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 .

TY  - JOUR
AU  - Pejčić, Zorica
AU  - Vučićević, Katarina
AU  - Garcia-Arieta, Alfredo
AU  - Miljković, Branislava
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3244
AB  - Aims Generic products can be regarded as therapeutically equivalent and switchable with the reference product. However, switchability between generics is unknown, as direct comparisons between generics are not performed. The aim of this study was to investigate the bioequivalence between generic clopidogrel products by means of adjusted indirect comparisons (AICs). Methods AICs were conducted to assess bioequivalence between 4 generic clopidogrel products that are authorised in Serbia. Generics are considered equivalent to the reference if the 90% confidence intervals (CIs) for the ratios test/reference of the maximum concentration (C-max) and area under the curve up to the last measurable concentration (AUC(0-t)) fall within the acceptance range 80.00-125.00%. However, for AICs between generics, the Canadian acceptance criterion for C-max was employed, where only the point estimate of C-max needs to be within 80.00-125.00%. Results The 90% CIs of the AICs demonstrated bioequivalence within 80.00-125.00% for all AUC(0-t) comparisons. The point estimates of C-max in all AICs were also within this range. Conclusion This study demonstrates that the bioavailability of these 4 generic clopidogrel products authorised in Serbia is very similar. Despite the limited power of AICs, bioequivalence was demonstrated for all 90% CIs of AUC(0-t) and all 90% CIs of C-max comparisons were within or very close to the acceptance range, being able to comply with the acceptance criterion employed in Canada for C-max. Therefore, these 4 generic clopidogrel products authorised in Serbia can be considered switchable with each other in clinical practice based on the adjusted indirect comparisons.
PB  - Wiley, Hoboken
T2  - British Journal of Clinical Pharmacology
T1  - Adjusted indirect comparisons to assess bioequivalence between generic clopidogrel products in Serbia
DO  - 10.1111/bcp.13997
ER  - 

@article{
author = "Pejčić, Zorica and Vučićević, Katarina and Garcia-Arieta, Alfredo and Miljković, Branislava",
year = "2019",
abstract = "Aims Generic products can be regarded as therapeutically equivalent and switchable with the reference product. However, switchability between generics is unknown, as direct comparisons between generics are not performed. The aim of this study was to investigate the bioequivalence between generic clopidogrel products by means of adjusted indirect comparisons (AICs). Methods AICs were conducted to assess bioequivalence between 4 generic clopidogrel products that are authorised in Serbia. Generics are considered equivalent to the reference if the 90% confidence intervals (CIs) for the ratios test/reference of the maximum concentration (C-max) and area under the curve up to the last measurable concentration (AUC(0-t)) fall within the acceptance range 80.00-125.00%. However, for AICs between generics, the Canadian acceptance criterion for C-max was employed, where only the point estimate of C-max needs to be within 80.00-125.00%. Results The 90% CIs of the AICs demonstrated bioequivalence within 80.00-125.00% for all AUC(0-t) comparisons. The point estimates of C-max in all AICs were also within this range. Conclusion This study demonstrates that the bioavailability of these 4 generic clopidogrel products authorised in Serbia is very similar. Despite the limited power of AICs, bioequivalence was demonstrated for all 90% CIs of AUC(0-t) and all 90% CIs of C-max comparisons were within or very close to the acceptance range, being able to comply with the acceptance criterion employed in Canada for C-max. Therefore, these 4 generic clopidogrel products authorised in Serbia can be considered switchable with each other in clinical practice based on the adjusted indirect comparisons.",
publisher = "Wiley, Hoboken",
journal = "British Journal of Clinical Pharmacology",
title = "Adjusted indirect comparisons to assess bioequivalence between generic clopidogrel products in Serbia",
doi = "10.1111/bcp.13997"
}

Pejčić, Z., Vučićević, K., Garcia-Arieta, A.,& Miljković, B.. (2019). Adjusted indirect comparisons to assess bioequivalence between generic clopidogrel products in Serbia. in British Journal of Clinical Pharmacology
Wiley, Hoboken..
https://doi.org/10.1111/bcp.13997

Pejčić Z, Vučićević K, Garcia-Arieta A, Miljković B. Adjusted indirect comparisons to assess bioequivalence between generic clopidogrel products in Serbia. in British Journal of Clinical Pharmacology. 2019;.
doi:10.1111/bcp.13997 .

Pejčić, Zorica, Vučićević, Katarina, Garcia-Arieta, Alfredo, Miljković, Branislava, "Adjusted indirect comparisons to assess bioequivalence between generic clopidogrel products in Serbia" in British Journal of Clinical Pharmacology (2019),
https://doi.org/10.1111/bcp.13997 . .