|Year : 2017 | Volume
| Issue : 1 | Page : 19-23
A study on off-label and unlicensed drug use by community pharmacists: A report from resource-limited settings of South India
Vigneshwaran Easwaran1, Bhanu Prakash Satrasala2, Sireesha Mallela2
1 Department of Clinical Pharmacy, King Khalid University, Abha, Kingdom of Saudi Arabia
2 Department of Pharmacy Practice, Raghavendra Institute of Pharmaceutical Education and Research, Anantapuramu, Andhra Pradesh, India
|Date of Submission||22-May-2016|
|Date of Acceptance||01-Dec-2016|
|Date of Web Publication||1-Feb-2017|
Department of Clinical Pharmacy, King Khalid University, Abha
Kingdom of Saudi Arabia
Source of Support: None, Conflict of Interest: None
Introduction: Labeled uses of drug use are approved by the regulatory authorities based on preclinical and clinical data which confirms their safety and efficacy. From the community pharmacist perspective, the most common off-label use is due to physician's prescriptions and usage of over-the-counter (OTC) medications. In India, huge number of medicines is easily available for off-label use from the community pharmacists with or without prescriptions. Objectives: It is a preliminary study to evaluate and describe the off-label drug use by community pharmacists in resource-limited settings. Materials and Methods: It is a prospective cross-sectional study conducted among community pharmacies located in and around of Anantapur district, a rural part of Andhra Pradesh, South India. The data were collected through questionnaire-based semi-structured interview and/or asked the community pharmacists to complete on their own at the spot to avoid manipulation of data. The questionnaire is of two types: the first type evaluates pharmacist perspective on off-label indication for randomly selected drugs (frequent moving) and the second type evaluates dispensing practice of drugs for off-label use based on symptoms. Results: The present study results show that the frequency of off-label drug use is high among community pharmacists; moreover, they dispense the drugs without aware of off-label or inappropriate indication, sometimes as OTC medications. It is an acceptable fact that off-label or unlicensed drug use is not illegal but has plenty of safety and other issues. Conclusion: Thus, the present study provides a preliminary data to frame future educational and interventional programs to improve the rational use of drugs with regard to it.
Keywords: Community pharmacists, off-label, over-the-counter medications
|How to cite this article:|
Easwaran V, Satrasala BP, Mallela S. A study on off-label and unlicensed drug use by community pharmacists: A report from resource-limited settings of South India
. J Health Res Rev 2017;4:19-23
|How to cite this URL:|
Easwaran V, Satrasala BP, Mallela S. A study on off-label and unlicensed drug use by community pharmacists: A report from resource-limited settings of South India
. J Health Res Rev [serial online] 2017 [cited 2020 Sep 19];4:19-23. Available from: http://www.jhrr.org/text.asp?2017/4/1/19/199327
| Introduction|| |
Labeled uses of drug use are approved by the regulatory authorities based on preclinical and clinical data which confirms their safety and efficacy. Once the drug is approved, physicians might use it in any way they see as medically appropriate. The way of drug use which is different from the approved drug label is known as “off-label” use. Prescribing off-label drugs is extremely common worldwide, but unfortunately, usually done without sufficient scientific data. Only 30% of off-label prescribing was supported by scientific data.,
Off-label drug use is not illegal, but sometimes it may be clinically unsuitable, might be associated with plenty of safety, efficacy, and ethical issues. Off-label prescribing is more frequent in various kinds of patients' populations. Around 21% of drugs prescribed in an outpatient setting were used for off-label indications.,,, Preferably, in pediatrics, drugs are frequently prescribed and dispensed based on the dose and indications which are approved for the adults. From the community pharmacist perspective, the most common off-label use is due to physician's prescriptions and usage of over-the-counter (OTC) medications. It is also very difficult to assess the benefits and risks of off-label use in the absence of data.,,
In India, huge number of medicines is easily available for off-label use from the community pharmacists with or without prescriptions, preferably in resource-limited settings.
Hence, the present research work has been undertaken as a preliminary study to evaluate and describe the off-label drug use among community pharmacists. This can serve as important information to frame the interventional programs on off-label drug use to increase the rational drug use.
| Materials and Methods|| |
It is a prospective cross-sectional study conducted among community pharmacies located in and around of Anantapur district, a rural part of Andhra Pradesh, South India. The Community pharmacies were enrolled through database available at Anantapur District Chemist and Druggist Association. Wholesale pharmacies and pharmaceutical closing and forwarding agencies have been excluded from the present study.
The registered community pharmacists those who are working in the enrolled pharmacies were approached by our research team randomly on to their working area to conduct the interview. The interview was conducted in the late afternoon on weekdays to avoid the interruption during their regular service. The present study was approved by the Institutional Review Board (IRB) of Raghavendra Institute of Pharmaceutical Education and Research (RIPER), and the approval number is RIPER/IRB/013/2014. The present study purpose and protocol were clearly explained to the study participants for study recruitment. Informed consent was obtained from all the study participants to participate in this investigation. No financial remuneration has been provided to study participants.
Initially, the questionnaire survey was done using validated questionnaire. It includes two different types, pharmacist perspective on off-label indication for randomly selected drugs (frequent moving) and questionnaire evaluates dispensing practice of drugs for off-label use based on symptoms. Off-label indication and inappropriate indication had been obtained from a standard reference such as clinicalpharmacology.com (Elsevier/gold Standard) and British national formulary, 67th edition. The drugs and symptoms have been selected based on the extensive literature search which are most commonly seen as off-label or unlicensed. The questionnaire was prepared by a group of experts comprises physicians, nurses, working pharmacists, and student pharmacists. The data were collected through semi-structured interview and/or asked the community pharmacists to complete on their own at the spot to avoid manipulation of data. Descriptive statistics were used to derive the results.
| Results|| |
A total of 70 community pharmacists were participated in the present study, which includes 90% of males. More than 80% of community pharmacists owned their pharmacy at least for a minimum period of 10 years. Most of them were found to have 6–10 years of experience (24%) and qualified with Diploma in Pharmacy degree (91%) for their practice. The basic characteristics are detailed in [Table 1].
Among the nine drugs selected for evaluation, cyproheptadine was found to be most frequently used drug for a single off-label indication known as appetite inducer (97%), preferably in the pediatric population. Even the fluconazole (18%), omeprazole (9%), and salbutamol (12%) were most commonly indicated for itching, indigestion, and cough, respectively.
Moreover, the present study results show that all the drugs which are selected for the evaluation were found to be used for various off-label indications. The antihistamines were found to be used for wide variety of off label indications apart from its labeled use. In addition to that, the interesting finding in this study is that the corticosteroids are most repeatedly used in the treatment of general pains. The details are given in [Table 2].
|Table 2: Drug-based scenario for off-label drug use (on randomly selected drugs)|
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Apart from off-labeled indication, few drugs are also evaluated for an inappropriate indication; the results revealed that corticosteroids are most repeatedly used for symptoms such as shortness of breath and cough. It was strange that fluconazole has been used for helminthiasis (3%) and in severe allergic conditions (33%). It is also poor to know with this study result is that around 50% of pharmacists are believed in corticosteroid for the treatment of cough. The details are illustrated in [Table 3].
|Table 3: Drug-based scenario for inappropriate drug use for various indications (on randomly selected drugs)|
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Based on a semi-structured interview to community pharmacists for the symptom-based scenario on off-label drug use, allergic reactions have been most frequently treated with a combination of prednisolone with cetirizine (40%), and even it is treated using ascorbic acid. Common cold was treated by phenylephrine at the maximum (60%), and throat pain was frequently managed by macrolide antibiotics preferably, erythromycin as highly used drug option (61%). In addition to that, fever and diarrhea are most commonly managed by various classes of antibiotics. A notable finding in this study includes vomiting was treated by doxylamine succinate and pyridoxine combination (3%); at the same time, headache was managed by domperidone (3%). Further, constipation was managed by sucralfate. The detailed information and data is given in [Table 4]. In addition to that the list of most commonly used off-label drugs are mentioned in [Table 5].
| Discussion|| |
There were plenty of national and international research studies that have been published on off-label and unlicensed use of drugs. However, most of them were concentrated on pediatrics, the rationale behind this might be, the pediatric population may not have access to medicines which are appropriately researched and licensed for their use.,,,
Several prospective and retrospective studies were also conducted in various health-care settings of different continents. All these have been reported that off-label drug use is more prevalent and antibiotics are the most commonly used off-label drug group. It is also clearly evident that the usage of off-label drugs is confined not only to hospital settings but also to the community settings.,,
Thus, the present study has concentrated on the community pharmacy settings, where the drugs directly meet their consumers. To the best of our knowledge, this is the first published study regarding off-label drug use in community pharmacy settings.
Numerous reports are available for the usage of off-label drugs among the pediatric population; here, the question arises that what is the impact of off-label drug use on other population preferably in community pharmacy settings? Studies have also reported the usage of off-label drug use at surgical wards, psychiatric outpatients, and even in adult population.,, Although we could not able to find much research work on off-label use among other than pediatrics population, we believed that off-label use or unlicensed use must be evaluated among them. The present study results show that antibiotics and steroids are most frequently used off-label drug by community pharmacists to their consumers. These results are very similar to other studies which are conducted among the pediatric population from physicians and other health-care professionals' perspective.,
Community pharmacists must ensure public health and safe medicine use by understanding the issues related to off-label drugs use which is essential. A study reported in Italy has clearly stated that pediatric practitioners in their study were well aware of off-label drug use and their negative consequences. Whereas community pharmacists are lacking to gain their knowledge during their undergraduate or through their experience than other health-care professionals.,
The present study results show that the frequency of off-label drug use is high among community pharmacists, moreover they dispense the drugs without aware of off-label or inappropriate indication. The present study has concentrated majorly on community pharmacists, where they appreciated the off-label drug use most of the time, sometimes even inappropriate drug indication. In contrast, it is a well-established fact that other health-care professionals are more familiar to off-label drugs.
This indicates the poor knowledge on off-label drug use among community pharmacists in the present study settings; even though we did not concentrate much on knowledge, attitude, and practice (KAP) aspects, it is necessary to evaluate KAP on off-label drug use in near future, which can be done as continuation of the present research work.
The present study results clearly imply that apart from the pediatric population, others are also treated or used with off-label drugs for various indications by community pharmacists, sometimes as OTC medications. It is an acceptable fact that off-label or unlicensed drug use is not illegal it has plenty of safety and other issues and may lead to potential health hazards.,,
The present study has few limitations that it has not classified the used drugs as OTC medications or prescribed medications. The drug users are also not classified on any basis due to nonavailability of data. In addition to that, the present study was conducted in one of the resource-limited settings; thus, it may not have the generalizability to apply in other settings.
| Conclusion|| |
The usage of off-label drugs may vary with pharmacy to pharmacy, but still, the overall usage was found to be high. Moreover, the community pharmacists are lacking with enough information and knowledge on off-label drug use. This may lead to risky situations to patients. Although off-label drug use may benefit sometimes, still the negative side has to be learned by the users and the knowledge must be disseminated to the end users too. Thus, the present study provides a preliminary data to frame future educational and interventional programs to improve the rational use of drugs with regard to it.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Khamar B. Off-label use of medicines: Medical research and medical practice. Indian J Ophthalmol 2007;55:411-2.
Gupta SK, Nayak RP. Off-label use of medicine: Perspective of physicians, patients, pharmaceutical companies and regulatory authorities. J Pharmacol Pharmacother 2014;5:88-92.
Emmerich J, Dumarcet N, Lorence A. France's new framework for regulating off-label drug use. N Engl J Med 2012;367:1279-81.
Gonçalves MG, Heineck I. Frequency of prescriptions of off-label drugs and drugs not approved for pediatric use in primary health care in a southern municipality of Brazil. Rev Paul Pediatr 2016;34:11-7.
Smithburger PL, Buckley MS, Culver MA, Sokol S, Lat I, Handler SM, et al.
A multicenter evaluation of off-label medication use and associated adverse drug reactions in adult medical ICUs. Crit Care Med 2015;43:1612-21.
Vohra F, Pawar S. Off-label drug use in pediatric wards: A prospective study in a tertiary care hospital in Pune. Egypt Pharm J 2016;15:70.
Magalhães J, Rodrigues AT, Roque F, Figueiras A, Falcão A, Herdeiro MT. Use of off-label and unlicenced drugs in hospitalised paediatric patients: A systematic review. Eur J Clin Pharmacol 2015;71:1-13.
Saullo F, Saullo E, Caloiero M, Menniti M, Carbone C, Chimirri S, et al.
A questionnaire-based study in Calabria on the knowledge of off-label drugs in pediatrics. J Pharmacol Pharmacother 2013;4 Suppl 1:S51-4.
Stewart D, Rouf A, Snaith A, Elliott K, Helms PJ, McLay JS. Attitudes and experiences of community pharmacists towards paediatric off-label prescribing: A prospective survey. Br J Clin Pharmacol 2007;64:90-5.
Mukattash TL, Millership JS, Collier PS, McElnay JC. Public awareness and views on unlicensed use of medicines in children. Br J Clin Pharmacol 2008;66:838-45.
Saiyed MM, Lalwani T, Rana D. Off-label medicine use in pediatric inpatients: A prospective observational study at a tertiary care hospital in India. Int J Pediatr 2014;2014:415815.
Bhadiyadara SN, Rana DA, Deepak SM, Patel VJ. Off-label and unlicensed drug use in paediatric outpatient department – A prospective study at a tertiary care teaching hospital. J Young Pharm 2015;7:164-70.
Corny J, Bailey B, Lebel D, Bussières JF. Unlicensed and off-label drug use in paediatrics in a mother-child tertiary care hospital. Paediatr Child Health 2016;21:83-7.
Abdulah R, Khairinisa MA, Pratiwi AA, Barliana MI, Pradipta IS, Halimah E, et al.
Off-label paediatric drug use in an Indonesian community setting. J Clin Pharm Ther 2015;40:409-12.
Patil AE, Shetty YC, Gajbhiye SV, Salgaonkar SV. Drug utilisation and off-label use of medications in anaesthesia in surgical wards of a teaching hospital. Indian J Anaesth 2015;59:721-7.
Kharadi D, Patel K, Rana D, Patel V. Off-label drug use in psychiatry outpatient department: A prospective study at a tertiary care teaching hospital. J Basic Clin Pharm 2015;6:45-9.
Eguale T, Buckeridge DL, Verma A, Winslade NE, Benedetti A, Hanley JA, et al.
Association of off-label drug use and adverse drug events in an adult population. JAMA Intern Med 2016;176:55-63.
Mukattash T, Hawwa AF, Trew K, McElnay JC. Healthcare professional experiences and attitudes on unlicensed/off-label paediatric prescribing and paediatric clinical trials. Eur J Clin Pharmacol 2011;67:449-61.
Ekins-Daukes S, Helms PJ, Taylor MW, McLay JS. Off-label prescribing to children: Attitudes and experience of general practitioners. Br J Clin Pharmacol 2005;60:145-9.
Horen B, Montastruc JL, Lapeyre-Mestre M. Adverse drug reactions and off-label drug use in paediatric outpatients. Br J Clin Pharmacol 2002;54:665-70.
AishwaryaLakshmi K, Sasikala B, Sreelalitha N, Vigneshwaran E, Padmanabha reddy Y. Assessment of Knowledge Perception and Attitudes on Medications in General Population. Indian J Pharm Pract 2012;5(3):75-8.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]