POTENTIAL OF DRUG INTERACTIONS IN HOSPITALIZED PATIENTS RECEIVING WARFARIN THERAPY FOR THE FIRST TIME

Authors

  • DIAN OKTIANTI Faculty of Pharmacy, Universitas Muhammadiyah Surakarta, Central Java, Indonesia. Pharmacy Study Program, Faculty of Health, Universitas Ngudi Waluyo, Central Java, Indonesia
  • ZAKKY CHOLISOH Faculty of Pharmacy, Universitas Muhammadiyah Surakarta, Central Java, Indonesia https://orcid.org/0000-0003-0357-6999
  • SITI MAISHARAH SHEIKH GHADZI Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor-11800, Pulau Pinang, Malaysia
  • HIDAYAH KARUNIAWATI Faculty of Pharmacy, Universitas Muhammadiyah Surakarta, Central Java, Indonesia https://orcid.org/0000-0003-2776-250X

DOI:

https://doi.org/10.22159/ijap.2025.v17s2.14

Keywords:

Warfarin, Drug interaction, Major severity, Hospitalised patients

Abstract

Objective: To identify potential interactions between warfarin and other drugs in hospitalized patients receiving warfarin therapy for the first time and determine parameters that are predicted to increase the risk of drug interactions resulting in major clinical severity. This is the first study in the field that was conducted in a multicenter setting in Central Java.

Methods: Data on the use of concomitant drugs with warfarin were collected from the medical records of hospitalized patients (August 2023-July 2024) who first received warfarin in a retrospective, multicentre study at 4 hospitals. Potential drug interaction was analyzed using a drug interaction checker.

Results: There were 148 patients who met the criteria, 78 patients (53%) were male and aged between 40-64 y. 78 patients (52%) received more than 8 types of drugs. Potential drug interactions occurred in all patients (100%), 62 patients (46.62%) experienced interactions in 6-8 drugs used. The parameter that had the strongest association with the severity of potential drug interactions was the number of drugs consumed with an Adjusted Odds Ratio (AOR) of 3.097 (95% CI 1.495-6.417) and a p-value of 0.002 (p<0.05) and Length of Stay (LOS) with an AOR of 0.344 (95% CI 0.125-0.945 and a p-value 0.038 (p<0.05).

Conclusion: All hospitalized patients receiving first-time warfarin therapy experienced potential drug interaction events. The strongest predictors contributing to potential drug interactions with major clinical impact severity were the number of drugs taken at the normal dose and length of stay.

References

Patel S, Singh R, Preuss CV, Patel N. Warfarin. Hemostasis and thrombosis. 4th ed; 2023. p. 161-8.

Perki. Pedoman tata laksana fibrilasi atrium non valvular. Perhimpunan Dokt Spesialis Kardiovaskuler Indones; 2019.

Musnelina L, Handayani F, Hoa VO TH, Pontoan J. Trends in use of direct oral anticoagulants and warfarin in atrial fibrillation patients. Indonesian J Pharm Sci. 2023;21(2):266-72. doi: 10.35814/jifi.v21i2.1475.

Crader MF, Johns T, Arnold JK. Warfarin drug interactions. StatPearls; 2023.

Putriana NA, Rusdiana T, Rostinawati T, Akbar MR, Megantara S, Hidayanti S. Prediction of the effect of single nucleotide polymorphisme (SNPS) in the CYP2C9 on warfarin metabolism by in silico study. Int J Appl Pharm. 2022 Dec 1;14(5):86-8. doi: 10.22159/IJAP.2022.V14S5.14.

Bloukh D, Hijazeen S, Al Noimi F. Effect of diuretics on the pharmacologic action of warfarin. Scholars Acad J Pharm (SAJP). 2018;7(1):54-9. doi: 10.21276/sajp.2018.7.1.8.

Vega AJ, Smith C, Matejowsky HG, Thornhill KJ, Borne GE, Mosieri CN. Warfarin and antibiotics: drug interactions and clinical considerations. Life (Basel). 2023;13(8):1661. doi: 10.3390/life13081661, PMID 37629518.

Teklay G, Shiferaw N, Legesse B, Bekele ML. Drug-drug interactions and risk of bleeding among inpatients on warfarin therapy: a prospective observational study. Thromb J. 2014 Sep 17;12(1):20. doi: 10.1186/1477-9560-12-20, PMID 25249791.

Rahma N, Andayani TM, Nurrochmad A. Risiko kejadian perdarahan pasca rawat inap pada penggunaan bersamaan warfarin dan antibiotik. J Sains Farm Klin. 2021 Aug 6;8(2):164. doi: 10.25077/jsfk.8.2.164-173.2021.

Wang M, Zeraatkar D, Obeda M, Lee M, Garcia C, Nguyen L. Drug-drug interactions with warfarin: a systematic review and meta-analysis. Br J Clin Pharmacol. 2021;87(11):4051-100. doi: 10.1111/bcp.14833, PMID 33769581.

Timur WW, Ussa RE, Widyaningrum N. Kajian interaksi antar obat terhadap profil glikemik pada pasien diabetes rawat inap rumah sakit islam sultan agung semarang the study of between drug interaction and glycemic profile among in patients with diabetes at sultan agung islamic hospital semarang. J Farmasi Indones. 2022;19(2):221-7. doi: 10.23917/pharmacon.v19i2.18583.

Marisya N, Putri A, Fortuna TA, Nyoman N, Mendra Y. Evaluasi drug related problems (DRPS) pada pasien demam tifoid di instalasi rawat inap rumah sakit x di klaten periode Nov 2021-Oct 2022. Usadha J Pharm. 2024;3(2):162-76. doi: 10.23917/ujp.v3i2.318.

DE Fatima Colet C, Amador TA, Heineck I. Drug interactions and adverse events in a cohort of warfarin users attending public health clinics. Int J Cardiovasc Sci. 2019;32(2):110-7. doi: 10.5935/2359-4802.20180091.

Tatro DS. Drug interaction facts. 8th ed. Vol. 1. Lippincott Williams & Wilkins; 2015.

World Health Organization (WHO). Medication Safety in Polypharmacy; 2019.

Dagnew SB, Tadesse TY, Zeleke MM, Yiblet TG, Addis GT, Mekonnen GB. Drug-drug interactions among hospitalized elderly in patients at medical wards of Northwest Ethiopia’s comprehensive specialized hospitals: a multicenter observational study. Sage Open Med. 2022;10:20503121221135874. doi: 10.1177/20503121221135874, PMID 36385798.

Kemenkes. Petunjuk teknis standar pelayanan kefarmasian di rumah sakit; 2019.

Du X, Guo L, Xia S, Du J, Anderson C, Arima H. Atrial fibrillation prevalence awareness and management in a nationwide survey of adults in China. Heart. 2021 Apr 1;107(7):535-41. doi: 10.1136/heartjnl-2020-317915, PMID 33509976.

Elewa H, Alhaddad A, Al Rawi S, Nounou A, Mahmoud H, Singh R. Trends in oral anticoagulant use in qatar: a 5 y experience. J Thromb Thrombolysis. 2017;43(3):411-6. doi: 10.1007/s11239-017-1474-4, PMID 28138812.

Zhang C, Wang J, Yang Y, Ma EL, Lin HW, Liu BL. Prescribing trends of oral anticoagulants from 2010 to 2020 in Shanghai, China: a retrospective study. Clin Appl Thromb Hemost. 2022;28:10760296221132551. doi: 10.1177/10760296221132551, PMID 36250531.

Schnabel RB, Yin X, Gona P, Larson MG, Beiser AS, McManus DD. 50 y trends in atrial fibrillation prevalence incidence risk factors and mortality in the framingham heart study: a cohort study. Lancet. 2015;386(9989):154-62. doi: 10.1016/S0140-6736(14)61774-8, PMID 25960110.

Kornej J, Borschel CS, Benjamin EJ, Schnabel RB. Epidemiology of atrial fibrillation in the 21st century: novel methods and new insights. Circ Res. 2020;127(1):4-20. doi: 10.1161/circresaha.120.316340, PMID 32716709.

Andrade J, Khairy P, Dobrev D, Nattel S. The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features epidemiology and mechanisms. Circ Res. 2014;114(9):1453-68. doi: 10.1161/circresaha.114.303211, PMID 24763464.

Staerk L, Sherer JA, Ko D, Benjamin EJ, Helm RH. Atrial fibrillation: epidemiology pathophysiology and clinical outcomes. Circ Res. 2017;120(9):1501-17. doi: 10.1161/circresaha.117.309732, PMID 28450367.

Sivakumar V, SS, AM, Kumar NG, CP A. Development of prediction tool for assessment of risk associated with acenocoumarol. Int J Pharm Pharm Sci. 2023;15(1):33-6. doi: 10.22159/ijpps.2023v15i1.46434.

Indrawan SA, Yulianti T. Probems IDR (DRPs) pada pasien diabetes mellitus di instalasi rawat jalan. Usadha. J Pharm. 2024;3(1):29-42. doi: 10.23917/ujp.v3i1.301.

Muliani K, Lakcita DM, Annisa. Hubungan faktor klinis terhadap drug related problems pada pasien pasien hipertensi rawat inap rumah sakit pusat di jawa tengah. Usadha J Pharm. 2024;3(1):65-79.

Leopoulou M, Theofilis P, Kordalis A, Papageorgiou N, Sagris M, Oikonomou E. Diabetes mellitus and atrial fibrillation from pathophysiology to treatment. World J Diabetes. 2023;14(5):512-27. doi: 10.4239/wjd.v14.i5.512, PMID 37273256.

Lorenzo Almoros A, Casado Cerrada J, Alvarez Sala Walther LA, Mendez Bailon M, Lorenzo Gonzalez O. Atrial fibrillation and diabetes mellitus: dangerous liaisons or innocent bystanders? J Clin Med. 2023;12(8):2868. doi: 10.3390/jcm12082868, PMID 37109205.

Proietti M, Raparelli V, Olshansky B, Lip GY. Polypharmacy and major adverse events in atrial fibrillation: observations from the AFFIRM trial. Clin Res Cardiol. 2016;105(5):412-20. doi: 10.1007/s00392-015-0936-y, PMID 26525391.

Wang Y, Singh S, Bajorek B. Old age high-risk medication polypharmacy: a trilogy of risks in older patients with atrial fibrillation. Pharm Pract (Granada). 2016;14(2):706. doi: 10.18549/PharmPract.2016.02.706, PMID 27382425.

Jaspers Focks J, Brouwer MA, Wojdyla DM, Thomas L, Lopes RD, Washam JB. Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the aristotle trial. BMJ. 2016;353:i2868. doi: 10.1136/bmj.i2868, PMID 27306620.

Shaikh F, Pasch LB, Newton PJ, Bajorek BV, Ferguson C. Addressing multimorbidity and polypharmacy in individuals with atrial fibrillation. Curr Cardiol Rep. 2018;20(5):32. doi: 10.1007/s11886-018-0975-x, PMID 29574524.

Kamiyama E, Yoshigae Y, Kasuya A, Takei M, Kurihara A, Ikeda T. Inhibitory effects of angiotensin receptor blockers on CYP2C9 activity in human liver microsomes. Drug Metab Pharmacokinet. 2007;22(4):267-75. doi: 10.2133/dmpk.22.267, PMID 17827781.

Guidoni CM, Camargo HP, Obreli Neto PR, Girotto E, Pereira LR. Study of warfarin utilization in hospitalized patients: analysis of possible drug interactions. Int J Clin Pharm. 2016;38(5):1048-51. doi: 10.1007/s11096-016-0336-z, PMID 27365092.

Kim KY, Mancano MA. Fenofibrate potentiates warfarin effects. Ann Pharmacother. 2003;37(2):212-5. doi: 10.1177/106002800303700210, PMID 12549950.

Ken Wey C, Chee Li Ching E, Jothy Nagesvararao N, Jagan N, Info A. Warfarin fenofibrate interaction: hospital kuala lumpur experience. Malaysian Journal of Pharmacy. 2021;7(1):7-10. doi: 10.52494/YCKM4957.

Kim KY, Mancano MA. Fenofibrate potentiates warfarin effects. Ann Pharmacother. 2003 Feb;37(2):212-5. doi: 10.1177/106002800303700210, PMID 12549950.

Nimura S, Kitahara K, Ueshima K, Mochizuki Y, Momo K, Shinke T. Potential drug-drug interaction between tolvaptan and warfarin in a geriatric patient with heart failure. Clin Case Rep. 2022;10(4):e05592. doi: 10.1002/ccr3.5592, PMID 35414910.

Saito M, Ajioka M, Iwao T, Suzuki T. Enhancement of warfarin anticoagulant reaction in patients with repeated oral tolvaptan administration. Biol Pharm Bull. 2018;41(7):1014-6. doi: 10.1248/bpb.b17-01008, PMID 29760305.

Kasichayanula S, Chang M, Liu X, Shyu WC, Griffen SC, LaCreta FP. Lack of pharmacokinetic interactions between dapagliflozin and simvastatin valsartan warfarin or digoxin. Adv Ther. 2012;29(2):163-77. doi: 10.1007/s12325-011-0098-x, PMID 22271159.

Berlowitz DR, Miller DR, Oliveria SA, Cunningham F, Gomez Caminero A, Rothendler JA. Differential associations of beta-blockers with hemorrhagic events for chronic heart failure patients on warfarin. Pharmacoepidemiol Drug Saf. 2006;15(11):799-807. doi: 10.1002/pds.1301, PMID 16892457.

Thabit AK, Almoalim SY, Altalhi R. Cephalosporins with warfarin increase the risk of bleeding: myth or fact? Expert Opin Drug Metab Toxicol. 2024;20(5):293-6. doi: 10.1080/17425255.2024.2349718, PMID 38712794.

Saum LM, Balmat RP. Ceftriaxone potentiates warfarin activity greater than other antibiotics in the treatment of urinary tract infections. J Pharm Pract. 2016;29(2):121-4. doi: 10.1177/0897190014544798, PMID 25092605.

Saum LM, Balmat RP. Ceftriaxone potentiates warfarin activity greater than other antibiotics in the treatment of urinary tract infections. J Pharm Pract. 2016;29(2):121-4. doi: 10.1177/0897190014544798, PMID 25092605.

Baillargeon J, Holmes HM, Lin YL, Raji MA, Sharma G, Kuo YF. Concurrent use of warfarin and antibiotics and the risk of bleeding in older adults. Am J Med. 2012;125(2):183-9. doi: 10.1016/j.amjmed.2011.08.014, PMID 22269622.

Reis AM, Cassiani SH. Prevalence of potential drug interactions in patients in an intensive care unit of a university hospital in Brazil. Clinics (Sao Paulo). 2011;66(1):9-15. doi: 10.1590/s1807-59322011000100003, PMID 21437429.

Henriksen DP, Stage TB, Hansen MR, Rasmussen L, Damkier P, Pottegard A. The potential drug-drug interaction between proton pump inhibitors and warfarin. Pharmacoepidemiol Drug Saf. 2015;24(12):1337-40. doi: 10.1002/pds.3881, PMID 26395871.

Tang J, Sharma U, Desai S, Molnar J, Perlmuter L, Feller A. A study of proton pump inhibitors and other risk factors in warfarin associated gastrointestinal bleeding. Cureus. 2021;13(1):e12624. doi: 10.7759/cureus.12624, PMID 33585113.

Seesin T, Pengsupsin P, Weesaphen S, Sriphong P, Limpapanasit U, Bhongchirawattana S. Evaluation of cefoperazone/sulbactam and vitamin K use in patients with bacterial infections. Int J Appl Pharm. 2019 Sep 1;11(5):191-3. doi: 10.22159/ijap.2019.v11s5.T0100.

Ahmad S, Ali S, Alam N, Alam I, Alam S, Ali D. Drug interactions of h2 receptor antagonists ranitidine: a review. Res J Pharm Technol. 2016;9(3):275-80. doi: 10.5958/0974-360X.2016.00051.2.

Blower PR. 5-HT3 receptor antagonists and the cytochrome P450 system: clinical implications. Cancer J. 2002;8(5):405-14. doi: 10.1097/00130404-200209000-00012, PMID 12416899.

Rajiv R, Khausik M, Mahajan S, Thakur R. Rare interaction of warfarin and digoxin in a case of digoxin toxicity. J Assoc Physicians India. 2020 Mar;68(3):85-6. PMID 32138495.

Sadaf S, Alam SA, Burhan-ul-Haq S, Raza-ul-Haq HM, Amna Y. Warfarin induced coagulopathy: is the digoxin the culprit? Pak Armed Forces Med J. 2024;74(1)s54-6. doi: 10.51253/pafmj.v74iSUPPL-1.10618.

Kumbhani DJ, Cannon CP, Beavers CJ, Bhatt DL, Cuker A, Gluckman TJ. 2020 ACC expert consensus decision pathway for anticoagulant and antiplatelet therapy in patients with atrial fibrillation or venous thromboembolism undergoing percutaneous coronary intervention or with atherosclerotic cardiovascular disease: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021;77(5):629-58. doi: 10.1016/j.jacc.2020.09.011, PMID 33250267.

Berg TM, O Meara JG, Ou NN, Daniels PR, Moriarty JP, Bergstrahl EJ. Risk factors for excessive anticoagulation among hospitalized adults receiving warfarin therapy using a pharmacist-managed dosing protocol. Pharmacotherapy. 2013;33(11):1165-74. doi: 10.1002/phar.1280, PMID 23625787.

Moura C, Prado N, Acurcio F. Potential drug-drug interactions associated with prolonged stays in the intensive care unit: a retrospective cohort study. Clin Drug Investig. 2011;31(5):309-16. doi: 10.1007/BF03256929, PMID 21344954.

Rodrigues AT, Stahlschmidt R, Granja S, Pilger D, Falcao AL, Mazzola PG. Prevalence of potential drug-drug interactions in the intensive care unit of a Brazilian teaching hospital. Braz J Pharm Sci. 2017;53(1):e16109. doi: 10.1590/s2175-97902017000116109.

Moura CS, Acurcio FA, Belo NO. Drug-drug interactions associated with length of stay and cost of hospitalization. J Pharm Pharm Sci. 2009;12(3):266-72. doi: 10.18433/j35c7z, PMID 20067703.

Mathur A, Sharma A. Quality of anticoagulation perdictors and consequences of deranged INR of patient on warfarin. Asian J Pharm Clin Res. 2024 Dec 1;17(12):80-4. doi: 10.22159/ajpcr.2024v17i12.52969.

Published

15-06-2025

How to Cite

OKTIANTI, D., CHOLISOH, Z., GHADZI, . S. M. S., & KARUNIAWATI, H. (2025). POTENTIAL OF DRUG INTERACTIONS IN HOSPITALIZED PATIENTS RECEIVING WARFARIN THERAPY FOR THE FIRST TIME. International Journal of Applied Pharmaceutics, 17(2), 93–99. https://doi.org/10.22159/ijap.2025.v17s2.14

Issue

Section

Original Article(s)

Similar Articles

<< < 1 2 3 4 5 > >> 

You may also start an advanced similarity search for this article.