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Efficasy and safety of Enoxaparin in deep vein thrombosis therapy


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Efficasy and safety of Enoxaparin in deep vein thrombosis therapy
(case report)
Mihailova L., Lazarova B., Kolarova S.
General Hospital Ljuben Ivanov bb Stip, community pharmacy “Sofia”
Hristijan Karpos 24a Stip, R. Makedonija
Low molecular weight heparins (LMWH) tend to take the place of unfractionated heparins in the treatment
of deep vein thrombosis (DVT) for in patients and out patients as well. Numerous studies showed that twice-daily
subcutaneous application of 1 mg/kg b.w. enoxaparin had better efficacy and clinical improvement to standard unfrac-
tionated heparins. Incidence of hemorrhagic complications remains comparable to or under those observed with unfrac-
tionated heparins. In this study we present a case of a 71-year-old woman with right hip fracture. She has undergone
orthopedic surgery and developed complete DVT soon after surgical intervention. For the risk of bleeding under unfrac-
tionated heparins, enoxaparin was administrated subcutaneous in doses of 80 mg twice daily for 15 days. In this peri-
od the condition got better and the dose was reduced to 40 mg twice daily for 7 days more allowing discharge of the
hospital. For all the time were performed biological controls and clinical examinations. No adverse effects were noted.
A complete recovery was achieved after 2.5 months. Because there is a not clinically relevant difference between
LMWH and standard heparin for prophylaxis postoperative venous thromboembolism and LMWH is effective and
safe in the treatment of established DVT it appears that LMWH are preferable in treatment of DVT particularly in
aged patients. The main advantages are administration in more convenient way and no risk of bleeding.
Macedonian pharmaceutical bulletin 53 (1,2) 138-139 (2007)
PP - 60
138
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Efikasna i bezbedna terapija so Enoxaparin kaj dlaboka venska
tromboza (izve{taj za slu~aj)
Mihailova. L., Lazarova. B., Kolarova. S.
JZU Op{ta bolnica Quben Ivanov bb [tip; PZO apteka ”Sofija”
Hristijan Karpo{ 24 a [tip, Makedonija
Heparinite so mala molekulska te`ina se stremat da go zazemat mestoto na standardnite hepari-
ni vo tretman na dlabola venska tromboza (DVT) kako za hospitaliziranite taka i za pacientite nadvor
od bolnica. Brojnite studii poka`uvaat subkutana aplikacija na enoxaparin dva pati dnevno vo dozi od
1mg/kg t.t. ima podobra efikasnost i klini~ko podobruvawe vo odnos na standardnite heparini.
Incidencata od hemoragi~ni komplikacii e sporedbena so ili pod onaa koja e observirana kaj nefrak-
cioniranite heparini. Vo ovaa studija prezentirame slu~aj na 71 godi{na `ena so fraktura na desen kolk.
Kaj pacientkata e izvr{ena ortopedska operacija, no nabrzo posle hirur{kata intervencija taa razvi
kompletna DVT. Poradi rizikot od krvarewe so nefrakcionirani heparini, be{e ordinirano subkutana
aplikacija na enoxaparin vo dozi od 80 mg dvapati dnevno vo tek na 15 dena. Vo ovoj period sostojbata na
pacientkata se podobruva{e, pa dozata be{e namalena na 40 mg dvapati dnevno u{te 7 dena po {to pacien-
tkata be{e pu{tena na doma{no lekuvawe. Za celo vreme na tretmanot bea izveduvani laboratoriski kon-
troli i klini~ki ispituvawa. Ne bea zabele`ani nikakvi nesakani efekti od lekot. Kompletno re{avawe
na problemot se postigna posle 2.5 meseci. Bidejki ne postojat klini~ki relevantni razliki pome|u hepari-
nite so mala molekulska te`ina i standardnite heparini profilaksata na postoperativniot venozen
tromboembolizam so heparinite so mala molekulska te`ina e efikasna i bezbedna vo tretmanot na
razviena DVT. Se smeta deka heparinite so mala molekulska te`ina se preferirani vo tretman na DVT
osobeno kaj postari pacienti. Glavni prednosti se posoodvetniot na~in na aplikacija i otsustvo na rizikot
od krvarewe.
Macedonian pharmaceutical bulletin 53 (1,2) 138-139 (2007)
PP - 60
139
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Rational Utilization of Cardiovascular Drugs
Kaja Djordjevic
1
, Dragana Jovanovic
1
, Ljiljana Tasic
2
1
Pharmacy Nis,, Brace Taskovica 6, Nis, Republic Serbia 
2
Faculty of Pharmacy, 450 Vojvode Stepe, Belgrade, Republic Serbia 
Introduction: According to Serbian health care parameters (total morbidity and mortality), as many as 55%
of total mortality in Serbia results from the implication of cardiovascular (CV) diseases, while in developed coun-
tries values ranges between 20 to 50% with huge variations. The American Society of Cardiology, European Society
of Cardiology and European Atherosclerosis Society adopted the Guidelines for primary and secondary prevention
of CV disease, and the national program is also made in Serbia. The Guidelines are based on the elimination of risk
factors in primary prevention and the appliance of drugs in secondary prevention.
Objective: Exploring the rational utilization of CV drugs and compatibility with Guidelines and Drug
Formularies in Nis region during 2003 – 2005 year.
Methods: The research was descriptive, quantitative and retrospective. The source of data was the database
of Pharmacy Institution (PI) Nis. We analyzed the number of boxes prescribed on receipt and each drug separately,
then the drugs were classified into therapeutical groups according to ATC classification. The data included the num-
ber of prescribed CV drugs, refunded by Republic Health Insurance Fund (RHIF) and sold per capita, as well as the
financial ratio, ATC groups distribution and their analyses.
Results and Discussion: Nis region has the total of 381757 inhabitants according to Census, 2002. That is
5.09% of the entire population in the Republic of Serbia. 
The total worth of consumed drugs was ascendant during the observed period, so as it was the total of 294,256
million RSD in 2005. As per the number of boxes, the consumption constantly increases during the past years being
1.170.528 (947.663 prescribed and 222.865 sold); 1.403.672 (1.145.177 prescriptions and 258.495 sold); and 1.570.224
(1.324.812 prescribed and 245.412 sold) in 2003, 2004, and 2005, respectively. In regard to the number of prescribed
CV drugs, which goes on RHIF per capita, it was 2.48; 3.00; and 3.47 for 2003, 2004, and 2005, respectively. The
number of prescribed drugs reimbursed by RHIF constantly increases for the reasons that are mainly: the enlarge-
ment of drugs list remunerated by RHIF, significant drug investments, improved health care and enhanced patient
concern for their own health. Each group consumption, according to ATC classification, rises perennially, and the
most progressive was in C03 group (diuretics). The maximum consumption was recorded for drugs from C09 group
(agents acting on renin – angiotensin system), the second was C07 group (beta blocking agents), and the third C01
group (cardiac therapy). Group C09, compared to CV drugs total consumption, participated with 28.42% in 2003,
while in 2005 the share increased at 31.80%. The consumption growth of this group is consistent with the Guidelines
for clinical practice, in which ACE inhibitors are the first choice for arterial hypertension and mandatory for the sec-
ondary prevention of CV diseases that indicates us the fact that prescribes are more and more conformed to the
Guidelines. On the other side, the total consumption of group C07 decreases slightly with 19,17% and 18.41% in
2003 and 2005.
The database on the total consumption of Pharmacy Institution Nis indicates that 50% of all consumed drugs
are from CV group of drugs, which is in coincide with the statistic result that CV disease share 50% of overall dis-
eases according to the previous mortality parameters. 
Conclusion: Our analysis proved that CV drugs have an increasing rate that is expected to continue in the
future, considering that Serbian population over 40 years is also 45.7% of total population that are the biggest con-
sumer group of CV drugs. It is estimated that drug consumption increases because of drug list enlargement and from
financial view there are indications for higher percentage of imported drugs on the market. The consumption of group
C03, C07 and C9 indicates conformity with national guidelines. Rational CV drugs utilization must be the perma-
nent purpose of drug monitoring policy for the prevention of CV diseases developing.
Macedonian pharmaceutical bulletin 53 (1,2) 140 (2007)
PP - 61
140
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Counterfeit drugs-current problem
Elena Najdovska, Zora Veljanova
Sluzba za infuzioni rastvori, Klinicka Bolnica Dr. Trifun Panovski, Bitola
WHO and the Pharmacopoeias defines the counterfeit drugs as medicines which are deliberately and fraud-
ulently mislabeled with respect to identify and/or source. It include products with the correct ingredients or with the
wrong ingredients, without active ingredients, with insufficient active ingredients or with fake packaging.
Counterfeiting can apply to both branded and generic products. The types of counterfeits reported included: prod-
ucts with no active ingredients 43%; low content of active ingredients 21%; poor quality drugs 24%; wrong ingre-
dients 2%; and wrong source 7%. The most counterfeit drugs are generally, high consumption, expensive and inno-
vative drugs, but also well established drugs. Usually antibiotics, antiprotozoals, hormones, steroids. The problem
of counterfeit drugs has been reported to occur worldwide, is not limited to developing countries only, and you can
also find it in developed countries. No country is immune to counterfeiting. Most developed countries with effec-
tive regulatory systems and market control (USA, EU, Japan, Canada, New Zealand) currently have a very low pro-
portion, less than 1% of market value. Many developing countries of Africa, parts of Asia, and parts of Latin America
have areas where more than 30% of the medicines on sale can be counterfeit. Other developing markets, however,
have less than 10%, overall, a reasonable estimate is between 10 and 30 %. Many of former Soviet republic have a
proportion of counterfeit medicines which is above 20 % of market value. Medicines purchased over the Internet
from sites that conceal their actual physical address are counterfeit in over 50 %. The contributing factors for coun-
terfeit drugs are:
• shortage or erratic supply of drugs – when the supply of drugs in a country is short or erratic, patients and
consumers tend to look for alternative sources.
• high prices of medicines-when the prices of medicines become excessively high and unaffordable ,patients
tend to look for cheaper sources.
• price differentials-when price differences exist between identical products, patients and consumers go for
the cheaper ones.
• inappropiate use of drugs-patients themselves may be contributing to the problem as well. Consumers who
use medicines inappropriately generate demand for such medicines, the sources of wich may be counterfeit.
• a governmental responsibility-lack of appropriate drug legislation ,weak enforcement, lack of control over
export drugs, corruption and conflict of interests.
A medicine is not just a simple mixture of chemical ingredients, it is a very complex equilibrium with poten-
tial interactions and, in order to benefit the patient without any risk of harm, it needs an approach, which is com-
pletely professional and responsible.
Macedonian pharmaceutical bulletin 53 (1,2) 141-142 (2007)
PP - 62
141
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Falsifikuvani lekovi – problem na dene{nicata
Elena Najdovska, Zora Veljanova
Slu`ba za infuzioni rastvori, Klini~ka bolnica Dr.Trifun Panovski, Bitola
Poimot falsifikuvani lekovi e definiran kako od Svetskata zdravstvena organizacija taka i od
site oficinelni farmakopei. Pod poimiot falsifikuvani lekovi se podrazbiraat lekovi koi se namer-
no ili nenamerno bez signatura, ne se znae nivniot proizvoditel ili lekovi ~ii sostav ne odgovara na
deklariraniot, sodr`at pomalku od aktivniot princip ili voop{to ne sodr`at aktiven princip, a mo`e
da sod`at duri i toksi~ni sostojki. Zaradi seto toa se opasni za pacientot, od edna strana neefektivni
(bolesta i ponatamu napreduva), od druga strana mo`at da predizvikaat dodatni zaboluvawa, o{tetuvawa
na organizmot pa duri i smrtFalsifikuvanite lekovi mo`at da se sretnat i kaj brendiranite i kaj
generi~kite lekovi.
Voobi~aenite statistiki poka`uvaat deka 43% od falsifikuvanite lekovi se odnesuvaat na lekovi
bez aktiven princip, 21%na lekovi so pomala koli~ina na aktvniot princip, 2%na lekovi so neto~en
aktiven princip, 24%na lekovi so slab kvalitet na aktivnite komponenti i 7%na lekovi so pogre{en
izvor (proizvoditel). Po podatocite na Svetskata zdravstvena organizacija bilo koj lek mo`e da bide
falsifikuvan. Dosega postojat podatoci za falsifikuvawe na: citostatici, antibiotici, antihiperten-
zivi ,antilipemici, hormoni, steroidi, analgetici i antihistaminici. Va`no e da se napomene podatokot
deka falsifikuvanite lekovi mo`at da se sretnat i vo razvienite i vo zemjite vo razvoj. Vo razvienite
zemji so efektivni regulatorni sistemi i kontrola na pazarot procentot e pomal od 1%, vo zemjite vo
razvoj vo Afrika, delovi od Azija i Ju`na Amerika 30%, vo biv{ite Ruski republiki okolu 20% i vari-
ra vo zavisnost od razvienosta na zemjata. Vo industrisko razvienite zemji, distribucijata na lekovi
preku internet e eden od najgolemite izvori na falsifikuvani lekovi. Osobeno vnimanie treba da se
posveti na internacionalnite distributeri koi nudat lekovi so nepoznat sostav i poteklo. Vo takvi
primeri falsifikuvaweto e i preku 50%. Vo dene{no vreme falsifikuvaweto stanuva se posofistici-
rano i te{ko se otkriva duri i vo dobro kontroliraniot pazar. Pri~ini za distribucija na falsifiku-
vani lekovi ima pove}e:
• nedostatno ili nepostojano snabduvawe na pazarot so potrebnite lekovi
• visoka cena na lekovite:pacientot vo nedostatok na sredstva bara alternative (~esto, falsi-
fikuvanite lekovi se so mnogu poniska cena)
• razli~ni ceni na eden ist lek(pacientot sekoga{go kupuva poeftiniot)
• nepravilna upotreba na lekovi, samole~ewe, pr. razni kremi koi sodr`at steroid , lekovi za
oblikuvawe na teloto, lekovi koi se {irat po nedefinirani kanali ili neavtorizirani distributeri
• odgovornost na vladata: nedovolna kontrola vrz pazarot so lekovi, slaba regulative, korupcija
i konflikt na interesi
FDA od 2004 godina pa dosega ima izdadeno tri izve{tai za itnosta na tretirawe na problemot
so falsifikuvanite lekovi a se so cel sigurnost i bezbednost pri snabduvaweto so lekovi. Pri toa e jasno
napomenato deka distribucijata na falsifikuvani lekovi e ilegalno, nebezbedno i mo`e seriozno da mu
na{teti najavnoto zdravstvo.
Problemot so falsifikuvanite lekovi ima globalna dimenzija i potreben e globalen pristap vo
re{avawe na problemot.
Macedonian pharmaceutical bulletin 53 (1,2) 141-142 (2007)
PP - 62
142
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
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Generic medicaments in Cardiology
Becic Fahir, Jandric Almasa, Kapic Elvedina, Mulabegovic Nedzad
Institute of Pharmacology, Clinical Pharmacology and Toxicology, Medical Phaculty University of Sarajevo 
Generic medicament is pharmacy’s product who is the identical or bioequivalent like the original medica-
ment according to dose, harmless, quality, form, aplication and indication. Also, generic medicament is pharmacy’s
product whose date patent has expired. After the expiring date to patent for certainly medicament, all other medica-
ment producer can produce the same generic medicament if they respect the principle of GMP and GLP. Generic
medicaments are very important model in medical treatment of cardiovascular diseases. In Europe there is an increase
of waste of medicament’s percent in about 80. In Cardiology generic medicaments significantly reduce expenses and
pullout in the health insurance protection.
Development and disbursment in the market of the generic medicaments is farless than the development and
disbursment in the market of the original medicament. In Cardiology application of the generic medicaments leads
up to the more important saving in the health sistem and increases a possible wider access to the patientes.
Macedonian pharmaceutical bulletin 53 (1,2) 143 (2007)
PP - 63
143
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
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Pharmacoinformatics in Continuing education 
and Lifelong Learning of the pharmacists
M. Kovaceva
1
, L. Petrusevska-Tozi
2
, K. Mladenovska
2
, Lj. Suturkova
2
1
The Pharmaceutical Chamber of Macedonja, Skopje, R. Macedonia
2
Faculty of Pharmacy, Univesityt Ss. Ciryl and Methodus, Skopje, R. Macedonia 
Longlife learning is a concept of promoting of the human beeing needs for continual elevating of the pro-
fessional and general education knoledge, while continual education is upgrade in the regulated proffesion, in order
to promote of the professional competences. 
Since 2004 year, in all EU member states, an integration programme for LLL and continual education is
established.
Professional development, in the manner of continuing education and LLL, of the heath-care proffesionals-
pharmacists in the Republic of Macedonia is largely absent, as a result of the:
• non adequate sistem of continuing education of the pharmacists;
• lack of approach and educational methods for learning through specific problems solving from common 
proffesional practice;
• lack of specialized educational programs; and
• lack and little intention for promoting of the knowledge, as a result of the general low economic condition 
of the state.
It is necessery to be taken great investments and activities, in order to prepare adequate programs, 
which will be affordable and adjusted towards every pharmacists, in his proffesional continuing development.
Proffesional education of the licensed pharmacists is based upon these principles of continuing education:
• involvment of all pharmacists in the proces of continuing education;
• equal pharmaceutical doctrine for all pharmacists, without difference if they work in public or private 
institution on all levels;
• scientific support of the whole process, which is going to provide transfer of the latest nacional and 
international knowledge and scientific achievments;
• equal methods of knowledge-transfer for providing equal levels of education;
• free-choise of the form (type) of the education according to the individual needs;
• stepwise categorization of the points of every form of the professional education.
In order to realize the stated principles, it has to be done continuing education strategy, which will provide
the pharmacists free choise of the possibilities to conduct their own education, free choise of the time of the educa-
tion, free choise of the methods, problems and activities of the education. 
The continuing education has to be completely planned, well structured, organized and mandatory.
The succesful education proces, has to satisfy these criteria: has to be continual and organized; has to answer
the needs of the pharmacists; has to regard towards all pharmacists in the manner of their speciality; has to be assess-
able, measurable for every member of the community, has to be adequatly pointed, to guarantee good pharmacy prac-
tice and good pharmaceutical care.
Macedonian pharmaceutical bulletin 53 (1,2) 144-145 (2007)
PP - 64
144
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Farmakoinformatikata vo kontinuirana
edukacija i do`ivotno u~ewe na farmacevtite
M. Kova~eva
1
, L. P. Tozi
2
, K. Mladenovska
2
, Q. [uturkova
2
1
Farmacevtska komora na Makedonija, Skopje
2
Farmacevtski fakultet, Univerzitet Sv. Kiril i Metodij, Skopje 
Do`ivotnoto u~ewe e koncept za izdigawe na potrebata na ~ovekot za kontinuirano nadgraduvawe
na stru~ni i op{toobrazovni znaewa, dodeka kontinuiranata edukacija e nadgraduvawe vo ramkite na regu-
liranata profesija so cel zgolemuvawe na kompetenciite vo profesijata.
Od 2004 god vo site zemji na Evropskata Unija se sproveduva Integrativna programa za do`ivotno
u~ewe i kontinunuirana edukacija. 
Profesionalniot razvoj na zdravstvenite profesionalci- farmacevti vo Makedonija, zna~ajno
nedostasuva{e vo Makedonija kako rezultat na:
• nesoodveten sistem na kontinuirana edukacija na farmacevtite;
• nedostatok na pristap i edukativni metodi za u~ewe preku re{avawe na specifi~ni problemi
od sekojdnevnata profesionalna praktika,
• nedostatok na specijalizirani edukativni programi;
• nedostatok i mala `elba za nadograba na znaeweto kako rezultat na vkupnata lo{a ekonomska
sostojba vo zemjata.
Neophodni se ogromni zalagawa i aktivnosti za da se podgotvat soovetni programi koi }e bidat
dostapni i prilagodeni za sekoj farmacevt vo tek na negoviot kontinuiran profesionalen razvoj.
Profesionalnata edukacija na licenciranite farmacevti se bazira na slednite principi na kon-
tinuiranata edukacija:
• vklu~uvawe na site farmacevti vo procesot na kontinuiranata edukacija;
• ednakva farmacevtska doktrina za site farmacevti bez razlika dali rabotat vo javni ili pri-
vatni institucii na site nivoa;
• nau~na potkrepa na celokupniot proces koj }e obezbedi transver na najnovite nacionalni i inter-
nacionalni znaewa i nau~ni dostigawa;
• ednakvi metodi na transver na znaewe za obezbeduvawe na ednakvi nivoa na edukacuja za postignu-
vawe na celta;
• sloboden izbor na formata (tipot) na edukacija sprema sopstvenite potrebi. 
• skalesto kategorizirawe na poenite za sekoja forma na profesionalna edukacija.
Za da se ovozmo`i realizacija na gorenavedenite principi, treba da se vospostavi strategijata za
kontinuiranata edukacija koja }e im ovozmo`i na farmacevtite sloboda vo izborot na na~inite na koi
}e ja izvr{at edukacijata, sloboda vo  izborot na  vremeto vo koe }e se odviva, sloboda vo izbor na metodot,
problemot i aktivnostite na edukacijata. Tekot na edukacijata treba da bide celosno obmislen, dobro
strukturiran, organiziran i zadol`itelen. 
Uspe{niot proces na edukacija, treba da ispolni odredeni kriteriumi: da bide kontinuiran
(prodol`itelen) i organiziran;  da odgovori na potrebite na farmacevtite; da gi pokriva site farma-
cevti vo ramkite na tesnata specijalnost; da e procenliv, merliv za sekoj ~len na op{testvoto; da bide
soodvetno bodiran; da garantira dobra farmacevtska praktika i dobra zdravstvena nega.
Macedonian pharmaceutical bulletin 53 (1,2) 144-145 (2007)
PP - 64
145
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

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