Investigating the knowledge, perception, and practice of healthcare practitioners toward rational use of compounded medications and its contribution to antimicrobial resistance: a cross-sectional study

Ensuring medication availability in healthcare facilities (HCFs) is crucial to providing good quality healthcare and reducing avoidable patient readmissions. In addition to manufacturing in the licensed pharmaceutical industries, extemporaneous compounding is the essential source of medication availability, especially for personalized healthcare [1‐4].

Since the mid-1980s, the number of patients seeking personalized healthcare has been increasing. It is due to one size medicine (strength and dosage form) does not fit all. Therefore prescribing, dispensing, and administering extemporaneously compounded medication is a good solution. Extemporaneous compounding is the art and science of combining, mixing, repackaging, and labeling a drug product. Historically, it has been a crucial part of the pharmaceutical process. It has long been a service provided by licensed pharmacists since the origin of pharmacy. Today, with the technological advancements in the pharmaceutical field and increased need, the compounding pharmacy industry is experiencing a resurgence and becoming more relevant than ever [3, 5‐11].

The medicine compounders compound according to a licensed practitioner’s prescription, medication order, or initiative based on the practitioner-patient-pharmacist relationship in the course of professional practice [1, 12]. It includes removal of allergenic ingredients, dosage form change, especially for easy swallow, altering strength, routes of the delivery, unpleasant flavor of available drug product, and allowing access to discontinued medications [5‐7, 9, 12‐14]. Therefore, compounding allows specific patients such as pediatric and geriatric patients, patients requiring dermatologic disease treatment and pain management, and others with more options [1, 8].

The compounded medications should be developed to meet unique medical needs and ensure patient safety. Therefore, compounding prescriptions should be prescribed by a licensed practitioner, compounded and dispensed by the licensed pharmacist, administered and used correctly. Compounding pharmacies must also comply with good compounding practice regulations for compounding within hospitals, community pharmacies, home infusion pharmacies, and, more recently, outsourced compounding facilities [1, 8, 9].

The regulatory scrutiny of pharmaceutical compounding practices is significantly less rigorous than that required for FDA-approved medications (commercially available medications). It is exempted from regular inspections, quality control testing, and rejection of material not meeting specifications. Furthermore, they are not clinically assessed for safety or efficacy before marketing. Moreover, there is no standard labeling or prescribing information with instructions for the safe use of compounded products. They are the potential causes for poor quality medication preparation (contamination, medication with too little or too much active ingredient, or failure to meet specifications). Finally, they may pose potentially fatal health risks for the users [5, 6, 12, 15‐19]. As evidence, FDA reported the prevalence and potential risks of poor quality compounded medications many times. These defects lead to serious patient illnesses, adverse events, and deaths linked to poor quality compounded drugs [16, 20, 21].

Poor quality of compounded medication causes administration of a low dose of active ingredients. Administration of lower-dose antimicrobials can cause microbes, including bacteria, fungi, parasites, and viruses, to adapt and become less susceptible to medical treatment. Therefore, it can play a role in the emergence and spread of antimicrobial resistance (AMR), which causes a profound threat to human health. Moreover, irrational prescribing, packaging and labeling, administering, and using compounded medicine can contribute to AMR prevalence [1, 22‐24]. Thus, the rational use of compounded antimicrobials can be the critical action to prevent the spread of antimicrobial-resistant infections. It mostly depends on healthcare practitioners' (HCPs') knowledge, perceptions, and practices. The presented study was aimed to investigate their knowledge, perception, and practice of extemporaneous compounding and its contribution to the prevalence of AMR.

The present study was conducted using 300 study participants who were voluntarily consented to participate in the study. They were working at different units at Jimma University Medical Center, such as hospital pharmacies and wards (148), Jimma Town community pharmacies (95), and Mettu Town community pharmacies (57). The respondents had worked as healthcare professionals for a mean of 5.78 ± 4.6 years (range 1–32 years) (Table 1).

The present study indicated that all the HCPs mentioned different reasons for requesting and performing compounding medication and their route of administration (Table 2).

Multiple response analysis indicated that 262 (87.33%) of the study participants had participated in at least one process of rational use of extemporaneously compounded medications (Fig. 1). They include administering 173 (44.1%%), preparing 114 (29.1%), prescribing 63 (16.1%), and repackaging and labeling of compounded medications 42 (10.7%), respectively. 91% of trained respondents on extemporaneous compounding of medication had practiced compounding services, especially administering (44, p = 0.60 and preparing (30) (p = 0.53). Most first-degree and specialty (master degree) holders had practiced more on prescribing (47), preparation (75), and repackaging and labeling (27) of compounded medications. However, most diploma holders (91) had practiced administration of compounded medications.

The study respondents practiced rational use of extemporaneously compounded antimicrobials at different frequencies. Most of them practiced like monthly (occasionally) 108 (36%), almost every day 93 (31%), not at all 77 (25.7%) and always 22 (7.3%), respectively. Most of the time, the respondents didn’t prescribe, dispense or prepare antimicrobial medicine extemporaneously due to different challenges (Table 3).

The present study showed the perception of HCPs on the development of AMR due to antimicrobial compounding. Moreover, most of them have knowledge concerning the compounding factors contributing to AMR development (Table 3).

Pharmaceutical compounding has long been an essential component of health care. So, rational use of compounded medications is a fundamental activity within HCFs (9). The main findings of the present investigation showed that most of the HCPs participated in the preparation and administration of the compounded medications (Fig. 1). Pharmacy professionals were the most common practitioners. It might be due to pharmacists being formally trained in the art and science of compounding medications in their undergraduate courses and licensed to compound medicine relative to other medical communities [1, 23]. Moreover, a limited number of respondents took training on the compounding of medications.

An earlier study has linked the prevalence of compounding services to requests for individualized therapy [29, 30]. Similarly, the present study showed that the most common reasons for requesting and providing compounding services are the unavailability of FDA-approved drugs in the prepackaged form in the market and the needed dosage regimen for individualized therapy (Table 2). Moreover, the availability of requested dosage regimens for individualized therapy contributes to users' adherence and therapeutic efficacy.

Various studies indicated the high demand for pharmaceutical compounding services at different levels of HCFs. However, the service is not prevalent due to several challenges [10, 31]. Accordingly, the present study reported HCPs' lack of trust in the quality of the compounded formulations and fear of poor patient compliance as common challenges (Table 3). This finding agreed with a study conducted by Abdel Naser Zaid et al. (2010) [31]. It can be due to the quality of compounded products is not regulated by the Ethiopian FDA. Moreover, patients who suffer from the side effects of the compounded medication may bring negligence and malpractice claims against HCPs [16]. As a result, HCPs should be careful during providing rational use of compounded products.

Previous studies reported a lack of prescriptions for requesting compounding services as one of the key reasons for not providing compounding services (27,32). However, the present study did not. It might be due to the prescribers' lack of confidence in the quality and effectiveness of the compounded medication.

Extemporaneously compounded medications are not undergoing regular inspections, quality control testing, and rejection of material not meeting specifications. However, their quality should be regulated to ensure safety [12]. The present study showed that most respondents strongly believed that substandard extemporaneous preparation of antimicrobials contributes to AMR development. They mentioned inappropriate preparation processes, under-dose administration, and contamination during compounding as the factors causing AMR development (Table 4). The responses agreed to the fact that a low dose of active ingredients in poor quality of compounded medications causes microbes to adapt and become less susceptible [1, 19‐21].

The present study indicated that most healthcare practitioners provide healthcare services using compounded medications. They apply rational use principles mainly for administering and preparing compounded medications. Unavailability of prepackaged products in the market and unavailability of needed dosage regimens were the most common reasons mentioned for practicing rational use of compounded medication. However, lack of trust in the quality of the compounded medication and poor patient compliance was the most listed challenges. The majority of them revealed that compounding caused inappropriate preparation processes, and under-dose medication administration can lead to the development and prevalence of antimicrobial resistance.

Due to individualized therapy is being in high demand, compounding services are becoming critical. Thus, healthcare practitioners should take training on extemporaneous compounding. Moreover, compounding services should be incorporated into professional development and continuing education programs, and the quality of compounded medication should be regulated.

The present study did not statistically analyze the degree of correlation between challenges and reasons of compounding to compounding practices. It can be a basic study point for future researchers.