1. Introduction
Drug–drug interactions (DDIs) are a significant contributor to medication-related harm, and a substantial proportion are preventable; DDIs account for approximately 26% of all adverse drug events (ADEs) [
1]. DDIs are a significant cause of adverse drug reactions (ADRs), which can vary from mild side effects to life-threatening conditions [
2]. They increase the risk of emergency visits and hospital admissions, prolong hospital stays, and raise costs [
2,
3,
4]. The World Health Organization estimates that the annual cost of medication errors reaches
$42 billion USD [
5]. They are a key focus of the Global Patient Safety Challenge, Medication Without Harm, which aims to reduce severe, avoidable medication-related harm by 50% globally [
5]. Potential DDIs are common in ambulatory care and community pharmacy, particularly in the context of multimorbidity and polypharmacy. Recent outpatient and community-based studies suggest that potential DDI prevalence estimates range from about one-third to over half of prescriptions in certain high-risk groups. However, these estimates differ based on patient populations, drug classes, and the sources referenced for DDIs [
2,
6]. Polypharmacy refers to a patient taking multiple medications (often five or more) at the same time. This practice in community pharmacy increases the risk of drug interactions and results in adverse health outcomes [
7,
8]. DDIs carry a considerable economic burden, reinforcing the need for robust prevention strategies across care settings.
Community pharmacists are strategically positioned to intercept DDIs through medication history taking, prospective review, clinical decision support, medication reconciliation, and patient counselling. Evidence syntheses indicate that interventions delivered by pharmacists can lower medication errors and unplanned healthcare visits. However, the extent of these effects varies based on local workflows, access to reliable drug interaction (DDI) references, and the strength of interprofessional communication channels [
9,
10]. Simultaneously, community pharmacy practice encounters several challenges, including limited patient-specific data, a high workload and competing priorities, poorly tailored computer alerts, and underreporting of OTC medications and supplements. These factors prevent pharmacists from effectively assessing potential interactions, which can lead to gaps in patient care and medication safety [
11].
In Saudi Arabia, the health system transformation under Vision 2030 aims to strengthen patient-centered, safety-focused care and expand pharmacists’ clinical roles across various settings, including community pharmacies [
12,
13]. Despite this policy momentum, the literature reveals uneven knowledge of DDIs among Saudi community pharmacists. Studies from different areas in Saudi Arabia reported below-optimal accuracy across multiple interaction pairs, with only a minority correctly identified by most of the respondents [
14,
15]. Additional research on pharmacists’ knowledge, attitudes, and practices regarding DDIs in Saudi Arabia shows the importance of understanding how skills, tools, and system factors influence DDI management [
16]. Moreover, few investigations integrate objective knowledge assessment with practice behaviors, perceived barriers, and guideline familiarity in the same cohort, limiting actionable insight for targeted quality improvement.
Jazan is a rapidly growing region with expanding community pharmacy services, but there is limited published data on DDI decision-making among community pharmacists. To address this gap, we conducted a cross-sectional study to (i) evaluate community pharmacists’ knowledge of clinically important DDIs in the Jazan Region; (ii) explore perceptions, behaviors, and system-level barriers related to DDI management; (iii) analyze demographic and training factors associated with knowledge. By combining item performance with workflow and systems data, our aim is to enhance and refine reference tools and clinical decision support, ultimately reducing preventable medication harm from DDIs in community settings.
4. Discussion
The aim of this study was to assess community pharmacists’ knowledge, attitudes, and practices regarding drug–drug interactions (DDIs) in the Jazan Region of Saudi Arabia and to identify factors associated with knowledge gaps and perceived barriers to effective DDI management. Overall, pharmacists demonstrated limited recognition of clinically significant DDIs, with knowledge scores varying according to demographic and professional characteristics, training exposure, and use of clinical decision-support tools. Commonly reported barriers included time constraints, limited prescriber accessibility, and patient-related challenges, while structured training and technology-based solutions.
The findings of this study emphasize a deficit in DDI knowledge among community pharmacists in Jazan Region. With a mean accuracy of 37%, our results are nearly identical to those from Jeddah (38.2%) [
14], and the central region of Saudi Arabia, where only 5 of 26 pairs were correctly identified by most participants [
15]. Such findings also align with Lebanon (mean 5.62/15) [
24] and Ethiopia, where major contraindications were frequently misclassified [
25]. In contrast, higher overall knowledge was reported in Egypt (58.3%) [
22], possibly reflecting structured continuing education and institutional emphasis on clinical safety. Collectively, these data indicate that while knowledge remains inconsistent across contexts, the Saudi performance in both Jeddah and Jazan mirrors wider regional challenges.
Specific interactions, such as sildenafil–isosorbide mononitrate, was the most reliably recognized interaction (61.6%) among participants, in line with regional studies where it consistently scored highest (74.6% in central region of Saudi Arabia; 78.8% in Egypt) [
15,
22]. However, other high-risk interactions mediated by CYP3A4 (e.g., simvastatin–itraconazole, pimozide–ketoconazole) were not consistently recognized. For example, Egyptian pharmacists reported an accuracy rate of 66.6% for simvastatin–itraconazole [
22], whereas our cohort achieved substantially lower rates. Furthermore, our very low recognition of dopamine–phenytoin (6.6%) and theophylline–omeprazole (10.2%) parallels Lebanon [
24] and Indonesia [
23], where less “classic” interactions were often missed. This pattern suggests selective familiarity: pharmacists recognize widely emphasized, life-threatening interactions but often overlook more mechanistically complex or monitoring-dependent combinations, which may still contribute substantially to preventable adverse drug events.
There were significant differences across demographic and educational factors. Female pharmacists, PharmD holders, those who graduated from Saudi Arabia, and those with fewer than 10 years of experience scored higher. Similar trends were reported in the study that was conducted in Jeddah, where both gender and years of practice predicted higher knowledge [
14] and in Indonesia, where female pharmacists showed greater awareness than males [
23]. Egypt also highlighted proactive DDI-checking behaviors as a positive predictor [
22], while Lebanon reported a U-shaped curve where very recent and very senior pharmacists outperformed mid-career peers, possibly reflecting knowledge decay without reinforcement [
24]. However, similar studies conducted in the central region of Saudi Arabia and Sudan reported no demographic differences [
15,
26]. Furthermore, pharmacists who received DDIs training through professional development activities outperformed those who received training only during formal undergraduate education. This is consistent with Egypt, where structured continuing education was a key predictor of DDI competence [
22]. On the other hand, reliance on ad hoc resources such as informal mobile apps, as reported in Lebanon, was associated with poorer outcomes [
24]. These comparisons highlight the need to embed DDIs into both undergraduate curricula and post-licensure professional development to ensure sustained competence.
Self-rated awareness could be correlated with performance, and that pharmacists who routinely reviewed medication histories, consulted colleagues, or encountered DDI cases performed better. This suggests that reflective practice and active engagement reinforce competence. In comparison, Sudanese pharmacists reported high vigilance, with 87.2% routinely screening prescriptions [
26], whereas Ethiopian pharmacists displayed favorable attitudes but limited implementation [
25]. Therefore, our results highlight the importance of transforming awareness into structured, repeatable practice, supported by both personal initiative and institutional mechanisms.
Pharmacists who relied on robust clinical decision-support software, such as Micromedex, Lexicomp, and UpToDate, achieved significantly higher DDI knowledge scores than those using Medscape or no software at all. This finding is supported by several comparative studies demonstrating substantial variability in the accuracy, sensitivity, and comprehensiveness of commonly used DDI databases and screening tools. For example, evaluations comparing multiple DDI software programs have shown that Lexi-Interact and Micromedex consistently outperform other platforms in detecting clinically important interactions, while lower agreement and reduced detection rates have been reported for less comprehensive tools [
27]. Similar variability has been observed across different therapeutic areas, reinforcing that reliance on a single or non-curated database may lead to missed or misclassified interactions. These findings parallel data from Lebanon, where reliance on non-curated tools such as Drugs.com was associated with weaker DDI knowledge [
24], and contrast with evidence from Indonesia, where high adherence to DDI screening (≈90%) was achieved largely through institutional mandates requiring accredited decision-support systems [
23]. Together, these data support the notion that pharmacists’ use of different DDI resources can lead to variation in interaction recognition and underscore the value of integrated, high-performance decision support.
Barriers were raised by pharmacists that could negatively impact effective DDI communication, including time constraints, limited prescriber accessibility, and patient comprehension challenges. Similar obstacles were identified in Lebanon [
24] and Ethiopia [
25] while Sudanese pharmacists displayed stronger assertiveness, with over 60% refusing to dispense unsafe prescriptions [
26]. Institutionalized hospital protocols, such as those in Indonesia, have mitigated such challenges by standardizing pharmacist–physician communication pathways [
23]. These comparisons suggest that local pharmacists’ willingness to act is insufficient without systemic reinforcement through policy and workflow redesign. In addition, workflow interruptions, prescriber inaccessibility, and limited patient understanding remain recurrent systemic barriers. Similar findings were reported in Lebanon, where workload and time constraints hindered practice; Ethiopia, where lack of standardized protocols was a limiting factor; and Sudan, where prescriber resistance was common [
24,
25,
26]. Additionally, a qualitative study from Canada reported that community pharmacists face substantial barriers to effective DDI assessment, including limited access to patient clinical information, high workload pressures, and alert fatigue associated with computerized decision-support systems. These challenges contributed to missed or deprioritized alerts, despite pharmacists’ awareness of their professional responsibility in preventing DDIs [
11]. These barriers highlight the importance of institutional governance—through audits, protocols, and compliance monitoring—in enabling pharmacists to effectively operationalize their knowledge.
Facilitators that were thought to enhance pharmacist awareness and knowledge, such as familiarity with guidelines and participation in institutional compliance strategies, such as audits and electronic alerts, were strongly associated with higher DDI knowledge. This aligns with Indonesian hospitals, where strong governance frameworks translated into high adherence to screening protocols [
23]. Not only that, but also emphasizing the pharmacists’ own calls for structured training (38%) and advanced technology (34%) as top priorities for improvement. These align with regional calls: Lebanon for structured Continuing Professional Development (CPD), Egypt for integration of point-of-care tools, and Indonesia for enhanced interprofessional collaboration [
22,
23,
24]. Collectively, this indicates that beyond individual competence, systemic enablers are central to consistent and safe DDI management.
Although the use of clinical decision-support software was associated with higher DDI knowledge in our study, reliance on software alone may be insufficient to ensure consistent detection of clinically significant drug–drug interactions. Evidence from a U.S. performance evaluation of community pharmacy DDI software demonstrated that commonly used systems failed to detect approximately one-third of clinically important interactions, with substantial variability in sensitivity across platforms and installations [
28]. These findings suggest that while technology can support pharmacists’ decision-making, it cannot fully compensate for gaps in clinical judgment or pharmacological knowledge. Consequently, CPD and structured training remain essential to reinforce pharmacists’ ability to critically interpret alerts, recognize high-risk interactions, and apply appropriate clinical management beyond automated recommendations.
These findings emphasize the importance of direct clinical interaction and interdisciplinary communication in fostering a deeper understanding of DDI awareness. They also indicate a positive link between the use of advanced tools and increased DDI awareness. The results support encouraging consistent use of specialized clinical software in pharmacy practice to enhance decision-making accuracy. Additionally, these findings suggest that ongoing professional education may be more effective in improving practical DDI knowledge than initial academic exposure alone. They highlight that most barriers to patient counseling stem from communication dynamics and workflow constraints rather than knowledge gaps, emphasizing the need for patient education resources and sufficient time to improve pharmacist–patient interactions in community pharmacy settings. Furthermore, these findings point to persistent communication challenges that could hinder interprofessional collaboration in managing drug–drug interactions. Overall, they underscore the importance of continuous education and technological support in community DDI management.
These findings are particularly important in the evolving healthcare landscape of Saudi Arabia. The government’s increasing reliance on the Wasfaty e-prescription program has expanded the clinical role of community pharmacists, enabling them to dispense a wider range of prescription medications that were previously limited to hospital pharmacies. This transformation aligns with the national Vision 2030 and Health Sector Transformation Program, which emphasize accessibility, digitalization, and continuity of care. As Wasfaty bridges governmental healthcare services with community-based dispensing, community pharmacists are becoming integral to ensuring medication safety, particularly through the identification and management of drug–drug interactions. Therefore, assessing and strengthening their knowledge and practices is timely and essential to optimize patient outcomes and support the ongoing advancement of pharmaceutical care in Saudi Arabia.