Abc-Analysis of Antibacterial Medicines

UDC: 615.1:615.281:614.27: 615.036 L. Iakovlieva, N. Matyashova ABC-ANALYSIS OF ANTIBACTERIAL MEDICINES National University of Pharmacy, Kharkiv, Department of pharmacoeconomics

ABSTRACT

Using ABC-analysis of medicines with International Non-patented Names (INN) the costs structure at the state level for the four groups of antibiotics (penicillins, cephalosporins, fluoroquinolones, carbapenems) was determined. ABC- analysis allowed us to identify the group of antibiotics the patients have spend the largest number their money, and rationalization of these. As a result, the distribution of antibacterial medicines for ABC-groups was as following: the group A – 11 INN that took 79.22 % of the total costs for all the investigated medicines; the group B – 11 INN (15.34 % of the costs); the group C – 25 INN (5.44 % of the costs).

The group A consists of new generation antibiotics with a broad spectrum of action. It means that money in general is spent effectively on new antibacterial medicines. Groups B and C include first-generation medicines, such as ampicillin, cephalexin, benzylpenicillin, cephadroxyl etc. There are some new expensive medicines in groups B and C that are used more rarely: moxifloxacin, meropenem, hemifloxacin and imipenem in combination with an inhibitor of the enzyme.

Keywords: antibacterial medicines, ABC analysis, penicillins, cephalosporins, fluoroquinolones, carbapenems.

The problem Gradual transition from the use of antiseptics to chemotherapy, and beginning with the middle of the XX century – the century of antibiotics, fundamentally changed the effectiveness of resistance to infectious diseases. When antibiotics has been discovered, the crippling blow was done to pathogenic organisms. However, it soon began to appear some bacteria resistant to the action of antibiotics. Microorganisms "learned" to fight and win the "war" with antibacterial medicines. The problem of rational antibiotic therapy does not lose relevance even nowadays. The presence of large arsenal of antibiotics on the one hand it extends the treatment of various infections, and on the other hand it requires from the doctor knowledge of many antibacterial medicines and their properties (action spectrum, pharmacokinetics, side effects etc.), the ability to take their bearingsin the issues of microbiology, clinical pharmacology and related disciplines. Currently, antimicrobial medicines are the most prescribed drugs that take a huge part of costs and a large proportion of irrational prescriptions. The interest in pharmacoeconomic and pharmacoepidemiologic researches in this area is associated with huge losses of patients, hospitals and public the general in case of irrational antibacterial medicines administration. Analysis of recent research and publications In recent years, there are increasing number of publications in special editions devoted to pharmacoeconomic analysis of antibacterial medicines administration in Ukraine. The scientific literature contains evidences of antibiotics consumption in cash and terms of quantity that are presented by analytical market research company (Morion) and researches are conducted by the department of pharmacoeconomics of National University of Pharmacy. Yu. Mostovoi and Demchuk A. researches were published dealing with the consumption of antimicrobial medicines conducted by ATC/DDD-methodology. However, researches at the level of the country using the ABC-analysis have not carried out still now. That is why it causes the relevance and necessity of further development of this direction. Unsolved parts of the problem With the constant increase of costs in medical care (medicines, medical products, medical services), unstable socio-economic situation in our country and the inability to increase government funding for health care, you need to pay more attention to the quality of medical treatment and look for the drugs that are prescribed by doctors, to evaluate the effectiveness, safety and rationality of the prescription both with the effectiveness of its cost. Taking into account that currently antibiotics are free sale at pharmacies, despite the legal prescription of medicines for this group, this problem becomes even more urgent. So, the analysis of antibacterial medicines consumption at the country level with the help of ABC-analysis remains unsolved aspect of this problem. The aims of the article The aim of this reseach is to create understanding about the ambulatory costs structure at the country level on the major groups of antibacterial medicines using ABC-analysis of medicinal INN that will identify antibiotics which take the majority of patients’ money, and to define the rationality of expenses. The main material of the research. For the retrospective assessment of financial costs of the investigated antibacterial medicines ABC-analysis was used. ABC-analysis is a method of medicines distribution in the total cost structure of pharmacotherapy beginning with the most expensive to the least expensive according to their actual usage during the researched period. It is based on the principle of Pareto – "the control of 20 % of the complex of items that are purchased lets you to control 80 % of the costs" [4]. According to ABC-analysis the medicines are distributed into three groups depending on costs: - the group А (is the most expensive) medicines that take 80 % of costs; - the group B (medium expensive) medicines that take 15-20 % of costs; - the group С (minimum expensive) medicines that take in general not more then 5 % of the total amount of costs for 3 groups in a whole (A, B, C). For the ABC-analysis the data of the analytic system of pharmaceutical market of Ukraine research "Pharmstandard" of company "MORION" for 2011 were taken. The research included four groups of antibiotics: penicillins (J01C), cephalosporins (J01D), carbapenems (J01D) and fluoroquinolones (J01M) [5, 10]. There were 47 INN in general, which included both mono-drugs and drugs in combination with inhibitors of lactamases. In 2011 the total cost of these groups of medicines totaled 97 781 647 UAH. It was about 67 % from the total costs of all antibiotics for systemic usage (ATC code – J01). For each of the antibiotics we have determined the percentage of the cost from the total amount of costs, we have calculated the saving percentage and the appropriate group of medicines was set, such as A, B and C. The results are presented in the table 1.

Table 1 ABC-analysis of the antibiotics administration during 2011

The part АТС- Group/ Accumu- Group INN Costs (UAH) of costs, code generation lated % А,В,С % 1. J01D D04 Ceph. /3 ceftriaxone 22 316 508,74 22,82 22.82 2. J01C R02 Protected pn. /3 amoxicillin + clavulanic acid 14 167 412,06 14,49 37.31 3. J01M A12 Fq. / 3 levofloxacin 9 343 211,92 9,56 46.87 4. J01C A04 Pn. / 3 amoxicillin 7 957 079,49 8,14 55.01 5. J01M A02 Fq. /3 ciprofloxacin 4 405 784,77 4,51 59.52 6. J01D C02 Cph. / 2 cefuroxime 4 365 430,74 4,46 63.98 7. J01D D13 Cph. / 3 cefpodoxime 3 576 456,27 3,66 67.64 А 79,22% 8. J01D D02 Cph. / 3 ceftazidime 3 162 534,28 3,23 70.87 9. J01D D08 Cph. / 3 cefixime 2 869 825,90 2,93 73.80 1 J01M A16 Fq./4 gatifloxacin 2 842 383,63 2,91 76.71 0. 1 J01D E01 Cph./4 cefepime 2 452 191,88 2,51 79.22 1. 1 J01D D12 Cph./3 cefoperazone 2 291 788,58 2,34 81.56 2. 1 J01M A01 Fq./2 ofloxacin 1 810 780,98 1,85 83.41 3. 1 J01D D01 Cph./3 cefotaxime 1 456 671,32 1,49 84.90 4. 1 J01M A06 Fq./2 норфлоксацин 1 377 873,70 1,41 86.31 5. 1 benzathine benzylpenicillin + J01C E30 Pn./1 1 221 187,06 1,25 87.56 6. benzylpenicillin 1 В J01M A14 Fq./4 moxifloxacin 1 210 491,79 1,24 88.80 7. 15,34% 1 J01D D54 Protected cph./3 ceftriaxone + sulbactam 1 209 173,68 1,24 90.04 8. 1 J01D H02 Carbapenems meropenem 1 192 640,99 1,22 91.26 9. 2 J01D D62 Protected cph./3 cefoperazone + sulbactam 1 158 293,71 1,18 92.44 0. 2 J01C A01 Pn. / 3 ampicillin 1 050 629,12 1,07 93.51 1. 2 J01D B01 Cph./1 cephalexin 1 027 896,97 1,05 94.56 2. 2 J01M B04 Chinolons/1 pypemydova acid 1 024 782,18 1,05 95.61 С 5,44% 2 J01D B04 Cph./1 цефазолін 881 773,48 0,90 96.51 4. 2 іміпенем і інгибитор J01D H51 Carbapenems 600 081,91 0,61 97.12 5. ферменту 2 J01C E01 Pn. / 1 бензилпеніцилін 513 054,36 0,52 97.64 6. 2 J01C R01 Protected pn./3 ампіцилін + сульбактам 408 858,02 0,42 98.06 7. 2 Combination of J01C A51 ампіцилін + оксацилін 402 967,75 0,41 98.47 8. pn. 2 J01D D14 Cph./3 цефтібутен 253 616,42 0,26 98.73 9. 3 J01M A07 Fq./2 ломефлоксацин 191 552,24 0,20 98.93 0. 3 J01D D54 Cph./3 цефтриаксон, комбінації 186 345,89 0,19 99.12 1. 3 J01C E08 Pn./1 бензатиа бензилпеніцилін 150 716,53 0,15 99.27 2. 3 J01C R02 Protected pn./3 амоксицилін + сульбактам 117 925,75 0,12 99.39 3. 3 J01D H03 Carbapenems ертапенем 113 644,93 0,12 99.51 4. 3 J01M A03 Fq./2 пефлоксацин 89 218,31 0,09 99.60 5. 3 J01D B05 Cph./1 цефадроксил 87 313,82 0,09 99.69 6. 3 J01M A09 Fq./3 спарфлоксацин 72 541,33 0,07 99.76 7. 3 J01C R50 Pn. / 3 амоксицилін + клоксацилін 62 539,29 0,06 99.82 8. 3 J01D D51 Cph./3 цефотаксим, комбінації 44 781,65 0,05 99.87 9. 4 тикарцилін і інгибитор J01C R03 Pn. / 4 26 823,89 0,03 99.90 0. ферменту 4 J01D H04 Carbapenems доріпенем 26 112,85 0,03 99.93 1. 4 Cph. J01D E51 амікацин+цефепім 23 507,79 0,02 99.95 2. +aminoglycoside 4 піперацилін і інгибитор J01C R05 Pn. / 5 13 035,58 0,01 99.96 3. ферменту 4 J01M A15 Cph./4 геміфлоксацін 11 410,40 0,01 99.97 4. 4 J01D D07 Cph./3 цефтізоксим 7 724,55 0,01 99.98 5. 4 J01D E02 Cph./4 цефпіром 4 992,18 0,01 99.99 6. 4 J01C E10 Pn. / 1 феноксіметілпеніцілін 78,50 0,01 100.00 7. Total: 97 781 647,18 100 % 100,00% Notes: Cph. – cephalosporins Fq. – fluoroquinolones Pn. – penicillins The distribution of antibacterial medicines for ABC-groups was as following: the group A – 11 INN took 79.22 % of the total costs for all the researched medicines; the group B – 11 INN (15.34 % of the costs); the group C – 25 INN (5.44 % of the costs). Then the group A was investigate in detail because it included the most expensive medicines. The first place in the rating for the most expensive medicines took drugs based on the active ingredient ceftriaxone, which included 22.82 % of all costs. Ceftriaxone is cephalosporin antibiotic from the III generation with broad spectrum of action for parenteral administration. Bactericidal activity is due to inhibition of the synthesis of bacterial cell wall. It has different resistant to most beta-lactamases of gram-negative and gram-positive microorganisms. Also ceftriaxone exceeds all other cephalosporin infusions in the duration of the half-life (8.5 hours in adults and 5-18 hours in children) and the degree of penetration to the organs and tissues. The benefits of the drug include double excretion pathways that lead to the need of dose correction only in case of both renal and hepatic failures and almost complete bioavailability in case of intramuscular administration [1, 2]. A broad spectrum of antimicrobial activity, bactericidal action, favorable pharmacokinetic properties, a little profile of side effects and good tolerance cause the convenience and safe administration of ceftriaxone in a lot of indications. The expensiveness of these medicines is associated with their pharmacological properties that explain the high level of their prescriptions by professionals [3]. The second place takes amoxicillin protected with clavulanic acid. Its costs took 14.49 % from the total costs. Protected aminopenicillins are characterized by high resistance to β-lactamases. Their antimicrobial spectrum is enlarged due to their action against gram-negative bacteria such as Klebsiella spp., P. vulgaris, C. diversus, and anaerobes from B. fragilis group. They are also active toward microorganisms with acquired resistance: staphylococci, gonococci, M. catarrhalis, E. coli, Haemophilus spp., P. mirabilis. More than 30-year term of clinical usage of the medicine and numerous clinical researches have shown high effectively of amoxicillin/clavulanate in the treatment of various infections. Currently protected aminopenicillins considered to be the first line drugs for the treatment of community- acquired lower respiratory tract infections [2, 6]. However, if we compare these data with previous researches the consumption of penicillins in DDDs/1000 inhabitants per day, amoxicillin in combination with clavulanic acid takes only the second place. The first place in the structure of consumption DDDs/1000 inhabitants per day is amoxicillin, it takes the fourth place among the costs level [7]. Maybe it is connected with the high price of amoxicillin with clavulanic acid compared to the price of monomedicine amoxicillin. Also, a significant part in the structure of costs (the third place) of antibacterial medicines takes the drug from fluoroquinolones group – levofloxacin. As the III generation fluoroquinolone levofloxacin has advantages in its antimicrobial activity comparing to medicines from previous generations. It is characterized by a broad spectrum of antimicrobial activity, which covers large number of clinically important pathogens [2, 8]. The bacteria that are sensitive to it: • a lot of gram-positive aerobic bacteria such as Staphylococcus aureus, Staphylococcus saprophyticus, Streptococcus pneumoniae (including penicillin sensitive strains), Streptococcus pyogenes, Streptococcus agalactiae, Enterococcus faecalis, Bacillus antracis; • most aerobic gram-negative bacteria – Escherichia coli, Shigella spp., Salmonella spp., Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, and others; • intracellular bacteria – Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella pneumophila; • mycobacteria According to our previous researches (the research of consumption of fluoroquinolone antibiotics using ATC/DDD-methodology), levofloxacin takes only the fourth place, which proves that the high level of costs associated with the high price of levofloxacin drugs [9]. The fifth place takes ciprofloxacin. This drug belongs to the "old" fluoroquinolones, however, is an exception from this group because still is named as the "gold standard" among all fluoroquinolones. It is widely prescribed from the late 80's to nowadays in case of number of infectious diseases, including the kidney and urinary tract, skin, soft tissues, bones, joints, pelvic, respiratory tract etc. It should be noted that ciprofloxacin is considered to be one of the most powerful antibiotics that act on the "problem" bacteria – Staphylococcus aureus (including some methicillinresistant ones) and Pseudomonas aeruginosa (including multiresistant ones). Dealing with the activity toward Pseudomonas aeruginosa ciprofloxacin can be compared to meropenem and the most effective antypseudomonal third-generation cephalosporin – ceftazidime [2, 11]. In the 6, 7, 8, 9 and 11 places are cephalosporins. This is cefuroxime (second generation), cefpodoxime, ceftazidime and cefixime (third generation drugs), and cefepime (fourth generation). These drugs have a broad spectrum of action. Currently the III generation cephalosporins designed to be administered parenterally, are used in the ambulatory practice, but were used before only in the treatment of serious infections in the hospital. Cephalosporins of the III generation, intended for oral administration, are used in community-acquired infections of moderate severity caused by gram-negative flora, as well as the second phase therapy after parenteral administration of medicines [12, 13]. B and C groups consist of the first generation medicines such as ampicillin (group B, 1.07 % of total costs), cephalexin (group B, 1.05 %), benzylpenicillin (group C, 0.52 %), cefadroxil (group B, 0.09 %) and others. Also groups B and C include new expensive drugs wich are used less frequently: moxifloxacin (group B, 1.24 % of total costs), meropenem (group B, 1.22 %), hemifloxacyn (group C, 0.01%) and imipenem in combination with an inhibitor of the enzyme (group C, 0.61 %). Conclusions and recommendations for further researches This quantitative epidemiological research allows us to evaluate the quality of antimicrobial therapy based on the investigated results. The researched results answer the question, which drugs are mainly used in medical practice, modern and previous medicines that have been used for decades and now are not so effective. But along with this we have to realize that the results do not allow us assessing the quality of individual antibiotic therapy and do not eliminate dose and prescription mistakes to specific patients who are not in the plan of this research. This aspect of antibiotic therapy quality can be determined only by the conditions of analysis of appointment letters and their accordance to diagnosis. Thus, the results of the ABC-analysis shows that the group A (the group of the most expensive medicines) includes 11 INN that take 79.22 % of the total costs among all antimicrobial medicines we have studied. All medicines are from the new generation of antibiotics and have a broad spectrum of action. That is why money is spent rational and clinically appropriate. For the further analysis of the costs of antibiotics should be closely examine the usage of these groups of medicines in specific disease, and compare with the standards and protocols of treatment. References

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