Research Article
Evaluation of Warfarin Drug Interactions Among Adult Outpatients at Public Hospitals in Nekemte Town: A Retrospective Cross-Sectional Study
- Firafan Shuma Teka 1*
- Ayana Tadesse Korsa 2
- Habte Gebeyehu Bayisa 2
- Birbirsa Sefera Senbeta 3
- Dinka Dugassa Iticha 2
- Gemechis Belay Dibera 2
- Refisa Shifera Beyene 2
- Chala Abera Bayisa 4
1Department of Clinical Pharmacy and Pharmacy Practice, Institute of Health Sciences, Dambi Dollo University, Dambi Dollo, Ethiopia.
2Department of Clinical Pharmacy and Pharmacy Practice, Institute of Health Sciences, Wallaga University, Oromia, Ethiopia.
3Department of Pharmacy, College of Health Science, Mettu University, Oromia, Ethiopia.
4Department of Clinical Pharmacy, Institute of Health Sciences, Wallaga University Referral Hospital, Oromia, Ethiopia.
*Corresponding Author: Firafan Shuma Teka, Department of Clinical Pharmacy and Pharmacy Practice, Institute of Health Sciences, Dambi Dollo University, Dambi Dollo, Ethiopia.
Citation: Teka F.S., Korsa A.T., Bayisa H.G., Senbeta B.S., Iticha D.D., et al. (2025). Evaluation of Warfarin Drug Interactions Among Adult Outpatients at Public Hospitals in Nekemte Town: A Retrospective Cross-Sectional Study, Journal of Clinical Cardiology and Cardiology Research, BioRes Scientia Publishers. 4(1);1-11, DOI: 10.59657/2837-4673.brs.25.044
Copyright: © 2025 Firafan Shuma Teka, this is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: December 23, 2024 | Accepted: February 07, 2025 | Published: February 14, 2025
Abstract
Background: Warfarin Interindividual variability in pharmacokinetics and pharmacodynamics and narrow therapeutic index properties pose the risk of potential interactions with several drugs and foods.
Objectives: This study aimed to evaluate warfarin drug interactions among adult outpatients at public hospitals in Nekemte town, Western Ethiopia from April 1, 2021, to March 31, 2023.
Methods: A hospital-based retrospective cross-sectional study was conducted from June 1 to July 31, 2023. Data were collected by using a semi-structured questionnaire. The collected data were entered into EpiData version 4.6.0 and the statistical package for social science (SPSS) software version 27.0 was used for data analysis. Descriptive statistics were used to present the data. Micromedex online drug interaction checker was performed to analyze the interaction between each concomitant medication with warfarin therapy.
Results: A total of 402 patient medical charts with warfarin indications were reviewed. The mean age of the study participants was 38.9 years (SD = 17.9) and 67.40% were female patients. The prevalence of warfarin drug interactions was 93.50%, with an average of 2.33 (SD = 1.36), where heparin (81.10%) and aspirin (16.7%) were the most predominant moderate and major interacting drugs with warfarin, respectively.
Conclusion: Warfarin drug interactions were found to be high in the present study. Heparin and aspirin were the most frequently prescribed medications that had moderate and major interactions with warfarin, respectively.
Keywords: drug interactions; nekemte town; public hospitals; warfarin
Introduction
Warfarin is a vitamin K antagonist (VKA) oral anticoagulant, indicated for the prevention of venous thromboembolism (VTE), stroke, thromboembolic complications in atrial fibrillation, and mechanical heart valves [1-3]. Warfarin has over 200 drug interactions [4-6] and its exposure to potential drug interaction is mainly due to its narrow therapeutic index [1,7]. Drug interactions with warfarin therapy are a major cause of excessive anticoagulation and important risk factors for bleeding events [8]. Interindividual variability in pharmacokinetics and or pharmacodynamics increases the risk of drug interactions with warfarin therapy [9]. Globally, warfarin drug interactions are a common concern for clinicians in the management of comorbidity involving co-administration of drugs [1]. Antimicrobials, non-steroidal anti-inflammatory drugs (NSAIDs) [10,11], statins, direct-acting oral anticoagulants, clonidine and beta-blockers, calcium channel blockers, phosphodiesterase 5-inhibitors, and nitrates are known to interact with warfarin [11]. The prevalence of warfarin drug interactions in large population-based studies ranges between 57% and 82% [5], NSAIDs and low-dose acetylsalicylic acid are the most common interacting drugs involved. In Ethiopia, the prevalence of warfarin drug interactions ranged between 21.1% and 99.2% [12-14]. To the best of our knowledge, studies on the prevalence of warfarin drug interactions are scarce, particularly in Ethiopia. Therefore, this study aimed to evaluate warfarin drug interactions among adult outpatients at Wallaga University Referral Hospital (WURH) and Nekemte Comprehensive Specialized Hospital (NCSH), Nekemte town, Western Ethiopia.
Methods and Materials
Study Setting and Period
The study was conducted among adult outpatients who received warfarin therapy from April 1, 2021, to March 31, 2023, at Wallaga University Referral Hospital (WURH) and Nekemte Comprehensive Specialized Hospital (NCSH), located 330 km west of Addis Ababa, the capital of Ethiopia. The hospitals provide both inpatient and outpatient services. Data were collected from June 1 to July 31, 2023.
Study Design
A hospital-based retrospective cross-sectional study was conducted to collect data among adult outpatients who received warfarin therapy at WURH and NCSH.
Inclusion and Exclusion Criteria
Inclusion Criteria: Adult patients (age ≥18 years), patients on warfarin for at least 1 month, and follow-up at the chronic care clinic at WURH and NCSH from April 1, 2021, to March 31, 2023, were included in the study.
Exclusion Criteria: Pregnant women and those patients on other direct-acting oral anticoagulants during the study period were excluded.
Sampling Procedure
A total of 402 patient medical charts with warfarin indications during the study period were reviewed using semi-structured questionnaires. All relevant information including socio-demographic characteristics of the study participants (sex and age), warfarin indications, each concomitant medication with warfarin therapy, and dose of warfarin per day were thoroughly reviewed.
Data Collection Method and Data Quality Control
Data were collected by data collectors (2 pharmacists) using structured tools. Daily supervision was made by supervisors at two public hospitals. Before data collection, 2-day training was given for both data collectors and supervisors.
Data Analysis and Interpretations
Data were entered into EpiData version 4.6.0 and analyzed for statistical package for social science software (SPSS) version 27.0. Descriptive statistics including the percentages, frequencies, mean, and standard deviation (SD) were reported. Micromedex online data interaction checker [15] was performed to analyze drug interaction between warfarin and each co-administered drug. Warfarin drug interactions were classified as major and minor drug interactions.
Operational Definitions
Drug-Drug Interactions (DDIs): a co-administered drug can change the pharmacology or clinical response of a medication. Drug interactions can range from minimal to substantial in severity [14].
Major Drug-Drug Interactions: are those that have the potential to be fatal, can result in long-term damage, and need for further care, hospitalization, or an extension of hospital stay. Such an interaction requires stopping the medication [16].
Moderate Drug-Drug Interactions: could worsen a patient's clinical condition and necessitate more care, hospitalization, or an extension of the patient's hospital stay. The patient needs to be closely watched during this period. It can call for stopping the course of treatment [1].
Ethical Considerations
The study was approved by the Research Ethics Review Committee (RERC) of Wallaga University (Minutes No: 1035/2023). All information’s pertinent to the present study were kept confidential.
Results
Socio-Demographic Characteristics of The Study Participants
A total of 402 patient medical charts were reviewed in this study. The mean age of the participants was 38.9 years (SD = 17.9), and 271(67.40%) were female patients (Table 1).
Table 1: Socio-demographic characteristics of patients on warfarin therapy at WURH and NCSH, Nekemte, Western Ethiopia from April 1, 2021-March 31, 2023 (N = 402).
| Characteristics | N | % | |
| Sex | Male | 131 | 32.60 |
| Female | 271 | 67.40 | |
| Age | 18-40 | 244 | 60.70 |
| 41-64 | 99 | 24.60 | |
| 65-74 | 45 | 11.20 | |
| ≥75 | 14 | 3.50 |
Indications of Warfarin Therapy
The primary indication of warfarin therapy was deep venous thrombosis in 266(66.20%) of patients (Table 2).
Table 2: Indications of warfarin therapy among outpatients at WURH and NCSH, Nekemte, Western Ethiopia from April 1, 2021-March 31, 2023 (N = 402).
| Indications Of Warfarin Therapy | N | % |
| Deep Venous Thrombosis | 266 | 66.20 |
| Atrial Fibrillation | 74 | 18.4 |
| Deep Vein Thrombosis and Pulmonary Thromboembolism | 45 | 11.2 |
| Pulmonary Thromboembolism | 7 | 1.70 |
| Left Atrial Thrombus | 4 | 1.0 |
| Inferior Vena Cava Thrombus | 2 | 0.5 |
| Deep Vein Thrombosis and Inferior Vena Cava Thrombus | 2 | 0.5 |
| Deep Vein Thrombosis and Acute Cerebral Venous Thrombosis | 2 | 0.5 |
Prevalence of Warfarin Drug Interactions
The prevalence of warfarin drug interactions was found to be 93.50%. On average, 2.33 warfarin drug interactions were identified (SD = 1.36). Heparin (81.10%) and aspirin (16.70%) were the most predominant moderate and major warfarin drug interactions, respectively (Table 3).
Table 3: Types and severity of identified warfarin drug interactions among outpatients at WURH and NCSH, Nekemte, Western Ethiopia from April 1, 2021-March 31, 2023 (N = 402).
| Number Of Warfarin Drug Interactions Per Patient | N | % | ||
| None | 25 | 6.20 | ||
| 1 | 69 | 17.20 | ||
| 2 | 168 | 41.80 | ||
| 3 | 70 | 17.40 | ||
| 4 | 44 | 10.90 | ||
| ≥5 | 26 | 6.50 | ||
| Identified Warfarin Drug Interactions | N | % | Severity of Interactions | |
| Diclofenac | 15 | 3.70 | Major | |
| Ibuprofen | 1 | 0.20 | Major | |
| Acetaminophen | 42 | 10.40 | Moderate | |
| Tramadol | 257 | 63.90 | Moderate | |
| Meloxicam | 3 | 0.70 | Major | |
| Heparin | 326 | 81.10 | Moderate | |
| Aspirin | 67 | 16.70 | Major | |
| Clopidogrel | 4 | 1.0 | Major | |
| Ceftriaxone | 79 | 19.70 | Moderate | |
| Azithromycin | 39 | 9.70 | Major | |
| Benzathine Penicillin | 34 | 8.50 | Major | |
| Cefepime | 3 | 0.70 | Major | |
| Vancomycin | 8 | 2.0 | Moderate | |
| Metronidazole | 19 | 4.70 | Major | |
| Cloxacillin | 15 | 3.70 | Major | |
| Ciprofloxacin | 3 | 0.70 | Major | |
| Norfloxacin | 1 | 0.20 | Major | |
| Cephalexin | 8 | 2.0 | Major | |
| Cefixime | 2 | 0.50 | Major | |
| Ceftazidime | 3 | 0.70 | Major | |
| Ketoconazole | 1 | 0.20 | Major | |
| Propyl Thio Uracil | 4 | 1.0 | Moderate | |
| Omeprazole | 12 | 3.0 | Major | |
| Pantoprazole | 1 | 0.20 | Moderate | |
| Cimetidine | 21 | 5.20 | Moderate | |
| Ranitidine | 3 | 0.70 | Moderate | |
| Others* | 4 | 1.0 | Major | |
| Others** | 8 | 2.0 | Moderate |
*Efavirenz and Trimethoprim/Sulfamethoxazole, **Isoniazid and Rifampicin.
Discussion
The present study aimed to evaluate warfarin drug interactions among adult outpatients at public hospitals in Nekemte town. Warfarin drug interactions were found in more than three-fourths of the patients. The mean age of the study participant was 38.9 years and the majority of the patients (67.40%) were females. The finding is similar to that of the study conducted in Kenya [17] and Ethiopia [18], in which the mean age of the participants was 42.7 and 35.3 years, respectively. Female patients were more predominant, 74.10% and 64.70%, respectively in those two studies. The primary indication for warfarin therapy was deep venous thrombosis (66.20%) followed by atrial fibrillation (18.40%), which was in line with the study conducted in Uganda (63%) [19] and Kenya (72.4%) [17]. The study differs from previous studies in China (67.7%) [20], Spain (64.6%) [21], and Ethiopia (59.52%) [13], where warfarin therapy is primarily used for managing atrial fibrillation. The probable reason for these disparities might be variations in the selection of study participants.
The prevalence of warfarin drug interactions was 93.50% in this study. This study finding was consistent with that of the study conducted in Brazil [16] and Northern Ethiopia [14], where 97.10% and 99.20% of warfarin drug interactions were identified, respectively. In contrast to the study from Estonia (62.0%) [22], Switzerland (More than 58%) [8] and Ethiopia (21.10%), the present finding was higher. These disparities might be due to multiple comorbid conditions that may necessitate co-prescribing of several drugs with warfarin therapy. The present study showed that the mean number of warfarin drug interactions identified by performing the Micromedex online drug interaction checker was 2.33 ± 1.36 and 81.10% of moderate warfarin-drug interaction encountered heparin. This is supported by the study conducted in Northern Ethiopia [14], in which on average, 3.2 ± 2.0 drug-drug interactions with warfarin were identified and heparin (75.9%) was the most frequently interacting drug. Among drugs identified to have major drug interactions with warfarin, aspirin (16.70%) encountered the highest proportion which was higher (3.28%) than the study conducted in Brazil [16]. This difference was probably due to differences in patient clinical characteristics like; the prevalence of cardiovascular disorders that may have necessitated aspirin indication and a larger sample size in comparison to the present study.
Limitations of the Study
Our study was not without limitations. The study didn’t include clinical pharmacist interventions which play a vital role in the management of drug-drug interactions. The study design by itself may lead to the risk of recall bias.
Conclusion and Recommendations
Warfarin drug interactions in the present study were found to be more prevalent. Heparin and aspirin were the most frequently prescribed drugs that had moderate and major interactions with warfarin therapy, respectively. Physicians treating the patient should emphasize those concomitant medications with warfarin therapy. Involving clinical pharmacist intervention in patient care decision-making minimizes the risk of potential drug interactions with warfarin therapy.
Acronyms and Abbreviations
NCSH: Nekemte Comprehensive Specialized Hospital; NSAIDS: Non-Steroidal Anti-Inflammatory Drugs; RERC: Research Ethics Review Committee; SD: Standard Deviation; VKAs: Vitamin K Antagonists; VTE: Venous Thromboembolism; WURH: Wallaga University Referral Hospital
Declarations
Authors Contribution
FSHT: Data curation, conceptualization, data analysis, manuscript writing and edition, grammar check, and review process. ATK: Data curation, conceptualization, analysis, manuscript writing and edition, grammar check, and review process. HGB: Data curation, analysis, manuscript writing and edition, grammar check, and review process. BSS: Data curation, analysis, manuscript writing, and edition and review process. DDI: Data curation, data analysis, manuscript writing, and edition and review process. GBD: Data curation, data analysis, manuscript writing, and edition and review process. RSHB: Data curation, review process, grammar and language check. CAB: Data curation, review process, grammar, and language check.
Acknowledgments
We would like to forward our heartfelt thanks to Wallaga University for sponsoring this study. We would also thank Wallaga University; Institute of Health Sciences for giving us the opportunity conduct this study. Moreover, we would like to thank Wallaga University Referral Hospital and Nekemte Comprehensive Specialized Hospital particularly the chronic care clinic for supporting us in getting detailed information.
Conflict of Interest
The authors declare they have no conflict of interest.
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