, Silvia, Lery, François-Xavier, Kardas, Przemysław, "Recommendations for wider adoption of clinical pharmacy in Central and Eastern Europe in order to optimise pharmacotherapy and improve patient outcomes" in Frontiers in Pharmacology, 14 (2023),
https://doi.org/10.3389/fphar.2023.1244151 . .
7
4
2

Pharmacokinetic characterization, benefits and barriers of subcutaneous administration of monoclonal antibodies in oncology

Homšek, Ana; Spasić, Jelena; Nikolić, Neda; Stanojković, Tatjana; Jovanović, Marija; Miljković, Branislava; Vučićević, Katarina

(SAGE Publications Ltd, 2023)

TY  - JOUR
AU  - Homšek, Ana
AU  - Spasić, Jelena
AU  - Nikolić, Neda
AU  - Stanojković, Tatjana
AU  - Jovanović, Marija
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4325
AB  - Objective: Therapeutic monoclonal antibodies in oncology are slowly becoming the dominant treatment option for many different cancer types. The main route of administration, infusion, requires extensive product preparations, patient hospitalization and close monitoring. Patient comfort improvement, staff workload reduction and cost savings dictated the development of subcutaneous formulations. The aim of this review is to present pharmacokinetic characteristics of subcutaneous products, discuss the differences between intravenous and subcutaneous routes and to point out the advantages as well as challenges of administration route shift from the formulation development and pharmacometric angle. Data sources: Food and Drug administration's Purple book database and electronic medicines compendium were used to identify monoclonal antibodies in oncology approved as subcutaneous forms. Using keywords subcutaneous, monoclonal antibodies, pharmacokinetics, model, as well as specific drugs previously identified, both PubMed and ScienceDirect databases were researched. Data summary: There are currently six approved subcutaneous onco-monoclonal antibodies on the market. For each of them, exposure to the drug was similar in relation to infusion, treatment effectiveness was the same, administration was well tolerated by the patients and costs of the medical service were reduced. Conclusion: Development of subcutaneous forms for existing and emerging new monoclonal antibodies for cancer treatment as well as shifting from administration via infusion should be encouraged due to patient preference, lower costs and overall lack of substantial differences in efficacy and safety between the two routes.
PB  - SAGE Publications Ltd
T2  - Journal of Oncology Pharmacy Practice
T1  - Pharmacokinetic characterization, benefits and barriers of subcutaneous administration of monoclonal antibodies in oncology
VL  - 29
IS  - 2
SP  - 431
EP  - 440
DO  - 10.1177/10781552221137702
ER  - 
@article{
author = "Homšek, Ana and Spasić, Jelena and Nikolić, Neda and Stanojković, Tatjana and Jovanović, Marija and Miljković, Branislava and Vučićević, Katarina",
year = "2023",
abstract = "Objective: Therapeutic monoclonal antibodies in oncology are slowly becoming the dominant treatment option for many different cancer types. The main route of administration, infusion, requires extensive product preparations, patient hospitalization and close monitoring. Patient comfort improvement, staff workload reduction and cost savings dictated the development of subcutaneous formulations. The aim of this review is to present pharmacokinetic characteristics of subcutaneous products, discuss the differences between intravenous and subcutaneous routes and to point out the advantages as well as challenges of administration route shift from the formulation development and pharmacometric angle. Data sources: Food and Drug administration's Purple book database and electronic medicines compendium were used to identify monoclonal antibodies in oncology approved as subcutaneous forms. Using keywords subcutaneous, monoclonal antibodies, pharmacokinetics, model, as well as specific drugs previously identified, both PubMed and ScienceDirect databases were researched. Data summary: There are currently six approved subcutaneous onco-monoclonal antibodies on the market. For each of them, exposure to the drug was similar in relation to infusion, treatment effectiveness was the same, administration was well tolerated by the patients and costs of the medical service were reduced. Conclusion: Development of subcutaneous forms for existing and emerging new monoclonal antibodies for cancer treatment as well as shifting from administration via infusion should be encouraged due to patient preference, lower costs and overall lack of substantial differences in efficacy and safety between the two routes.",
publisher = "SAGE Publications Ltd",
journal = "Journal of Oncology Pharmacy Practice",
title = "Pharmacokinetic characterization, benefits and barriers of subcutaneous administration of monoclonal antibodies in oncology",
volume = "29",
number = "2",
pages = "431-440",
doi = "10.1177/10781552221137702"
}
Homšek, A., Spasić, J., Nikolić, N., Stanojković, T., Jovanović, M., Miljković, B.,& Vučićević, K.. (2023). Pharmacokinetic characterization, benefits and barriers of subcutaneous administration of monoclonal antibodies in oncology. in Journal of Oncology Pharmacy Practice
SAGE Publications Ltd., 29(2), 431-440.
https://doi.org/10.1177/10781552221137702
Homšek A, Spasić J, Nikolić N, Stanojković T, Jovanović M, Miljković B, Vučićević K. Pharmacokinetic characterization, benefits and barriers of subcutaneous administration of monoclonal antibodies in oncology. in Journal of Oncology Pharmacy Practice. 2023;29(2):431-440.
doi:10.1177/10781552221137702 .
Homšek, Ana, Spasić, Jelena, Nikolić, Neda, Stanojković, Tatjana, Jovanović, Marija, Miljković, Branislava, Vučićević, Katarina, "Pharmacokinetic characterization, benefits and barriers of subcutaneous administration of monoclonal antibodies in oncology" in Journal of Oncology Pharmacy Practice, 29, no. 2 (2023):431-440,
https://doi.org/10.1177/10781552221137702 . .
1
3
2

Association of clozapine and norclozapine levels with patient and therapy characteristics—focus on interaction with valproic acid

Panić, Bojana; Jovanović, Marija; Lukić, Vera; Vučićević, Katarina; Miljković, Branislava; Milovanović, Srđan

(Springer, 2023)

TY  - JOUR
AU  - Panić, Bojana
AU  - Jovanović, Marija
AU  - Lukić, Vera
AU  - Vučićević, Katarina
AU  - Miljković, Branislava
AU  - Milovanović, Srđan
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5040
AB  - Purpose: The goal of the study was to examine clozapine (CLZ) and norclozapine (NCLZ) therapeutic drug monitoring (TDM) data and associated sources of pharmacokinetic variability, particularly the impact of valproic acid (VPA) use. Methods: This study included 126 patients with psychiatric disorders on mono- or co-therapy with CLZ. Patients’ data during routine TDM were collected retrospectively from clinical records. The descriptive and statistical analysis was computed using IBM SPSS Statistics software (version 22, NY, USA). Multiple linear regression, based on the last observations, was used to assess correlation between demographic characteristics, life habits and co-therapy with dose-corrected serum levels (C/D) of CLZ and NCLZ, as well as CLZ/NCLZ. Results: A total of 295 CLZ concentrations were measured in 126 patients, with a mean of 275.5 ± 174.4 µg/L, while 124 NCLZ concentrations were determined in 74 patients, with a mean of 194.6 ± 149.8 µg/L. A statistically significant effect on ln-transformed CLZ C/D was confirmed for sex and smoking, whereas sex, smoking and VPA therapy were associated with ln-transformed NCLZ C/D. According to the final models, lower values of NCLZ C/D for about 45.9% can be expected in patients receiving VPA. Concomitant use of VPA was the only factor detected to contribute in CLZ/NCLZ variability. Conclusion: The results of this study may help clinicians interpret TDM data and optimize CLZ dosing regimens, especially in patients concomitantly treated with VPA. Our results show that VPA primarily decreases NCLZ levels, while alteration of the parent drug is not statistically significant.
PB  - Springer
T2  - European Journal of Clinical Pharmacology
T1  - Association of clozapine and norclozapine levels with patient and therapy characteristics—focus on interaction with valproic acid
DO  - 10.1007/s00228-023-03569-2
ER  - 
@article{
author = "Panić, Bojana and Jovanović, Marija and Lukić, Vera and Vučićević, Katarina and Miljković, Branislava and Milovanović, Srđan",
year = "2023",
abstract = "Purpose: The goal of the study was to examine clozapine (CLZ) and norclozapine (NCLZ) therapeutic drug monitoring (TDM) data and associated sources of pharmacokinetic variability, particularly the impact of valproic acid (VPA) use. Methods: This study included 126 patients with psychiatric disorders on mono- or co-therapy with CLZ. Patients’ data during routine TDM were collected retrospectively from clinical records. The descriptive and statistical analysis was computed using IBM SPSS Statistics software (version 22, NY, USA). Multiple linear regression, based on the last observations, was used to assess correlation between demographic characteristics, life habits and co-therapy with dose-corrected serum levels (C/D) of CLZ and NCLZ, as well as CLZ/NCLZ. Results: A total of 295 CLZ concentrations were measured in 126 patients, with a mean of 275.5 ± 174.4 µg/L, while 124 NCLZ concentrations were determined in 74 patients, with a mean of 194.6 ± 149.8 µg/L. A statistically significant effect on ln-transformed CLZ C/D was confirmed for sex and smoking, whereas sex, smoking and VPA therapy were associated with ln-transformed NCLZ C/D. According to the final models, lower values of NCLZ C/D for about 45.9% can be expected in patients receiving VPA. Concomitant use of VPA was the only factor detected to contribute in CLZ/NCLZ variability. Conclusion: The results of this study may help clinicians interpret TDM data and optimize CLZ dosing regimens, especially in patients concomitantly treated with VPA. Our results show that VPA primarily decreases NCLZ levels, while alteration of the parent drug is not statistically significant.",
publisher = "Springer",
journal = "European Journal of Clinical Pharmacology",
title = "Association of clozapine and norclozapine levels with patient and therapy characteristics—focus on interaction with valproic acid",
doi = "10.1007/s00228-023-03569-2"
}
Panić, B., Jovanović, M., Lukić, V., Vučićević, K., Miljković, B.,& Milovanović, S.. (2023). Association of clozapine and norclozapine levels with patient and therapy characteristics—focus on interaction with valproic acid. in European Journal of Clinical Pharmacology
Springer..
https://doi.org/10.1007/s00228-023-03569-2
Panić B, Jovanović M, Lukić V, Vučićević K, Miljković B, Milovanović S. Association of clozapine and norclozapine levels with patient and therapy characteristics—focus on interaction with valproic acid. in European Journal of Clinical Pharmacology. 2023;.
doi:10.1007/s00228-023-03569-2 .
Panić, Bojana, Jovanović, Marija, Lukić, Vera, Vučićević, Katarina, Miljković, Branislava, Milovanović, Srđan, "Association of clozapine and norclozapine levels with patient and therapy characteristics—focus on interaction with valproic acid" in European Journal of Clinical Pharmacology (2023),
https://doi.org/10.1007/s00228-023-03569-2 . .
1

Potentially inappropriate prescribing among older patients and associated factors: comparison of two versions of STOPP/START criteria

Jovanović, Marija; Kovačević, Milena; Catić-Đorđević, Aleksandra; Ćulafić, Milica; Stefanović, Nikola; Mitić, Branka; Vučićević, Katarina; Vezmar-Kovačević, Sandra; Veličković-Radovanović, Radmila; Miljković, Branislava

(2023)

TY  - JOUR
AU  - Jovanović, Marija
AU  - Kovačević, Milena
AU  - Catić-Đorđević, Aleksandra
AU  - Ćulafić, Milica
AU  - Stefanović, Nikola
AU  - Mitić, Branka
AU  - Vučićević, Katarina
AU  - Vezmar-Kovačević, Sandra
AU  - Veličković-Radovanović, Radmila
AU  - Miljković, Branislava
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4921
AB  - The study aimed to estimate and compare the prevalence and type of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) between the STOPP/START original (v1) and updated version (v2) among older patients in various settings, as well as associated factors. The study included 440 patients attending a community pharmacy, 200 outpatients and 140 nursing home users. An increase in the prevalence of STOPP v2 (57.9%) compared to v1 (56.2%) was not statistically significant in the total sample and within each setting (p>0.05). A decrease in the prevalence of START v1 (55.8%) to v2 (41.2%) was statistically significant (p<0.001) in the total sample and within each setting (p<0.05). Drug indication (32.9%) and fall-risk medications (32.2%) were most commonly identified for STOPP v2, while cardiovascular system criteria (30.5%) were the most frequently detected for START v2. The number of medications was the strongest predictor for both STOPP v1 and v2, with odds ratio values of 1.35 and 1.34, respectively. Patients’ characteristics associated with the occurrence of STOPP and START criteria were identified. According to both STOPP/START versions, the results indicate a substantial rate of potentially inappropriate prescribing among elderly patients. The prevalence of PIMs was slightly higher with the updated version, while the prevalence of PPOs was significantly lower.
T2  - Brazilian Journal of Pharmaceutical Sciences
T1  - Potentially inappropriate prescribing among older patients and associated factors: comparison of two versions of STOPP/START criteria
VL  - 59
DO  - 10.1590/s2175-97902023e22549
ER  - 
@article{
author = "Jovanović, Marija and Kovačević, Milena and Catić-Đorđević, Aleksandra and Ćulafić, Milica and Stefanović, Nikola and Mitić, Branka and Vučićević, Katarina and Vezmar-Kovačević, Sandra and Veličković-Radovanović, Radmila and Miljković, Branislava",
year = "2023",
abstract = "The study aimed to estimate and compare the prevalence and type of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) between the STOPP/START original (v1) and updated version (v2) among older patients in various settings, as well as associated factors. The study included 440 patients attending a community pharmacy, 200 outpatients and 140 nursing home users. An increase in the prevalence of STOPP v2 (57.9%) compared to v1 (56.2%) was not statistically significant in the total sample and within each setting (p>0.05). A decrease in the prevalence of START v1 (55.8%) to v2 (41.2%) was statistically significant (p<0.001) in the total sample and within each setting (p<0.05). Drug indication (32.9%) and fall-risk medications (32.2%) were most commonly identified for STOPP v2, while cardiovascular system criteria (30.5%) were the most frequently detected for START v2. The number of medications was the strongest predictor for both STOPP v1 and v2, with odds ratio values of 1.35 and 1.34, respectively. Patients’ characteristics associated with the occurrence of STOPP and START criteria were identified. According to both STOPP/START versions, the results indicate a substantial rate of potentially inappropriate prescribing among elderly patients. The prevalence of PIMs was slightly higher with the updated version, while the prevalence of PPOs was significantly lower.",
journal = "Brazilian Journal of Pharmaceutical Sciences",
title = "Potentially inappropriate prescribing among older patients and associated factors: comparison of two versions of STOPP/START criteria",
volume = "59",
doi = "10.1590/s2175-97902023e22549"
}
Jovanović, M., Kovačević, M., Catić-Đorđević, A., Ćulafić, M., Stefanović, N., Mitić, B., Vučićević, K., Vezmar-Kovačević, S., Veličković-Radovanović, R.,& Miljković, B.. (2023). Potentially inappropriate prescribing among older patients and associated factors: comparison of two versions of STOPP/START criteria. in Brazilian Journal of Pharmaceutical Sciences, 59.
https://doi.org/10.1590/s2175-97902023e22549
Jovanović M, Kovačević M, Catić-Đorđević A, Ćulafić M, Stefanović N, Mitić B, Vučićević K, Vezmar-Kovačević S, Veličković-Radovanović R, Miljković B. Potentially inappropriate prescribing among older patients and associated factors: comparison of two versions of STOPP/START criteria. in Brazilian Journal of Pharmaceutical Sciences. 2023;59.
doi:10.1590/s2175-97902023e22549 .
Jovanović, Marija, Kovačević, Milena, Catić-Đorđević, Aleksandra, Ćulafić, Milica, Stefanović, Nikola, Mitić, Branka, Vučićević, Katarina, Vezmar-Kovačević, Sandra, Veličković-Radovanović, Radmila, Miljković, Branislava, "Potentially inappropriate prescribing among older patients and associated factors: comparison of two versions of STOPP/START criteria" in Brazilian Journal of Pharmaceutical Sciences, 59 (2023),
https://doi.org/10.1590/s2175-97902023e22549 . .
1
1

Lidocaine Clearance as Pharmacokinetic Parameter of Metabolic Hepatic Activity in Patients with Impaired Liver

Jovanović, Marija; Kovačević, Milena; Vezmar-Kovačević, Sandra; Palibrk, Ivan; Bjelanović, Jasna; Miljković, Branislava; Vučićević, Katarina

(Beograd : Društvo medicinskih biohemičara Srbije, 2023)

TY  - JOUR
AU  - Jovanović, Marija
AU  - Kovačević, Milena
AU  - Vezmar-Kovačević, Sandra
AU  - Palibrk, Ivan
AU  - Bjelanović, Jasna
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4378
AB  - Background: The study aimed to estimate lidocaine (LID)
pharmacokinetic parameter values in patients with
impaired liver function, level of correlation between the
pharmacokinetic parameters and Child-Pugh class and
change in pharmacokinetic parameters after liver tumor
resection compared to the preoperative value.
Methods: Patients with impaired liver function were subject
to the LID test 1 day prior to, 3 and 7 days after the inter-
vention. LID was administered in single i.v. dose of 1 mg/kg.
Blood samples were collected at 15, 30 and 90 minutes
after drug administration. Non-compartmental analysis was
applied for calculating the pharmacokinetic parameters.
Results: The study included 17 patients with the diagnosis of
cirrhosis and 41 patients with liver tumor. In both groups of
patients, the values of the coefficients of correlation show
the best correlation between clearance (CL) and Child-Pugh
score (-0.693, p<0.005) over other pharmacokinetic
parameters. The results indicate worsening hepatic function
on 3rd day after operation in comparison to the values of
LID CL prior to operation (mean LID CL for patients with
Child-Pugh class A are 25.91 L/h, 41.59 L/h, respectively;
while for B class are 16.89 L/h, 22.65 L/h, respectively). On
day 7th, the values of LID CL (mean value for patients with
Child-Pugh class A and B are 40.98 L/h and 21.46 L/h,
respectively) are increased in comparison to 3rd day after.
Conclusions: LID pharmacokinetic parameters consequent-
ly changed according to the severity of liver impairment,
assessed by Child-Pugh score. Values of LID CL and vol-
ume of distribution (Vd) coupled with standard biochemical
parameters may be used for preoperative assessment of
liver function and monitoring of its postoperative recovery.
AB  - Uvod: Cilj studije bila je procena vrednosti farmako-
kinetičkih parametara lidokaina (LID) kod pacijenata sa
oštećenom funkcijom jetre, stepena korelacije izme|u
farmakokinetičkih parametara i Child-Pugh klase i promene farmakokinetičkih parametara posle resekcije tumora
jetre u odnosu na preoperativnu vrednost.
Metode: Pacijenti sa o{te}enom funkcijom jetre bili su
podvrgnuti LID testu 1 dan pre, 3. i 7. dana nakon
intervencije. LID je primenjen u pojedinačnoj i.v. dozi od 1
mg/kg. Uzorci krvi su sakupljeni 15, 30 i 90 minuta nakon
primene leka. Za izračunavanje farmakokinetičkih
parametara primenjena je neprostorna analiza.
Rezultati: Studijom je obuhvaćeno 17 pacijenata sa
dijagnozom ciroze i 41 pacijent sa tumorom jetre. Kod obe
grupe pacijenata, vrednosti koeficijenata korelacije
pokazuju najbolju korelaciju izme|u klirensa LID (CL) i
Child-Pugh skora (-0,693, p<0,005) u odnosu na ostale
farmakokinetičke parametre. Rezultati ukazuju na pogoršanje funkcije jetre 3. dana nakon operacije u pore|enju sa
vrednostima LID CL pre operacije (srednje vrednosti LID CL
kod pacijenata Child-Pugh grupe A iznosile su 25,91 L/h,
41,59 L/h, respektivno; dok su kod pacijenata u klasi B
iznosile 16,89 L/h, 22,65 L/h, respektivno). Sedmog dana
vrednosti LID CL (srednja vrednost u Child-Pugh grupi A i B
iznosile su 40,98 L/h i 21,46 L/h, respektivno) bile su veće
u odnosu na 3. dan posle hirur{ke intervencije.
Zaključak: Farmakokinetički parametri LID se razlikuju u
zavisnosti od težine oštećenja jetre, procenjenih Child-Pugh
skorom. Vrednosti farmakokinetičkih parametara LID u
kombinaciji sa standardnim biohemijskim parametrima
mogu se koristiti za preoperativnu procenu funkcije jetre i
praćenje njenog postoperativnog oporavka
PB  - Beograd : Društvo medicinskih biohemičara Srbije
T2  - Journal of Medical Biochemistry
T1  - Lidocaine Clearance as Pharmacokinetic Parameter of Metabolic Hepatic Activity in Patients with Impaired Liver
T1  - Klirens lidokaina kao farmakokinetički parametar metaboličke aktivnosti kod pacijenata sa oštećenjem jetre
VL  - 42
SP  - 1
EP  - 7
DO  - 10.5937/jomb0-38952
ER  - 
@article{
author = "Jovanović, Marija and Kovačević, Milena and Vezmar-Kovačević, Sandra and Palibrk, Ivan and Bjelanović, Jasna and Miljković, Branislava and Vučićević, Katarina",
year = "2023",
abstract = "Background: The study aimed to estimate lidocaine (LID)
pharmacokinetic parameter values in patients with
impaired liver function, level of correlation between the
pharmacokinetic parameters and Child-Pugh class and
change in pharmacokinetic parameters after liver tumor
resection compared to the preoperative value.
Methods: Patients with impaired liver function were subject
to the LID test 1 day prior to, 3 and 7 days after the inter-
vention. LID was administered in single i.v. dose of 1 mg/kg.
Blood samples were collected at 15, 30 and 90 minutes
after drug administration. Non-compartmental analysis was
applied for calculating the pharmacokinetic parameters.
Results: The study included 17 patients with the diagnosis of
cirrhosis and 41 patients with liver tumor. In both groups of
patients, the values of the coefficients of correlation show
the best correlation between clearance (CL) and Child-Pugh
score (-0.693, p<0.005) over other pharmacokinetic
parameters. The results indicate worsening hepatic function
on 3rd day after operation in comparison to the values of
LID CL prior to operation (mean LID CL for patients with
Child-Pugh class A are 25.91 L/h, 41.59 L/h, respectively;
while for B class are 16.89 L/h, 22.65 L/h, respectively). On
day 7th, the values of LID CL (mean value for patients with
Child-Pugh class A and B are 40.98 L/h and 21.46 L/h,
respectively) are increased in comparison to 3rd day after.
Conclusions: LID pharmacokinetic parameters consequent-
ly changed according to the severity of liver impairment,
assessed by Child-Pugh score. Values of LID CL and vol-
ume of distribution (Vd) coupled with standard biochemical
parameters may be used for preoperative assessment of
liver function and monitoring of its postoperative recovery., Uvod: Cilj studije bila je procena vrednosti farmako-
kinetičkih parametara lidokaina (LID) kod pacijenata sa
oštećenom funkcijom jetre, stepena korelacije izme|u
farmakokinetičkih parametara i Child-Pugh klase i promene farmakokinetičkih parametara posle resekcije tumora
jetre u odnosu na preoperativnu vrednost.
Metode: Pacijenti sa o{te}enom funkcijom jetre bili su
podvrgnuti LID testu 1 dan pre, 3. i 7. dana nakon
intervencije. LID je primenjen u pojedinačnoj i.v. dozi od 1
mg/kg. Uzorci krvi su sakupljeni 15, 30 i 90 minuta nakon
primene leka. Za izračunavanje farmakokinetičkih
parametara primenjena je neprostorna analiza.
Rezultati: Studijom je obuhvaćeno 17 pacijenata sa
dijagnozom ciroze i 41 pacijent sa tumorom jetre. Kod obe
grupe pacijenata, vrednosti koeficijenata korelacije
pokazuju najbolju korelaciju izme|u klirensa LID (CL) i
Child-Pugh skora (-0,693, p<0,005) u odnosu na ostale
farmakokinetičke parametre. Rezultati ukazuju na pogoršanje funkcije jetre 3. dana nakon operacije u pore|enju sa
vrednostima LID CL pre operacije (srednje vrednosti LID CL
kod pacijenata Child-Pugh grupe A iznosile su 25,91 L/h,
41,59 L/h, respektivno; dok su kod pacijenata u klasi B
iznosile 16,89 L/h, 22,65 L/h, respektivno). Sedmog dana
vrednosti LID CL (srednja vrednost u Child-Pugh grupi A i B
iznosile su 40,98 L/h i 21,46 L/h, respektivno) bile su veće
u odnosu na 3. dan posle hirur{ke intervencije.
Zaključak: Farmakokinetički parametri LID se razlikuju u
zavisnosti od težine oštećenja jetre, procenjenih Child-Pugh
skorom. Vrednosti farmakokinetičkih parametara LID u
kombinaciji sa standardnim biohemijskim parametrima
mogu se koristiti za preoperativnu procenu funkcije jetre i
praćenje njenog postoperativnog oporavka",
publisher = "Beograd : Društvo medicinskih biohemičara Srbije",
journal = "Journal of Medical Biochemistry",
title = "Lidocaine Clearance as Pharmacokinetic Parameter of Metabolic Hepatic Activity in Patients with Impaired Liver, Klirens lidokaina kao farmakokinetički parametar metaboličke aktivnosti kod pacijenata sa oštećenjem jetre",
volume = "42",
pages = "1-7",
doi = "10.5937/jomb0-38952"
}
Jovanović, M., Kovačević, M., Vezmar-Kovačević, S., Palibrk, I., Bjelanović, J., Miljković, B.,& Vučićević, K.. (2023). Lidocaine Clearance as Pharmacokinetic Parameter of Metabolic Hepatic Activity in Patients with Impaired Liver. in Journal of Medical Biochemistry
Beograd : Društvo medicinskih biohemičara Srbije., 42, 1-7.
https://doi.org/10.5937/jomb0-38952
Jovanović M, Kovačević M, Vezmar-Kovačević S, Palibrk I, Bjelanović J, Miljković B, Vučićević K. Lidocaine Clearance as Pharmacokinetic Parameter of Metabolic Hepatic Activity in Patients with Impaired Liver. in Journal of Medical Biochemistry. 2023;42:1-7.
doi:10.5937/jomb0-38952 .
Jovanović, Marija, Kovačević, Milena, Vezmar-Kovačević, Sandra, Palibrk, Ivan, Bjelanović, Jasna, Miljković, Branislava, Vučićević, Katarina, "Lidocaine Clearance as Pharmacokinetic Parameter of Metabolic Hepatic Activity in Patients with Impaired Liver" in Journal of Medical Biochemistry, 42 (2023):1-7,
https://doi.org/10.5937/jomb0-38952 . .

Telepharmacy service experience during the COVID-19 pandemic in the Republic of Srpska, Bosnia and Herzegovina

Kovačević, Milena; Ćulafić, Milica; Vezmar-Kovačević, Sandra; Borjanić, Slavenka; Keleč, Branka; Miljković, Branislava; Amidžić, Rada

(John Wiley and Sons Inc, 2022)

TY  - JOUR
AU  - Kovačević, Milena
AU  - Ćulafić, Milica
AU  - Vezmar-Kovačević, Sandra
AU  - Borjanić, Slavenka
AU  - Keleč, Branka
AU  - Miljković, Branislava
AU  - Amidžić, Rada
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3973
AB  - The COVID-19 pandemic exerted a profound impact on health systems worldwide. Moreover, significant concerns were raised in terms of middle- and long-term consequences of postponing care in non-COVID patients. The primary aim of the study was to describe the remote pharmaceutical care service (telepharmacy) during the COVID-19 pandemic in the Republic of Srpska (RS), Bosnia and Herzegovina. The secondary aim was to identify service users’ needs and concerns and to describe community pharmacists’ interventions. Ten community pharmacists were appointed by the Pharmaceutical Society of the RS to deliver telepharmacy services. After obtaining users’ verbal permission, pharmacists documented issues discussed with them. The prospective data collection included the period from April 13 to May 21, 2020. Descriptive and statistical analysis was performed using IBM SPSS Statistics software (ver. 22). A total of 71 service users’ charts were analyzed. Telepharmacy users were on average 61.31 ± 13.27 years of age, with almost equal gender distribution. Patients with chronic or acute/subacute conditions were predominant with a share of 84.5%. Chronic diseases were the main reason for searching pharmacists’ consultation (74.6%), 7% had a complaint about worsening of a chronic condition, 9.9% reported only acute/subacute conditions as ambulatory conditions, whereas 15.5% asked information about coronavirus or COVID-19. The vast majority of patients’ and users’ needs were addressed by a pharmacist during counseling and only 15.5% of the patients required immediate referral to a doctor for refill/prescribing purposes. Remote pharmaceutical care service (telepharmacy) is deemed a convenient model in the RS during the COVID-19 pandemic. Patients and users presented with explicit and specific needs and concerns, both COVID- and non-COVID-related, which should not be neglected. Community pharmacists showed a high level of resilience and ability in addressing patients' needs.
PB  - John Wiley and Sons Inc
T2  - Health and Social Care in the Community
T1  - Telepharmacy service experience during the COVID-19 pandemic in the Republic of Srpska, Bosnia and Herzegovina
VL  - 30
IS  - 5
SP  - e1639
EP  - e1650
DO  - 10.1111/hsc.13590
ER  - 
@article{
author = "Kovačević, Milena and Ćulafić, Milica and Vezmar-Kovačević, Sandra and Borjanić, Slavenka and Keleč, Branka and Miljković, Branislava and Amidžić, Rada",
year = "2022",
abstract = "The COVID-19 pandemic exerted a profound impact on health systems worldwide. Moreover, significant concerns were raised in terms of middle- and long-term consequences of postponing care in non-COVID patients. The primary aim of the study was to describe the remote pharmaceutical care service (telepharmacy) during the COVID-19 pandemic in the Republic of Srpska (RS), Bosnia and Herzegovina. The secondary aim was to identify service users’ needs and concerns and to describe community pharmacists’ interventions. Ten community pharmacists were appointed by the Pharmaceutical Society of the RS to deliver telepharmacy services. After obtaining users’ verbal permission, pharmacists documented issues discussed with them. The prospective data collection included the period from April 13 to May 21, 2020. Descriptive and statistical analysis was performed using IBM SPSS Statistics software (ver. 22). A total of 71 service users’ charts were analyzed. Telepharmacy users were on average 61.31 ± 13.27 years of age, with almost equal gender distribution. Patients with chronic or acute/subacute conditions were predominant with a share of 84.5%. Chronic diseases were the main reason for searching pharmacists’ consultation (74.6%), 7% had a complaint about worsening of a chronic condition, 9.9% reported only acute/subacute conditions as ambulatory conditions, whereas 15.5% asked information about coronavirus or COVID-19. The vast majority of patients’ and users’ needs were addressed by a pharmacist during counseling and only 15.5% of the patients required immediate referral to a doctor for refill/prescribing purposes. Remote pharmaceutical care service (telepharmacy) is deemed a convenient model in the RS during the COVID-19 pandemic. Patients and users presented with explicit and specific needs and concerns, both COVID- and non-COVID-related, which should not be neglected. Community pharmacists showed a high level of resilience and ability in addressing patients' needs.",
publisher = "John Wiley and Sons Inc",
journal = "Health and Social Care in the Community",
title = "Telepharmacy service experience during the COVID-19 pandemic in the Republic of Srpska, Bosnia and Herzegovina",
volume = "30",
number = "5",
pages = "e1639-e1650",
doi = "10.1111/hsc.13590"
}
Kovačević, M., Ćulafić, M., Vezmar-Kovačević, S., Borjanić, S., Keleč, B., Miljković, B.,& Amidžić, R.. (2022). Telepharmacy service experience during the COVID-19 pandemic in the Republic of Srpska, Bosnia and Herzegovina. in Health and Social Care in the Community
John Wiley and Sons Inc., 30(5), e1639-e1650.
https://doi.org/10.1111/hsc.13590
Kovačević M, Ćulafić M, Vezmar-Kovačević S, Borjanić S, Keleč B, Miljković B, Amidžić R. Telepharmacy service experience during the COVID-19 pandemic in the Republic of Srpska, Bosnia and Herzegovina. in Health and Social Care in the Community. 2022;30(5):e1639-e1650.
doi:10.1111/hsc.13590 .
Kovačević, Milena, Ćulafić, Milica, Vezmar-Kovačević, Sandra, Borjanić, Slavenka, Keleč, Branka, Miljković, Branislava, Amidžić, Rada, "Telepharmacy service experience during the COVID-19 pandemic in the Republic of Srpska, Bosnia and Herzegovina" in Health and Social Care in the Community, 30, no. 5 (2022):e1639-e1650,
https://doi.org/10.1111/hsc.13590 . .
1
11
6

Outcomes of Clostridioides difficile infection in adult cancer and non-cancer patients hospitalised in a tertiary hospital: a prospective cohort study

Milenković, Bojana; Šuljagić, Vesna; Perić, Aneta; Dragojević-Simić, Viktorija; Tarabar, Olivera; Milanović, Milomir; Putić, Vesna; Tomić, Diana; Miljković, Branislava; Vezmar-Kovačević, Sandra

(British Medical Journal, 2022)

TY  - JOUR
AU  - Milenković, Bojana
AU  - Šuljagić, Vesna
AU  - Perić, Aneta
AU  - Dragojević-Simić, Viktorija
AU  - Tarabar, Olivera
AU  - Milanović, Milomir
AU  - Putić, Vesna
AU  - Tomić, Diana
AU  - Miljković, Branislava
AU  - Vezmar-Kovačević, Sandra
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4829
AB  - Background Clostridioides difficile infection (CDI) is one of the most common healthcare-associated (HA) infections. Cancer patients, particularly haemato-oncological patients, have an increased risk for CDI due to more risk factors compared with non-cancer patients. The aim of this study was to investigate differences in outcomes associated with HA CDI in patients with solid and haematological malignancies compared with patients with no underlying malignant disease in a tertiary healthcare centre in Serbia.

Methods A prospective cohort study was conducted including adult patients diagnosed with an initial episode of HA CDI. Their demographic and clinical characteristics associated with risk factors for CDI were documented. Outcomes such as all-cause 30-day mortality, cure of infection, diarrhoea relaps and recurrence of disease were followed. Patients were assigned to cancer and non-cancer groups. Within the cancer group, patients were divided into the solid tumour subgroup and haematological malignancy subgroup.

Results During a 7-year period, HA CDI was observed in 28 (5.1%) patients with haematological malignancy, 101 (18.3%) patients with solid tumours and 424 (76.7%) non-cancer patients. Older age (OR 1.04, 95% CI 1.02 to 1.07, p<0.001), admission to the intensive care unit (ICU) (OR 2.61, 95% CI 1.37 to 4.95, p=0.003), mechanical ventilation (OR 5.19, 95% CI 2.78 to 9.71, p<0.001) and use of antibiotics prior to CDI (OR 1.04, 95% CI 1.02 to 1.06, p=0.02) were associated with increased mortality. Compared with patients with solid tumours, patients with haematological malignancy were younger (65 vs 57 years, p=0.015), did not require ICU admission (25.0% vs 0%) or mechanical ventilation (8.9% vs 0%) and were treated longer with antibiotics prior to CDI (14 vs 24 days, p=0.002).

Conclusions Patients with haematological malignancy were exposed to different risk factors for CDI associated with mortality compared with patients with solid tumours and non-cancer patients. Older age, ICU stay and mechanical ventilation, but not presence or type of cancer, predicted the all-cause 30-day mortality.
PB  - British Medical Journal
T2  - European Journal of Hospital Pharmacy
T1  - Outcomes of Clostridioides difficile infection in adult cancer and non-cancer patients hospitalised in a tertiary hospital: a prospective cohort study
VL  - 29
IS  - e1
SP  - e15
EP  - e22
DO  - 10.1136/ejhpharm-2020-002574
ER  - 
@article{
author = "Milenković, Bojana and Šuljagić, Vesna and Perić, Aneta and Dragojević-Simić, Viktorija and Tarabar, Olivera and Milanović, Milomir and Putić, Vesna and Tomić, Diana and Miljković, Branislava and Vezmar-Kovačević, Sandra",
year = "2022",
abstract = "Background Clostridioides difficile infection (CDI) is one of the most common healthcare-associated (HA) infections. Cancer patients, particularly haemato-oncological patients, have an increased risk for CDI due to more risk factors compared with non-cancer patients. The aim of this study was to investigate differences in outcomes associated with HA CDI in patients with solid and haematological malignancies compared with patients with no underlying malignant disease in a tertiary healthcare centre in Serbia.

Methods A prospective cohort study was conducted including adult patients diagnosed with an initial episode of HA CDI. Their demographic and clinical characteristics associated with risk factors for CDI were documented. Outcomes such as all-cause 30-day mortality, cure of infection, diarrhoea relaps and recurrence of disease were followed. Patients were assigned to cancer and non-cancer groups. Within the cancer group, patients were divided into the solid tumour subgroup and haematological malignancy subgroup.

Results During a 7-year period, HA CDI was observed in 28 (5.1%) patients with haematological malignancy, 101 (18.3%) patients with solid tumours and 424 (76.7%) non-cancer patients. Older age (OR 1.04, 95% CI 1.02 to 1.07, p<0.001), admission to the intensive care unit (ICU) (OR 2.61, 95% CI 1.37 to 4.95, p=0.003), mechanical ventilation (OR 5.19, 95% CI 2.78 to 9.71, p<0.001) and use of antibiotics prior to CDI (OR 1.04, 95% CI 1.02 to 1.06, p=0.02) were associated with increased mortality. Compared with patients with solid tumours, patients with haematological malignancy were younger (65 vs 57 years, p=0.015), did not require ICU admission (25.0% vs 0%) or mechanical ventilation (8.9% vs 0%) and were treated longer with antibiotics prior to CDI (14 vs 24 days, p=0.002).

Conclusions Patients with haematological malignancy were exposed to different risk factors for CDI associated with mortality compared with patients with solid tumours and non-cancer patients. Older age, ICU stay and mechanical ventilation, but not presence or type of cancer, predicted the all-cause 30-day mortality.",
publisher = "British Medical Journal",
journal = "European Journal of Hospital Pharmacy",
title = "Outcomes of Clostridioides difficile infection in adult cancer and non-cancer patients hospitalised in a tertiary hospital: a prospective cohort study",
volume = "29",
number = "e1",
pages = "e15-e22",
doi = "10.1136/ejhpharm-2020-002574"
}
Milenković, B., Šuljagić, V., Perić, A., Dragojević-Simić, V., Tarabar, O., Milanović, M., Putić, V., Tomić, D., Miljković, B.,& Vezmar-Kovačević, S.. (2022). Outcomes of Clostridioides difficile infection in adult cancer and non-cancer patients hospitalised in a tertiary hospital: a prospective cohort study. in European Journal of Hospital Pharmacy
British Medical Journal., 29(e1), e15-e22.
https://doi.org/10.1136/ejhpharm-2020-002574
Milenković B, Šuljagić V, Perić A, Dragojević-Simić V, Tarabar O, Milanović M, Putić V, Tomić D, Miljković B, Vezmar-Kovačević S. Outcomes of Clostridioides difficile infection in adult cancer and non-cancer patients hospitalised in a tertiary hospital: a prospective cohort study. in European Journal of Hospital Pharmacy. 2022;29(e1):e15-e22.
doi:10.1136/ejhpharm-2020-002574 .
Milenković, Bojana, Šuljagić, Vesna, Perić, Aneta, Dragojević-Simić, Viktorija, Tarabar, Olivera, Milanović, Milomir, Putić, Vesna, Tomić, Diana, Miljković, Branislava, Vezmar-Kovačević, Sandra, "Outcomes of Clostridioides difficile infection in adult cancer and non-cancer patients hospitalised in a tertiary hospital: a prospective cohort study" in European Journal of Hospital Pharmacy, 29, no. e1 (2022):e15-e22,
https://doi.org/10.1136/ejhpharm-2020-002574 . .
2
5
1
3

Assessment of cyclosporin A exposure and identification of variability factors in the early posttransplantation period

Roganović, Maša; Cvetković, Mirjana; Gojković, Ivana; Spasojević, Brankica; Kostić, Mirjana; Miljković, Branislava; Vučićević, Katarina

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Roganović, Maša
AU  - Cvetković, Mirjana
AU  - Gojković, Ivana
AU  - Spasojević, Brankica
AU  - Kostić, Mirjana
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4532
AB  - Cyclosporin A (CyA) is an immunosuppressant used as part of a post-transplant
therapeutic protocol to prevent graft rejection. Due to the large pharmacokinetic variability
that characterizes it, it is necessary to conduct therapeutic drug monitoring (TDM). The aim
of the conducted research is to assess the exposure of CyA in the period of up to 3 months
after transplantation (early post-transplantation period) with the identification of factors
that influence the values of the pharmacokinetic parameters of CyA. From pediatric patients
with kidney transplants, at the University Children ́s Hospital Tiršova, data about dosage
regimens, cotherapy, and measured CyA concentrations (C0 - immediately before the next
dose and C2 - 2 hours after the morning dose) were collected retrospectively. Data were
analysed in NONMEM® (version 7.4). Twenty six patients (up to 12 years old) were
included in the analysis. The pharmacokinetic model that best described the data is a one-
compartment model with first-order absorption. Haematocrit, serum creatinine and body
mass were identified as the main factors of variability. In further analysis, it is necessary to
include data about genetic polymorphism, which is expected to have the greatest impact on
drug exposure and change the power ratio of factors that influence CyA parameter values
and concentrations.The obtained results are expected considering the characteristics of CyA.
In addition to identification, quantification of the influence of the mentioned factors is crucial
for establishing an optimal dosing regimen in the early post-transplantation period in
children, when the risk of graft rejection is the highest.
AB  - Ciklosporin A (CyA) je imunosupresiv koji se koristi kao deo posttransplantacionog
terapijskog protokola u cilju prevencije odbacivanja grafta. Zbog velike farmakokinetičke
varijabilnosti koja ga karakteriše, neophodno je sprovođenje terapijskog monitoringa
(therapeutic drug monitoring, TDM). Cilj sprovedenog istraživanja je procena izloženosti CyA
u periodu do 3 meseca nakon transplantacije (rani posttransplantacioni period) uz
identifikaciju faktora koji utiču na vrednosti farmakokinetičkih parametara CyA. Od
pedijatrijskih pacijenata sa transplantiranim bubregom, u Univerzitetskoj klinici Tiršova,
retrospektivno su prikupljani podaci o primenjenoj dozi CyA, koterapiji, izmerenim
koncentracijama CyA (C0 – neposredno pred davanje naredne doze i C2 – 2 sata nakon
jutarnje doze) i vrednostima laboratorijskih parametara od značaja. Podaci su obrađivani
upotrebom populacione farmakokinetičke analize u programu NONMEM® (verzija 7.4). U
analizu je uključeno 26 pacijenata starosti do 12 godina. Farmakokinetički model koji
najbolje opisuje dostupne podatke je jednoprostorni model sa apsorpcijom prvog reda. Kao
glavni faktori varijabilnosti identifikovani su hematokrit, serumski kreatinin i telesna masa.
U daljoj analizi, neophodno je uključiti podatke o genetskom polimorfizmu, za koje se
očekuje da će imati najveći uticaj na izloženost leku i promeniti odnos snaga faktora koji
utiču na vrednosti parametara CyA i koncentraciju. Dobijeni rezultati su očekivani imajući u
vidu karakteristike CyA. Pored identifikacije, i kvantifikacija uticaja navedenih faktora je
ključna za uspostavljanje optimalnog režima doziranja u ranom posttransplantacionom
periodu kod dece, kada je rizik od odbacivanja grafta najveći.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Assessment of cyclosporin A exposure and identification of variability factors in the early posttransplantation period
T1  - Procena izloženosti ciklosporinu a i identifikacija faktora varijabilnosti u ranom posttransplantacionom periodu
VL  - 72
IS  - 4 suplement
SP  - S304
EP  - S305
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4532
ER  - 
@conference{
author = "Roganović, Maša and Cvetković, Mirjana and Gojković, Ivana and Spasojević, Brankica and Kostić, Mirjana and Miljković, Branislava and Vučićević, Katarina",
year = "2022",
abstract = "Cyclosporin A (CyA) is an immunosuppressant used as part of a post-transplant
therapeutic protocol to prevent graft rejection. Due to the large pharmacokinetic variability
that characterizes it, it is necessary to conduct therapeutic drug monitoring (TDM). The aim
of the conducted research is to assess the exposure of CyA in the period of up to 3 months
after transplantation (early post-transplantation period) with the identification of factors
that influence the values of the pharmacokinetic parameters of CyA. From pediatric patients
with kidney transplants, at the University Children ́s Hospital Tiršova, data about dosage
regimens, cotherapy, and measured CyA concentrations (C0 - immediately before the next
dose and C2 - 2 hours after the morning dose) were collected retrospectively. Data were
analysed in NONMEM® (version 7.4). Twenty six patients (up to 12 years old) were
included in the analysis. The pharmacokinetic model that best described the data is a one-
compartment model with first-order absorption. Haematocrit, serum creatinine and body
mass were identified as the main factors of variability. In further analysis, it is necessary to
include data about genetic polymorphism, which is expected to have the greatest impact on
drug exposure and change the power ratio of factors that influence CyA parameter values
and concentrations.The obtained results are expected considering the characteristics of CyA.
In addition to identification, quantification of the influence of the mentioned factors is crucial
for establishing an optimal dosing regimen in the early post-transplantation period in
children, when the risk of graft rejection is the highest., Ciklosporin A (CyA) je imunosupresiv koji se koristi kao deo posttransplantacionog
terapijskog protokola u cilju prevencije odbacivanja grafta. Zbog velike farmakokinetičke
varijabilnosti koja ga karakteriše, neophodno je sprovođenje terapijskog monitoringa
(therapeutic drug monitoring, TDM). Cilj sprovedenog istraživanja je procena izloženosti CyA
u periodu do 3 meseca nakon transplantacije (rani posttransplantacioni period) uz
identifikaciju faktora koji utiču na vrednosti farmakokinetičkih parametara CyA. Od
pedijatrijskih pacijenata sa transplantiranim bubregom, u Univerzitetskoj klinici Tiršova,
retrospektivno su prikupljani podaci o primenjenoj dozi CyA, koterapiji, izmerenim
koncentracijama CyA (C0 – neposredno pred davanje naredne doze i C2 – 2 sata nakon
jutarnje doze) i vrednostima laboratorijskih parametara od značaja. Podaci su obrađivani
upotrebom populacione farmakokinetičke analize u programu NONMEM® (verzija 7.4). U
analizu je uključeno 26 pacijenata starosti do 12 godina. Farmakokinetički model koji
najbolje opisuje dostupne podatke je jednoprostorni model sa apsorpcijom prvog reda. Kao
glavni faktori varijabilnosti identifikovani su hematokrit, serumski kreatinin i telesna masa.
U daljoj analizi, neophodno je uključiti podatke o genetskom polimorfizmu, za koje se
očekuje da će imati najveći uticaj na izloženost leku i promeniti odnos snaga faktora koji
utiču na vrednosti parametara CyA i koncentraciju. Dobijeni rezultati su očekivani imajući u
vidu karakteristike CyA. Pored identifikacije, i kvantifikacija uticaja navedenih faktora je
ključna za uspostavljanje optimalnog režima doziranja u ranom posttransplantacionom
periodu kod dece, kada je rizik od odbacivanja grafta najveći.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Assessment of cyclosporin A exposure and identification of variability factors in the early posttransplantation period, Procena izloženosti ciklosporinu a i identifikacija faktora varijabilnosti u ranom posttransplantacionom periodu",
volume = "72",
number = "4 suplement",
pages = "S304-S305",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4532"
}
Roganović, M., Cvetković, M., Gojković, I., Spasojević, B., Kostić, M., Miljković, B.,& Vučićević, K.. (2022). Assessment of cyclosporin A exposure and identification of variability factors in the early posttransplantation period. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S304-S305.
https://hdl.handle.net/21.15107/rcub_farfar_4532
Roganović M, Cvetković M, Gojković I, Spasojević B, Kostić M, Miljković B, Vučićević K. Assessment of cyclosporin A exposure and identification of variability factors in the early posttransplantation period. in Arhiv za farmaciju. 2022;72(4 suplement):S304-S305.
https://hdl.handle.net/21.15107/rcub_farfar_4532 .
Roganović, Maša, Cvetković, Mirjana, Gojković, Ivana, Spasojević, Brankica, Kostić, Mirjana, Miljković, Branislava, Vučićević, Katarina, "Assessment of cyclosporin A exposure and identification of variability factors in the early posttransplantation period" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S304-S305,
https://hdl.handle.net/21.15107/rcub_farfar_4532 .

A population pharmacokinetic model of tacrolimus in adult liver transplant recipients

Jovanović, Marija; Ćulafić, Milica; Pejić, Nina; Štulić, Miloš; Kovačević, Milena; Vezmar-Kovačević, Sandra; Miljković, Branislava; Ćulafić, Đorđe; Vučićević, Katarina

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Jovanović, Marija
AU  - Ćulafić, Milica
AU  - Pejić, Nina
AU  - Štulić, Miloš
AU  - Kovačević, Milena
AU  - Vezmar-Kovačević, Sandra
AU  - Miljković, Branislava
AU  - Ćulafić, Đorđe
AU  - Vučićević, Katarina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4531
AB  - Tacrolimus is an immunosuppressant used to prevent graft rejection after liver
transplantation. The narrow therapeutic range and great variability in pharmacokinetics
indicate the need for therapy individualization. The aim of the study was to develop and
validate the base pharmacokinetic model of tacrolimus using data collected during
therapeutic drug monitoring. The study included 29 liver transplant recipients followed up
at Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia. Using the
NONMEM® program, we analyzed tacrolimus concentrations (Ctrough) measured in whole
blood (260). Pharmacokinetics have been described as one-compartment model with first-
order absorption and elimination. Internal validation was performed using graphical
assessment, bootstrap method and visual predictive check (VPC). Typical value of oral
clearance (CL/F) was 30.4 L/h, while value of oral volume of distribution was 5770 L. The
value of the absorption rate constant was fixed at 4.48 h-1 . Interindividual variability was
best described by the exponential model, and residual by the additive model. Interindividual
variability for CL/F was 38.2%. Individual predicted concentrations (IPRED) showed better
agreement with the measured values than population predicted values (PRED). Conditional
weighted residuals (CWRES vs PRED, CWRES vs TIME) were mostly between -2 and +2
standard deviations. The parameters obtained by bootstrap analysis do not deviate
significantly from the model. Median, 5th and 95th percentiles in the VPC method mostly
were within the simulated 95% confidence interval. The obtained population
pharmacokinetic model, after additional optimization, can be used for individualization of
the tacrolimus dosing regimen in the population of liver transplant recipients.
AB  - Takrolimus je imunosupresiv koji se primenjuje za prevenciju odbacivanja grafta
nakon transplantacije jetre. Uzak terapijski opseg i velika varijabilnost u farmakokinetici
ukazuju na neophodnost individualizacije terapije. Cilj istraživanja bio je razvoj i validacija
osnovnog farmakokinetičkog modela takrolimusa baziranog na podacima prikupljenim
tokom terapijskog praćenja leka. Studija je uključila 29 pacijenata sa transplantiranom
jetrom, praćenih na Klinici za gastroenterologiju i hepatologiju, Kliničkog centra Srbije.
Primenom NONMEM® programa analizirane su koncentracije takrolimusa izmerene u punoj
krvi (260), neposredno pre primene jutarnje doze (Ctrough). Farmakokinetika je opisana
jednoprostornim modelom sa resorpcijom i eliminacijom prvog reda. Interna validacija je
vršena primenom grafičke metode procene, metode umnožavanja podataka (bootstrap) i
vizuelne prediktivne provere (VPC). Procenjena tipična vrednost oralnog klirensa (CL/F)
iznosila je 30,4 L/h, dok je vrednost oralnog volumena distribucije bila 5770 L. Vrednost
konstante brzine resorpcije je fiksirana na 4,48 h-1 . Interindividualna varijabilnost je najbolje
opisana eksponencijalnim modelom, a rezidualna aditivnim modelom. Zabeležena je
interindividualna varijabilnost za CL/F od 38,2%. Predviđene individualne koncentracije
(IPRED) pokazuju bolje slaganje sa izmerenim vrednostima, nego populacione predviđene
vrednosti (PRED). Uslovni težinski reziduali (CWRES vs PRED, CWRES vs TIME) su većinom
raspoređeni između -2 i +2 standardne devijacije. Parametri dobijeni bootstrap analizom ne
odstupaju značajno od modela, dok su vrednosti medijane, 5. i 95. percentila u VPC metodi
uglavnom bile u okviru simuliranih 95% intervala pouzdanosti. Dobijeni populacioni
farmakokinetički model, može se nakon dodatne optimizacije, primeniti u svrhu
individualizacije režima doziranja takrolimusa u populaciji pacijenata sa transplantiranom
jetrom.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - A population pharmacokinetic model of tacrolimus in adult liver transplant recipients
T1  - Populacioni farmakokinetički model takrolimusa kod pacijenata sa transplantiranom jetrom
VL  - 72
IS  - 4 suplement
SP  - S298
EP  - S299
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4531
ER  - 
@conference{
author = "Jovanović, Marija and Ćulafić, Milica and Pejić, Nina and Štulić, Miloš and Kovačević, Milena and Vezmar-Kovačević, Sandra and Miljković, Branislava and Ćulafić, Đorđe and Vučićević, Katarina",
year = "2022",
abstract = "Tacrolimus is an immunosuppressant used to prevent graft rejection after liver
transplantation. The narrow therapeutic range and great variability in pharmacokinetics
indicate the need for therapy individualization. The aim of the study was to develop and
validate the base pharmacokinetic model of tacrolimus using data collected during
therapeutic drug monitoring. The study included 29 liver transplant recipients followed up
at Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia. Using the
NONMEM® program, we analyzed tacrolimus concentrations (Ctrough) measured in whole
blood (260). Pharmacokinetics have been described as one-compartment model with first-
order absorption and elimination. Internal validation was performed using graphical
assessment, bootstrap method and visual predictive check (VPC). Typical value of oral
clearance (CL/F) was 30.4 L/h, while value of oral volume of distribution was 5770 L. The
value of the absorption rate constant was fixed at 4.48 h-1 . Interindividual variability was
best described by the exponential model, and residual by the additive model. Interindividual
variability for CL/F was 38.2%. Individual predicted concentrations (IPRED) showed better
agreement with the measured values than population predicted values (PRED). Conditional
weighted residuals (CWRES vs PRED, CWRES vs TIME) were mostly between -2 and +2
standard deviations. The parameters obtained by bootstrap analysis do not deviate
significantly from the model. Median, 5th and 95th percentiles in the VPC method mostly
were within the simulated 95% confidence interval. The obtained population
pharmacokinetic model, after additional optimization, can be used for individualization of
the tacrolimus dosing regimen in the population of liver transplant recipients., Takrolimus je imunosupresiv koji se primenjuje za prevenciju odbacivanja grafta
nakon transplantacije jetre. Uzak terapijski opseg i velika varijabilnost u farmakokinetici
ukazuju na neophodnost individualizacije terapije. Cilj istraživanja bio je razvoj i validacija
osnovnog farmakokinetičkog modela takrolimusa baziranog na podacima prikupljenim
tokom terapijskog praćenja leka. Studija je uključila 29 pacijenata sa transplantiranom
jetrom, praćenih na Klinici za gastroenterologiju i hepatologiju, Kliničkog centra Srbije.
Primenom NONMEM® programa analizirane su koncentracije takrolimusa izmerene u punoj
krvi (260), neposredno pre primene jutarnje doze (Ctrough). Farmakokinetika je opisana
jednoprostornim modelom sa resorpcijom i eliminacijom prvog reda. Interna validacija je
vršena primenom grafičke metode procene, metode umnožavanja podataka (bootstrap) i
vizuelne prediktivne provere (VPC). Procenjena tipična vrednost oralnog klirensa (CL/F)
iznosila je 30,4 L/h, dok je vrednost oralnog volumena distribucije bila 5770 L. Vrednost
konstante brzine resorpcije je fiksirana na 4,48 h-1 . Interindividualna varijabilnost je najbolje
opisana eksponencijalnim modelom, a rezidualna aditivnim modelom. Zabeležena je
interindividualna varijabilnost za CL/F od 38,2%. Predviđene individualne koncentracije
(IPRED) pokazuju bolje slaganje sa izmerenim vrednostima, nego populacione predviđene
vrednosti (PRED). Uslovni težinski reziduali (CWRES vs PRED, CWRES vs TIME) su većinom
raspoređeni između -2 i +2 standardne devijacije. Parametri dobijeni bootstrap analizom ne
odstupaju značajno od modela, dok su vrednosti medijane, 5. i 95. percentila u VPC metodi
uglavnom bile u okviru simuliranih 95% intervala pouzdanosti. Dobijeni populacioni
farmakokinetički model, može se nakon dodatne optimizacije, primeniti u svrhu
individualizacije režima doziranja takrolimusa u populaciji pacijenata sa transplantiranom
jetrom.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "A population pharmacokinetic model of tacrolimus in adult liver transplant recipients, Populacioni farmakokinetički model takrolimusa kod pacijenata sa transplantiranom jetrom",
volume = "72",
number = "4 suplement",
pages = "S298-S299",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4531"
}
Jovanović, M., Ćulafić, M., Pejić, N., Štulić, M., Kovačević, M., Vezmar-Kovačević, S., Miljković, B., Ćulafić, Đ.,& Vučićević, K.. (2022). A population pharmacokinetic model of tacrolimus in adult liver transplant recipients. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S298-S299.
https://hdl.handle.net/21.15107/rcub_farfar_4531
Jovanović M, Ćulafić M, Pejić N, Štulić M, Kovačević M, Vezmar-Kovačević S, Miljković B, Ćulafić Đ, Vučićević K. A population pharmacokinetic model of tacrolimus in adult liver transplant recipients. in Arhiv za farmaciju. 2022;72(4 suplement):S298-S299.
https://hdl.handle.net/21.15107/rcub_farfar_4531 .
Jovanović, Marija, Ćulafić, Milica, Pejić, Nina, Štulić, Miloš, Kovačević, Milena, Vezmar-Kovačević, Sandra, Miljković, Branislava, Ćulafić, Đorđe, Vučićević, Katarina, "A population pharmacokinetic model of tacrolimus in adult liver transplant recipients" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S298-S299,
https://hdl.handle.net/21.15107/rcub_farfar_4531 .

Analysis of restricted antibiotics’ implementation in Clinical center of Montenegro during 2019. and the impact of COVID-19 epidemic on their usage

Lukač, Džana; Miljković, Branislava

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Lukač, Džana
AU  - Miljković, Branislava
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4530
AB  - Restricted antibiotics include the ones that are not used as first-line antibiotics, for
they are preserved for treating infections that cannot be cured with common antibiotics. In
2016, Clinical center of Montenegro filed a restriction on implementation of amikacin,
tobramycin, ceftazidime, cefotaxime, cefixime, cefepime, colistin, linezolid, moxifloxacin,
ofloxacin, levofloxacin, meropenem, imipenem/cilastatin, ertapenem,
piperacillin/tazobactam, tigecycline, vancomycin and teicoplanin. The goal of this research is
analysis of restricted antibiotics’ implementation during 2019. and their usage during the
COVID-19 epidemic. 174 requests for restricted antibiotics from 2019. and the usage of
restricted antibiotics during the COVID-19 pandemic were retrospectively analyzed. By data
analysis it was determined that the antibiogram has been done only in 21,84% of cases. In
72.25% of cases restricted antibiotic was included in therapy without prior antimicrobial
therapy using unrestricted antibiotic. Monotherapy was included in the largest number of
cases (75,28%), two antibiotics were used in 19,54% of cases, combination of three in 4,02%
of cases, and there were 1,15% of cases of using 4 restricted antibiotics in therapy. The
average therapy duration was 8.84 days, though there was a large range of shortest (3 days)
and longest (40 days) therapy duration. Most commonly used antibiotics were meropenem
(53 cases – 30,45%), amikacin (36 cases – 20,68%), vancomycin (33 cases – 18,7%). The
combination of imipenem and cilastatin was used in 13 cases (7,47%). Most commonly
isolated causative agents were Acinetobacter spp. (8), Pseudomonas aeruginosa (8),
Staphylococcus aureus (6) and Clostridium difficile (4). Usage of restricted antibiotics has
increased during COVID-19 (2021) – usage of amikacin has risen 1,5 times more than in
2019, ceftazidime 2,3 times, cefixime 1,6, meropenem 2,3, piperacillin/tazobactam 2,57 and
vancomycin 1,63 times.The increase of restricted antibiotics’ usage during COVID-19 could
highly negatively affect rational antibiotic use implementation, as well as the antimicrobial
resistance.
AB  - Koncept rezervnih antibiotika podrazumijeva usvajanje liste antibiotika koji se ne
koriste kao ljekovi prvog izbora, već se čuvaju za infekcije koje ne reaguju na antibiotike
prvog izbora. U Kliničkom centru Crne Gore je 2016. godine uvedena restrikcija u
propisivanju amikacina, tobramicina, ceftazidima, cefotaksima, cefiksima, cefepima, kolistina,
linezolida, moksifloksacina, ofloksacina, levofloksacina, meropenema, imipenem/cilastatina,
ertapenema, piperacilin/tazobaktama, tigeciklina, vankomicina i teikoplanina. Cilj
istraživanja je analiza primjene rezervnih antibiotika tokom 2019. godine i njihove potrošnje
tokom epidemije COVID-19.Retrospektivno su analizirana 174 zahtjeva za izdavanje
rezervnih antibiotika iz 2019. godine i potrošnja rezervnih antibiotika tokom epidemije
COVID-19. Analizom je utvrđeno da je antibiogram rađen u 21,84% slučajeva (38). U 72,25%
slučajeva rezervni antibiotik je uključen u terapiju bez prethodne terapije nerezervnim
antibiotikom. U 75,28% analiziranih slučajeva korišćen je jedan rezervni antibiotik, u
19,54% slučajeva korišćena su dva, u 4,02% slučajeva tri, a u 1,15% slučajeva su u terapiji
bila zastupljena četiri rezervna antibiotika. Prosječna dužina trajanja terapije bila je 8,84
dana, sa velikim rasponom između minimalne (3 dana) i maksimalne dužine trajanja (40
dana). Najčešće su korišćeni meropenem (30,45%), amikacin (20,68%) i vankomicin
(18,7%). Najčešće su izolovani Acinetobacter spp. (8), Pseudomonas aeruginosa (8),
Staphylococcus aureus (6) i Clostridium difficile (4). Potrošnja rezervnih antibiotika tokom
epidemije COVID-19 (2021. god.) u odnosu na 2019. godinu bila je povećana – potrošnja
amikacina je bila veća 1,5 puta, ceftazidima 2,3, cefiksima 1,6, meropenema 2,3,
piperacilin/tazobaktama 2,57, a vankomicina 1,63 puta. Povećanje potrošnje rezervnih
antibiotika tokom epidemije COVID-19 može negativno uticati na mogućnost implementacije
principa racionalne primjene antibiotika i pojavu antimikrobne rezistencije.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Analysis of restricted antibiotics’ implementation in Clinical center of Montenegro during 2019. and the impact of COVID-19 epidemic on their usage
T1  - Analiza primjene rezervnih antibiotika u kliničkom centru crne gore tokom 2019. godine i uticaj epidemije COVID‐19 na njihovu potrošnju
VL  - 72
IS  - 4 suplement
SP  - S292
EP  - S293
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4530
ER  - 
@conference{
author = "Lukač, Džana and Miljković, Branislava",
year = "2022",
abstract = "Restricted antibiotics include the ones that are not used as first-line antibiotics, for
they are preserved for treating infections that cannot be cured with common antibiotics. In
2016, Clinical center of Montenegro filed a restriction on implementation of amikacin,
tobramycin, ceftazidime, cefotaxime, cefixime, cefepime, colistin, linezolid, moxifloxacin,
ofloxacin, levofloxacin, meropenem, imipenem/cilastatin, ertapenem,
piperacillin/tazobactam, tigecycline, vancomycin and teicoplanin. The goal of this research is
analysis of restricted antibiotics’ implementation during 2019. and their usage during the
COVID-19 epidemic. 174 requests for restricted antibiotics from 2019. and the usage of
restricted antibiotics during the COVID-19 pandemic were retrospectively analyzed. By data
analysis it was determined that the antibiogram has been done only in 21,84% of cases. In
72.25% of cases restricted antibiotic was included in therapy without prior antimicrobial
therapy using unrestricted antibiotic. Monotherapy was included in the largest number of
cases (75,28%), two antibiotics were used in 19,54% of cases, combination of three in 4,02%
of cases, and there were 1,15% of cases of using 4 restricted antibiotics in therapy. The
average therapy duration was 8.84 days, though there was a large range of shortest (3 days)
and longest (40 days) therapy duration. Most commonly used antibiotics were meropenem
(53 cases – 30,45%), amikacin (36 cases – 20,68%), vancomycin (33 cases – 18,7%). The
combination of imipenem and cilastatin was used in 13 cases (7,47%). Most commonly
isolated causative agents were Acinetobacter spp. (8), Pseudomonas aeruginosa (8),
Staphylococcus aureus (6) and Clostridium difficile (4). Usage of restricted antibiotics has
increased during COVID-19 (2021) – usage of amikacin has risen 1,5 times more than in
2019, ceftazidime 2,3 times, cefixime 1,6, meropenem 2,3, piperacillin/tazobactam 2,57 and
vancomycin 1,63 times.The increase of restricted antibiotics’ usage during COVID-19 could
highly negatively affect rational antibiotic use implementation, as well as the antimicrobial
resistance., Koncept rezervnih antibiotika podrazumijeva usvajanje liste antibiotika koji se ne
koriste kao ljekovi prvog izbora, već se čuvaju za infekcije koje ne reaguju na antibiotike
prvog izbora. U Kliničkom centru Crne Gore je 2016. godine uvedena restrikcija u
propisivanju amikacina, tobramicina, ceftazidima, cefotaksima, cefiksima, cefepima, kolistina,
linezolida, moksifloksacina, ofloksacina, levofloksacina, meropenema, imipenem/cilastatina,
ertapenema, piperacilin/tazobaktama, tigeciklina, vankomicina i teikoplanina. Cilj
istraživanja je analiza primjene rezervnih antibiotika tokom 2019. godine i njihove potrošnje
tokom epidemije COVID-19.Retrospektivno su analizirana 174 zahtjeva za izdavanje
rezervnih antibiotika iz 2019. godine i potrošnja rezervnih antibiotika tokom epidemije
COVID-19. Analizom je utvrđeno da je antibiogram rađen u 21,84% slučajeva (38). U 72,25%
slučajeva rezervni antibiotik je uključen u terapiju bez prethodne terapije nerezervnim
antibiotikom. U 75,28% analiziranih slučajeva korišćen je jedan rezervni antibiotik, u
19,54% slučajeva korišćena su dva, u 4,02% slučajeva tri, a u 1,15% slučajeva su u terapiji
bila zastupljena četiri rezervna antibiotika. Prosječna dužina trajanja terapije bila je 8,84
dana, sa velikim rasponom između minimalne (3 dana) i maksimalne dužine trajanja (40
dana). Najčešće su korišćeni meropenem (30,45%), amikacin (20,68%) i vankomicin
(18,7%). Najčešće su izolovani Acinetobacter spp. (8), Pseudomonas aeruginosa (8),
Staphylococcus aureus (6) i Clostridium difficile (4). Potrošnja rezervnih antibiotika tokom
epidemije COVID-19 (2021. god.) u odnosu na 2019. godinu bila je povećana – potrošnja
amikacina je bila veća 1,5 puta, ceftazidima 2,3, cefiksima 1,6, meropenema 2,3,
piperacilin/tazobaktama 2,57, a vankomicina 1,63 puta. Povećanje potrošnje rezervnih
antibiotika tokom epidemije COVID-19 može negativno uticati na mogućnost implementacije
principa racionalne primjene antibiotika i pojavu antimikrobne rezistencije.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Analysis of restricted antibiotics’ implementation in Clinical center of Montenegro during 2019. and the impact of COVID-19 epidemic on their usage, Analiza primjene rezervnih antibiotika u kliničkom centru crne gore tokom 2019. godine i uticaj epidemije COVID‐19 na njihovu potrošnju",
volume = "72",
number = "4 suplement",
pages = "S292-S293",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4530"
}
Lukač, D.,& Miljković, B.. (2022). Analysis of restricted antibiotics’ implementation in Clinical center of Montenegro during 2019. and the impact of COVID-19 epidemic on their usage. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S292-S293.
https://hdl.handle.net/21.15107/rcub_farfar_4530
Lukač D, Miljković B. Analysis of restricted antibiotics’ implementation in Clinical center of Montenegro during 2019. and the impact of COVID-19 epidemic on their usage. in Arhiv za farmaciju. 2022;72(4 suplement):S292-S293.
https://hdl.handle.net/21.15107/rcub_farfar_4530 .
Lukač, Džana, Miljković, Branislava, "Analysis of restricted antibiotics’ implementation in Clinical center of Montenegro during 2019. and the impact of COVID-19 epidemic on their usage" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S292-S293,
https://hdl.handle.net/21.15107/rcub_farfar_4530 .

Assessment of concentrations and normalized concentrations of variability in methotrexate concentrations between cycles

Škorić, Biljana; Jovanović, Marija; Miljković, Branislava; Kuzmanović, Miloš; Vučićević, Katarina

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Škorić, Biljana
AU  - Jovanović, Marija
AU  - Miljković, Branislava
AU  - Kuzmanović, Miloš
AU  - Vučićević, Katarina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4529
AB  - Administration of high dose methotrexate (HDMTX) is common part of pediatric
protocols for acute lymphoblastic leukemia (ALL) and non-Hodking lymphoma (NHL).
Methotrexate is used in certain phase of therapy in doses 3 g/m 2 or 5 g/m 2 with the objective
to achieve concentration that will ensure eradication of tumor cells with minimal toxic effect.
The aim of this study is overview of drug concentration and assessment of therapy safety in
relation to referent values. After obtaining Ethics committee approval at The Institute for
mother and child Healthcare of Serbia “Dr Vukan Cupic” 50 pediatric patients with ALL or
NHL were enrolled. Data on MTX usage was retrospectively collected from the patient
history. Concentrations and normalized concentrations per applied dose were compared
with nonparametric tests in SPSS (version 18). MTX concentration mean (± standard
deviation) following administration of 3 g/m 2 respectively 5 g/m2 doses were 19.72±6.62
mg/L respectively 34.73±17.13 at 24 h, 0.20±0.36 mg/L respectively 0.24±0.58 mg/L at 48h
and 0.14±0.44 mg/L respectively 0.12±0.89 mg/L at 72h after start of the infusion.
Statistically significant difference (p<0.001) is only seen at 24h concentration between 3
g/m 2 (mean rank 43.97) and 5 g/m 2 (mean rank 103.36). In all other time points, there was
no difference during comparison of concentrations nor normalized concentration, even
though it is seen trend of higher values in 5 g/m2 group. Results of analysis show that
administration of higher dose during simultaneous distribution and elimination phase leads
to higher concentrations while during elimination phase this effect is less visible. However,
administration of the high doses brings the risk of side effects due to reaching higher
concentrations.
AB  - Primena visokih doza metotreksata je uobičajena u pedijatrijskim protokolima za
lečenje akutne limfoblastne leukemije (ALL) i non-Hodking limfoma (NHL). Metotreksat se u
određenoj fazi terapije primenje u dozi od 3 g/m2 ili 5 g/m 2 u cilju postizanja koncentracije
koje uništavaju tumorske ćelije uz minimalan toksičan efekat. Cilj ovog rada je prikaz
koncentracije leka u zavisnosti od primenjene doze i procena bezbednosti terapije u odnosu
na referentne vrednosti koncentracije. Nakon odobrenja etičkog odbora Instituta za
zdravstvenu zaštitu majke i deteta Srbije „Dr Vukan Čupić“ uključeno je 50 pedijatrijski
pacijenata sa ALL ili NHL. Podaci o primeni MTX su retrospektivno prikupljeni iz istorija
bolesti. Koncentracije i normalizovane koncentracije po primenjenoj dozi su statistički
analizirani neparametarskim testovima u SPSS-u (verzija 18). Srednja vrednost
koncentracija (± standardna devijacija) MTX pri primeni 3 g/m2 odnosno 5 g/m2 je iznosila
19,72±6,62 mg/L odnosno 34,73±17,13 u 24h, 0,20±0,36 mg/L odnosno 0,24±0,58 mg/L u
48h i 0,14±0,44 mg/L odnosno 0,12±0,89 mg/L u 72h posle početka infuzije. Statistički
značajna razlika (p<0,001) je uočena kod koncentracija u 24h između doza 3 g/m2 (mean
rank = 43,97) i 5 g/m2 (mean rank= 103,36). U ostalim vremenskim tačkama i pri poređenju
normalizovanih koncentracija nije bilo statistički značajne razlike, iako je primetan trend
viših vrednosti u grupi 5 g/m 2 . Rezultati analize pokazuju da pri primeni veće doze leka
tokom istovremene distribucije i eliminacije leka postoji mogućnost detektovanja visokih
koncentracija, dok je tokom faze eliminacije uticaj primenjene doze manje uočljiv. Ipak,
primena veće doze nosi rizik od neželjenih efekata.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Assessment of concentrations and normalized concentrations of variability in methotrexate concentrations between cycles
T1  - Ispitivanje koncentracija i normalizovanih koncentracija metotreksata u zavisnosti od primenjene doze u pedijatrijskoj populaciji sa ALL i NHL
VL  - 72
IS  - 4 suplement
SP  - S290
EP  - S291
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4529
ER  - 
@conference{
author = "Škorić, Biljana and Jovanović, Marija and Miljković, Branislava and Kuzmanović, Miloš and Vučićević, Katarina",
year = "2022",
abstract = "Administration of high dose methotrexate (HDMTX) is common part of pediatric
protocols for acute lymphoblastic leukemia (ALL) and non-Hodking lymphoma (NHL).
Methotrexate is used in certain phase of therapy in doses 3 g/m 2 or 5 g/m 2 with the objective
to achieve concentration that will ensure eradication of tumor cells with minimal toxic effect.
The aim of this study is overview of drug concentration and assessment of therapy safety in
relation to referent values. After obtaining Ethics committee approval at The Institute for
mother and child Healthcare of Serbia “Dr Vukan Cupic” 50 pediatric patients with ALL or
NHL were enrolled. Data on MTX usage was retrospectively collected from the patient
history. Concentrations and normalized concentrations per applied dose were compared
with nonparametric tests in SPSS (version 18). MTX concentration mean (± standard
deviation) following administration of 3 g/m 2 respectively 5 g/m2 doses were 19.72±6.62
mg/L respectively 34.73±17.13 at 24 h, 0.20±0.36 mg/L respectively 0.24±0.58 mg/L at 48h
and 0.14±0.44 mg/L respectively 0.12±0.89 mg/L at 72h after start of the infusion.
Statistically significant difference (p<0.001) is only seen at 24h concentration between 3
g/m 2 (mean rank 43.97) and 5 g/m 2 (mean rank 103.36). In all other time points, there was
no difference during comparison of concentrations nor normalized concentration, even
though it is seen trend of higher values in 5 g/m2 group. Results of analysis show that
administration of higher dose during simultaneous distribution and elimination phase leads
to higher concentrations while during elimination phase this effect is less visible. However,
administration of the high doses brings the risk of side effects due to reaching higher
concentrations., Primena visokih doza metotreksata je uobičajena u pedijatrijskim protokolima za
lečenje akutne limfoblastne leukemije (ALL) i non-Hodking limfoma (NHL). Metotreksat se u
određenoj fazi terapije primenje u dozi od 3 g/m2 ili 5 g/m 2 u cilju postizanja koncentracije
koje uništavaju tumorske ćelije uz minimalan toksičan efekat. Cilj ovog rada je prikaz
koncentracije leka u zavisnosti od primenjene doze i procena bezbednosti terapije u odnosu
na referentne vrednosti koncentracije. Nakon odobrenja etičkog odbora Instituta za
zdravstvenu zaštitu majke i deteta Srbije „Dr Vukan Čupić“ uključeno je 50 pedijatrijski
pacijenata sa ALL ili NHL. Podaci o primeni MTX su retrospektivno prikupljeni iz istorija
bolesti. Koncentracije i normalizovane koncentracije po primenjenoj dozi su statistički
analizirani neparametarskim testovima u SPSS-u (verzija 18). Srednja vrednost
koncentracija (± standardna devijacija) MTX pri primeni 3 g/m2 odnosno 5 g/m2 je iznosila
19,72±6,62 mg/L odnosno 34,73±17,13 u 24h, 0,20±0,36 mg/L odnosno 0,24±0,58 mg/L u
48h i 0,14±0,44 mg/L odnosno 0,12±0,89 mg/L u 72h posle početka infuzije. Statistički
značajna razlika (p<0,001) je uočena kod koncentracija u 24h između doza 3 g/m2 (mean
rank = 43,97) i 5 g/m2 (mean rank= 103,36). U ostalim vremenskim tačkama i pri poređenju
normalizovanih koncentracija nije bilo statistički značajne razlike, iako je primetan trend
viših vrednosti u grupi 5 g/m 2 . Rezultati analize pokazuju da pri primeni veće doze leka
tokom istovremene distribucije i eliminacije leka postoji mogućnost detektovanja visokih
koncentracija, dok je tokom faze eliminacije uticaj primenjene doze manje uočljiv. Ipak,
primena veće doze nosi rizik od neželjenih efekata.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Assessment of concentrations and normalized concentrations of variability in methotrexate concentrations between cycles, Ispitivanje koncentracija i normalizovanih koncentracija metotreksata u zavisnosti od primenjene doze u pedijatrijskoj populaciji sa ALL i NHL",
volume = "72",
number = "4 suplement",
pages = "S290-S291",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4529"
}
Škorić, B., Jovanović, M., Miljković, B., Kuzmanović, M.,& Vučićević, K.. (2022). Assessment of concentrations and normalized concentrations of variability in methotrexate concentrations between cycles. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S290-S291.
https://hdl.handle.net/21.15107/rcub_farfar_4529
Škorić B, Jovanović M, Miljković B, Kuzmanović M, Vučićević K. Assessment of concentrations and normalized concentrations of variability in methotrexate concentrations between cycles. in Arhiv za farmaciju. 2022;72(4 suplement):S290-S291.
https://hdl.handle.net/21.15107/rcub_farfar_4529 .
Škorić, Biljana, Jovanović, Marija, Miljković, Branislava, Kuzmanović, Miloš, Vučićević, Katarina, "Assessment of concentrations and normalized concentrations of variability in methotrexate concentrations between cycles" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S290-S291,
https://hdl.handle.net/21.15107/rcub_farfar_4529 .

An overview of drug interactions in patients with affective bipolar disorder

Jovanović, Nina; Marković, Aleksandra; Miljković, Branislava; Vezmar-Kovačević, Sandra

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Jovanović, Nina
AU  - Marković, Aleksandra
AU  - Miljković, Branislava
AU  - Vezmar-Kovačević, Sandra
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4527
AB  - Drug interactions are classified as quantitative and/or qualitative alterations in the
effects of one drug in the presence of another one. Bipolar disorder is an affective disorder
characterized by manic and depressive episodes and often requires more than one drug in its
treatment. In patients with comorbidities higher prevalence of clinically significant
interactions could be expected. The aim was to evaluate clinically significant drug
interactions in patients with bipolar disorder and determine whether patients’
characteristics such as age, number of comorbidities and polypharmacy are related with
their appearance. A retrospective study included 50 patients treated at the Institute of
mental health in Belgrade. Data were obtained from patients’ medical documentation.
Epocrates® database was used to identify potential drug interactions. SPSS® software was
used for statistical analysis. Patients’ average age was 46.19 ± 11.49. The average number of
drugs in therapy was 6.46±2.58 per patient. Total of 549 interactions were detected,
approximately 10.98±5.97 per patient. Most interactions (59.2%) demanded
monitoring/modification of therapy. Caution was advised in 28.78% of interactions while
11.66% of them suggested use of an alternative treatment. Only 0.36% drug interactions
were classified as contraindicated. A positive correlation between the total number of used
drugs and number of drug interactions is shown (p<0.001), as well as the patients’ age and
number of drug interactions (p<0.05). The results show a high prevalence of interactions in
the examined population which implies the importance of monitoring in order to secure
patients’ safety and avoid adverse effects.
AB  - Interakcije lekova predstavljaju kvalitativne i/ili kvantitativne promene delovanja
jednog leka u prisustvu drugog. Bipolarni poremećaj je afektivni poremećaj koji karakterišu
manične i depresivne epizode pa se u terapiji često primenjuje više od jednog leka. U
prisustvu pridruženih bolesti ukupan broj lekova u terapiji znatno raste, pa se može
očekivati visoka prevalenca klinički značajnih interakcija. Cilj istraživanja je procena
potencijalno klinički značajnih interakcija lekova kod pacijenata sa afektivnim bipolarnim
poremećajima. Takođe je ispitano da li karakteristike poput starosti, broja komorbiditeta,
polifarmacije utiču na ispoljavanje interakcija. Sprovedeno je retrospektivno istraživanje na
populaciji od 50 pacijenata lečenih na Institutu za mentalno zdravlje u Beogradu. Podaci su
prikupljeni iz medicinske dokumentacije pacijenata. Za analizu potencijalnih interakcije
korišćena je Epocrates ® baza podataka. Dobijeni rezultati obrađeni su pomoću SPSS®
programa. Prosečna starost pacijenta bila je 46,19 ± 11,49 godina, a prosečan broj lekova u
terapiji iznosio je 6,46 ± 2,58. Detektovano je 549 interakcija, dok je prosek po pacijentu bio
10,98 ± 5,97. U većini slučajeva je bilo potrebno praćenje/modifikacija terapije (59,2%),
oprez je bio potreban kod 28,78% interakcija dok je u 11,66% slučajeva bilo potrebno izbeći
kombinaciju ispitivanih lekova i uvesti alternativnu terapiju. Udeo interakcija lekova čija je
primena kontraindikovana iznosio je 0,36%. Analiza je pokazala statistički uticaj broja
lekova u terapiji na broj interakcija (p<0,001), kao i starosti pacijenta na broj interakcija
(p<0,05). Dobijeni rezultati ukazuju na postojanje velikog broja klinički značajnih interakcija
u ispitivanoj populaciji i na značaj procene interakcija u prisustvu komorbiditeta kako bi se
osigurala bezbednost pacijenta i izbegli neželjeni efekti.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - An overview of drug interactions in patients with affective bipolar disorder
T1  - Pregled interakcija lekova kod pacijenata sa afektivnim bipolarnim poremećajem
VL  - 72
IS  - 4 suplement
SP  - S272
EP  - S273
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4527
ER  - 
@conference{
author = "Jovanović, Nina and Marković, Aleksandra and Miljković, Branislava and Vezmar-Kovačević, Sandra",
year = "2022",
abstract = "Drug interactions are classified as quantitative and/or qualitative alterations in the
effects of one drug in the presence of another one. Bipolar disorder is an affective disorder
characterized by manic and depressive episodes and often requires more than one drug in its
treatment. In patients with comorbidities higher prevalence of clinically significant
interactions could be expected. The aim was to evaluate clinically significant drug
interactions in patients with bipolar disorder and determine whether patients’
characteristics such as age, number of comorbidities and polypharmacy are related with
their appearance. A retrospective study included 50 patients treated at the Institute of
mental health in Belgrade. Data were obtained from patients’ medical documentation.
Epocrates® database was used to identify potential drug interactions. SPSS® software was
used for statistical analysis. Patients’ average age was 46.19 ± 11.49. The average number of
drugs in therapy was 6.46±2.58 per patient. Total of 549 interactions were detected,
approximately 10.98±5.97 per patient. Most interactions (59.2%) demanded
monitoring/modification of therapy. Caution was advised in 28.78% of interactions while
11.66% of them suggested use of an alternative treatment. Only 0.36% drug interactions
were classified as contraindicated. A positive correlation between the total number of used
drugs and number of drug interactions is shown (p<0.001), as well as the patients’ age and
number of drug interactions (p<0.05). The results show a high prevalence of interactions in
the examined population which implies the importance of monitoring in order to secure
patients’ safety and avoid adverse effects., Interakcije lekova predstavljaju kvalitativne i/ili kvantitativne promene delovanja
jednog leka u prisustvu drugog. Bipolarni poremećaj je afektivni poremećaj koji karakterišu
manične i depresivne epizode pa se u terapiji često primenjuje više od jednog leka. U
prisustvu pridruženih bolesti ukupan broj lekova u terapiji znatno raste, pa se može
očekivati visoka prevalenca klinički značajnih interakcija. Cilj istraživanja je procena
potencijalno klinički značajnih interakcija lekova kod pacijenata sa afektivnim bipolarnim
poremećajima. Takođe je ispitano da li karakteristike poput starosti, broja komorbiditeta,
polifarmacije utiču na ispoljavanje interakcija. Sprovedeno je retrospektivno istraživanje na
populaciji od 50 pacijenata lečenih na Institutu za mentalno zdravlje u Beogradu. Podaci su
prikupljeni iz medicinske dokumentacije pacijenata. Za analizu potencijalnih interakcije
korišćena je Epocrates ® baza podataka. Dobijeni rezultati obrađeni su pomoću SPSS®
programa. Prosečna starost pacijenta bila je 46,19 ± 11,49 godina, a prosečan broj lekova u
terapiji iznosio je 6,46 ± 2,58. Detektovano je 549 interakcija, dok je prosek po pacijentu bio
10,98 ± 5,97. U većini slučajeva je bilo potrebno praćenje/modifikacija terapije (59,2%),
oprez je bio potreban kod 28,78% interakcija dok je u 11,66% slučajeva bilo potrebno izbeći
kombinaciju ispitivanih lekova i uvesti alternativnu terapiju. Udeo interakcija lekova čija je
primena kontraindikovana iznosio je 0,36%. Analiza je pokazala statistički uticaj broja
lekova u terapiji na broj interakcija (p<0,001), kao i starosti pacijenta na broj interakcija
(p<0,05). Dobijeni rezultati ukazuju na postojanje velikog broja klinički značajnih interakcija
u ispitivanoj populaciji i na značaj procene interakcija u prisustvu komorbiditeta kako bi se
osigurala bezbednost pacijenta i izbegli neželjeni efekti.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "An overview of drug interactions in patients with affective bipolar disorder, Pregled interakcija lekova kod pacijenata sa afektivnim bipolarnim poremećajem",
volume = "72",
number = "4 suplement",
pages = "S272-S273",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4527"
}
Jovanović, N., Marković, A., Miljković, B.,& Vezmar-Kovačević, S.. (2022). An overview of drug interactions in patients with affective bipolar disorder. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S272-S273.
https://hdl.handle.net/21.15107/rcub_farfar_4527
Jovanović N, Marković A, Miljković B, Vezmar-Kovačević S. An overview of drug interactions in patients with affective bipolar disorder. in Arhiv za farmaciju. 2022;72(4 suplement):S272-S273.
https://hdl.handle.net/21.15107/rcub_farfar_4527 .
Jovanović, Nina, Marković, Aleksandra, Miljković, Branislava, Vezmar-Kovačević, Sandra, "An overview of drug interactions in patients with affective bipolar disorder" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S272-S273,
https://hdl.handle.net/21.15107/rcub_farfar_4527 .

Application of adjusted indirect comparisons to assess bioequivalence and switchability between generic drugs – example of clopidogrel

Pejčić, Zorica; Vučićević, Katarina; García Arieta, Alfredo; Miljković, Branislava

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Pejčić, Zorica
AU  - Vučićević, Katarina
AU  - García Arieta, Alfredo
AU  - Miljković, Branislava
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4526
AB  - Generic medicines are bioequivalent (BE) and switchable with the reference medicine,
however, between generics BE is not demonstrated. In practice, patients are often offered
generic substitution, where information on BE between generics may be useful, especially
when there is a doubt that substitution may potentially pose a risk to the patient. These
information can be obtained by assessing BE between generics, applying the method of
adjusted indirect comparison (AIC). This method is based on data from BE studies in which
generics were compared with the same reference medicine. Thus, it is possible to identify
generics for which efficacy and safety problems are not expected upon substitution (1,2).
The AIC was used to compare four generic clopidogrel medicines. Publicly available data
from original BE studies, in which each generic medicine was compared with the reference
medicine Plavix film-coated tablets 75 mg, were analysed. Generics were considered BE if the
90% confidence interval (CI) for the ratio of their pharmacokinetic parameters maximum
plasma concentration (Cmax) and area under the curve up to the last measurable
concentration (PIK 0-t), was within the acceptance range 80.00-125.00%. In all the tested
combinations, 90% CIs for PIK0-t were within the acceptance range, while for C max 90% CIs
were within or very close to the limits, with the point estimate being within the range in all
cases. The results obtained by the AIC indicated that the bioavailability of these four generic
clopidogrel medicines is very similar, therefore they can be considered switchable with each
other in clinical practice.
AB  - Generički lekovi su biološki ekvivalentni (BE) i zamenjivi sa referentnim lekom,
međutim, između samih generičkih lekova BE nije potvrđena. Pacijentima se u praksi često
nudi odgovarajuća generička zamena, pri kojoj od koristi mogu biti informacije o BE između
generika, naročito u slučaju kada postoji sumnja da zamena generika može potencijalno
predstavljati rizik za pacijenta. Ove informacije mogu se dobiti procenom BE između
generičkih lekova metodom prilagođenog indirektnog poređenja, na osnovu podataka iz već
sprovedenih individualnih studija BE u kojima su generički lekovi poređeni sa istim
referentnim lekom. Na taj način identifikuju se generički lekovi za koje se prilikom zamene u
praksi ne očekuju problemi u pogledu efikasnosti i bezbednosti (1,2). Navedena metoda
korišćena je za poređenje četiri generička leka koji sadrže klopidogrel. Analizirani su javno
dostupni podaci iz studija BE u kojima je svaki generički lek poređen sa referentnim lekom
Plavix film tablete 75 mg. Dva generička leka smatraju se BE ukoliko je 90% interval
pouzdanosti (CI) za odnos njihovih farmakokinetičkih parametara maksimalna koncenracija
u plazmi (C max) i površina ispod krive do poslednje merljive koncentracije (PIK 0-t ), unutar
raspona 80,00-125,00%. U svim ispitanim kombinacijama 90% CI za PIK0-t bili su unutar
dozvoljenog raspona, dok su 90% CI za Cmax bili unutar ili veoma blizu granica ovog raspona,
pri čemu je point estimate u svim slučajevima bio unutar raspona. Rezultati dobijeni
metodom prilagođenog indirektnog poređenja pokazali su da je biološka raspoloživost ova
četiri generička leka koja sadrže klopidogrel veoma slična, te se oni mogu smatrati
međusobno zamenjivim u kliničkoj praksi.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Application of adjusted indirect comparisons to assess bioequivalence and switchability between generic drugs – example of clopidogrel
T1  - Primena metode prilagođenog indirektnog poređenja u proceni biološke ekvivalnetnosti i zamenjivosti generičkih lekova – primer klopidogrela
VL  - 72
IS  - 4 suplement
SP  - S262
EP  - S263
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4526
ER  - 
@conference{
author = "Pejčić, Zorica and Vučićević, Katarina and García Arieta, Alfredo and Miljković, Branislava",
year = "2022",
abstract = "Generic medicines are bioequivalent (BE) and switchable with the reference medicine,
however, between generics BE is not demonstrated. In practice, patients are often offered
generic substitution, where information on BE between generics may be useful, especially
when there is a doubt that substitution may potentially pose a risk to the patient. These
information can be obtained by assessing BE between generics, applying the method of
adjusted indirect comparison (AIC). This method is based on data from BE studies in which
generics were compared with the same reference medicine. Thus, it is possible to identify
generics for which efficacy and safety problems are not expected upon substitution (1,2).
The AIC was used to compare four generic clopidogrel medicines. Publicly available data
from original BE studies, in which each generic medicine was compared with the reference
medicine Plavix film-coated tablets 75 mg, were analysed. Generics were considered BE if the
90% confidence interval (CI) for the ratio of their pharmacokinetic parameters maximum
plasma concentration (Cmax) and area under the curve up to the last measurable
concentration (PIK 0-t), was within the acceptance range 80.00-125.00%. In all the tested
combinations, 90% CIs for PIK0-t were within the acceptance range, while for C max 90% CIs
were within or very close to the limits, with the point estimate being within the range in all
cases. The results obtained by the AIC indicated that the bioavailability of these four generic
clopidogrel medicines is very similar, therefore they can be considered switchable with each
other in clinical practice., Generički lekovi su biološki ekvivalentni (BE) i zamenjivi sa referentnim lekom,
međutim, između samih generičkih lekova BE nije potvrđena. Pacijentima se u praksi često
nudi odgovarajuća generička zamena, pri kojoj od koristi mogu biti informacije o BE između
generika, naročito u slučaju kada postoji sumnja da zamena generika može potencijalno
predstavljati rizik za pacijenta. Ove informacije mogu se dobiti procenom BE između
generičkih lekova metodom prilagođenog indirektnog poređenja, na osnovu podataka iz već
sprovedenih individualnih studija BE u kojima su generički lekovi poređeni sa istim
referentnim lekom. Na taj način identifikuju se generički lekovi za koje se prilikom zamene u
praksi ne očekuju problemi u pogledu efikasnosti i bezbednosti (1,2). Navedena metoda
korišćena je za poređenje četiri generička leka koji sadrže klopidogrel. Analizirani su javno
dostupni podaci iz studija BE u kojima je svaki generički lek poređen sa referentnim lekom
Plavix film tablete 75 mg. Dva generička leka smatraju se BE ukoliko je 90% interval
pouzdanosti (CI) za odnos njihovih farmakokinetičkih parametara maksimalna koncenracija
u plazmi (C max) i površina ispod krive do poslednje merljive koncentracije (PIK 0-t ), unutar
raspona 80,00-125,00%. U svim ispitanim kombinacijama 90% CI za PIK0-t bili su unutar
dozvoljenog raspona, dok su 90% CI za Cmax bili unutar ili veoma blizu granica ovog raspona,
pri čemu je point estimate u svim slučajevima bio unutar raspona. Rezultati dobijeni
metodom prilagođenog indirektnog poređenja pokazali su da je biološka raspoloživost ova
četiri generička leka koja sadrže klopidogrel veoma slična, te se oni mogu smatrati
međusobno zamenjivim u kliničkoj praksi.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Application of adjusted indirect comparisons to assess bioequivalence and switchability between generic drugs – example of clopidogrel, Primena metode prilagođenog indirektnog poređenja u proceni biološke ekvivalnetnosti i zamenjivosti generičkih lekova – primer klopidogrela",
volume = "72",
number = "4 suplement",
pages = "S262-S263",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4526"
}
Pejčić, Z., Vučićević, K., García Arieta, A.,& Miljković, B.. (2022). Application of adjusted indirect comparisons to assess bioequivalence and switchability between generic drugs – example of clopidogrel. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S262-S263.
https://hdl.handle.net/21.15107/rcub_farfar_4526
Pejčić Z, Vučićević K, García Arieta A, Miljković B. Application of adjusted indirect comparisons to assess bioequivalence and switchability between generic drugs – example of clopidogrel. in Arhiv za farmaciju. 2022;72(4 suplement):S262-S263.
https://hdl.handle.net/21.15107/rcub_farfar_4526 .
Pejčić, Zorica, Vučićević, Katarina, García Arieta, Alfredo, Miljković, Branislava, "Application of adjusted indirect comparisons to assess bioequivalence and switchability between generic drugs – example of clopidogrel" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S262-S263,
https://hdl.handle.net/21.15107/rcub_farfar_4526 .

Assessment of pembrolizumab exposure in different patient subpopulations using pharmacometric simulation

Homšek, Ana; Jovanović, Marija; Miljković, Branislava; Vučićević, Katarina

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Homšek, Ana
AU  - Jovanović, Marija
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4508
AB  - Monoclonal antibodies’ pharmacokinetics is, due to their specific properties, highly
variable among different patients. Beside body weight and albumin levels, pembrolizumab
pharmacokinetics may also be affected by patient's condition depicted as ECOG (Eastern
Cooperative Oncology Group) performance status and tumor burden. The study aim was to
compare pembrolizumab exposure in different patient subpopulations after administration
of fixed (200 mg) and weight-based dosing regimen (2 mg/kg) every three weeks. Two
virtual populations were generated in the R software: normal body weight patients with
preserved renal function, normal albumin levels (3.4-5.8 g/dL) and good prognosis (ECOG 0,
low burden); and underweight patients with decreased renal function, hypoalbuminemia
(<3.4 g/dL) and poor prognosis (ECOG 1, high burden). The simulation was performed using
an already developed two-compartment covariate model. Drug exposure is expected to be
higher in the underweight group after the fixed dose administration compared to normal
patients. As for weight-based administration, equivalent drug exposure was observed in both
groups, as reduced clearance in the underweight group leads to similar drug concentrations.
In the group of normal patients, no significant difference was observed between the two
proposed dosing methods. Based on the conducted simulation, it is expected that all patients,
regardless of the dosing method, will have exposures to pembrolizumab that provide
effective treatment. Since the use of a fixed dose is more cost-effective, and increased
pembrolizumab exposure in underweight patients with poor prognosis could lead to adverse
reactions, therapeutic-drug-monitoring-based dosing should be considered in such patients.
AB  - Farmakokinetika monoklonskih antitela je, zbog njihovih specifičnih svojstava, veoma
varijabilna među različitim pacijentima. Pored uticaja telesne mase i nivoa albumina,
pretpostavlja se da na farmakokinetiku pembrolizumaba može uticati i stanje pacijenta
okarakterisano ECOG (Eastern Cooperative Oncology Group) performans statusom i
opterećenjem tumorom. Cilj ovog istraživanja bio je da se uporedi izloženost
pembrolizumabu u različitim subpopulacijama pacijenata nakon primene fiksnog (200 mg) i
režima doziranja po kilogramu telesne mase (2 mg/kg) svake tri nedelje. Upotrebom
softvera R generisane su dve virtuelne populacije: pacijenti normalne telesne mase sa
očuvanom bubrežnom funkcijom, normalnim nivoom albumina (3,4-5,8 g/dL) i dobrom
prognozom (ECOG 0, nisko opterećenje); i pothranjeni pacijenti sa smanjenom bubrežnom
funkcijom, hipoalbuminemiom (< 3,4 g/dL) i lošom prognozom (ECOG 1, visoko
opterećenje). Simulacija je urađena pomoću već razvijenog dvoprostornog modela sa
kovarijatama. Izloženost leku očekivano je veća u grupi pothranjenih pacijenata prilikom
primene fiksne doze u odnosu na normalne pacijente. Kada je u pitanju primena po telesnoj
masi, ekvivalentna izloženost leku primećena je u obe grupe, pošto smanjen klirens u grupi
pothranjenih dovodi do postizanja sličnih koncentracija leka. U grupi normalnih pacijenata
nije primećena značajna razlika između dva predložena načina doziranja.Na osnovu
sprovedene simulacije očekuje se da kod svih pacijenata, bez obzira na način doziranja, bude
postignuta izloženost leku koja obezbeđuje efikasnu terapiju. Kako je primena fiksne doze
isplativija, a povećana izloženost pembrolizumabu kod pothranjenih pacijenata sa lošom
prognozom može dovesti do pojave neželjenih reakcija, potrebno je kod ovakvih pacijenata
razmotriti doziranje bazirano na terapijskom monitoringu.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Assessment of pembrolizumab exposure in different patient subpopulations using pharmacometric simulation
T1  - Procena izloženosti pembrolizumabu u različitim subpopulacijama pacijenata upotrebom farmakometrijske simulacije
VL  - 72
IS  - 4 suplement
SP  - S227
EP  - S228
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4508
ER  - 
@conference{
author = "Homšek, Ana and Jovanović, Marija and Miljković, Branislava and Vučićević, Katarina",
year = "2022",
abstract = "Monoclonal antibodies’ pharmacokinetics is, due to their specific properties, highly
variable among different patients. Beside body weight and albumin levels, pembrolizumab
pharmacokinetics may also be affected by patient's condition depicted as ECOG (Eastern
Cooperative Oncology Group) performance status and tumor burden. The study aim was to
compare pembrolizumab exposure in different patient subpopulations after administration
of fixed (200 mg) and weight-based dosing regimen (2 mg/kg) every three weeks. Two
virtual populations were generated in the R software: normal body weight patients with
preserved renal function, normal albumin levels (3.4-5.8 g/dL) and good prognosis (ECOG 0,
low burden); and underweight patients with decreased renal function, hypoalbuminemia
(<3.4 g/dL) and poor prognosis (ECOG 1, high burden). The simulation was performed using
an already developed two-compartment covariate model. Drug exposure is expected to be
higher in the underweight group after the fixed dose administration compared to normal
patients. As for weight-based administration, equivalent drug exposure was observed in both
groups, as reduced clearance in the underweight group leads to similar drug concentrations.
In the group of normal patients, no significant difference was observed between the two
proposed dosing methods. Based on the conducted simulation, it is expected that all patients,
regardless of the dosing method, will have exposures to pembrolizumab that provide
effective treatment. Since the use of a fixed dose is more cost-effective, and increased
pembrolizumab exposure in underweight patients with poor prognosis could lead to adverse
reactions, therapeutic-drug-monitoring-based dosing should be considered in such patients., Farmakokinetika monoklonskih antitela je, zbog njihovih specifičnih svojstava, veoma
varijabilna među različitim pacijentima. Pored uticaja telesne mase i nivoa albumina,
pretpostavlja se da na farmakokinetiku pembrolizumaba može uticati i stanje pacijenta
okarakterisano ECOG (Eastern Cooperative Oncology Group) performans statusom i
opterećenjem tumorom. Cilj ovog istraživanja bio je da se uporedi izloženost
pembrolizumabu u različitim subpopulacijama pacijenata nakon primene fiksnog (200 mg) i
režima doziranja po kilogramu telesne mase (2 mg/kg) svake tri nedelje. Upotrebom
softvera R generisane su dve virtuelne populacije: pacijenti normalne telesne mase sa
očuvanom bubrežnom funkcijom, normalnim nivoom albumina (3,4-5,8 g/dL) i dobrom
prognozom (ECOG 0, nisko opterećenje); i pothranjeni pacijenti sa smanjenom bubrežnom
funkcijom, hipoalbuminemiom (< 3,4 g/dL) i lošom prognozom (ECOG 1, visoko
opterećenje). Simulacija je urađena pomoću već razvijenog dvoprostornog modela sa
kovarijatama. Izloženost leku očekivano je veća u grupi pothranjenih pacijenata prilikom
primene fiksne doze u odnosu na normalne pacijente. Kada je u pitanju primena po telesnoj
masi, ekvivalentna izloženost leku primećena je u obe grupe, pošto smanjen klirens u grupi
pothranjenih dovodi do postizanja sličnih koncentracija leka. U grupi normalnih pacijenata
nije primećena značajna razlika između dva predložena načina doziranja.Na osnovu
sprovedene simulacije očekuje se da kod svih pacijenata, bez obzira na način doziranja, bude
postignuta izloženost leku koja obezbeđuje efikasnu terapiju. Kako je primena fiksne doze
isplativija, a povećana izloženost pembrolizumabu kod pothranjenih pacijenata sa lošom
prognozom može dovesti do pojave neželjenih reakcija, potrebno je kod ovakvih pacijenata
razmotriti doziranje bazirano na terapijskom monitoringu.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Assessment of pembrolizumab exposure in different patient subpopulations using pharmacometric simulation, Procena izloženosti pembrolizumabu u različitim subpopulacijama pacijenata upotrebom farmakometrijske simulacije",
volume = "72",
number = "4 suplement",
pages = "S227-S228",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4508"
}
Homšek, A., Jovanović, M., Miljković, B.,& Vučićević, K.. (2022). Assessment of pembrolizumab exposure in different patient subpopulations using pharmacometric simulation. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S227-S228.
https://hdl.handle.net/21.15107/rcub_farfar_4508
Homšek A, Jovanović M, Miljković B, Vučićević K. Assessment of pembrolizumab exposure in different patient subpopulations using pharmacometric simulation. in Arhiv za farmaciju. 2022;72(4 suplement):S227-S228.
https://hdl.handle.net/21.15107/rcub_farfar_4508 .
Homšek, Ana, Jovanović, Marija, Miljković, Branislava, Vučićević, Katarina, "Assessment of pembrolizumab exposure in different patient subpopulations using pharmacometric simulation" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S227-S228,
https://hdl.handle.net/21.15107/rcub_farfar_4508 .

Analysis of clozapine and norclozapine concentrations in adult patients with schizophrenia

Panić, Bojana; Jovanović, Marija; Lukić, Vera; Bulat, Zorica; Vučićević, Katarina; Miljković, Branislava; Milovanović, Srđan

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Panić, Bojana
AU  - Jovanović, Marija
AU  - Lukić, Vera
AU  - Bulat, Zorica
AU  - Vučićević, Katarina
AU  - Miljković, Branislava
AU  - Milovanović, Srđan
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4507
AB  - The atypical antipsychotic clozapine (CLZ) is primarily used for the treatment-
resistant schizophrenia. Due to low therapeutic index and high pharmacokinetic variability,
therapeutic drug monitoring (TDM) is highly recommended (1). The aim of this retrospective
study was to analyze TDM data of CLZ and its active metabolite norclozapine (NCLZ) in adult
patient with schizophrenia. The study included CLZ TDM data obtained from 69 patients (22-
67 years) treated at the Clinic for Psychiatry, Clinical Center of Serbia, while NCLZ data were
available from 43 patients. Serum concentrations were determined at the Institute of
Forensic Medicine, Belgrade, Serbia using liquid chromatography with tandem mass
spectrometry (LC‐MS/MS). Statistical analysis was performed by SPSS software® (version
18). The daily doses of CLZ ranged between 37.5 and 600 mg. The mean value of CLZ and
NCLZ levels were 0.285 ± 0.174 mg/L and 0.189 ± 0.132 mg/L, respectively. 73.06% and
26.83% of measured CLZ and NCLZ concentrations were outside reference range (mostly
below), respectively. Significant positive correlation (p<0.05) was observed between daily
dose and CLZ levels, as well as between dose and NCLZ levels. Significant correlations of dose
and CLZ levels were confirmed in males and females, smokers and nonsmokers, separately.
Parent drug and metabolite levels varied 13 and 16-fold in patients receiving 300 mg/day,
respectively. The results indicate considerable variability in CLZ and NCLZ concentrations in
adult patients with schizophrenia, and positive association with dose. Further multivariate
analysis is required to assess, in addition to dose, potential influences of other patient and
co-therapy factors.
AB  - Atipični antipsihotik klozapin (clozapine, CLZ) se primarno koristi kod shizofrenije
rezistentne na terapiju. Zbog niskog terapijskog indeksa i velike farmakokinetičke
varijabilnosti, terapijsko prać enje lekova (therapeutic drug monitoring, TDM) se preporučuje
(1). Cilj ovog retrospektivnog istraživanja je bio ispitivanje TDM podataka o CLZ i njegovom
aktivnom metabolitu norklozapinu (norclozapine, NCLZ) kod odraslih pacijenata sa
shizofrenijom. Studija je obuhvatila TDM podatke o CLZ dobijene od 69 pacijenata (22-67
godina) lečenih na Klinici za psihijatriju Kliničkog centra Srbije, dok su podaci za NCLZ bili
dostupni od 43 pacijenta. Koncentracije u serumu su merene na Institutu za sudsku
medicinu, Beograd, Srbija tečnom hromatografijom sa tandem masenom spektrometrijom
(LC‐MS/MS). Statistička analiza je izvršena pomoć u softvera SPSS® (verzija 18). Dnevne doze
CLZ kretale su se između 37,5 i 600 mg. Srednja vrednost je bila 0,285 ± 0,174 mg/L za CLZ i
0,189 ± 0,132 mg/L za NCLZ. 73,06% i 26,83% izmerenih koncentracija CLZ i NCLZ bile su
izvan referentnog opsega (uglavnom ispod), respektivno. Detektovana je pozitivna korelacija
(p<0,05) između dnevne doze i nivoa CLZ, kao i doze i nivoa NCLZ. Značajna korelacija doze i
nivoa CLZ je potvrđena i pri odvojenom ispitivanju kod muškaraca, žena, pušača i nepušača.
Nivoi leka i metabolita varirali su 13 i 16 puta kod pacijenata koji su uzimali 300 mg/dan,
respektivno. Rezultati ukazuju na značajnu varijabilnost u koncentracijama CLZ i NCLZ kod
odraslih pacijenata sa shizofrenijom i pozitivnu povezanost sa dozom. Potrebna je dalja
multivarijantna analiza da bi se procenili, pored doze, potencijalni uticaji karakteristika
pacijenata i kombinovane terapije.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Analysis of clozapine and norclozapine concentrations in adult patients with schizophrenia
T1  - Analiza koncentracija klozapina i norklozapina kod odraslih pacijenata sa shizofrenijom
VL  - 72
IS  - 4 suplement
SP  - S225
EP  - S226
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4507
ER  - 
@conference{
author = "Panić, Bojana and Jovanović, Marija and Lukić, Vera and Bulat, Zorica and Vučićević, Katarina and Miljković, Branislava and Milovanović, Srđan",
year = "2022",
abstract = "The atypical antipsychotic clozapine (CLZ) is primarily used for the treatment-
resistant schizophrenia. Due to low therapeutic index and high pharmacokinetic variability,
therapeutic drug monitoring (TDM) is highly recommended (1). The aim of this retrospective
study was to analyze TDM data of CLZ and its active metabolite norclozapine (NCLZ) in adult
patient with schizophrenia. The study included CLZ TDM data obtained from 69 patients (22-
67 years) treated at the Clinic for Psychiatry, Clinical Center of Serbia, while NCLZ data were
available from 43 patients. Serum concentrations were determined at the Institute of
Forensic Medicine, Belgrade, Serbia using liquid chromatography with tandem mass
spectrometry (LC‐MS/MS). Statistical analysis was performed by SPSS software® (version
18). The daily doses of CLZ ranged between 37.5 and 600 mg. The mean value of CLZ and
NCLZ levels were 0.285 ± 0.174 mg/L and 0.189 ± 0.132 mg/L, respectively. 73.06% and
26.83% of measured CLZ and NCLZ concentrations were outside reference range (mostly
below), respectively. Significant positive correlation (p<0.05) was observed between daily
dose and CLZ levels, as well as between dose and NCLZ levels. Significant correlations of dose
and CLZ levels were confirmed in males and females, smokers and nonsmokers, separately.
Parent drug and metabolite levels varied 13 and 16-fold in patients receiving 300 mg/day,
respectively. The results indicate considerable variability in CLZ and NCLZ concentrations in
adult patients with schizophrenia, and positive association with dose. Further multivariate
analysis is required to assess, in addition to dose, potential influences of other patient and
co-therapy factors., Atipični antipsihotik klozapin (clozapine, CLZ) se primarno koristi kod shizofrenije
rezistentne na terapiju. Zbog niskog terapijskog indeksa i velike farmakokinetičke
varijabilnosti, terapijsko prać enje lekova (therapeutic drug monitoring, TDM) se preporučuje
(1). Cilj ovog retrospektivnog istraživanja je bio ispitivanje TDM podataka o CLZ i njegovom
aktivnom metabolitu norklozapinu (norclozapine, NCLZ) kod odraslih pacijenata sa
shizofrenijom. Studija je obuhvatila TDM podatke o CLZ dobijene od 69 pacijenata (22-67
godina) lečenih na Klinici za psihijatriju Kliničkog centra Srbije, dok su podaci za NCLZ bili
dostupni od 43 pacijenta. Koncentracije u serumu su merene na Institutu za sudsku
medicinu, Beograd, Srbija tečnom hromatografijom sa tandem masenom spektrometrijom
(LC‐MS/MS). Statistička analiza je izvršena pomoć u softvera SPSS® (verzija 18). Dnevne doze
CLZ kretale su se između 37,5 i 600 mg. Srednja vrednost je bila 0,285 ± 0,174 mg/L za CLZ i
0,189 ± 0,132 mg/L za NCLZ. 73,06% i 26,83% izmerenih koncentracija CLZ i NCLZ bile su
izvan referentnog opsega (uglavnom ispod), respektivno. Detektovana je pozitivna korelacija
(p<0,05) između dnevne doze i nivoa CLZ, kao i doze i nivoa NCLZ. Značajna korelacija doze i
nivoa CLZ je potvrđena i pri odvojenom ispitivanju kod muškaraca, žena, pušača i nepušača.
Nivoi leka i metabolita varirali su 13 i 16 puta kod pacijenata koji su uzimali 300 mg/dan,
respektivno. Rezultati ukazuju na značajnu varijabilnost u koncentracijama CLZ i NCLZ kod
odraslih pacijenata sa shizofrenijom i pozitivnu povezanost sa dozom. Potrebna je dalja
multivarijantna analiza da bi se procenili, pored doze, potencijalni uticaji karakteristika
pacijenata i kombinovane terapije.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Analysis of clozapine and norclozapine concentrations in adult patients with schizophrenia, Analiza koncentracija klozapina i norklozapina kod odraslih pacijenata sa shizofrenijom",
volume = "72",
number = "4 suplement",
pages = "S225-S226",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4507"
}
Panić, B., Jovanović, M., Lukić, V., Bulat, Z., Vučićević, K., Miljković, B.,& Milovanović, S.. (2022). Analysis of clozapine and norclozapine concentrations in adult patients with schizophrenia. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S225-S226.
https://hdl.handle.net/21.15107/rcub_farfar_4507
Panić B, Jovanović M, Lukić V, Bulat Z, Vučićević K, Miljković B, Milovanović S. Analysis of clozapine and norclozapine concentrations in adult patients with schizophrenia. in Arhiv za farmaciju. 2022;72(4 suplement):S225-S226.
https://hdl.handle.net/21.15107/rcub_farfar_4507 .
Panić, Bojana, Jovanović, Marija, Lukić, Vera, Bulat, Zorica, Vučićević, Katarina, Miljković, Branislava, Milovanović, Srđan, "Analysis of clozapine and norclozapine concentrations in adult patients with schizophrenia" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S225-S226,
https://hdl.handle.net/21.15107/rcub_farfar_4507 .

Clinically significant drug-drug interactions in the treatment of cardiovascular diseases on hospital admission

Drndarević, Aneta; Draganov, Ivana; Miljković, Branislava; Davidović, Aleksandar; Cvijanović, Dane; Savković, Tatjana; Vezmar-Kovačević, Sandra

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Drndarević, Aneta
AU  - Draganov, Ivana
AU  - Miljković, Branislava
AU  - Davidović, Aleksandar
AU  - Cvijanović, Dane
AU  - Savković, Tatjana
AU  - Vezmar-Kovačević, Sandra
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4506
AB  - Clinically significant drug-drug interactions (DDIs) are expected in patients with
cardiovascular diseases due to the number of drugs in therapy. The aim of the research was
to analyze DDIs during treatment which preceeded the admission to the cardiology
department. In the cardiology department of the Clinical Hospital Center Zvezdara, the
treatment of patients with ≥2 drugs before admission was analyzed. DDIs were identified
using the Lexicomp database (Lexi-Interact). Data were analyzed descriptively and with
linear regression analysis. During research, out of 132 participants 88.6% had ≥1, while
41.7% had ≥5 DDIs. The total number of DDIs was 648 (median 3, range 0-19). Men
constituted 64.4% of the population, with a median age of 70 years (32-90). Patients had 4
diagnoses (1-13) and 6 medications on admission (2-15). In 3.8% of patients,
contraindicated DDIs of anticholinergics were observed, 23.5% had DDIs that required
caution or a change in therapy, while interactions requiring follow-up were observed in
86.4% of patients. Angiotensin-converting enzyme inhibitors (30.4%), acetylsalicylic acid
(26.6%) and loop diuretics (16.5%) were most frequently involved in DDIs, while the most
common adverse events could be renal failure (21.5%), hypotension 19.7%) and bleeding
(13.7%). The number of drugs in therapy was a predictor of DDIs (p <0.001). Patients with
cardiovascular disease are often exposed to polypharmacy and consequently DDIs.
Cardiovascular drugs were most frequently involved in DDIs, but contraindicated DDIs were
present in anticholinergic drugs. In patients with cardiovascular diseases, monitoring of
renal function, hypotension and bleeding is required.
AB  - Klinički značajne interakcije (KZI) očekuju se kod pacijenata sa kardiovaskularnim
bolestima usled većeg broja lekova u terapiji. Cilj istraživanja je bio da se identifikuju i
analiziraju KZI pacijenata koje su prethodile prijemu na odeljenje kardiologije. U Kliničko-
bolničkom centru Zvezdara, na odeljenju kardiologije, analizirana je terapija pacijenata sa ≥2
leka pre prijema. KZI su identifikovane upotrebom baze Lexicomp (Lexi-Interact). Podaci su
analizirani deskriptivno i primenom linearne regresione analize. Od 132 učesnika u
istraživanju 88,6% je imalo ≥1, dok je 41,7% imalo ≥5 KZI. Ukupan broj KZI bio je 648
(medijana 3, opseg 0-19). U populaciji je bilo 64,4% muškaraca medijane starosti 70 godina
(32-90). Pacijenti su imali 4 dijagnoze (1-13) i 6 lekova na prijemu (2-15). Kod 3,8%
pacijenata utvrđene su KZI antiholinergika koje se smatraju kontraindikovanim. Približno
jedna četvrtina pacijenata (23,5%) je imala KZI koja zahteva oprez ili izmenu u terapiji dok
su kod 86,4% pacijenata uočene interakcije koje zahtevaju praćenje ishoda. Najčešće su u KZI
stupali inhibitori angiotenzin-konvertujućeg enzima (30,4%), acetilsalicilna kiselina (26,6%)
i diuretici petlje (16,5%) dok su najčešći neželjeni ishodi mogli biti bubrežna insuficijencija
(21,5%), hipotenzija (19,7%) i krvarenje (13,7%). Broj lekova u terapiji bio je prediktor za
KZI (p<0,001). Pacijenti sa kardiovaskularnim bolestima su često izloženi polifarmaciji i
posledično većem broju KZI. U KZI su najčešće stupali lekovi u terapiji kardiovaskularnih
bolesti ali su kontraindikovane KZI bile zastupljene kod antiholinergičkih lekova. Kod
pacijenata sa kardiovaskularnim bolestima potrebno je praćenje renalne funkcije,
hipotenzije i krvarenja.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Clinically significant drug-drug interactions in the treatment of cardiovascular diseases on hospital admission
T1  - Pregled klinički značajnih interakcija u terapiji kardiovaskularnih bolesti kod pacijenata na prijemu u bolnicu
VL  - 72
IS  - 4 suplement
SP  - S223
EP  - S224
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4506
ER  - 
@conference{
author = "Drndarević, Aneta and Draganov, Ivana and Miljković, Branislava and Davidović, Aleksandar and Cvijanović, Dane and Savković, Tatjana and Vezmar-Kovačević, Sandra",
year = "2022",
abstract = "Clinically significant drug-drug interactions (DDIs) are expected in patients with
cardiovascular diseases due to the number of drugs in therapy. The aim of the research was
to analyze DDIs during treatment which preceeded the admission to the cardiology
department. In the cardiology department of the Clinical Hospital Center Zvezdara, the
treatment of patients with ≥2 drugs before admission was analyzed. DDIs were identified
using the Lexicomp database (Lexi-Interact). Data were analyzed descriptively and with
linear regression analysis. During research, out of 132 participants 88.6% had ≥1, while
41.7% had ≥5 DDIs. The total number of DDIs was 648 (median 3, range 0-19). Men
constituted 64.4% of the population, with a median age of 70 years (32-90). Patients had 4
diagnoses (1-13) and 6 medications on admission (2-15). In 3.8% of patients,
contraindicated DDIs of anticholinergics were observed, 23.5% had DDIs that required
caution or a change in therapy, while interactions requiring follow-up were observed in
86.4% of patients. Angiotensin-converting enzyme inhibitors (30.4%), acetylsalicylic acid
(26.6%) and loop diuretics (16.5%) were most frequently involved in DDIs, while the most
common adverse events could be renal failure (21.5%), hypotension 19.7%) and bleeding
(13.7%). The number of drugs in therapy was a predictor of DDIs (p <0.001). Patients with
cardiovascular disease are often exposed to polypharmacy and consequently DDIs.
Cardiovascular drugs were most frequently involved in DDIs, but contraindicated DDIs were
present in anticholinergic drugs. In patients with cardiovascular diseases, monitoring of
renal function, hypotension and bleeding is required., Klinički značajne interakcije (KZI) očekuju se kod pacijenata sa kardiovaskularnim
bolestima usled većeg broja lekova u terapiji. Cilj istraživanja je bio da se identifikuju i
analiziraju KZI pacijenata koje su prethodile prijemu na odeljenje kardiologije. U Kliničko-
bolničkom centru Zvezdara, na odeljenju kardiologije, analizirana je terapija pacijenata sa ≥2
leka pre prijema. KZI su identifikovane upotrebom baze Lexicomp (Lexi-Interact). Podaci su
analizirani deskriptivno i primenom linearne regresione analize. Od 132 učesnika u
istraživanju 88,6% je imalo ≥1, dok je 41,7% imalo ≥5 KZI. Ukupan broj KZI bio je 648
(medijana 3, opseg 0-19). U populaciji je bilo 64,4% muškaraca medijane starosti 70 godina
(32-90). Pacijenti su imali 4 dijagnoze (1-13) i 6 lekova na prijemu (2-15). Kod 3,8%
pacijenata utvrđene su KZI antiholinergika koje se smatraju kontraindikovanim. Približno
jedna četvrtina pacijenata (23,5%) je imala KZI koja zahteva oprez ili izmenu u terapiji dok
su kod 86,4% pacijenata uočene interakcije koje zahtevaju praćenje ishoda. Najčešće su u KZI
stupali inhibitori angiotenzin-konvertujućeg enzima (30,4%), acetilsalicilna kiselina (26,6%)
i diuretici petlje (16,5%) dok su najčešći neželjeni ishodi mogli biti bubrežna insuficijencija
(21,5%), hipotenzija (19,7%) i krvarenje (13,7%). Broj lekova u terapiji bio je prediktor za
KZI (p<0,001). Pacijenti sa kardiovaskularnim bolestima su često izloženi polifarmaciji i
posledično većem broju KZI. U KZI su najčešće stupali lekovi u terapiji kardiovaskularnih
bolesti ali su kontraindikovane KZI bile zastupljene kod antiholinergičkih lekova. Kod
pacijenata sa kardiovaskularnim bolestima potrebno je praćenje renalne funkcije,
hipotenzije i krvarenja.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Clinically significant drug-drug interactions in the treatment of cardiovascular diseases on hospital admission, Pregled klinički značajnih interakcija u terapiji kardiovaskularnih bolesti kod pacijenata na prijemu u bolnicu",
volume = "72",
number = "4 suplement",
pages = "S223-S224",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4506"
}
Drndarević, A., Draganov, I., Miljković, B., Davidović, A., Cvijanović, D., Savković, T.,& Vezmar-Kovačević, S.. (2022). Clinically significant drug-drug interactions in the treatment of cardiovascular diseases on hospital admission. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S223-S224.
https://hdl.handle.net/21.15107/rcub_farfar_4506
Drndarević A, Draganov I, Miljković B, Davidović A, Cvijanović D, Savković T, Vezmar-Kovačević S. Clinically significant drug-drug interactions in the treatment of cardiovascular diseases on hospital admission. in Arhiv za farmaciju. 2022;72(4 suplement):S223-S224.
https://hdl.handle.net/21.15107/rcub_farfar_4506 .
Drndarević, Aneta, Draganov, Ivana, Miljković, Branislava, Davidović, Aleksandar, Cvijanović, Dane, Savković, Tatjana, Vezmar-Kovačević, Sandra, "Clinically significant drug-drug interactions in the treatment of cardiovascular diseases on hospital admission" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S223-S224,
https://hdl.handle.net/21.15107/rcub_farfar_4506 .

Drug-related problems of patients with cardiovascular diseases on hospital admission

Draganov, Ivana; Drndarević, Aneta; Miljković, Branislava; Davidović, Aleksandar; Cvijanović, Dane; Savković, Tatjana; Vezmar-Kovačević, Sandra

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Draganov, Ivana
AU  - Drndarević, Aneta
AU  - Miljković, Branislava
AU  - Davidović, Aleksandar
AU  - Cvijanović, Dane
AU  - Savković, Tatjana
AU  - Vezmar-Kovačević, Sandra
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4501
AB  - In patients with cardiovascular diseases drug-related problems (DRPs) can be
associated with hospitalization or rehospitalization. The aim of the research was to analyse
DRPs in the cardiology department on admission to the hospital. All patient records on
admission to the cardiology department of the Clinical Hospital Center Zvezdara during
2018., were analyzed. Demographic and treatment data of the patient before admission to
the hospital were collected. DRPs associated with pre-hospital treatment were identified and
classified according to the PCNE (Pharmaceutical Care Network Europe, version 9.1)
classification. DRPs were also evaluated as cause of the patient's hospitalization. Data were
analyzed descriptively and with linear regression analysis. During the research period, 143
patients were admitted to the cardiology department, with an average age of 69.75 ± 10.11
years, of which 65.7% were male. Patients had an average of 4.36±2.13 diagnoses and
5.24±3.39 medications on admission. We observed 1.85±1.37 DRPs per patient (range 0-5).
The most common DRP (75.6%) was lack of ≥1 drugs in the therapy preceding the
admission, most often statins (30.1% of patients), beta-blockers (25.9%), angiotensin-
converting enzyme inhibitors (17.5%) and antiarrhythmics/anticoagulants (12.6%). In 96
patients (67.1%) the identified DRPs could be associated with the cause of hospitalization.
Atrial fibrillation was the predictor of the number of DRPs in patients (p <0.001). In most
cardiovascular patients, the cause of hospitalization could be associated with DRPs before
admission. Incomplete therapy of the patient was commonly observed, the cause of which
may be inadequate prescribing or lack of adherence of the patient.
AB  - Pacijenti sa kardiovaskularnim bolestima susreću se sa brojnim problemima u terapiji
od kojih pojedini mogu biti uzrok hospitalizacije ili rehospitalizacije. Cilj istraživanja je bio da
se prikaže analiza terapijskih problema pacijenata na odeljenju kardiologije, prilikom
prijema u bolnicu. Analizirani su kartoni svih pacijenata primljenih na odeljenje kardiologije,
Kliničko-bolničkog centra Zvezdara tokom 2018. godine. Prikupljeni su demografski i podaci
o celokupnoj terapiji pacijenta pre prijema u bolnicu. Identifikovani su problemi u vezi sa
terapijom pre prijema u bolnicu i klasifikovani su prema PCNE (Pharmaceutical Care
Network Europe, verzija 9.1) klasifikaciji. Takođe, procenjeno je da li problemi u vezi sa
terapijom mogu biti uzrok hospitalizacije pacijenta. Podaci su analizirani deskriptivno i
primenom linearne regresione analize. U periodu istraživanja 143 pacijenta je primljeno na
odeljenje kardiologije, prosečne starosti 69,75±10,11 godina, od kojih je 65,7% bilo muškog
pola. Pacijenti su u proseku imali 4,36±2,13 dijagnoze i 5,24±3,39 lekova na prijemu.
Utvrđeno je prisustvo 1,85±1,37 terapijskih problema po pacijentu (opseg 0-5). Najčešći
terapijski problem (75,6%) bio je nedostatak ≥1 leka u terapiji i to najčešće statina (30,1%
pacijenata), beta-blokatora (25,9%), inhibitora angiotenzin-konvertujućeg enzima (17,5%) i
antiaritmika/anitkoagulanasa (12,6%). Kod 96 pacijenata (67,1%) su identifikovani
terapijski problemi dovedeni u vezu sa uzrokom hospitalizacije. Prediktivni faktor za broj
terapijskih problema kod pacijenata je bilo prisustvo atrijalne fibrilacije u anamnezi
(p<0,001). Uzrok hospitalizacije pacijenata sa kardiovaskularnim bolestima se često može
povezati sa problemima u terapiji pre prijema. Najčešće se uočava nepotpuna terapija
pacijenta čiji uzrok može biti neodgovarajuće propisivanje ili nedostatak adherence
pacijenta.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Drug-related problems of patients with cardiovascular diseases on hospital admission
T1  - Terapijski problemi pacijenata sa kardiovaskularnim bolestima na prijemu u bolnicu
VL  - 72
IS  - 4 suplement
SP  - S221
EP  - S222
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4501
ER  - 
@conference{
author = "Draganov, Ivana and Drndarević, Aneta and Miljković, Branislava and Davidović, Aleksandar and Cvijanović, Dane and Savković, Tatjana and Vezmar-Kovačević, Sandra",
year = "2022",
abstract = "In patients with cardiovascular diseases drug-related problems (DRPs) can be
associated with hospitalization or rehospitalization. The aim of the research was to analyse
DRPs in the cardiology department on admission to the hospital. All patient records on
admission to the cardiology department of the Clinical Hospital Center Zvezdara during
2018., were analyzed. Demographic and treatment data of the patient before admission to
the hospital were collected. DRPs associated with pre-hospital treatment were identified and
classified according to the PCNE (Pharmaceutical Care Network Europe, version 9.1)
classification. DRPs were also evaluated as cause of the patient's hospitalization. Data were
analyzed descriptively and with linear regression analysis. During the research period, 143
patients were admitted to the cardiology department, with an average age of 69.75 ± 10.11
years, of which 65.7% were male. Patients had an average of 4.36±2.13 diagnoses and
5.24±3.39 medications on admission. We observed 1.85±1.37 DRPs per patient (range 0-5).
The most common DRP (75.6%) was lack of ≥1 drugs in the therapy preceding the
admission, most often statins (30.1% of patients), beta-blockers (25.9%), angiotensin-
converting enzyme inhibitors (17.5%) and antiarrhythmics/anticoagulants (12.6%). In 96
patients (67.1%) the identified DRPs could be associated with the cause of hospitalization.
Atrial fibrillation was the predictor of the number of DRPs in patients (p <0.001). In most
cardiovascular patients, the cause of hospitalization could be associated with DRPs before
admission. Incomplete therapy of the patient was commonly observed, the cause of which
may be inadequate prescribing or lack of adherence of the patient., Pacijenti sa kardiovaskularnim bolestima susreću se sa brojnim problemima u terapiji
od kojih pojedini mogu biti uzrok hospitalizacije ili rehospitalizacije. Cilj istraživanja je bio da
se prikaže analiza terapijskih problema pacijenata na odeljenju kardiologije, prilikom
prijema u bolnicu. Analizirani su kartoni svih pacijenata primljenih na odeljenje kardiologije,
Kliničko-bolničkog centra Zvezdara tokom 2018. godine. Prikupljeni su demografski i podaci
o celokupnoj terapiji pacijenta pre prijema u bolnicu. Identifikovani su problemi u vezi sa
terapijom pre prijema u bolnicu i klasifikovani su prema PCNE (Pharmaceutical Care
Network Europe, verzija 9.1) klasifikaciji. Takođe, procenjeno je da li problemi u vezi sa
terapijom mogu biti uzrok hospitalizacije pacijenta. Podaci su analizirani deskriptivno i
primenom linearne regresione analize. U periodu istraživanja 143 pacijenta je primljeno na
odeljenje kardiologije, prosečne starosti 69,75±10,11 godina, od kojih je 65,7% bilo muškog
pola. Pacijenti su u proseku imali 4,36±2,13 dijagnoze i 5,24±3,39 lekova na prijemu.
Utvrđeno je prisustvo 1,85±1,37 terapijskih problema po pacijentu (opseg 0-5). Najčešći
terapijski problem (75,6%) bio je nedostatak ≥1 leka u terapiji i to najčešće statina (30,1%
pacijenata), beta-blokatora (25,9%), inhibitora angiotenzin-konvertujućeg enzima (17,5%) i
antiaritmika/anitkoagulanasa (12,6%). Kod 96 pacijenata (67,1%) su identifikovani
terapijski problemi dovedeni u vezu sa uzrokom hospitalizacije. Prediktivni faktor za broj
terapijskih problema kod pacijenata je bilo prisustvo atrijalne fibrilacije u anamnezi
(p<0,001). Uzrok hospitalizacije pacijenata sa kardiovaskularnim bolestima se često može
povezati sa problemima u terapiji pre prijema. Najčešće se uočava nepotpuna terapija
pacijenta čiji uzrok može biti neodgovarajuće propisivanje ili nedostatak adherence
pacijenta.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Drug-related problems of patients with cardiovascular diseases on hospital admission, Terapijski problemi pacijenata sa kardiovaskularnim bolestima na prijemu u bolnicu",
volume = "72",
number = "4 suplement",
pages = "S221-S222",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4501"
}
Draganov, I., Drndarević, A., Miljković, B., Davidović, A., Cvijanović, D., Savković, T.,& Vezmar-Kovačević, S.. (2022). Drug-related problems of patients with cardiovascular diseases on hospital admission. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S221-S222.
https://hdl.handle.net/21.15107/rcub_farfar_4501
Draganov I, Drndarević A, Miljković B, Davidović A, Cvijanović D, Savković T, Vezmar-Kovačević S. Drug-related problems of patients with cardiovascular diseases on hospital admission. in Arhiv za farmaciju. 2022;72(4 suplement):S221-S222.
https://hdl.handle.net/21.15107/rcub_farfar_4501 .
Draganov, Ivana, Drndarević, Aneta, Miljković, Branislava, Davidović, Aleksandar, Cvijanović, Dane, Savković, Tatjana, Vezmar-Kovačević, Sandra, "Drug-related problems of patients with cardiovascular diseases on hospital admission" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S221-S222,
https://hdl.handle.net/21.15107/rcub_farfar_4501 .

Populacioni farmakokinetički model takrolimusa kod pacijenata sa transplantiranom jetrom

Jovanović, Marija; Ćulafić, Milica; Pejić, Nina; Štulić, Miloš; Kovačević, Milena; Vezmar-Kovačević, Sandra; Miljković, Branislava; Vučićević, Katarina; Ćulafić, Đorđe

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Jovanović, Marija
AU  - Ćulafić, Milica
AU  - Pejić, Nina
AU  - Štulić, Miloš
AU  - Kovačević, Milena
AU  - Vezmar-Kovačević, Sandra
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
AU  - Ćulafić, Đorđe
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4395
AB  - Takrolimus je imunosupresiv koji se primenjuje za prevenciju odbacivanja grafta
nakon transplantacije jetre. Uzak terapijski opseg i velika varijabilnost u farmakokinetici
ukazuju na neophodnost individualizacije terapije. Cilj istraživanja bio je razvoj i validacija
osnovnog farmakokinetičkog modela takrolimusa baziranog na podacima prikupljenim
tokom terapijskog praćenja leka. Studija je uključila 29 pacijenata sa transplantiranom
jetrom, praćenih na Klinici za gastroenterologiju i hepatologiju, Kliničkog centra Srbije.
Primenom NONMEM® programa analizirane su koncentracije takrolimusa izmerene u punoj
krvi (260), neposredno pre primene jutarnje doze (Ctrough). Farmakokinetika je opisana
jednoprostornim modelom sa resorpcijom i eliminacijom prvog reda. Interna validacija je
vršena primenom grafičke metode procene, metode umnožavanja podataka (bootstrap) i
vizuelne prediktivne provere (VPC). Procenjena tipična vrednost oralnog klirensa (CL/F)
iznosila je 30,4 L/h, dok je vrednost oralnog volumena distribucije bila 5770 L. Vrednost
konstante brzine resorpcije je fiksirana na 4,48 h-1 . Interindividualna varijabilnost je najbolje
opisana eksponencijalnim modelom, a rezidualna aditivnim modelom. Zabeležena je
interindividualna varijabilnost za CL/F od 38,2%. Predviđene individualne koncentracije
(IPRED) pokazuju bolje slaganje sa izmerenim vrednostima, nego populacione predviđene
vrednosti (PRED). Uslovni težinski reziduali (CWRES vs PRED, CWRES vs TIME) su većinom
raspoređeni između -2 i +2 standardne devijacije. Parametri dobijeni bootstrap analizom ne
odstupaju značajno od modela, dok su vrednosti medijane, 5. i 95. percentila u VPC metodi
uglavnom bile u okviru simuliranih 95% intervala pouzdanosti. Dobijeni populacioni
farmakokinetički model, može se nakon dodatne optimizacije, primeniti u svrhu
individualizacije režima doziranja takrolimusa u populaciji pacijenata sa transplantiranom
jetrom.
AB  - Tacrolimus is an immunosuppressant used to prevent graft rejection after liver transplantation. The narrow therapeutic range and great variability in pharmacokinetics indicate the need for therapy individualization. The aim of the study was to develop and validate the base pharmacokinetic model of tacrolimus using data collected during therapeutic drug monitoring. The study included 29 liver transplant recipients followed up at Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia. Using the NONMEM® program, we analyzed tacrolimus concentrations (Ctrough) measured in whole blood (260). Pharmacokinetics have been described as one-compartment model with first- order absorption and elimination. Internal validation was performed using graphical assessment, bootstrap method and visual predictive check (VPC). Typical value of oral clearance (CL/F) was 30.4 L/h, while value of oral volume of distribution was 5770 L. The value of the absorption rate constant was fixed at 4.48 h-1 . Interindividual variability was best described by the exponential model, and residual by the additive model. Interindividual variability for CL/F was 38.2%. Individual predicted concentrations (IPRED) showed better agreement with the measured values than population predicted values (PRED). Conditional weighted residuals (CWRES vs PRED, CWRES vs TIME) were mostly between -2 and +2 standard deviations. The parameters obtained by bootstrap analysis do not deviate significantly from the model. Median, 5th and 95th percentiles in the VPC method mostly were within the simulated 95% confidence interval. The obtained population pharmacokinetic model, after additional optimization, can be used for individualization of the tacrolimus dosing regimen in the population of liver transplant recipients.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Populacioni farmakokinetički model takrolimusa kod pacijenata sa transplantiranom jetrom
T1  - A population pharmacokinetic model of tacrolimus in adult liver transplant recipients
VL  - 72
IS  - 4 Suplement
SP  - S298
EP  - S299
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4395
ER  - 
@conference{
author = "Jovanović, Marija and Ćulafić, Milica and Pejić, Nina and Štulić, Miloš and Kovačević, Milena and Vezmar-Kovačević, Sandra and Miljković, Branislava and Vučićević, Katarina and Ćulafić, Đorđe",
year = "2022",
abstract = "Takrolimus je imunosupresiv koji se primenjuje za prevenciju odbacivanja grafta
nakon transplantacije jetre. Uzak terapijski opseg i velika varijabilnost u farmakokinetici
ukazuju na neophodnost individualizacije terapije. Cilj istraživanja bio je razvoj i validacija
osnovnog farmakokinetičkog modela takrolimusa baziranog na podacima prikupljenim
tokom terapijskog praćenja leka. Studija je uključila 29 pacijenata sa transplantiranom
jetrom, praćenih na Klinici za gastroenterologiju i hepatologiju, Kliničkog centra Srbije.
Primenom NONMEM® programa analizirane su koncentracije takrolimusa izmerene u punoj
krvi (260), neposredno pre primene jutarnje doze (Ctrough). Farmakokinetika je opisana
jednoprostornim modelom sa resorpcijom i eliminacijom prvog reda. Interna validacija je
vršena primenom grafičke metode procene, metode umnožavanja podataka (bootstrap) i
vizuelne prediktivne provere (VPC). Procenjena tipična vrednost oralnog klirensa (CL/F)
iznosila je 30,4 L/h, dok je vrednost oralnog volumena distribucije bila 5770 L. Vrednost
konstante brzine resorpcije je fiksirana na 4,48 h-1 . Interindividualna varijabilnost je najbolje
opisana eksponencijalnim modelom, a rezidualna aditivnim modelom. Zabeležena je
interindividualna varijabilnost za CL/F od 38,2%. Predviđene individualne koncentracije
(IPRED) pokazuju bolje slaganje sa izmerenim vrednostima, nego populacione predviđene
vrednosti (PRED). Uslovni težinski reziduali (CWRES vs PRED, CWRES vs TIME) su većinom
raspoređeni između -2 i +2 standardne devijacije. Parametri dobijeni bootstrap analizom ne
odstupaju značajno od modela, dok su vrednosti medijane, 5. i 95. percentila u VPC metodi
uglavnom bile u okviru simuliranih 95% intervala pouzdanosti. Dobijeni populacioni
farmakokinetički model, može se nakon dodatne optimizacije, primeniti u svrhu
individualizacije režima doziranja takrolimusa u populaciji pacijenata sa transplantiranom
jetrom., Tacrolimus is an immunosuppressant used to prevent graft rejection after liver transplantation. The narrow therapeutic range and great variability in pharmacokinetics indicate the need for therapy individualization. The aim of the study was to develop and validate the base pharmacokinetic model of tacrolimus using data collected during therapeutic drug monitoring. The study included 29 liver transplant recipients followed up at Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia. Using the NONMEM® program, we analyzed tacrolimus concentrations (Ctrough) measured in whole blood (260). Pharmacokinetics have been described as one-compartment model with first- order absorption and elimination. Internal validation was performed using graphical assessment, bootstrap method and visual predictive check (VPC). Typical value of oral clearance (CL/F) was 30.4 L/h, while value of oral volume of distribution was 5770 L. The value of the absorption rate constant was fixed at 4.48 h-1 . Interindividual variability was best described by the exponential model, and residual by the additive model. Interindividual variability for CL/F was 38.2%. Individual predicted concentrations (IPRED) showed better agreement with the measured values than population predicted values (PRED). Conditional weighted residuals (CWRES vs PRED, CWRES vs TIME) were mostly between -2 and +2 standard deviations. The parameters obtained by bootstrap analysis do not deviate significantly from the model. Median, 5th and 95th percentiles in the VPC method mostly were within the simulated 95% confidence interval. The obtained population pharmacokinetic model, after additional optimization, can be used for individualization of the tacrolimus dosing regimen in the population of liver transplant recipients.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Populacioni farmakokinetički model takrolimusa kod pacijenata sa transplantiranom jetrom, A population pharmacokinetic model of tacrolimus in adult liver transplant recipients",
volume = "72",
number = "4 Suplement",
pages = "S298-S299",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4395"
}
Jovanović, M., Ćulafić, M., Pejić, N., Štulić, M., Kovačević, M., Vezmar-Kovačević, S., Miljković, B., Vučićević, K.,& Ćulafić, Đ.. (2022). Populacioni farmakokinetički model takrolimusa kod pacijenata sa transplantiranom jetrom. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 Suplement), S298-S299.
https://hdl.handle.net/21.15107/rcub_farfar_4395
Jovanović M, Ćulafić M, Pejić N, Štulić M, Kovačević M, Vezmar-Kovačević S, Miljković B, Vučićević K, Ćulafić Đ. Populacioni farmakokinetički model takrolimusa kod pacijenata sa transplantiranom jetrom. in Arhiv za farmaciju. 2022;72(4 Suplement):S298-S299.
https://hdl.handle.net/21.15107/rcub_farfar_4395 .
Jovanović, Marija, Ćulafić, Milica, Pejić, Nina, Štulić, Miloš, Kovačević, Milena, Vezmar-Kovačević, Sandra, Miljković, Branislava, Vučićević, Katarina, Ćulafić, Đorđe, "Populacioni farmakokinetički model takrolimusa kod pacijenata sa transplantiranom jetrom" in Arhiv za farmaciju, 72, no. 4 Suplement (2022):S298-S299,
https://hdl.handle.net/21.15107/rcub_farfar_4395 .

Značaj monitoringa primene direktnih oralnih antikoagulanasa kod starijih pacijenata u apotekama javnog tipa u Srbiji

Anđelković, Jasna; Kovačević, Milena; Miljković, Branislava

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Anđelković, Jasna
AU  - Kovačević, Milena
AU  - Miljković, Branislava
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4393
AB  - Primena direktnih oralnih antikoagulanasa (DOAK) kod starijih pacijenta nosi veći
rizik od krvarenja, ali i od tromboembolijskih događaja, u poređenju sa mlađim pacijentima.
Cilj istraživanja bila je identifikacija terapijskih problema i intervencija farmaceuta na
primarnom nivou zdravstvene zaštite. U Apoteci Kragujevac u periodu 2019-2022. godine
sprovedeno je prospektivno istraživanje koje je uključilo pacijente starosti ≥65 godina koji
su primenjivali DOAK. Za potrebe istraživanja kreiran je upitnik koji je popunjavan u toku
razgovora sa pacijentom. Istraživanjem je obuhvaćeno 78 pacijenata, prosečne starosti 71±8
godina, od kojih su 68% bili muškarci. Pacijenti su u proseku imali 3±1 dijagnoze i 5±2
lekova u terapiji. Apiksaban je koristilo 44%, rivaroksaban 31%, dabigatran 25%. Indikacije
za primenu bile su atrijalna fibrilacija 59% i venski tromboembolizam 41%. Uočena su 102
terapijska problema. Skoro četvrtina pacijenata (24%) nije ispravno primenjivala lek (npr.
uzimanje rivaroksabana našte bez hrane, otvaranje dabigatran kapsula), 38% imalo je
problem sa adherencom, 12% primenjivalo je nisku doza leka, 9% visoku dozu leka, dok su
potencijalne interakcije bile prisutne kod 41%. Od značajnih faktora rizika, 23% pacijenata
imalo je nestabilan krvni pritisak, 33% nije obavešteno o značaju praćenja renalne funkcije
tokom primene leka, i jedan pacijent je imao nizak nivo hemoglobina. Dva pacijenta su
upućena lekaru, od kojih je jedan imao epizodu krvarenja. Farmaceuti su sve pacijente
edukovali o važnosti adherence i pravilnoj primeni DOAK i obavešteni su o značaju
posedovanja kartice sa upozorenjima. Rezultati pokazuju neophodnost monitoringa primene
DOAK kod pacijenata ≥65 godina sprovođenjem standardizovane farmaceutske usluge na
primarnom nivou zdravstvene zaštite.
AB  - The use of direct oral anticoagulants (DOACs) in older patients carries a higher risk of
both thromboembolic events and anticoagulant-associated bleeding, in comparison to
younger patients. The aim of this study was to identify drug-related problems (DRPs) and
pharmacists’ interventions related to DOACs. A prospective survey was conducted at
Pharmacy Kragujevac from 2019 to 2022. Data were obtained for patients aged ≥65 with
DOACs prescription, using a questionnaire that was filled out during a conversation with the
patient. The study included 78 patients, aged 71±8 years, 68% of whom were men. On
average, patients had 3±1 diagnoses and 5±2 medications. Apixaban was used by 44%,
rivaroxaban 31%, dabigatran 25%. Atrial fibrillation was present in 59% and deep vein
thrombosis in 41%. A total of 102 DRPs were detected: inappropriate drug use in 24% (e.g.
taking rivaroxabane without food, opening dabigatran capsules), adherence in 38%, low
dose in 12%, high dose in 9%, while potential interactions were present in 41%. Among the
significant risk factors, 23% had unstable blood pressure, 33% were not informed about the
importance of renal function monitoring during the drug use, and one patient had low
hemoglobin level. Two patients were referred to a doctor, one of whom had an episode of
bleeding. Pharmacists educated all the patients about the importance of adherence, proper
application of DOACs and the importance of DOACs alert card. The results demonstrate the
necessity of monitoring the use of DOACs in elderly patients by implementing standardized
pharmaceutical services at the primary level of health care.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Značaj monitoringa primene direktnih oralnih antikoagulanasa kod starijih pacijenata u apotekama javnog tipa u Srbiji
T1  - Importance of monitoring the use of direct oral anticoagulants in older patients in community pharmacies in Serbia
VL  - 72
IS  - 4 Suplement
SP  - S270
EP  - S271
EP  - S270
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4393
ER  - 
@conference{
author = "Anđelković, Jasna and Kovačević, Milena and Miljković, Branislava",
year = "2022",
abstract = "Primena direktnih oralnih antikoagulanasa (DOAK) kod starijih pacijenta nosi veći
rizik od krvarenja, ali i od tromboembolijskih događaja, u poređenju sa mlađim pacijentima.
Cilj istraživanja bila je identifikacija terapijskih problema i intervencija farmaceuta na
primarnom nivou zdravstvene zaštite. U Apoteci Kragujevac u periodu 2019-2022. godine
sprovedeno je prospektivno istraživanje koje je uključilo pacijente starosti ≥65 godina koji
su primenjivali DOAK. Za potrebe istraživanja kreiran je upitnik koji je popunjavan u toku
razgovora sa pacijentom. Istraživanjem je obuhvaćeno 78 pacijenata, prosečne starosti 71±8
godina, od kojih su 68% bili muškarci. Pacijenti su u proseku imali 3±1 dijagnoze i 5±2
lekova u terapiji. Apiksaban je koristilo 44%, rivaroksaban 31%, dabigatran 25%. Indikacije
za primenu bile su atrijalna fibrilacija 59% i venski tromboembolizam 41%. Uočena su 102
terapijska problema. Skoro četvrtina pacijenata (24%) nije ispravno primenjivala lek (npr.
uzimanje rivaroksabana našte bez hrane, otvaranje dabigatran kapsula), 38% imalo je
problem sa adherencom, 12% primenjivalo je nisku doza leka, 9% visoku dozu leka, dok su
potencijalne interakcije bile prisutne kod 41%. Od značajnih faktora rizika, 23% pacijenata
imalo je nestabilan krvni pritisak, 33% nije obavešteno o značaju praćenja renalne funkcije
tokom primene leka, i jedan pacijent je imao nizak nivo hemoglobina. Dva pacijenta su
upućena lekaru, od kojih je jedan imao epizodu krvarenja. Farmaceuti su sve pacijente
edukovali o važnosti adherence i pravilnoj primeni DOAK i obavešteni su o značaju
posedovanja kartice sa upozorenjima. Rezultati pokazuju neophodnost monitoringa primene
DOAK kod pacijenata ≥65 godina sprovođenjem standardizovane farmaceutske usluge na
primarnom nivou zdravstvene zaštite., The use of direct oral anticoagulants (DOACs) in older patients carries a higher risk of
both thromboembolic events and anticoagulant-associated bleeding, in comparison to
younger patients. The aim of this study was to identify drug-related problems (DRPs) and
pharmacists’ interventions related to DOACs. A prospective survey was conducted at
Pharmacy Kragujevac from 2019 to 2022. Data were obtained for patients aged ≥65 with
DOACs prescription, using a questionnaire that was filled out during a conversation with the
patient. The study included 78 patients, aged 71±8 years, 68% of whom were men. On
average, patients had 3±1 diagnoses and 5±2 medications. Apixaban was used by 44%,
rivaroxaban 31%, dabigatran 25%. Atrial fibrillation was present in 59% and deep vein
thrombosis in 41%. A total of 102 DRPs were detected: inappropriate drug use in 24% (e.g.
taking rivaroxabane without food, opening dabigatran capsules), adherence in 38%, low
dose in 12%, high dose in 9%, while potential interactions were present in 41%. Among the
significant risk factors, 23% had unstable blood pressure, 33% were not informed about the
importance of renal function monitoring during the drug use, and one patient had low
hemoglobin level. Two patients were referred to a doctor, one of whom had an episode of
bleeding. Pharmacists educated all the patients about the importance of adherence, proper
application of DOACs and the importance of DOACs alert card. The results demonstrate the
necessity of monitoring the use of DOACs in elderly patients by implementing standardized
pharmaceutical services at the primary level of health care.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Značaj monitoringa primene direktnih oralnih antikoagulanasa kod starijih pacijenata u apotekama javnog tipa u Srbiji, Importance of monitoring the use of direct oral anticoagulants in older patients in community pharmacies in Serbia",
volume = "72",
number = "4 Suplement",
pages = "S270-S271-S270",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4393"
}
Anđelković, J., Kovačević, M.,& Miljković, B.. (2022). Značaj monitoringa primene direktnih oralnih antikoagulanasa kod starijih pacijenata u apotekama javnog tipa u Srbiji. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 Suplement), S270-S271.
https://hdl.handle.net/21.15107/rcub_farfar_4393
Anđelković J, Kovačević M, Miljković B. Značaj monitoringa primene direktnih oralnih antikoagulanasa kod starijih pacijenata u apotekama javnog tipa u Srbiji. in Arhiv za farmaciju. 2022;72(4 Suplement):S270-S271.
https://hdl.handle.net/21.15107/rcub_farfar_4393 .
Anđelković, Jasna, Kovačević, Milena, Miljković, Branislava, "Značaj monitoringa primene direktnih oralnih antikoagulanasa kod starijih pacijenata u apotekama javnog tipa u Srbiji" in Arhiv za farmaciju, 72, no. 4 Suplement (2022):S270-S271,
https://hdl.handle.net/21.15107/rcub_farfar_4393 .

Procena kvaliteta života kod pacijenata sa hroničnim bolestima

Damjanović, Maja; Kovačević, Milena; Musić, Nina; Vezmar-Kovačević, Sandra; Miljković, Branislava

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Damjanović, Maja
AU  - Kovačević, Milena
AU  - Musić, Nina
AU  - Vezmar-Kovačević, Sandra
AU  - Miljković, Branislava
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4392
AB  - Kvalitet života je postao značajan aspekt praćenja ishoda terapije u istraživanjima i
svakodnevnoj praksi. Cilj istraživanja bila je procena kvaliteta života u odnosu na
karakteristike pacijenata ili terapije. U istraživanje su uključeni odrasli pacijenti (≥18
godina) sa najmanje jednom hroničnom bolešću. Za procenu kvaliteta života korišćen je
upitnik Euro‐Qol 5D‐5L. Statistička obrada podataka izvršena je primenom softvera SPSS (ver
27). Analizom su obuhvaćena 193 pacijenta, većinom žene (72%), prosečne starosti
53,7±17,3 godina (opseg 21-91). Polifarmacija (≥5 lekova) je bila prisutna kod 23,4%, dok je
19,2% pacijenata imalo polimorbidnost (≥3 bolesti). Najzastupljenije su bile bolesti
cirkulatornog sistema (54,9%), endokrine, bolesti ishrane i metabolizma (36,3%) i
muskuloskeletnog sistema (20,2%). Dobru kontrolu bolesti prijavilo je 68,4% pacijenata.
Prosečna vrednost QoL iznosila je 71,1±18,6 (opseg 7-100). Određeni stepen problema sa
pokretljivošću prijavilo je 46,1%, brigom o sebi 5,7%, obavljanjem svakodnevnih aktivnosti
36,3%, bolom ili nelagodnošću 58%, prisustvom anksioznih ili depresivnih osećanja 46,9%.
Vrednost QoL bila je statistički značajno viša kod pacijenata koji su naveli da imaju dobru
kontrolu bolesti (p=0,006), dok je bila značajno niža kod pacijenata na polifarmaciji
(p<0,001) ili sa polimorbiditetima (p<0,001). Nije pokazana značajna korelacija vrednosti
QoL i dužine trajanja bolesti, niti starosti pacijenta. Od vrste zdravstvenog problema,
vrednost QoL razlikovala se značajno samo u odnosu na prisustvo oboljenja oka (p=0,024).
Značajan procenat pacijenata prijavio je uticaj hronične bolesti na različite dimenzije
kvaliteta života. Kvalitet života bio je dodatno niži kod pacijenata sa istovremeno prisutnim
većim brojem lekova u terapiji, većim brojem komorbiditeta, kao i sa oboljenjima oka.
AB  - Quality of life (QoL) has become an important aspect of the therapy outcomes
assessment in research and daily practice. The aim was to assess the quality of life in relation
to the characteristics of patients or therapy. The study included adult patients (≥18 years)
with at least one chronic disease. The Euro-Qol 5D-5L questionnaire was used to assess QoL.
Statistical analysis was performed using SPSS software (ver 27). The analysis included 193
patients, mostly women (72%), with mean age 53.7 ± 17.3 years (range 21-91).
Polypharmacy (≥5 drugs) was present in 23.4%, and polymorbidity (≥3 diseases) in 19.2%
of patients. The most common were diseases of the circulatory system (54.9%), endocrine,
nutritional or metabolic diseases (36.3%) and diseases of the musculoskeletal system
(20.2%). Good disease control was self-reported by 68.4%. The mean QoL value was
71.1±18.6 (range 7-100). A certain degree of mobility problems was reported by 46.1%, self-
care 5.7%, usual activities 36.3%, pain or discomfort 58%, anxiety or depressive feelings
46.9%. The QoL value was significantly higher in patients who stated good disease control
(p=0.006), while it was significantly lower in patients with polypharmacy or polymorbidities
(both p<0.001). No significant correlation was shown between QoL and disease duration or
patient age. The QoL value differed significantly only in relation to the presence of eye
diseases (p=0.024). A significant percentage of patients reported the impact of chronic
disease on various dimensions of QoL. The QoL was additionally lower in patients with
polypharmacy, polymorbidity, as well as with eye diseases.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Procena kvaliteta života kod pacijenata sa hroničnim bolestima
T1  - Evaluation of quality of life in chronic disease patients
VL  - 72
IS  - 4-suplement
SP  - 260
EP  - 261
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4392
ER  - 
@conference{
author = "Damjanović, Maja and Kovačević, Milena and Musić, Nina and Vezmar-Kovačević, Sandra and Miljković, Branislava",
year = "2022",
abstract = "Kvalitet života je postao značajan aspekt praćenja ishoda terapije u istraživanjima i
svakodnevnoj praksi. Cilj istraživanja bila je procena kvaliteta života u odnosu na
karakteristike pacijenata ili terapije. U istraživanje su uključeni odrasli pacijenti (≥18
godina) sa najmanje jednom hroničnom bolešću. Za procenu kvaliteta života korišćen je
upitnik Euro‐Qol 5D‐5L. Statistička obrada podataka izvršena je primenom softvera SPSS (ver
27). Analizom su obuhvaćena 193 pacijenta, većinom žene (72%), prosečne starosti
53,7±17,3 godina (opseg 21-91). Polifarmacija (≥5 lekova) je bila prisutna kod 23,4%, dok je
19,2% pacijenata imalo polimorbidnost (≥3 bolesti). Najzastupljenije su bile bolesti
cirkulatornog sistema (54,9%), endokrine, bolesti ishrane i metabolizma (36,3%) i
muskuloskeletnog sistema (20,2%). Dobru kontrolu bolesti prijavilo je 68,4% pacijenata.
Prosečna vrednost QoL iznosila je 71,1±18,6 (opseg 7-100). Određeni stepen problema sa
pokretljivošću prijavilo je 46,1%, brigom o sebi 5,7%, obavljanjem svakodnevnih aktivnosti
36,3%, bolom ili nelagodnošću 58%, prisustvom anksioznih ili depresivnih osećanja 46,9%.
Vrednost QoL bila je statistički značajno viša kod pacijenata koji su naveli da imaju dobru
kontrolu bolesti (p=0,006), dok je bila značajno niža kod pacijenata na polifarmaciji
(p<0,001) ili sa polimorbiditetima (p<0,001). Nije pokazana značajna korelacija vrednosti
QoL i dužine trajanja bolesti, niti starosti pacijenta. Od vrste zdravstvenog problema,
vrednost QoL razlikovala se značajno samo u odnosu na prisustvo oboljenja oka (p=0,024).
Značajan procenat pacijenata prijavio je uticaj hronične bolesti na različite dimenzije
kvaliteta života. Kvalitet života bio je dodatno niži kod pacijenata sa istovremeno prisutnim
većim brojem lekova u terapiji, većim brojem komorbiditeta, kao i sa oboljenjima oka., Quality of life (QoL) has become an important aspect of the therapy outcomes
assessment in research and daily practice. The aim was to assess the quality of life in relation
to the characteristics of patients or therapy. The study included adult patients (≥18 years)
with at least one chronic disease. The Euro-Qol 5D-5L questionnaire was used to assess QoL.
Statistical analysis was performed using SPSS software (ver 27). The analysis included 193
patients, mostly women (72%), with mean age 53.7 ± 17.3 years (range 21-91).
Polypharmacy (≥5 drugs) was present in 23.4%, and polymorbidity (≥3 diseases) in 19.2%
of patients. The most common were diseases of the circulatory system (54.9%), endocrine,
nutritional or metabolic diseases (36.3%) and diseases of the musculoskeletal system
(20.2%). Good disease control was self-reported by 68.4%. The mean QoL value was
71.1±18.6 (range 7-100). A certain degree of mobility problems was reported by 46.1%, self-
care 5.7%, usual activities 36.3%, pain or discomfort 58%, anxiety or depressive feelings
46.9%. The QoL value was significantly higher in patients who stated good disease control
(p=0.006), while it was significantly lower in patients with polypharmacy or polymorbidities
(both p<0.001). No significant correlation was shown between QoL and disease duration or
patient age. The QoL value differed significantly only in relation to the presence of eye
diseases (p=0.024). A significant percentage of patients reported the impact of chronic
disease on various dimensions of QoL. The QoL was additionally lower in patients with
polypharmacy, polymorbidity, as well as with eye diseases.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Procena kvaliteta života kod pacijenata sa hroničnim bolestima, Evaluation of quality of life in chronic disease patients",
volume = "72",
number = "4-suplement",
pages = "260-261",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4392"
}
Damjanović, M., Kovačević, M., Musić, N., Vezmar-Kovačević, S.,& Miljković, B.. (2022). Procena kvaliteta života kod pacijenata sa hroničnim bolestima. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4-suplement), 260-261.
https://hdl.handle.net/21.15107/rcub_farfar_4392
Damjanović M, Kovačević M, Musić N, Vezmar-Kovačević S, Miljković B. Procena kvaliteta života kod pacijenata sa hroničnim bolestima. in Arhiv za farmaciju. 2022;72(4-suplement):260-261.
https://hdl.handle.net/21.15107/rcub_farfar_4392 .
Damjanović, Maja, Kovačević, Milena, Musić, Nina, Vezmar-Kovačević, Sandra, Miljković, Branislava, "Procena kvaliteta života kod pacijenata sa hroničnim bolestima" in Arhiv za farmaciju, 72, no. 4-suplement (2022):260-261,
https://hdl.handle.net/21.15107/rcub_farfar_4392 .

Procena terapije i komorbiditeta kod pacijenata sa hroničnom opstruktivnom bolešću pluća

Marković, Aleksandra; Kovačević, Milena; Ćulafić, Milica; Roganović, Maša; Jovanović, Marija; Vezmar-Kovačević, Sandra; Vučićević, Katarina; Miljković, Branislava

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Marković, Aleksandra
AU  - Kovačević, Milena
AU  - Ćulafić, Milica
AU  - Roganović, Maša
AU  - Jovanović, Marija
AU  - Vezmar-Kovačević, Sandra
AU  - Vučićević, Katarina
AU  - Miljković, Branislava
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4391
AB  - Hronična opstruktivna bolest pluća (HOBP) je oboljenje sa visokom prevalencom koje
karakteriše progresivna, ireverzibilna opstrukcija disajnih puteva često udružena sa
pojačanim inflamatornim odgovorom. Simptomi dispneje, kašlja i umora mogu negativno
uticati na kvalitet života obolelih. HOBP je često udružen sa drugim hroničnim bolestima što
doprinosi njegovom morbiditetu i mortalitetu. Cilj ovog istraživanja je procena terapije u
lečenju HOBP i pridruženih komorbiditeta. Sprovedena je opservaciona studija koja je
uključila pacijente koji su dolazili u javne apoteke da preuzmu lek na recept za lečenje HOBP.
Podaci o pacijentima su prikupljeni popunjavanjem upitnika. Deskriptivna analiza urađena je
u programu Microsoft ® Office Excel 2010. U istraživanje je uključeno 82 ispitanika, od kojih
su brojniji bili muškarci (56,1%). Prosečna starost ispitanika iznosila je 66,1±10,6, sa
prosečnim trajanjem bolesti 10,2±3,8 godina. Najveći broj (89%) primenjivao je
kombinovane inhalacione preparate (antiholinergik+β-agonista), antiholinergik 46,3%,
salbutamol 24,4%, teofilin/aminofilin 26,9%, inhalacioni kortikosteroid 11.0%, antibiotike
14,6% i oralne kortikosteroide 4,9%. Čak 97,6% pacijenata imao je pridruženu hroničnu
bolest - broj komorbiditeta po pacijentu 1-5. U 73,8% slučajeva je u pitanju hipertenzija,
21,3% imalo je astmu, i 12,2% dijabetes ili srčanu slabost. Primenom mMRC (modified
Medical Research Council) skale za procenu dispneje, vrednosti ≥2 imalo je 53,7% ispitanika
što ukazuje na slabo kontrolisanu bolest. Skoro četvrtina pacijenata bila je hospitalizovana
zbog egzacerbacije (23,2%), 53,7% vakcinisano protiv gripa, a samo 3,7% protiv
pneumokoka. Oko trećina ispitanika bili su pušači (35,4%). Uzimajući u obzir zastupljenost
komorbiditeta u ovoj populaciji i složenost terapije, savetovanje i praćenje od strane
farmaceuta moglo bi značajno doprineti sprečavanju potencijalnih terapijskih problema.
AB  - Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease
characterized by progressive, irreversible airway obstruction often associated with
increased inflammatory response. Symptoms including dyspnea, cough and fatigue can
negatively affect patients’ quality of life. COPD is often associated with other chronic diseases
that contribute to its morbidity and mortality. The aim of this research was to evaluate the
therapy of COPD and comorbidities. An observational study included patients with a
prescription for COPD medications. Patients’ data were collected by completing
questionnaires in the community pharmacies. Descriptive analysis was performed in
Microsoft® Office Excel 2010. Among 82 participants most of them were men (56.1%).
Participants’ average age was 66.1±10.6 with an average disease duration of 10.2±3.8 years.
Most participants (89%) used combined inhalation preparations (anticholinergic+β-agonist),
anticholinergic 46.3%, salbutamol 24.4%, theophylline/aminophylline 26.9%, inhaled
corticosteroid 11.0%, antibiotics 14.6% and oral corticosteroids 4.9%. Additional chronic
disease was present in 97.6% of patients, with 1-5 comorbidities per patient. The majority of
patients also had hypertension 73.8%, 21.3% asthma and 12.2% diabetes or heart failure.
Using the mMRC (modified Medical Research Council) scale for the assessment of dyspnea,
53.7% had a score ≥2, indicating a poorly controlled disease. Almost a quarter of patients
were hospitalized for exacerbation (23.2%), 53.7% were vaccinated against influenza, only
3.7% against pneumococcus and about a third were smokers (35.4%). Given the prevalence
of comorbidities in this population and the complexity of therapy, counseling and monitoring
by pharmacists could make a significant contribution to preventing potential drug-related
problems.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Procena terapije i komorbiditeta kod pacijenata sa hroničnom opstruktivnom bolešću pluća
T1  - Assessment of therapy and comorbidities in patients with chronic obstructive pulmonary disease
VL  - 72
IS  - 4-suplement
SP  - S282
EP  - S283
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4391
ER  - 
@conference{
author = "Marković, Aleksandra and Kovačević, Milena and Ćulafić, Milica and Roganović, Maša and Jovanović, Marija and Vezmar-Kovačević, Sandra and Vučićević, Katarina and Miljković, Branislava",
year = "2022",
abstract = "Hronična opstruktivna bolest pluća (HOBP) je oboljenje sa visokom prevalencom koje
karakteriše progresivna, ireverzibilna opstrukcija disajnih puteva često udružena sa
pojačanim inflamatornim odgovorom. Simptomi dispneje, kašlja i umora mogu negativno
uticati na kvalitet života obolelih. HOBP je često udružen sa drugim hroničnim bolestima što
doprinosi njegovom morbiditetu i mortalitetu. Cilj ovog istraživanja je procena terapije u
lečenju HOBP i pridruženih komorbiditeta. Sprovedena je opservaciona studija koja je
uključila pacijente koji su dolazili u javne apoteke da preuzmu lek na recept za lečenje HOBP.
Podaci o pacijentima su prikupljeni popunjavanjem upitnika. Deskriptivna analiza urađena je
u programu Microsoft ® Office Excel 2010. U istraživanje je uključeno 82 ispitanika, od kojih
su brojniji bili muškarci (56,1%). Prosečna starost ispitanika iznosila je 66,1±10,6, sa
prosečnim trajanjem bolesti 10,2±3,8 godina. Najveći broj (89%) primenjivao je
kombinovane inhalacione preparate (antiholinergik+β-agonista), antiholinergik 46,3%,
salbutamol 24,4%, teofilin/aminofilin 26,9%, inhalacioni kortikosteroid 11.0%, antibiotike
14,6% i oralne kortikosteroide 4,9%. Čak 97,6% pacijenata imao je pridruženu hroničnu
bolest - broj komorbiditeta po pacijentu 1-5. U 73,8% slučajeva je u pitanju hipertenzija,
21,3% imalo je astmu, i 12,2% dijabetes ili srčanu slabost. Primenom mMRC (modified
Medical Research Council) skale za procenu dispneje, vrednosti ≥2 imalo je 53,7% ispitanika
što ukazuje na slabo kontrolisanu bolest. Skoro četvrtina pacijenata bila je hospitalizovana
zbog egzacerbacije (23,2%), 53,7% vakcinisano protiv gripa, a samo 3,7% protiv
pneumokoka. Oko trećina ispitanika bili su pušači (35,4%). Uzimajući u obzir zastupljenost
komorbiditeta u ovoj populaciji i složenost terapije, savetovanje i praćenje od strane
farmaceuta moglo bi značajno doprineti sprečavanju potencijalnih terapijskih problema., Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease
characterized by progressive, irreversible airway obstruction often associated with
increased inflammatory response. Symptoms including dyspnea, cough and fatigue can
negatively affect patients’ quality of life. COPD is often associated with other chronic diseases
that contribute to its morbidity and mortality. The aim of this research was to evaluate the
therapy of COPD and comorbidities. An observational study included patients with a
prescription for COPD medications. Patients’ data were collected by completing
questionnaires in the community pharmacies. Descriptive analysis was performed in
Microsoft® Office Excel 2010. Among 82 participants most of them were men (56.1%).
Participants’ average age was 66.1±10.6 with an average disease duration of 10.2±3.8 years.
Most participants (89%) used combined inhalation preparations (anticholinergic+β-agonist),
anticholinergic 46.3%, salbutamol 24.4%, theophylline/aminophylline 26.9%, inhaled
corticosteroid 11.0%, antibiotics 14.6% and oral corticosteroids 4.9%. Additional chronic
disease was present in 97.6% of patients, with 1-5 comorbidities per patient. The majority of
patients also had hypertension 73.8%, 21.3% asthma and 12.2% diabetes or heart failure.
Using the mMRC (modified Medical Research Council) scale for the assessment of dyspnea,
53.7% had a score ≥2, indicating a poorly controlled disease. Almost a quarter of patients
were hospitalized for exacerbation (23.2%), 53.7% were vaccinated against influenza, only
3.7% against pneumococcus and about a third were smokers (35.4%). Given the prevalence
of comorbidities in this population and the complexity of therapy, counseling and monitoring
by pharmacists could make a significant contribution to preventing potential drug-related
problems.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Procena terapije i komorbiditeta kod pacijenata sa hroničnom opstruktivnom bolešću pluća, Assessment of therapy and comorbidities in patients with chronic obstructive pulmonary disease",
volume = "72",
number = "4-suplement",
pages = "S282-S283",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4391"
}
Marković, A., Kovačević, M., Ćulafić, M., Roganović, M., Jovanović, M., Vezmar-Kovačević, S., Vučićević, K.,& Miljković, B.. (2022). Procena terapije i komorbiditeta kod pacijenata sa hroničnom opstruktivnom bolešću pluća. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4-suplement), S282-S283.
https://hdl.handle.net/21.15107/rcub_farfar_4391
Marković A, Kovačević M, Ćulafić M, Roganović M, Jovanović M, Vezmar-Kovačević S, Vučićević K, Miljković B. Procena terapije i komorbiditeta kod pacijenata sa hroničnom opstruktivnom bolešću pluća. in Arhiv za farmaciju. 2022;72(4-suplement):S282-S283.
https://hdl.handle.net/21.15107/rcub_farfar_4391 .
Marković, Aleksandra, Kovačević, Milena, Ćulafić, Milica, Roganović, Maša, Jovanović, Marija, Vezmar-Kovačević, Sandra, Vučićević, Katarina, Miljković, Branislava, "Procena terapije i komorbiditeta kod pacijenata sa hroničnom opstruktivnom bolešću pluća" in Arhiv za farmaciju, 72, no. 4-suplement (2022):S282-S283,
https://hdl.handle.net/21.15107/rcub_farfar_4391 .