Microsoft word - aop080907.doc

Original Article
Comparative Analysis of Patient Package Inserts of Local and
Imported Anti-Infective Agents in Palestine
Sawalha AF1,2, Sweileh WM1, Zyoud SH2, Jabi SW1 1College of Pharmacy. 2Poison Control and Drug Information Center (PCDIC). An- Najah National University, Nablus, Palestine Received for publication on 06 May 2008. Accepted in revised form 23 June 2008 Key words: patient package insert, evaluation, Palestine, drug information
ABSTRACT
Background and Objective: The patient package insert is an important source of drug information.
The aim of this study was to evaluate and compare the PPI of the anti-infective agents manufactured
in Palestine with the imported equivalents. Method: The selection criteria generated 15 different anti-
infective agents available as 36 locally manufactured products and 15 imported equivalents. The
design of the patient package insert was evaluated in terms of the number of words used in eight
main headings and the presence or absence of certain information regarding nine statements.
Results: Inserts of locally manufactured products have significantly fewer words than those of
imported products with respect to warnings, dosage and administration, and side effects. The most
significant difference was found in the warnings. Moreover, differences were found between inserts of
local and imported products in terms of the presence of the nine informative statements. Locally
manufactured products did not mention inactive ingredients, clinical pharmacology or date of last
revision, but all of them provided information on the use of the drug during pregnancy and lactation
and on the duration of therapy. However, in general they provided less information than the imported
equivalents. Conclusion: Palestinian authorities and local manufacturers should implement
appropriate measures to regulate the quality and quantity of information in the patient package insert
of locally produced anti-infective agents. PPI improvement will better direct health practices to the
benefit of the patients.
INTRODUCTION
information in PPI, which leads to reduced The patient package insert (PPI) is important for providing essential drug information for patients taking over-the-counter as well as The design and the amount of information in prescription-only medications. In developing the PPI are usually regulated by the legislative countries, the PPI is considered an important health authorities. The PPI should increase source of drug information for health-care patient's awareness of medication-related providers as well, because of a limited ability issues, contribute to the safe and correct use to access up-to-date information about drugs. of the medication, and help in the success of In addition, studies have shown that the PPI the treatment plan. The European Directive helps bridge the information gap between stipulates that in all European Union member states every drug should include an easily medications [1,2]. The quality and quantity of legible and clearly comprehensible package information available in the PPI has been insert [7]. The European Commission provides shown to influence patients’ compliance and guidelines for the contents of package inserts, satisfaction [3,4]. There are also indications including style and terminology [8,9]. In that patients who read the PPI are more likely comparison to Europe, package inserts in the to follow the instructions, especially if the instructions of the physician and/or pharmacist frequently feature smaller font and many [5]. A study carried out in Denmark found that technical terms and consist of up to six A4 patients may be confused by inconsistent pages [10,11]. Despite all efforts, PPI are still criticized in USA, many European countries [12], and Australia [13,14]. For example, it was Evaluation and Assessment of the PPI
The PPIs were initially evaluated according to found in patients who felt frightened after they evaluated by two methods. The first was a experts have suggested that the PPI for drugs simple word count of eight major headings: description, indications, contraindications, should include symbols and special features warnings, drug interactions, side effects, dosage and administration, and storage. The “warning” heading included both the caution and precaution headings. The words under companies produce about 1000 of the different medical products on the Palestinian market. Besides the locally manufactured medical products, many imported drugs are registered The second method of evaluation was carried in the Palestinian market. The Palestinian Ministry of Health (MOH) recommends that all presence of information on the following nine marketed medications be supplied with a PPI statements in the PPI: inactive ingredients, that is written in both Arabic and English, but therapeutic class, clinical pharmacology, use there are no regulations regarding the quality during pregnancy and lactation, overdose, or the quantity of the information, design and missed doses, duration of therapy, instructions not to consume after the expiration date, and the date of last revision. Presence of the information was scored as 1 and its absence as 0. The total score was calculated for each selected anti-infective medications anti-infective agent. The percent score was manufactured locally to the imported calculated as a percentage of the possible maximal score for each local company as well MATERIALS & METHODS
Inclusion Criteria:
All data were entered into the statistical Anti-infective agents were selected for study package for social sciences (SPSS) version because infectious diseases are one of the most common causes of mortality in Palestine imported anti-infective agents. Statistical [16]. The inclusion criteria were as follows: (i) comparison was carried out using Student’s t- imported equivalent; (iii) available in oral solid form; (iv) registered in the department of General evaluation of the PPI
available in the local market. Based on these available in the Palestinian market as 36 local criteria, 15 different anti-infective agents were and 15 imported products (Table 1). The 36 amoxicillin/clavulanic acid, azithromycin, pharmaceutical companies designated as A (4 clarithromycin, metronidazole, terbinafin, products), B (8 products), C (10 products), and ketoconazole, trimethoprim/sulfamethoxazole, D (14 products). The 15 most popular imported doxycycline, ofloxacin, ciprofloxacin and American and European companies (Table 1). fluconazole. The imported products selected in this study were the most popular equivalents All the inserts of all local and imported that are manufactured outside the Palestinian products were printed in both Arabic and authority areas. The popularity of a certain English. In the local products, Arabic was on imported product was judged through a phone one side of the insert and English on the other. survey of 100 randomly selected community In contrast, most of the imported products had pharmacies in Palestine. In this survey, the both languages on the same side. Inserts of pharmacists were asked to state the most locally manufactured products used smaller commonly dispensed imported equivalent(s) font than those of the corresponding imported
Table 1: Anti-infective agents available in the Palestinian market that was included in the study.
Anti-infective agent
Local products
Most popular imported equivalents
Amox/Clav = amoxicillin/ clavulanic acid; Trim/Sulfa = Trimethoprim/sulfamethoxazole. The design of the inserts was also evaluated. ofloxacin, and cephalexin inserts had three- to The criteria used to assess design included size of the leaflet, text font size, and size and colour of headings. The overall design was Amoxicillin/clavulanic acid had the highest different from one local company to another word count compared to the other drugs, but the imported product had 2989 words whereas exception of one local company, the headings in all local inserts were printed in black. In Analysis of scores
addition, the inserts of the local products differ All inserts were also evaluated using the from those of the imported equivalents in the scoring method. The total score was 65.4 for the locally manufactured anti-infective agents and 81 for the imported equivalents (P= 0.02) (Table 3). None of the inserts achieved a full Word count
We compared the word counts of the eight information on “inactive ingredients,” “clinical headings in the PPI of local and imported pharmacology” and “date of last revision,” products. Significant differences in word count whereas one third to one half of the imported products provided this type of information imported products in the headings “warnings”, (Table 4). By contrast, all inserts contained “side effects”, and “dosage and administration” instructions about use during pregnancy and with P values of 0.008, 0.016, and 0.024, lactation, overdose and duration of therapy respectively (Table 2A,B). The word counts in concerning pregnancy and lactation in the horizontally. The mean word counts for the local products was given under different “warnings” heading was 64.7 words in all local headings, such as “contraindications,” “warnings” or “precautions,” or otherwise imported products combined, which is a 2.5- stated separately as follows: “inform your fold difference. Similar findings were observed in the “side effects” and “dosage and breastfeeding.” In addition, local products differed from imported products in the amount We also counted all words in each insert. With of information. Local products did not explain the exception of azithromycin, the total number whether that can be used during pregnancy. In of words in the eight tested headings was greater in the imported than in the local detailed information for both patients and amoxicillin/clavulanic acid, terbinafin, medication during pregnancy and lactation. The pattern was similar for the statement pertaining to “overdose” and its consequences and first aid. “Go to the hospital in case of treatment”, most inserts of local products state: overdose”, and/or “do not induce vomiting” are “duration is as directed by the physician,” or the most common instructions found in the “do not stop the medication without informing inserts of most local anti-infective agents. In the physician.” By contrast, most imported products informed patients about how long the mentioned in details the effects expected from
Table 2 A and B: Word counts and statistical analysis
A. Word counts of the major eight headings in the patient package inserts of the locally produced and imported anti-infective
agents.
Variable
Amoxicillin
Amox/ Clav
Azithromycin
Doxycyclin
Trim/ Sulfa
Ofloxacin
Cefuroxime
Ciprofloxacin
Cephalexin
Metronidazole
Fluconazole
Ketoconazole
Mebendazole
Clarithromycin
Terbinafin
Amox/Clav = amoxicillin/ clavulanic acid; Trim/Sulfa = Trimethoprim/sulfamethoxazole; Loc.= local; Imp.= Imported
B. Statistical difference between local and imported anti-infective agents for all products combined
Variable
Mean ± S.E of the total word count
Local agents
Imported agents
Description
Indications
Contraindications
Warnings
Drug Interaction
Dosage and Administration
Side effects
Table 3: Scores of the nine statements in the PPI of local
the product. The differences between the local and imported anti-infective agents used in the Palestinian information in the insert indicates that there is Anti- infective agent
Imported
Amoxicillin
no governmental supervision over locally Amoxicillin/Clavulanic acid
produced anti-infective agents, and probably Azithromycin
other drugs as well, and that regulation is Doxycylin
required to ensure that patients are provided Trimethoprim /
Sulfamethoxazole
Ofloxacine
pharmacists who depend on locally written PPI Cefuroxime
as a source of drug information may not be Ciprofloxacin
able to provide good patient counselling and to Cephalexine
obtain up-to-date information. For example, Metronidazol
Fluconazol
Mebendazol
lactation was not fully explained in inserts of Clarithromycin
local anti-infective products. Lack of detailed Terbinafin
information about overdose makes health care Ketoconzole
providers and/or the general public unable to Total scores
make the best decisions in case of poisoning. The score of each medication represents the number of statement in the PPI out of nine tested statements. Early management of poisoning is important Significant difference exists in the total scores between local and imported products. P value for difference of total hospital visits and medical expenditure. Inserts of imported cefuroxime, Inadequate information in the PPI has been amoxicillin/clavulanic acid and metronidazole reported by authors in different countries. In a have the highest total score on the nine study carried out in Saudi Arabia, the authors statements (Table 3). For the local products, found that there was substantial disagreement amoxicillin/clavulanic acid has the highest score (5.5; Table 3). Among the four local inserts and the British National Formulary and the package inserts of the brand products percent score (percent of the maximal score) marketed in Saudi Arabia [17]. In another study of non-steroidal anti-inflammatory agents marketed in Saudi Arabia, the authors showed pharmaceutical companies combined (Table generally conveyed limited and incomplete information compared to their counterparts DISCUSSION
marketed in USA [18]. In the USA, it was We found significant differences in the quantity shown that PPI do not fully meet the federal and quality of information in the inserts of regulations [19]. A European study found locally produced compared to imported anti- substantial disagreement in the materials infective medications. Although the word available to prescribers and patients in counts for the “indications” were not different countries [20]. A study in Perugia significantly different, there were differences in found that all people in the study complained the quality of the information. Most of the local that the print size used in the PPI is too small. “indications” in general terms: “for the treatment of infections”. However, in the imported products, the “indications” heading included, in most of the cases, the sites and A recent study carried out in Germany found types of infections and in a few cases the that reading PPI might have less impact than assumed and that they are read selectively Differences between inserts of local and [22]. The authors concluded that personal statements regarding inactive ingredients, pharmacist is more helpful and more willingly clinical pharmacology and date of last revision. accepted than information in PPI [22]. In the It is important to list the inactive ingredients, such as sodium salts or artificial sweeteners, computer-generated labels as a method of for the sake of patients with certain types of leaflet delivery. In contrast to package inserts, diseases or allergies. Not mentioning the date of last revision of the insert might negatively personalized and thus irrelevant information influence the patient’s and physician’s trust in information included, leading to a shorter but In conclusion, there is a significant difference in the quantity and quality of information advantage of electronically generated leaflets provided in the PPI of locally and imported anti-infective agents in Palestine. Experts in Introduction of a computerized system for labeling and dispensing of medications in approve the PPI content, to fulfill its role in Palestine would be beneficial, but that requires the introduction of automation and internet services to local community pharmacies
beforehand.
Table 4: Scores of the nine statements written in the leaflets inserted in the local and imported anti-infective agents.
Local companies
Total scores
Total scores
(imported
Statements
(local products)
products)
Total score
Maximal score
Percent score
The locally produced anti-infective agents are manufactured by four companies (A,B,C,D). The score represents number of statements written in the PPI. Percentage is calculated by dividing total score by the maximal score. CORRESPONDING AUTHOR:
Sawalha AF, e-mail: [email protected] REFERENCES
Regner MJ, Hermann F, Ried LD. Effectiveness Pharmacoepidemiol Drug Saf. 2003; 12(1):55- of a printed leaflet for enabling patients to use digoxin side-effect information. Drug Intell Clin The European Parliament and the Council of the European Union, Directive 2001/83/EC of the Mottram DR, Reed C. Comparative evaluation European Parliament and of the Council of 6 of patient information leaflets by pharmacists, November 2001 on the community code relating doctors and the general public. J Clin Pharm to medicinal products for human use, Off J Eur Gibbs S, Waters WE, George CF. Prescription 8. EMEA, Compilation of QRD decisions on information leaflets: a national survey. J R Soc stylistic matters in product information. Version http://www.emea.europa.eu/htms/vet/qrd/qrdrefe Gibbs S, Waters WE, George CF. The benefits of prescription information leaflets. Br J Clin 9. CMD(h), CMD(h) annotated QRD template for MR/’DC procedures. Based on version 7.2 of Weitbrecht WU, Vosskamper C. Influence of the the QRD template for CP; revision 3rd October drug package information paper on compliance of neurological and psychiatric outpatients. http://www.hma.eu/uploads/media/QRD_annotat Fortschr Neurol Psychiatr. 2000; 70(4):178-84. Bjerrum L, Foged A. Patient information leaflets- -helpful guidance or a source of confusion? 10. FDA, Prescribing Information: Imdicon capsules. http:/www.fda.gov/cder/regulatory/physLabel/Im 11. Lal R, Kremzner M. Introduction to the new 18. Bawazir SA, al-Hassan MI, al-Khamis KI, Abou- prescription drug labeling by the Food and Drug Auda HS, Gubara OA. Comparative study of Administration. Am J Health Syst Pharm. 2007 Saudi-marketed products and US drug labeling. 12. Fuchs J, Hippius M. Inappropriate dosage 19. Svarstad BL, Mount JK, Tabak ER. Expert and instructions in package inserts. Patient Educ consumer evaluation of patient medication leaflets provided in U.S. pharmacies. J Am 13. Koo MM, Krass I, Aslani P. Factors influencing consumer use of written drug information. Ann 20. Reggi V, Balocco-Mattavelli R, Bonati M, Breton I, Figueras A, Jambert E, Kopp C, Montane E, 14. TGA, Review of the labelling requirements for medicines consumer-focused labelling—a way Collaborative Group. Prescribing information in 26 countries. A comparative study. Eur J Clin http://www.tga.gov.au/docs/pdf/labelrev.pdf 21. Bernardini C, Ambrogi V, Fardella G, Perioli L, 15. Basara LR, Jurgens JP. Patient package insert Grandolini G. How to improve the readability of readability and design. Am Pharm. 1994; NS34 the patient package leaflet: a survey on the use of colour, print size and layout. Pharmacol Res. 16. http://www.moh.ps/en. (2003 mortality report) 22. Stahl C, Brauer S, Zeitler H, Gulich M. How 17. Gebran N, Al Haidari K. Assessment of important is a package insert for drug therapy in prescribing information for generic drugs manufactured in the Middle East and marketed
To cite this article: Sawalha AF, Sweileh WM, Zyoud SH, Jabi SW. Comparative Analysis of Patient
Package Inserts of Local and Imported Anti-Infective Agents in Palestine. Libyan J Med, AOP:
080907.

Source: http://www.najah.edu/sites/default/files/Centers_document/Document/Comparative_Analysis_of_Patient.pdf