Concerns with current Drug Laws regarding the purchasing antibiotics without a prescription in Pakistan; ways forward to assist the national action plan

KEYWORDS:

• AwaRe classification
• Drug Laws
• national action plans
• purchasing antibiotics without a prescription
• Pakistan

1. Introduction

Antimicrobial Resistance (AMR) is a global public health threat due to its continued impact on morbidity, mortality, and costs [1,2]. This requires a multi-pronged approach to reduce current inappropriate use, with a key strategy being the implementation of national action plans (NAPs) to reduce AMR following the World Health Organization’s (WHO) initiative [3]. The WHO AMR manual for developing NAPs includes the mapping of stakeholders, conducting a situational analysis as well as developing strategic objectives to develop the NAP for their country [3]. Pakistan is no exception with the development of its NAP to reduce AMR [4]. However, there are challenges with implementing NAPs across countries, including Pakistan, exacerbated by the lack of available resources including personnel and available funds [1,4]. In addition, the continued purchasing of antibiotics without a prescription remains a key challenge [5].

2. Body of the paper

A key area to address in NAPs to reduce AMR, especially among low- and middle-income countries (LMICs), is to improve antibiotic use in ambulatory care, i.e. reducing inappropriate prescribing and dispensing of antibiotics. This is because ambulatory care, i.e. non-inpatient care, currently accounts for 90% or more of total antibiotic use in LMICs [6]. Within this, the dispensing of antibiotics without a prescription for essentially self-limiting conditions, including acute respiratory infections, is common practice across countries including Pakistan with up to 96.9% of antibiotics dispensed without a prescription among community pharmacies and medical stores [5,7–9]. This practice is enhanced by patients believing antibiotics can cure viral infections [9,10]. Alongside this, the convenience of local pharmacies and trust in them, no additional co-payments to see a physician and take time off work, and pharmacists may be the only health-care professional available especially in rural areas [9]. Consequently, a key area to address to reduce AMR, particularly in LMICs. The NAP of Pakistan on AMR sought to address the growing threat of AMR in the country, building on the recommendations of the WHO in its Global Action Plan launched in 2015 [3,4]. However, there are issues with implementing the NAP in Pakistan, which, as mentioned, include resource, knowledge, and personnel issues [4]. These concerns and issues were comprehensively discussed in our previously published paper in Expert Review of Anti-infective Therapy [4]. The identified barriers and challenges need to be addressed going forward to reduce rising rates of AMR in the country. This includes initiatives to reduce current high rates of purchasing antibiotics without a prescription in Pakistan, especially antibiotics from the ‘Watch’ and ‘Reserve’ categories with their potential for increasing resistance rates [5,6]. Currently in Pakistan, Schedule D in the Drug Sale rules, under the Drug Laws of Pakistan, prohibits the sale of antibiotics without a prescription in the country [11]. Nonetheless, implementation of this law has typically been poor in Pakistan, and the unrestricted availability of antimicrobials, alongside high rates of dispensing of ‘Watch’ (49.3%) and ‘Reserve’ (19.0%) antibiotics without a prescription, continues to be a major public health concern [5]. Reducing the use of ‘Watch’ and ‘Reserve’ antibiotics will be one of the key ways of reducing AMR in Pakistan along with initiatives to address other critical issues including poor governance along with concerns with hygiene and sanitation [6,12].

The first step to reduce inappropriate dispensing of especially ‘Watch’ and ‘Reserve’ antibiotics in Pakistan is to address the list of antibiotics currently mentioned in Schedule D of the Drug Law of Pakistan. The list currently contains 27 ‘antibiotics’ that are randomly listed without following any ATC classification (Table 1) or the recent AWaRe classification [6].

Table 1. Antibiotics specified below, their salts, derivatives, and salts of their derivatives (adapted from [11]).

Bacitracine	Carbomycin	Chloramphenicol
Chlortetracycline	Colimycin	Dihydro streptomycin
Erythromycin	Framyceten	Gramicidin
Griseofulvin	Kanamycin	Neomycin
Novobiocine	Nystatin	Oleandomycin
Oxytetracycline	Penicilline	Paromomycin
Polymyxin	Spiramycin	Streptomycin
Tetracycline	Tyrothyricin	Vancomycin
Viomycin	Cephalosporins	Amitriptylline, its salts

Most of the ‘antibiotics’ mentioned in the list are currently not typically prescribed. The antibiotics currently listed include bacitracin, carbomycin, cephalosporines, chloramphenicol, chlortetracycline, colimycin, erythromycin, framyceten, gramicidin, kanamycin, neomycin, novobiocine, oleandomycin, oxytetracycline, penicillin, polymyxin, spiramycin, streptomycin, dihydro streptomycin, tetracycline, tyrothricin, and viomycin [11].

In addition, the list currently only includes two antifungal medicines, namely griseofulvin and nystatin, with most of the macrolides and aminoglycosides missing. Additionally, many important antibiotics classes including the fluoroquinolones, carbapenems, monobactams, sulfonamides, and lincosamides as well as antivirals, antimalarials, antiprotozoals, and antimycobacterials are entirely absent from the list. Ironically, the list includes a tricyclic antidepressant, amitriptyline, while antibiotics from the ‘Reserve’ group including carbapenem, colistin, and linezolid, which are essential for treating serious infections caused by multi-drug resistant bacteria when the need arises, are currently missing. This is a concern and potentially impacting on patient care [13]. However, this will be rare in practice. This current list of 27 ‘antibiotics’ we believe also demonstrates a lack of awareness, implementation, and enforcement of regulations that were designed to prevent AMR in Pakistan. To address this issue, there is an urgent need to update Schedule D of the Drug Law regarding 'antibiotics' expanded to antimicrobials. The suggestion is that this list now contains all key antimicrobials listed in the recently available AWaRe book [6]. The AWaRe book currently includes treatment suggestions to cover 34 common infections typically seen in both hospital and ambulatory care, covering both children and adults [6]. There is also a section on the suggested prescribing of ‘Reserve’ antibiotics. These antibiotics should be restricted to pre-defined selected cases only when an infection is confirmed or suspected to be caused by multidrug-resistant pathogens, and should be the subject of antimicrobial stewardship programs in hospitals where there are concerns with their current prescribing [6]. Alongside this, typically promoting ‘Access’ or no antibiotics where pertinent [6].

The second step is to enhance appropriate dispensing of antibiotics without a prescription through pharmacists or their assistants discussing more pertinent alternatives, especially for self-limiting conditions, including non-antibiotic choices [9]. This could also include measures to typically ban, or appreciably reduce, the dispensing of ‘Reserve’ antibiotics unless for very specific circumstances given appreciable documented rates (19.0% of antibiotics dispensed) that have been seen in Pakistan [5]. Alongside this, instigate initiatives and measures to reduce the dispensing of ‘Watch’ antibiotics in favor of ‘Access’ antibiotics where pertinent given current high rates of dispensing of 'Watch' antibiotics (49.3%) and limited dispensing of Access antibiotics (31.7%) in some studies [5]. We are aware that measures to reduce the dispensing of antibiotics without a prescription in Saudi Arabia, including considerable fines for such practices (equivalent to US$26,666), coupled with the cancellation of licenses to practice, have been successful in appreciably reducing such practices [14]. However, such initiatives are difficult in Pakistan, especially given high co-payment levels for both physicians and pharmacists, alongside travel times and costs to see a physician versus the typical convenience of community pharmacies and drug stores. In addition, such fines would be difficult to implement in Pakistan. On the other hand, limited fines for illegally dispensing antibiotics without a prescription (US$15 – US$25), coupled with limited enforcement, were unsuccessful in Vietnam [15].

Consequently, this approach is also not recommended Pakistan. Suggested next steps include greater education of community pharmacists and pharmacy technicians starting in universities and continued post qualification along with patient education given considerable concerns with their knowledge levels [9,16]. In addition, greater monitoring of antibiotics dispensed through improved technologies alongside the instigation of indicators based on the AWaRe book. We will be following this up in future research projects given the imperative to reduce AMR in Pakistan. In the meantime, there is an urgent need to rapidly update Schedule D of the Drug Law now that the AWaRe classification and the book with its multiple suggestions is being adopted across countries. This applies to other LMICs with similar issues.

3. Expert opinion

The purchasing of antibiotics without a prescription remains a key concern among LMICs especially if this involves antibiotics from the ‘Watch’ category for essentially self-limiting conditions. It is difficult to ban such practices, and potentially morally wrong, especially in rural areas in LMICs where there are high co-payments for medicines and to see a physician. Alongside this, potential loss of income through taking considerable time off work to see a physician combined with possibly appreciable travel costs.

Consequently, the emphasis must be on improving appropriate dispensing of antibiotics as well as recommending alternative treatments especially for self-limiting conditions such as acute respiratory tract infections. This is now made easier by the publication of the WHO AWaRe book with its guidance regarding the management of infectious diseases typically seen in ambulatory care. This includes encouraging the use of ‘Access’ as opposed to ‘Watch’ and ‘Reserve’ antibiotics where these are justified on the balance of risk. Alongside this, making sure community pharmacists and their assistants have appropriate knowledge of antibiotics and AMR through improved education. In addition, greater monitoring of their activities. This involves improved tracking of antibiotics dispensed through mobile and other technologies as well as the development and instigation of appropriate quality indicators based on the AWaRe book. Consequently, it is essential that Drug Laws and treatment guidance within countries align themselves with the AWaRe guidance to avoid confusion and improve future patient care. This is currently not the case in Pakistan, which needs urgent addressing. The focus on these areas will remain until addressed given concerns with rising AMR rates in Pakistan and beyond.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or mending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution

All authors substantially contributed to the conception and design of this Editorial and have been involved in writing the initial paper and its revision.

Additional information

Funding

This paper was not funded.