Assessment of Knowledge, Attitude, and Practice of Pharmacists towards Drug Interactions in Saudi Arabia

Background: Drug interactions, which are generally encountered in medical prescriptions, may lead to severe health issues. Pharmacists in both the public and private pharmacy setting are by profession in a unique position to gain and use their competencies to find and prohibit drug interactions. Original Research Article Imam et al.; JPRI, 33(46B): 538-545, 2021; Article no.JPRI.75360 539 Aim of the Study: To assess knowledge, attitude and practice of pharmacists toward drug interactions in Saudi Arabia. Materials and Methods: A cross-sectional study was conducted using a selfadministered questionnaire. Results: Two hundred sixty-three pharmacists participated in the survey and results were expressed in frequencies and percentages. The mean age of participant pharmacists was (31.7) years showing a relatively young participant’s population. Males were (75.3%), while females were (24.7%). Majority of pharmacists (67.3%) were working in public sector. Half of them had a bachelor’s degree in pharmacy as their latest academic degree. Participants’ averages of awareness, attitude and practice regarding drug interactions, correct knowledge of drug-drug, drug-food, drug-disease interactions were, (90.7%), (65.3%), (67.7%), (61.7%) respectively. Most (79.8%) of the participants asserted that the notified doctors usually agree with pharmacists’ opinion and decision. This percentage indicates a good cooperation when compared to other studies. Conclusion: Pharmacists’ knowledge about drug interactions was inadequate. Lack of knowledge of drug interactions may lead to improper patient counseling and the appearance of adverse effects. There is a need to improve the knowledge and to uplift the level of awareness of pharmacists about the potential drug interactions that are clinically related.


INTRODUCTION
Drug-drug interactions (DDI) can be specified as the clinical or pharmacological response of a drug combination that is dissimilar from that expected from the known effects of the two drugs when given alone and that may lead to a decrease in efficacy or increase in toxicity. Three levels of DDI severity are minor, moderate and major [1]. Drug interactions may change the pharmacodynamics and/or pharmacokinetics of a drug. The pharmacodynamics interaction may be antagonistic, additive, or synergistic effects of a drug. One of the widely and important sources of medication errors is the drug interactions (DIs) [2]. Food may have negative or positive effects on the bioavailability of the drug and may lead to drug toxicity or therapeutic failure. Food-drug interactions (FDIs) are a serious issue in the medical practice; they may negatively affect the drug's efficacy, extend the patient's hospitalization or threaten their life [3].
The prevalence of potential FDIs is variable in different countries and it ranges from 6 to 70 % [4][5][6]. Food may change the bioavailability of drugs by introducing some changes in the GI physiology such as GI motility, gastric pH, gastric emptying, transport proteins such as Pglycoprotein and the activity of the metabolizing enzymes. Moreover, food components may chelate or bind to the active pharmaceutical ingredients [7].
Drug-disease interactions (DDIs) are conditions whereby a new drug treatment elicits the preexisting medical condition. It may also indicate the ability of a newly prescribed drug to lead adverse effects similar to one of the patient's diseases conditions [8]. In addition, the most recurrent interactions between the prescriptions studied included treatment with non-steroidal anti-inflammatory drugs (NSAIDs) in hypertensive patients and chronic heart failure patients and co-administration of ACE inhibitors and non-steroidal anti-inflammatory drugs [9].
Pharmacists, especially in the community setting are on the front line to detect DDIs. In addition, the evaluation of drug interaction knowledge in the kingdom of Saudi Arabia seems missing. The Evaluation of and then improving the knowledge of potential common DDIs among pharmacists by implementing helpful programs could limit the incidence of harmful effects, emergency visits, hospitalizations, and health cost [10].

Aims of Study
To assess knowledge, attitude and practice of pharmacists towards drug interactions in Saudi Arabia.

Study Design
A cross-sectional study was carried using the self-administered questionnaire. The questionnaire was performed over a period of 7 months from April to October 2018. This study involved pharmacists in Saudi Arabia.

Sample Size Calculation
The online calculator (RaosoftInc) was used to estimate the study sample size (263 pharmacists) and this based on total number of pharmacists licensed to practice (Saudi commission for health specialties, 2018). This study used the rate tolerates of 5% and 95% confidence level to give 263 pharmacists.

Survey Questionnaire
The questionnaire used contained three sections; the 1st section was related to demographic data including the age, years of practice, area of practice and academic qualification. The second section was related to attitude and practice of participants regarding drug interactions. The third section regarded the evolution of the pharmacist's knowledge about drug interactions (DIs). Twenty-four (24) selected drug interaction pairs were used to investigate the potential pharmacist's knowledge about drug interactions (drug-food, drug-drug and drug-disease interactions). They were selected, as they are the most prevalent drug interactions mentioned in medical literature.

Data Analysis
Data were entered into Excel (Microsoft office) worksheets and then transferred to SPSS (version 26, IBM) for statistical analyses. Categorical analyses of frequencies and cross tabulations were done using the Chi-square and standardized residual analysis in SPSS.

RESULTS
This study was conducted from April to October 2018. Two hundred sixty-three pharmacists participated in the survey and results were expressed in frequencies and percentages. The mean age of participant pharmacists was (31.7) years showing a relatively young participant's population. Males were (75.3%), while females were (24.7%). Majority of pharmacists (67.3%) were working in public sector. Half of them had a bachelor's degree in pharmacy as their latest academic degree.

DISCUSSION
Participants' attitude and practice towards drug interactions was evaluated. Results showed that around (85.9%) of them had come across druginteractions during their practice, which confirms the potential high incidence of drug interactions in the patient's prescriptions which is comparable to other studies [11,12].
Regarding the attitude of the participant pharmacists toward cooperation with the prescribers on drug-interactions in their prescription, most (98.1%) of the participants used to contact the prescribers, before dispensing the prescription, mainly by telephone the prescriber for verification. Most (79.8%) of the participants asserted that the notified doctors usually agreed with the pharmacists' opinion and decision and without reservations. This percentage indicates a good cooperation when compared to other studies.  Despite all ongoing and implemented initiatives, DDIs are still an international problem. DDIs identification is varied according to the practice setting. In a hospital pharmacy, for example, there are various methods that may help in recognizing drug interactions and preventing them such as attainable scientific resources and electronic systems [13][14][15]. In most community pharmacies in the kingdom of Saudi Arabia, these tools are not available. Also, many medication safety standards are not available in this setting yet. The deficiency of electronic systems in the community pharmacy setting has a remarkable effect on both patient and medication safety. Subsequently, most of the medication safety standards are based on pharmacist's knowledge only.
Is there Drug-drug interaction between the Aspirin with Ibuprofen?
Is there Drug-drug interaction between the Metronidazole with Phenytoin?
Is there Drug-drug interaction between the Warfarin with Atorvastatin?
Is there Drug-drug interaction between the Azithromycin with Citalopram?
Is there Drug-drug interaction between the Captopril with Fluoxetine?
Is there Drug-drug interaction between the Colchicine with Fluconazole?
Is there Drug-drug interaction between the Cyclosporine with Pantoprazole?
Is there Drug-food interaction between Ciprofloxacin with Dairy product?
Is there Drug-food interaction between Griseofulvin with Low fat meals?
Is there Drug-food interaction between Itraconazole (solution) with Food?
Is there Drug-food interaction between Simvastatin with Grapefruit juice?
Is there Drug-food interaction between Tetracycline (oral) with dairy products?
Is there Drug-food interaction between Vardenafil with highfat meal?
Is there Drug-food interaction between Levodopa with highprotein diets?
% of Wrong answer % of Correct answer

Fig. 3. Pharmacists' knowledge of drug-disease interactions
The results of the present study declared that the knowledge of pharmacists about DDIs was inadequate. Electronic and education systems can help pharmacists in detecting such interactions easily which is comparable to other studies in Saudi Arabia [16].
Regarding drug-food interactions, the most common interactions involved questions in the knowledge part of the collection data tool and the pharmacists were asked to answer them. Most of the pharmacists thought that they had enough information regarding this issue. But they did not appear to have the adequate knowledge to realize a number of these interactions. In comparison to other studies there is improvement in pharmacist's knowledge regarding FDIs [17].
Regarding drug-disease interaction the use of calcium channel blockers (Amlodipine) in patients suffering from congestive heart failure (CHF), the correct responses were (41.4%) which is the lowest percentage in this issue. These results showed the poor knowledge of pharmacists toward drug-disease interactions, especially for heart disease, which is comparable to other studies [12].

CONCLUSION AND RECOMMENDA-TION
In conclusion, pharmacist's knowledge about all drug interactions was insufficient and inadequate. The deficiency in drug interaction knowledge may lead to the appearance of adverse effects and improper patient counseling. Therefore, there is a need to improve the knowledge and to uplift the level of awareness of pharmacists about all the potential drug interactions that are clinically related. Finally, pharmacists still need more training and education programs about drug interactions in order to be more competent to improve patient's therapeutic outcomes and supply better pharmaceutical care.

DISCLAIMER
The products used for this research are commonly and predominantly use products in our area of research and country. There is absolutely 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Is there Drug-disease interaction between Aspirin with Hemophilia?
Is there Drug-disease interaction between Co-trimethoxazole with megaloblastic anemia?
Is there Drug-disease interaction between Hydrochlorothiazide with Gout?
Is there Drug-disease interaction between Enalapril with Congestive heart failure?
Is there Drug-disease interaction between Propranolol with Asthma?
Is there Drug-disease interaction between Spironolactone with Congestive heart failure?
Is there Drug-disease interaction between Scopolamine (Systemic) with Benign prostatic hyperplasia?
Is there Drug-disease interaction between Amlodipine with congestive heart failure?
% of Wrong answer % of Correct answer no conflict of interest between the authors and producers of the products because we do not intend to use these products as an avenue for any litigation but for the advancement of knowledge. Also, the research was not funded by the producing company rather it was funded by personal efforts of the authors.

CONSENT
As per international standard or university standard, respondents' written consent has been collected and preserved by the author(s).