The Frequency of Use of Warfarin-Interfering Drugs in Patients Suffering from Warfarin Toxicity Referred to the Emergency Department of Imam Reza Hospital, Mashhad
Morteza Khaksar
Department of Emergency Medicine, Faculty of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran.
Hamidreza Reihani
Department of Pharmacology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Seyed Hadi Mousavi
Department of Emergency Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Samad Nazemi
*
Department of Physiology, Cellular and Molecular Research Center, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran.
*Author to whom correspondence should be addressed.
Abstract
Aims: With the progress made in the treatment of cardiovascular patients, the use of anticoagulants such as warfarin, aspirin, ticlopidine, etc. have increased. This study aimed to investigate the frequency of use of warfarin-interfering drugs in warfarin toxicity patients admitted to the emergency ward of Imam Reza Hospital, Mashhad, Iran, from March to August 2016.
Materials and Methods: In this original cross-sectional study after obtaining the approval of the university's ethics committee, 133 patients with warfarin toxicity admitted from March to August 2016 were included in the study. The hospital records of the patients were reviewed, and based on the detailed history taken from the patients the information related to the simultaneous use of different drugs, the duration of warfarin use, the reasons for warfarin use, and the symptoms of warfarin toxicity were extracted. SPSS version 24 software was used for data analysis (p<0.05).
Results: Artificial heart valve was the most common indication for warfarin use (48%). Potentially fatal bleeding occurred in 85% of patients, and gastrointestinal bleeding was the most common symptom of warfarin toxicity (37.6%). The most common drugs used were aspirin (62.4%), metoprolol (33.1%), and statins (28.8%).
Conclusion: In this study, a high frequency of drug interactions with warfarin was observed, which seems to play a significant role in the occurrence of warfarin toxicity. The most common drug interactions were observed in the simultaneous use of aspirin, metoprolol, and statins. Careful monitoring of the type of drugs used by patients is extremely important in providing safe and effective treatment and reducing side effects.
Keywords: Warfarin toxicity, drug interaction, aspirin, cardiovascular disease
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Di Minno A, Frigerio B, Spadarella G, Ravani A, Sansaro D, Amato M, et al. Old and new oral anticoagulants: Food, herbal medicines and drug interactions. Blood Rev. 2017;31(4):193-203.
DOI: 10.1016/j.blre.2017.02.001.
Tadros R, Shakib S. Warfarin: Indications, risks and drug interactions. Aust Fam Physician. 2010;39(7):476-479.
PMID: 20628660
Carpenter M, Berry H, and Pelletier AL. Clinically relevant drug-drug interactions in primary care. Am Fam Physician. 2019;99(9):558-564.
DOI: 31730323
Mourad AP, Aslani P, D'Souza M, Brieger D. The acceptability of a direct oral anticoagulant monitoring regimen among patients with atrial fibrillation: A pilot study. Int J Clin Pharm. 2019;41(3):682-686.
DOI: 10.1007/s11096-019-00830-6
Ramsay NA, Kenny MW, Davies G, Patel JP. Complimentary and alternative medicine use among patients starting warfarin. Br J Haematol. 2005;130(5):777-780.
DOI: 10.1111/j.1365-2141.2005.05689.x
Wittkowsky AK, Devine EB. Frequency and causes of overanticoagulation and underanticoagulation in patients treated with warfarin. Pharmacotherapy. 2004; 24(10):1311-6.
DOI: 10.1592/phco.24.14.1311.43144.
Wittkowsky AK. Drug interactions update: Drugs, herbs, and oral anticoagulation. J Thromb Thrombolysis. 2001;12(1):67-71.
DOI: 10.1023/a:1012742628628
Berling I, Mostafa A, Grice JE, Roberts MS, Isbister GK. Warfarin poisoning with delayed rebound toxicity. J Emerg Med. 2017;52(2):194-196.
DOI: 10.1016/j.jemermed.2016.05.068
Piatkov I, Rochester C, Jones T, Boyages S. Warfarin toxicity and individual variability-clinical case. Toxins (Basel). 2010;2(11):2584-92.
DOI: 10.3390/toxins2112584
Wang M, Zeraatkar D, Obeda M, Lee M, Garcia C, Nguyen L, et al. Drug-drug interactions with warfarin: A systematic review and meta-analysis. Br J Clin Pharmacol; 2021.
DOI: 10.1111/bcp.14833
Shalansky S, Lynd L, Richardson K, Ingaszewski A, Kerr C. Risk of warfarin-related bleeding events and supratherapeutic international normalized ratios associated with complementary and alternative medicine: A longitudinal analysis. Pharmacotherapy. 2007;27(9): 1237-47.
DOI: 10.1592/phco.27.9.1237
Deaton JG, Nappe TM. Warfarin toxicity. Stat Pearls. Treasure Island (FL); 2022.
Mujtaba M, Khanzada MF, Aman S, Ahmed K, Ahmed N, Haider MU, et al. Predisposing Factors leading to warfarin toxicity. J Pharmaceu Res Inter. 2022:23-29.
DOI: 10.9734/JPRI/2022/v34i32B36116
Patil AS, Shriya S, Dhimole N, More J. Intramural jejunal hematoma causing intermittent bowel obstruction-a rare manifestation of warfarin toxicity. Surg J (N Y). 2022;8(4):e290-e292.
DOI: 10.1055/s-0042-1755223
Mirkov I, Popov Aleksandrov A, Ninkov M, Mileusnic D, Demenesku J, Zolotarevski L, et al. Strain differences in intestinal toxicity of warfarin in rats. Environ Toxicol Pharmacol. 2016;48:175-182.
DOI: 10.1016/j.etap.2016.10.019.
Muyambo S, Ndadza A, Soko ND, Kruger B, Kadzirange G, Chimusa E, et al. Warfarin pharmacogenomics for precision medicine in real-life clinical practice in Southern Africa: Harnessing 73 variants in 29 pharmacogenes. OMICS. 2022;26(1):35-50.
DOI: 10.1089/omi.2021.0199.
Raphael A. Moving towards ideal and appropriate models of anticoagulation management service. Ann Afr Med. 2020;19(3):153-163.
DOI: 10.4103/aam.aam_30_19.
Jacobs A, Bassa F, Decloedt EH. A preliminary review of warfarin toxicity in a tertiary hospital in Cape Town, South Africa. Cardiovasc J Afr. 2017;28(6):346-349.
DOI: 10.5830/CVJA-2017-029.
Cruickshank J, Ragg M, Eddey D. Warfarin toxicity in the emergency department: Recommendations for management. Emerg Med (Fremantle). 2001;13(1):91-7.
DOI: 10.1046/j.1442-2026.2001.00185.x.
Larsen TR, Gelaye A, Durando C. Acute warfarin toxicity: An unanticipated consequence of amoxicillin/clavulanate administration. Am J Case Rep. 2014; 15:45-8.
DOI: 10.12659/AJCR.889866.
Choumane NS, Malaeb DN, Malaeb B, Hallit S. A multicenter, prospective study evaluating the impact of the clinical pharmacist-physician counselling on warfarin therapy management in Lebanon. BMC Health Serv Res. 2018;18(1):80.
DOI: 10.1186/s12913-018-2874-7.
Zhang L, Chen W, Gan D. Analysis of the physiological and pathological factors of hospitalized patients taking warfarin and the correlation between drug interactions and warfarin efficacy. Ann Palliat Med. 2021;10(5):5400-5406.
DOI: 10.21037/apm-21-830.
Sonuga BO, Hellenberg DA, Cupido CS, Jaeger C. Profile and anticoagulation outcomes of patients on warfarin therapy in an urban hospital in Cape Town, South Africa. Afr J Prim Health Care Fam Med. 2016;8(1):e1-8.
DOI: 10.4102/phcfm.v8i1.1032.
Kabiri M, Hosseini SM, Veisi F, Mortezaei S, Ahmadi A, Agashteh Z, et al. Investigation of poisoning prevalence and its related factors in patients referred to Farsan’s Hospital during 2018-2019, Iran. International Journal of Epidemiologic Research, 2022:75-79.
Abbas A, Al-Shaibi S, Sankaralingam S, Awaisu A, Kattezhathu VS, Wongwiwatthananukit S, et al. Determination of potential drug-drug interactions in prescription orders dispensed in a community pharmacy setting using Micromedex ((R)) and Lexicomp ((R)): A retrospective observational study. Int J Clin Pharm. 2022;44(2):348-356.
DOI: 10.1007/s11096-021-01346-8
Arbring K, Uppugunduri S, Lindahl TL. Comparison of prothrombin time (INR) results and main characteristics of patients on warfarin treatment in primary health care centers and anticoagulation clinics. BMC Health Serv Res. 2013;13(1):85.
DOI: 10.1186/1472-6963-13-85
Poli D, Antonucci E, Testa S, Tosetto A, Ageno W, Palareti G, et al. Bleeding risk in very old patients on vitamin K antagonist treatment: Results of a prospective collaborative study on elderly patients followed by Italian centres for anticoagulation. Circulation. 2011;124(7):824-829.
Wieloch M, Sjalander A, Frykman V, Rosenqvist M, Eriksson N, Svensson PJ. Anticoagulation control in Sweden: Reports of time in therapeutic range, major bleeding, and thrombo-embolic complications from the national quality registry auricul A. Eur Heart J, 2011.32(18):2282-9.
DOI: 10.1093/eurheartj/ehr134.
Schmitt L, Speckman J, Ansell J. Quality assessment of anticoagulation dose management: Comparative evaluation of measures of time-in-therapeutic range. J Thromb Thrombolysis. 2003;15(3):213-6.
DOI: 10.1023/B:THRO.0000011377.78585.63
Liew C-L, Yen J-H, Liu A-B, and Liu IY. Sex differences in the effective warfarin dosage in Han and aboriginal Taiwanese patients with the VKORC1-1639AA genotype. Tzu Chi Medical Journal. 2013;25(4):213-217.
DOI: 10.1016/j.tcmj.2013.06.005
Garg P, Yagnik VD, Kaur G. Increased risk of bleeding with topical metronidazole in a postoperative wound after anal fistula and hemorrhoid surgery: A propensity score-matched case-control study. Clin Pract. 2022;12(1):133-139.
DOI: 10.3390/clinpract12010017
Howard-Thompson A, Hurdle AC, Arnold LB, Finch CK, Sands C, Self TH. Intracerebral hemorrhage secondary to a warfarin-metronidazole interaction. Am J Geriatr Pharmacother. 2008.6(1):33-6.
DOI: 10.1016/j.amjopharm.2008.03.003
Lin SW, Kang WY, Lin DT, Lee J, Wu FL, Chen CL, et al. Comparison of warfarin therapy clinical outcomes following implementation of an automated mobile phone-based critical laboratory value text alert system. BMC Med Genomics. 2014;7(1):S13.
DOI: 10.1186/1755-8794-7-S1-S13