**1. Introduction**

Within Australia, vitamins, minerals, nutritional supplements, essential oils, and homoeopathic and herbal preparations are collectively termed and regulated as Complementary Medicines (CMs) by the Australian Therapeutic Goods Administration (TGA) [1]. The prevalent use of CMs has steadily increased over the last two decades [2,3]. An estimated 53% of CMs are self-selected and mainly accessed through pharmacy outlets, providing pharmacists, technicians, and sales assistants an opportunity to engage with the public about their CM use [4,5]. CMs are currently non-scheduled products in Australia. However, as they are provided from within pharmacy premises. According to the principles of professional ethics clearly articulated in the Code of Ethics for Pharmacists [6], pharmacists and pharmacy personnel are expected to counsel patients and provide sufficient information to ensure safe and appropriate use, and pharmacists are expected to adopt an engaged professional role in relation to CMs provision [4,5]. This is particularly important in light of the growing body of evidence reporting potential side effects and drug-CM interactions that can impact patient safety and clinical outcomes of therapy. A well-established drug-herb interaction is *Hypericum perforatum* (St John's Wort,

or SJW) [7], which is used in the managemen<sup>t</sup> of mild to moderate depression [7]. In Australia, St John's Wort is easily accessed over-the-counter (OTC). Hyperforin, an active constituent of John's Wort, is known to induce the cytochrome P-3A4 (CYP3A4) enzyme and the drug transporter p-glycoprotein, which are involved in the metabolism of many medications [8,9]. Concurrent use of SJW with these CYP3A4-metabolized medicines is well documented as resulting in significant interactions associated with patient harm [10].

Despite this, there are reports that barriers exist in the pharmacy environment which prevent pharmacists and pharmacy personnel from adopting professional standards regarding CMs. These barriers appear to be: time constraints, limited resources within the pharmacy, and a lack of knowledge about CMs [11]. Some pharmacists report that CMs were secondary to their primary concerns in patient care. They considered these products as being mostly "retail" products, available through a range of retail outlets in addition to pharmacies, indicating the uncertainty about whether they should assume professional responsibility for ensuring the appropriate and safe use of widely available CMs [11]. Consumers' lack of respect towards the potential safety issues with the use of CMs was suggested to be ye<sup>t</sup> another challenge experienced by pharmacists when trying to provide professional care related to CMs. To some consumers, as reflected by some pharmacists, having the CMs available at di fferent retail outlets might indicate an "assurance of safe"; thus, pharmacists' advice or intervention was not needed [11]. Whilst there appears to be consensus among pharmacists and associated stakeholders about the responsibility of the pharmacist to actively supervise provision of CMs, as is legally required in the case of 'Pharmacist-Only' (Schedule 3 in Australia) and 'Prescription-Only' (Schedule 4 in Australia) medicines [5], as well as clearly mentioned in the Code of Ethics for Pharmacists, it is unclear whether such professional responsibility could be extended to CMs in their current status; or should up-scheduling be considered?

Scheduling of medicines is one of the global key pillars of the pharmacy practice business model, with decisions to reschedule or up-schedule medicines made in an attempt to improve medicine use at a population level [12]. In Australia, the scheduling of medications is assigned according to the appropriate level of safety and control over the accessibility and availability of medicines. The aim of rescheduling is to safeguard the health and safety of the public. There are several schedules within the Australian classification system. Schedule 2 medications, also known as "Pharmacy Medicines", are restricted to pharmacies and can be managed by non-pharmacist sta ff within the pharmacy. Provision of Schedule 3 medications ("Pharmacist-only Medicines") require a pharmacist to engage in a consultation session with the patient to ascertain if there is a therapeutic need for the medication and to advise on its use [12]. Provision of "Prescription-only" medicines are classified under Schedule 4 and require a prescriber to fill a prescription for it to be dispensed by the pharmacist.

One example of the complexities and impact of rescheduling was the rescheduling in Australia of codeine-containing products (CCPs) in 2010, which was a very controversial topic at the time. Some low dose CCPs were previously scheduled at Schedule 2 or over-the-counter (OTC). However, with intense scrutiny of the misuse of opioid-containing medicines, and the rising incidence of addiction on these medicines in Australia, on the 1 May 2010, regulatory changes were made to minimize access and misuse, and all low dose CCPs were up-scheduled from Schedule 2 to Schedule 3 [13]. In Australia, patients could therefore no longer self-select CCPs, and the pharmacist was required to have some level of consultation with the patient before supply of the product. Being a Pharmacist-Only Medicine implied that the pharmacist had all professional and legal responsibilities for the supply of the Schedule 3 medicine, and as such, up-scheduling impacted on the practice of community pharmacists all around Australia [13]. Inadvertently, however, pharmacists became involved in the supply and identification of misuse of CCPs. Thus, despite the rescheduling in 2010, the rate of misuse did not decline with heightened pharmacists' involvement. According to Cairns et al., even after the change in drug scheduling, phone calls made to New South Wales Poisons Information Centre (NSWPIC), coded under codeine-misuse, continued to rise [14]. Therefore, in December 2016, the TGA announced that CCPs were to undergo another round of up-scheduling to make them unavailable OTC or pharmacist-only, due to the safety issues of codeine. Accordingly, codeine was up-scheduled to Schedule 4 (prescription only) by the TGA on 1 February 2018, in an effort to address the increasing use and/or misuse of pharmaceutical opioids, particularly in relation to codeine abuse. The action of regulatory up-scheduling was therefore undertaken in the interest of patient safety and to minimize the risks of drug dependence and toxicity [14].

While the safety and implications of most CMs is incomparable to CCPs, the role of scheduling in relation to the accessibility of products and professionalism of pharmacists is worthy of discussion. To date, the scheduling of CMs has not even been considered or explored. Despite rising consumption and current safety concerns around some CMs, CMs remain unscheduled. And while CMs are clearly not drugs of abuse, there is an increasing demand from professional organizations, and within the literature, advocating for pharmacists and pharmacy personnel to adopt heightened professional duties as related to the supply of CMs [15]. According to the position statement issued by the Pharmaceutical Society of Australia, "*pharmacists are recommended to assume the responsibility of providing sound evidence-based advice to assist consumers in making informed decisions regarding CMs*" [16]. In the United States of America, where CMs are also over the counter, the position statement published by the American Society of Health System Pharmacists also urged pharmacists to integrate awareness of patients' use of dietary supplements into everyday practice and to increase efforts to prevention of interactions between these products and prescriptions medicines [17]. This responsibility may be aided by community workforce personnel, such as pharmacy assistants, who, if trained appropriately, may direct requests for CMs to the pharmacist in charge, where necessary.

The Australian Industry and Skills Committee published a report on community pharmacy in April 2020 [18], stating the following: "*The Community Pharmacy sector plays an important role in the Health Care sector through the supply to the general public of prescription-based medicine, non-prescription-based medicine when permitted, and a range of information and health care services* ... *As a result, the community pharmacy sector is pivotal in reducing the demand and burden on primary health care facilities* ... *The Community Pharmacy sector includes a workforce of 41,400 pharmacy sales assistants and generated \$18.4 billion in revenue in the 2018-19 period, up from \$16.3 billion in 2016-17.*" And according to Australian governmen<sup>t</sup> statistics, approximately 59% of the community pharmacy workforce is comprised of pharmacy assistants, many of whom undergo specific training to enable them to undertake tasks allocated to them in pharmacy [19]. As most requests for CMs come from the OTC areas (or shelves) within a typical community pharmacy, usually allocated to oversight of pharmacy assistants, there may be an important role for pharmacy personnel, such as pharmacy assistants, to support the pharmacist with streamlining of requests for CMs in a community pharmacy. This role would be particularly effective if CMs were to be scheduled in Australia.

We hypothesize that the scheduling of CMs to enable holding pharmacists and pharmacy personnel responsible for oversight of the supply of CMs could, theoretically at least, be a reasonable approach to enhance safe and appropriate use of self-selected CMs [11]. It would therefore follow that we seek to explore the literature for evidence of the impact of re-scheduling of other medicines in Australia. Hence, this is an exploratory study aimed to investigate the potential effect on pharmacy practice if scheduling of CMs was adopted, using the case of up-scheduling of codeine in Australia as an example.
