Pattern of antibiotic consumption in Iran during 2000-2009

Akbar Abdollahiasl1, Abbas Kebriaeezadeh

1,2, Amir Farshchi

1,3, Golbarg Ghiasi

1, Shekoufeh

Nikfar1,4

, Mohammad Abdollahi2*

1Department of Pharmacoeconomics and Pharmaceutical Administration, Faculty of Pharmacy,

Tehran University of Medical Sciences, Tehran, Iran; 2 Department of Toxicology and

Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran

University of Medical Sciences, Tehran, Iran; Pharmaceutical Sciences Branch, Islamic Azad

University, Young Researchers Club; 4Food and Drug Laboratory Research Center, Ministry of

Health and Medical Education, Tehran, Iran

*Correspondence

Abstract

Objectives: Increase in antibiotic resistance and drug expenditure threaten the community health

specially when there is no updated data for making appropriate policies in the country. Describing

the overall patterns of antibacterial drugs sale as a surrogate of consumption in Iran from 2000 to

2009 has been the main objective of this study.

Methods: Annual pharmaceutical sales data were acquired from the Ministry of Health (MOH).

Data were collected in a central database and cross-checked to other data come from

manufacturers and importers. To express data, Anatomical Therapeutic Chemical (ATC)

classification and Defined Daily Dose (DDD) were used. DDD/1000 Inhabitants/Day (DID) was

the main unit for measuring drug sales and J01 (antibacterial for systemic use) was considered as

antibiotic here.

Results: Average consumption of antibacterial drugs in J01 group was 46.8 DDD/1000

inhabitants/day with a range between 39.1 in 2000 to 51.8 in 2009. 5.3% of usage was in the

parentral form. Penicillines (ATC: J01C) including procaine and benzathine penicilline G and

other beta-lactams (ATC: J01D) such as ceftriaxone and cefazolin with an ascending trend have

shaped the consumption pattern of parenteral antibacterials. Oral penicillins including amoxicillin

formed 55.8% of total consumption as the principal antibiotic with an ascending trend in the

period. While the third generation of cephalosporins as well as macrolids and quinolons showed a

noticeable growth, the first generation of cephalosporins, aminoglycosides, amphenicoles and

sulfonamides lost their share in the market. Tetracyclines as other antibacterial medicines

preserved their tiny contribution in the market during the period.

Conclusion: consumption of systemic antibacterial medicines in Iran is higher than almost other

countries. Ascending trend of third generation of cephalosporins, quinolones, and wide spectrum

penicillins and some other new antibacterials is an evidence for policy makers to promote rational

prescribing, dispensing and consuming of antibacterials. Better regulations on pharmacies, pricing

mechanisms, and insurance systems are essential to rationalize the huge consumption of

antibacterial medicines in the country.

Keywords: Antibiotics, Iran, Utilization, Pharmacoepidemiology

Introduction

In spite of valuable benefits that could be gained by the public availability of antibacterial

medicines, the consequences of irrational use is a major concern. In a developing country such as

Iran with a population of 72.4 million (2009)1 and Per Capita Gross Domestic Product of 4540

USD2 with 6.8% spending on health, increase in antibiotic resistance

3-6 and growth in drug

expenditures are the main outcomes of irrational antibiotic consumptions in the community.7 Lack

of national standard therapeutic guidelines for infectious diseases,8 self-medication and tending

towards new medicines could exaggerate these problems.9 For many years, some health policy

makers have tried to prevent overuse of antibiotics in Iran but they have not a comparable data for

the consumption. There is only one report in 1998 that evaluated total consumption of antibiotics

in Iran.10

Lack of updated drug consumption data causes some non-evidence-based policy making

in the country.11

Descriptive reporting of antibiotic consumption based on internationally known

measurement units such as Defined Daily Dose (DDD) not only could provide initiative

information for better decision making12

but also could make some data for comparison to other

countries.13

However DDD has some limitations in children and topical medicines and sometimes

there are differences between DDD and routine prescription dose14

, it is the best existing system

for reporting drug consumption data so far.

Lack of exact national surveillance databases makes sales data better surrogate for consumption.

Antibiotic leftovers make the main gap between sales and exact consumption. This gap decreases

when some parts of leftovers are rationally or irrationally used in the next time.15

Sales data cover

consumption in outpatients and inpatients. The aim of this study was to describe the overall

patterns of antibacterial drugs sales as a surrogate of consumption in Iran from 2000 to 2009

considering the price of these medicines during the period.

Methods

Annual pharmaceutical sales data were acquired from the Ministry of Health (MOH), division of

pharmaceutical affairs. For more than twenty five recent years, all pharmaceutical producers and

importers have distributed their products to pharmacies all around the country through a few main

pharmaceutical distributors which send their monthly sales’ reports to the MOH. These data

include the amount of drugs sold to pharmacies, their pack size and the price per pack. In this

study, distributors’ sale data have been collected and converted to a uniform format for statistical

calculations. Data were cross-checked to other sporadic MOH databases come from manufacturers

and importers.

Anatomical Therapeutic Chemical (ATC) classification and DDD were used to choose

antibacterial medicines and calculation of their consumption as described by WHO collaborating

centre for drug statistics methodology.14

We considered J01 ATC class (antibacterial for systemic

use) as antibiotic in this study. Total consumption was reported based on DDD/1000

inhabitants/day (DID) which calculated by the following formula14

:

Here, DID was calculated for each medicine in J01 class. Then, total DID for J01 class and its

subgroups were determined. Population of each year was considered for calculation of DID of that

year. The average price of each DDD in each ATC class (at third level) was calculated by the

following formula:

For comparison to other countries’ data, major databases like PubMed, Scopus, and ISI web of

knowledge were searched by the key words of “drug, medicine, utilization, consumption, ATC,

DDD”.

Results

During 2000 to 2009, DID was 46.8 which means each 1000 Iranians have used 46.8 (95% CI,

44.2-49.5) DDD of antibacterial drugs in J01 group. As shown in Figure 1, the total consumption

of antibacterial medicines have reached 51.8 DDD/1000 inhabitants/day in 2009 from 39.1 in

2000 showing a marked 3.3% annual growth.

Figure 1 shows that the main part (94.7%) of antibacterial consumption has been oral dosage

forms as 4.3 (95% CI, 41.7-47) DDD/1000 inhabitants per day vs. 2.5 (CI 95%, 2.4-2.6) DID for

parenteral.

The pattern of total consumption based on therapeutic subgroups in the third level of ATC (J01*)

has been presented in Table 1. It shows the share of each ATC subgroup in each year. Penicillins

(J01C) have been the principal antibiotics in the period; they have been used 26.1 DDD/1000

inhabitants/day (55.8% of total use). Although the trend shows 5.3 DID increase from 2000 to

2009 but the share has been decreased (4.1%). Amoxicillin (with and without clavulanic acid) has

been the main medicine in this group (Figure 2).

Consumption of other beta-lactams (J01D) including cephalosporins has been tripled in the period

and reached to 20.2% (10.46 DID) of total use in 2009. Figure 3 shows consumption of the first

generation of cephalosporins against the third generation. Cephalexin as the main first generation

was used 2.9 DID in 2000 and 3.1 DID in 2009. The consumption of cefixim as the representative

of the third generations has reached 6.26 DID in 2009 from 0.09 DID in 2000.

The use of sulfonamides and trimethoprim (J01E) including cotrimoxazole which had been in the

second top in 2000, was halved at the end of period.

Comment [11 :]clavulanic is correct

Comment [M2]: Check this

Both macrolids (J01F) and quinolons (J01M) show a noticeable growth. These two classes had

12.7% of the market equals to 6.6 DID. Azithromycin and ciprofloxacine as headers of these

groups showed an increased usage in the period (Figure 4).

Aminoglycosides (J01G) sale after a drop off reached to 0.3 DID (0.5% of the market) in 2009.

Figure 5 shows the key role of gentamicin in this group. Interestingly, amphenicoles (J01B) have

lost their tiny share during the period. Even with a small decrease in the market share, the

utilization of tetracyclines (J01A) did not have significant change.

Apart from a sharp peak in 2007, which is due to an unexpected increase in sales of nitrofurantoin

(100 mg tablet), other antibacterials (J01X) totally preserved their tiny contribution in the market

during the period.

In parenteral forms, penicillins (J01C) and other beta-lactam drugs (J01D) were the main classes

which shaped the total trend of parentral antibacterial medicines (Figure 6). Penicilline G procain

(J01CE09), penicilline G benzathine (J01CE08) in J01C, ceftriaxon (J01DD05) and cefazolin

(J01DE04) in J01D were the main drugs in parentral form (Figure 7, 8). These four formed 63-

78% of total parentral antibacterial consumption during tested period. The descending trend of

parenteral penicillins was against ascending trend of ceftriaxon.

For comparison to other countries, we gathered available consumption data in some European

countries in the years 2002 and 2006 which have been shown in Figure 9.16-21

Figure 10 shows the

share of penicillins as one of the main antibiotic classes between selected countries.

For an overview on price of antibacterials in the period of study, Table 2 shows the average price

of each DDD in each subclass of J01. Prices of two main classes of antibacterials (J01C, J01D)

were compared as shown in Figure 11.

Discussion

In a country that prescriptions databases or drug surveillance data are not available and non-

prescribed medicines can be provided with no trouble, 9

the distributor’s sales data can be a good

surrogate for drug consumption.22

The present results indicate that consumption of systemic

antibacterial medicines in Iran is much higher than those of all European countries16

and Turkey.7

As shown, a 3.3% annual growth rate is evident. Total consumption reached to 51.8 DID in 2009

which was 12.8 DID higher than that of 2000 (39.1 DID). These data reveal that use of parenteral

forms has not been changed during the period and descending consumption of parenteral

penicillins has been compensated by increasing use of ceftriaxon (Figure 6). Growth in adverse

drug reaction reported (Iranian MOH, Adverse Drug Reaction Office; unpublished data) about

ceftriaxon confirms this substitution in the market. Although, total consumption of parenteral

antibacterials has not been changed in the period but there is a tendency to consumption of newer

medicines for inpatients and outpatients. People rarely use parenteral antibiotics without

prescription,9 thus, clinicians and prescribers are more responsible for rationality in use of

parentral medicines.

In spite of constant trend of parenteral antibiotics consumption, oral antibacterials have had

ascending trend during the period. Total trend of oral dosage forms was caused by penicillins

(J01C). More than half of total antibacterial consumption during the period (26.1 DID; 55.8% of

total) has been in this group. Amoxicillin with or without clavulanic acid as a wide spectrum

antibacterial has been the main drug in this group which averagely showed 19.9 DID (42.6% of

total). In Figure 10, large difference between Iran’s consumption and other countries would be

decreased if penicillin group was omitted from calculation. The main reason for high consumption

of oral penicillins specially amoxicillin is easy access to them without prescription in pharmacies.9

Sales of other beta-lactams (J01D) including cephalosporins have been tripled and made 20.2%

(10.46 DID) of total market in 2009. The third generation of cephalosporins increasingly has

raised their share in the market while the first generation has kept the constant trend. Cefixime as

the only oral drug in the third generation plays the main role in J01D’s trend. In 2009, cefixime

made 12.1% of total antibacterial consumption in the country. Some reasons including a) oral

dosage forms, b) long-acting effect and c) newer than other competitors cause this growth.

All oral antibacterial medicines are produced by domestic manufacturers; and due to pricing

method in Iran, profit margin of cephalosporins specially cefixime is higher than that of other

drugs (Figure 11). Thus many manufacturers do some hidden advertizing (as discounting to

pharmacies) for increasing the sale of their products seeming the hidden reason for high cefixime

consumption.

Quinolones with 6.8% market (3.18 DID) show an ascending trend. Ciprofloxacin has 2/3 of the

quinolone’s market and the trend of quinolones follows its trend (Figure 4).

Although the use of cotrimoxazole in sulfonamide and trimethoprim group (J01E) has been halved

at the end of period, it still has the third position in market. Based on the indication, descending

trend of this group could be explained by ascending trends of quinolones and the third generation

of cephalosporins.

Doubling the use of macrolids (J01F) is due to introduction of azithromycin and clarithromycin.

Erythromycin as the main drug of this group in 2000 has lost its share in 2009 (Figure 4).

Tetracyclines (J01A) did not have considerable change during the period. Aminoglycosides

(J01G) and amphenicoles (J01B) had a small share in the market which their changes could not

affect the whole consumption.

The average price of each DDD of antibacterial medicines in J01 group has been 24.5 cents (USD)

showing about 11% annual growth during the period. Introduction of new expensive medicines to

market and inflation rate are the main reasons behind this growth. Except some sporadic drugs in

other groups (J01X), the J01D including cephalosporins had been the most expensive drugs while

sulfonamides were the cheapest ones.

Conclusion

The present study reveals that consumption of systemic antibacterials in Iran is higher than all

compared countries. Ascending trend in use of third generation cephalosporins, quinolones, and

wide spectrum penicillins is a good evidence for policy makers to promote rationality in

prescribing, dispensing and consuming of antibacterial medicines. Our previous experiences show

that there are some gaps between rules and those were done practically.23

Revising the rules and

regulations related to pricing mechanism, insurance systems and more control on supply chain are

needed to rationalize this huge consumption of antibacterial medicines in the country.

Acknowledgement: This paper is the outcome of an in-house non-financially supported study and authors

declare no conflict of ineterst.

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Figure 1: Consumption of antibacterial drugs in Iran during 2000-2009 based on route of administration.

Figure 2: Consumption of amoxicillin (J01CA04) against whole penicillins class (J01C) in Iran during

2000-2009.

Figure 3: Main role player in consumption of other beta-lactam (J01D) class in Iran during 2000-2009.

Figure 4: Consumption of quinolones (J01M) and macrolids (J01F) and the main medicine in each class in

Iran during 2000-2009.

Figure 5: Consumption of gentamicin (J01GB03) against whole aminoglycosides class (J01G) in Iran

during 2000-2009.

Figure 6. Comparison of penicillines (J01C) and other beta-lactams (J01D) as parenteral antibacterial

medicines in Iran during 2000-2009.

Figure 7. Comparison of ppenicilline g procain (J01CE09) and penicilline g benzathine (J01CE08) form

beta-lactam (J01C) class in Iran during 2000-2009.

Figure 8. Comparison of ceftriaxon (J01DD05) and cefazolin (J01DE04) form beta-lactam (J01D) class in

Iran during 2000-2009.

Figure 9. Consumption of antibacterial drugs in Iran and some other countries in 2002 and 2006.

Figure 10. Consumption of penicillins vs. other antibacterial drugs in Iran and some other countries in

2006.

Figure 11. Price of each DDD in beta-lactam class (J01C, J01D) against price of each DDD in whole

systemic antibacterials (J01) in Iran during 2000-2009.

Table 1. Consumption pattern of antibacterial drugs for systemic use (J01) in Iran during 2000-2009.

DID Annual share

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 Average

B-Lactam, Penicillins (J01C) 22.7 25.1 26.9 26.1 24.7 27.4 27.6 26.1 26.5 28.0 26.1

(58.2%) (59.2%) (59.4%) (57.2%) (56.7%) (56.3%) (55.9%) (50.9%) (52%) (54.1%) (55.8%)

Other B-Lactam (J01D) 3.4 3.8 4.5 5.4 6.0 6.7 7.3 7.9 9.7 10.5 6.53

(8.7%) (8.9%) (10%) (11.9%) (13.8%) (13.9%) (14.8%) (15.4%) (19.1%) (20.2%) (13.9%)

Quinolone (J01M) 1.8 2.4 2.6 2.8 3.2 3.8 3.7 4.1 4.0 3.5 3.18

(4.5%) (5.7%) (5.8%) (6.1%) (7.3%) (7.7%) (7.6%) (8%) (7.8%) (6.8%) (6.8%)

Tetracyclines (J01A) 3.3 3.2 3.4 3.9 3.3 3.8 4.0 3.5 3.7 3.3 3.53

(8.4%) (7.5%) (7.6%) (8.5%) (7.6%) (7.8%) (8.1%) (6.9%) (7.2%) (6.3%) (7.5%)

Macrolide & Lincosamide

(J01F) 1.2 1.3 1.3 1.5 1.4 1.8 2.2 2.7 3.1 3.1 1.96

(3.2%) (3%) (2.8%) (3.3%) (3.3%) (3.8%) (4.5%) (5.2%) (6.1%) (5.9%) (4.2%)

Sulfonamide & Trimethoprim

(J01E)

5.6 5.8 5.8 5.2 4.3 4.5 3.4 3.9 3.5 3.0 4.50 (14.4%) (13.8%) (12.8%) (11.4%) (9.8%) (9.3%) (6.9%) (7.6%) (6.8%) (5.9%) (9.6%)

Aminoglycoside (J01G) 0.6 0.5 0.5 0.4 0.4 0.4 0.3 0.3 0.3 0.3 0.40

(1.5%) (1.1%) (1.2%) (1%) (1%) (0.8%) (0.6%) (0.5%) (0.6%) (0.5%) (0.9%)

Other Antibacterials (J01X) 0.3 0.2 0.2 0.3 0.3 0.3 0.9 2.8 0.3 0.2 0.58

(0.8%) (0.6%) (0.5%) (0.7%) (0.6%) (0.6%) (1.8%) (5.5%) (0.5%) (0.4%) (1.2%)

Amphenicols (J01B) 0.1 0.1 - - - - - - - - 0.03

(0.2%) (0.3%) (0.1%) (0%) (0%) (0%) (0%) (0%) (0%) (0%) (0.1%)

Total (J01) 39.1 42.4 45.4 45.7 43.6 48.6 49.4 51.2 51.0 51.8 46.8

(100%) (100%) (100%) (100%) (100%) (100%) (100%) (100%) (100%) (100%) (100%)

Data are based on DDDs/1000 Inhabitants/Days (DID) and percent of each J01 subgroup in each year.

Table 2. Price of antibacterial drugs for systemic use (J01) in Iran during 2000-2009 based on USD/DDD.

US$/DDD

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 Avg

Aminoglycoside (J01G) 0.274 0.285 0.297 0.376 0.414 0.511 0.595 0.639 0.712 0.847 0.495

Amphenicols (J01B) 0.205 0.182 0.231 0.277 0.216 0.485 0.687 1.117 0.466 0.465 0.433

B-Lactam, Penicillins (J01C) 0.114 0.115 0.131 0.167 0.173 0.163 0.187 0.203 0.250 0.247 0.175

Macrolide, Lincosamide (J01F) 0.336 0.337 0.372 0.475 0.507 0.562 0.630 0.595 0.551 0.536 0.490

Other Antibacterials (J01X) 0.374 0.563 0.933 0.752 0.936 1.007 0.373 0.139 1.169 2.004 0.825

Other B-Lactam (J01D) 0.362 0.427 0.528 0.614 0.649 0.709 0.786 0.815 0.869 0.810 0.657

Quinolone (J01M) 0.149 0.161 0.164 0.176 0.169 0.168 0.187 0.189 0.223 0.230 0.182

Sulfonamide & Trimethoprim (J01E) 0.029 0.035 0.039 0.047 0.047 0.051 0.057 0.066 0.074 0.080 0.052

Tetracyclines (J01A) 0.030 0.030 0.030 0.037 0.051 0.046 0.045 0.045 0.051 0.053 0.042

Total (J01) 0.130 0.140 0.166 0.212 0.235 0.243 0.281 0.294 0.365 0.364 0.243