Risk Factors for Potential Drug-Drug Interactions in Outpatients with Dyslipidemia
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Abstract
Background: Patients with dyslipidemia are usually multimorbid and require polypharmacy. Therefore, it is important to identify potential drug-drug interactions (pDDIs) in time to prevent their consequences. We aimed to identify and analyze risk factors contributing to their occurrence to guide health professionals. Methods: A prospective cross-sectional study of 216 outpatients with dyslipidemia was conducted from May 2021 to April 2022 in Podgorica, the capital of Montenegro. pDDIs were identified using Medscape, Epocrates, and Drugs online interaction checkers. Multivariate regression analysis was performed to evaluate the potential predictors of interactions. Results: pDDIs were detected in 212 (98.1%) participants, whereas pDDIs with high clinical significance were detected in 25.46%, 40.74%, and 58.8% of subjects by Drugs, Epocrates, and Medscape, respectively. Polypharmacy emerged as a risk factor for the occurrence of pDDIs in all three checkers in each category of clinical significance. The use of non-steroidal anti-inflammatory drugs and antiplatelet drugs contributes to the incidence of severe pDDIs B=1.014, 95%CI 0.681-1.346, P=0.000 and B=0.492, 95%CI 0.286-0.698, P=0.000, by Epocrates and Medscape respectively. The number of prescribers per patient was a protective factor against moderate pDDI B= -0.858, 95%CI -1.572-(-0.144), P=0.019 and B= -0.956, 95%CI -1.671-(-0.241), P=0.009, by Medscape and Epocrates, respectively, but a risk factor for the occurrence of minor pDDIs B=0.373, 95%CI 0.033-0.712 P=0.032 and B=0.143, 95%CI 0.042-0.244, P=0.006, by the same checkers.Conclusion: Knowledge of the risk factors contributing to the occurrence of pDDIs is important for the development and implementation of strategies for their prevention, and given the high prevalence of dyslipidemia, understanding these factors seems crucial nowadays.
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4. Stafford G, Villén N, Roso-Llorach A, Troncoso-Mariño A, Monteagudo M, Violán C (2021). Combined multimor-bidity and polypharmacy patterns in the elderly: A cross-sectional study in pri-mary health care. Int J Environ Res Public Health, 18(17):9216.
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6. Zhelyazkova-Savova M, Gancheva S, Sira-kova V (2014). Potential statin-drug in-teractions: prevalence and clinical sig-nificance. Springerplus, 3:168.
7. Janković SM, Pejčić AV, Milosavljević MN, et al (2018). Risk factors for potential drug-drug interactions in intensive care unit patients. J Crit Care, 43:1–6.
8. Farooqui R, Hoor T, Karim N, Muneer M (2018). Potential drug-drug interactions among patient’s prescriptions collected from medicine out-patient setting. Pak J Med Sci, 34(1):144–8.
9. Lee KJ, Kim KR, Seong JM, et al (2020). Evaluation of Potential Drug-Drug In-teractions in Patients Taking HMG CoA-reductase Inhibitors. Korean Journal of Clinical Pharmacy, 30(1):31–5.
10. Faizah AK, Wijayanti N, Nurrahman D (2021). Evaluation of Potential Drug-Drug Interactions in Hypercholesterol-emia Patients at Teaching Hospital Su-rabaya. Available from: 10.2991/ahsr.k.210115.064
11. Rätz Bravo AE, Tchambaz L, Krähenb A, et al (2005). Prevalence of Potentially Severe Drug-Drug Interactions in Ambu-latory Patients with Dyslipidaemia Re-ceiving HMG-CoA Reductase Inhibitor Therapy. Drug Saf, 28(3):263-75.
12. Scheife RT, Hines LE, Boyce RD, et al (2015). Consensus Recommendations for Systematic Evaluation of Drug–Drug In-teraction Evidence for Clinical Deci-sion Support. Drug Saf, 38(2):197–206.
13. Israel GD (1992). Determining sample size. Program Evaluation and Organizational Development, IFAS. PEOD-6. Florida (FL): University of Florida.
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20. Maxwell WD, Ramsey LB, Johnson SG, et al (2017). Impact of Pharmacogenetics on Efficacy and Safety of Statin Thera-py for Dyslipidemia. Pharmacotherapy, 37(9):1172-1190.
21. Kheshti R, Aalipour M, Namazi S (2016). A comparison of five common drug–drug interaction software programs regarding accuracy and comprehensiveness. J Res Pharm Pract, 5(4):257-263.
22. Muhič N, Mrhar A, Brvar M (2017). Com-parative analysis of three drug–drug in-teraction screening systems against probable clinically relevant drug–drug interactions: a prospective cohort study. Eur J Clin Pharmacol, 73(7):875–82.
23. Nusair MB, Al-Azzam SI, Arabyat RM, Amawi HA, Alzoubi KH, Rabah AA (2020). The prevalence and severity of potential drug-drug interactions among adult polypharmacy patients at outpa-tient clinics in Jordan. Saudi Pharm J, 28(2):155–60.
24. Chen Y, Ding L (2023). Potential drug-drug interactions in outpatients with depres-sion of a psychiatry department. Saudi Pharm J, 31(2):207-213.
25. Al-Qerem W, Jarrar YB, Al-Sheikh I, Elmaadani A (2018). The prevalence of drug-drug interactions and polypharma-cy among elderly patients in Jordan. Bi-omed Res, 29(12):2561-2569.
26. Obreli Neto PR, Nobili A, Marusic S, et al (2012). Prevalence and predictors of po-tential drug-drug interactions in the el-derly: a cross-sectional study in the bra-zilian primary public health system. J Pharm Pharm Sci, 15(2):344-54.
27. Ismail M, Iqbal Z, Khattak MB, et al (2013). Potential drug-drug interactions in in-ternal medicine wards in hospital setting in Pakistan. Int J Clin Pharm, 35(3):455–62.
28. Jazbar J, Locatelli I, Horvat N, Kos M (2018). Clinically relevant potential drug–drug interactions among outpa-tients: A nationwide database study. Res Social Adm Pharm, 14(6):572–80.
29. Stojadinovic D, Zivkovic Zaric R, Jankovic S, Lazic Z, Cekerevac I, Susa R (2020). Risk factors for potential drug-drug in-teractions in patients with chronic ob-structive pulmonary disease. Ir J Med Sci, 189(3):1123–5.
30. Assiri GA, Shebl NA, Mahmoud MA, et al (2018). What is the epidemiology of medication errors, error-related adverse events and risk factors for errors in adults managed in community care con-texts? A systematic review of the interna-tional literature. BMJ Open, 8(5):e019101.
31. Lin CF, Wang CY, Bai CH (2011). Polypharmacy, Aging and Potential Drug-Drug Interactions in Outpatients in Taiwan A Retrospective Computer-ized Screening Study. Drugs Aging, 28(3):219-25.
32. Chelkeba L, Alemseged F, Bedada W (2013). Assessment of potential drug-drug interactions among outpatients re-ceiving cardiovascular medications at Jimma University specialized hospital, South West Ethiopia. Int J Basic Clin Pharmacol, 2(2):144.
33. Majithia A, Bhatt DL (2019). Novel An-tiplatelet Therapies for Atherothrom-botic Diseases. Arterioscler Thromb Vasc Bi-ol, 39(4):546-557.
34. Aleksić DZ, Milosavljević MN, Stefanović SM, et al (2021). Risk factors for poten-tial drug–drug interactions in patients with myasthenia gravis. Neurol Res, 43(12):1023–30.
35. Szilvay A, Somogyi O, Dobszay A, Meskó A, Zelkó R, Hankó B (2021). Analysis of interaction risks of patients with polypharmacy and the pharmacist in-terventions performed to solve them - A multicenter descriptive study according to medication reviews in Hungarian community pharmacies. PLoS One, 16(6):e0253645.
36. Sobhy K, AbdelMagged O, Abdelaty K, Khalil D, Abdelgaied M (2021). Potential Cardiovascular Drug Interactions in Egypt: Incidence, Outcomes, Mecha-nism, and Management. Kafrelsheikh Vet-erinary Medical Journal, 19(2):22–7.
37. Wongrakpanich S, Wongrakpanich A, Melhado K, Rangaswami J (2018). A comprehensive review of non-steroidal anti-inflammatory drug use in the elder-ly. Aging Dis, 9(1):143-150.
38. Moore N, Pollack C, Butkerait P (2015). Adverse drug reactions and drug–drug interactions with over-the-counter NSAIDs. Ther Clin Risk Manag, 11:1061-75.
39. Pejčić AV, Janković SM, Davidović G (2019). Drug–drug interactions in pa-tients with acute coronary syndrome across phases of treatment. Intern Emerg Med, 14(3):411–22.
40. Andersson ML, Böttiger Y, Kockum H, Ei-ermann B (2018). High Prevalence of Drug–Drug Interactions in Primary Health Care is caused by Prescriptions from other Healthcare Units. Basic Clin Pharmacol Toxicol, 122(5):512–6.
41. Kostić MJ, Zarić RSŽ, Janković SM (2021). Risk factors for potential drug-drug in-teractions in a general neurology ward. Vojnosanit Pregl, 78(6):607–14.
42. Andersson ML, Böttiger Y, Lindh JD, Wet-termark B, Eiermann B (2013). Impact of the drug-drug interaction database SFINX on prevalence of potentially se-rious drug-drug interactions in primary health care. Eur J Clin Pharmacol, 69(3):565–71.
43. Ylä-Rautio H, Siissalo S, Leikola S (2020). Drug-related problems and pharmacy interventions in non-prescription medi-cation, with a focus on high-risk over-the-counter medications. Int J Clin Pharm, 42(2):786–95.
2. Liu G, Shepherd J, Rane P, et al (2019). Characteristics of patients with dyslipidemia treated in routine care set-ting in China. J Drug Assess, 8(1):192–8.
3. Mach F, Baigent C, Catapano AL, et al (2020). 2019 ESC/EAS Guidelines for the management of dyslipidaemias: li-pid modification to reduce cardiovascu-lar risk. Eur Heart J, 41(1):111–88.
4. Stafford G, Villén N, Roso-Llorach A, Troncoso-Mariño A, Monteagudo M, Violán C (2021). Combined multimor-bidity and polypharmacy patterns in the elderly: A cross-sectional study in pri-mary health care. Int J Environ Res Public Health, 18(17):9216.
5. Johnell K, Klarin I (2007). The Relation-ship between Number of Drugs and Po-tential Drug-Drug Interactions in the Elderly A Study of Over 600 000 Elderly Patients from the Swedish Prescribed Drug Register. Drug Saf, 30(10):911-8.
6. Zhelyazkova-Savova M, Gancheva S, Sira-kova V (2014). Potential statin-drug in-teractions: prevalence and clinical sig-nificance. Springerplus, 3:168.
7. Janković SM, Pejčić AV, Milosavljević MN, et al (2018). Risk factors for potential drug-drug interactions in intensive care unit patients. J Crit Care, 43:1–6.
8. Farooqui R, Hoor T, Karim N, Muneer M (2018). Potential drug-drug interactions among patient’s prescriptions collected from medicine out-patient setting. Pak J Med Sci, 34(1):144–8.
9. Lee KJ, Kim KR, Seong JM, et al (2020). Evaluation of Potential Drug-Drug In-teractions in Patients Taking HMG CoA-reductase Inhibitors. Korean Journal of Clinical Pharmacy, 30(1):31–5.
10. Faizah AK, Wijayanti N, Nurrahman D (2021). Evaluation of Potential Drug-Drug Interactions in Hypercholesterol-emia Patients at Teaching Hospital Su-rabaya. Available from: 10.2991/ahsr.k.210115.064
11. Rätz Bravo AE, Tchambaz L, Krähenb A, et al (2005). Prevalence of Potentially Severe Drug-Drug Interactions in Ambu-latory Patients with Dyslipidaemia Re-ceiving HMG-CoA Reductase Inhibitor Therapy. Drug Saf, 28(3):263-75.
12. Scheife RT, Hines LE, Boyce RD, et al (2015). Consensus Recommendations for Systematic Evaluation of Drug–Drug In-teraction Evidence for Clinical Deci-sion Support. Drug Saf, 38(2):197–206.
13. Israel GD (1992). Determining sample size. Program Evaluation and Organizational Development, IFAS. PEOD-6. Florida (FL): University of Florida.
14. International Statistical Classification of Diseases and Related Health Problems 10th Revision. Available from: https://icd.who.int/browse10/2019/en#/
15. Charlson Comorbidity Index (CCI). Avail-able from: https://www.mdcalc.com/calc/3917/charlson-comorbidity-index-cci.
16. Drugs.com. Drug Interactions Checker. Available from: https://www.drugs.com/interaction/list/
17. Epocrates. Interaction Check. Available from: https://online.epocrates.com/interaction-check.
18. Medscape. Drug Interaction Checker. Available from: https://reference.medscape.com/drug-interactionchecker.
19. Rasool MF, ur Rehman A, Khan I, et al (2023). Assessment of risk factors associ-ated with potential drug-drug interac-tions among patients suffering from chronic disorders. PLoS One, 18(1):e0276277.
20. Maxwell WD, Ramsey LB, Johnson SG, et al (2017). Impact of Pharmacogenetics on Efficacy and Safety of Statin Thera-py for Dyslipidemia. Pharmacotherapy, 37(9):1172-1190.
21. Kheshti R, Aalipour M, Namazi S (2016). A comparison of five common drug–drug interaction software programs regarding accuracy and comprehensiveness. J Res Pharm Pract, 5(4):257-263.
22. Muhič N, Mrhar A, Brvar M (2017). Com-parative analysis of three drug–drug in-teraction screening systems against probable clinically relevant drug–drug interactions: a prospective cohort study. Eur J Clin Pharmacol, 73(7):875–82.
23. Nusair MB, Al-Azzam SI, Arabyat RM, Amawi HA, Alzoubi KH, Rabah AA (2020). The prevalence and severity of potential drug-drug interactions among adult polypharmacy patients at outpa-tient clinics in Jordan. Saudi Pharm J, 28(2):155–60.
24. Chen Y, Ding L (2023). Potential drug-drug interactions in outpatients with depres-sion of a psychiatry department. Saudi Pharm J, 31(2):207-213.
25. Al-Qerem W, Jarrar YB, Al-Sheikh I, Elmaadani A (2018). The prevalence of drug-drug interactions and polypharma-cy among elderly patients in Jordan. Bi-omed Res, 29(12):2561-2569.
26. Obreli Neto PR, Nobili A, Marusic S, et al (2012). Prevalence and predictors of po-tential drug-drug interactions in the el-derly: a cross-sectional study in the bra-zilian primary public health system. J Pharm Pharm Sci, 15(2):344-54.
27. Ismail M, Iqbal Z, Khattak MB, et al (2013). Potential drug-drug interactions in in-ternal medicine wards in hospital setting in Pakistan. Int J Clin Pharm, 35(3):455–62.
28. Jazbar J, Locatelli I, Horvat N, Kos M (2018). Clinically relevant potential drug–drug interactions among outpa-tients: A nationwide database study. Res Social Adm Pharm, 14(6):572–80.
29. Stojadinovic D, Zivkovic Zaric R, Jankovic S, Lazic Z, Cekerevac I, Susa R (2020). Risk factors for potential drug-drug in-teractions in patients with chronic ob-structive pulmonary disease. Ir J Med Sci, 189(3):1123–5.
30. Assiri GA, Shebl NA, Mahmoud MA, et al (2018). What is the epidemiology of medication errors, error-related adverse events and risk factors for errors in adults managed in community care con-texts? A systematic review of the interna-tional literature. BMJ Open, 8(5):e019101.
31. Lin CF, Wang CY, Bai CH (2011). Polypharmacy, Aging and Potential Drug-Drug Interactions in Outpatients in Taiwan A Retrospective Computer-ized Screening Study. Drugs Aging, 28(3):219-25.
32. Chelkeba L, Alemseged F, Bedada W (2013). Assessment of potential drug-drug interactions among outpatients re-ceiving cardiovascular medications at Jimma University specialized hospital, South West Ethiopia. Int J Basic Clin Pharmacol, 2(2):144.
33. Majithia A, Bhatt DL (2019). Novel An-tiplatelet Therapies for Atherothrom-botic Diseases. Arterioscler Thromb Vasc Bi-ol, 39(4):546-557.
34. Aleksić DZ, Milosavljević MN, Stefanović SM, et al (2021). Risk factors for poten-tial drug–drug interactions in patients with myasthenia gravis. Neurol Res, 43(12):1023–30.
35. Szilvay A, Somogyi O, Dobszay A, Meskó A, Zelkó R, Hankó B (2021). Analysis of interaction risks of patients with polypharmacy and the pharmacist in-terventions performed to solve them - A multicenter descriptive study according to medication reviews in Hungarian community pharmacies. PLoS One, 16(6):e0253645.
36. Sobhy K, AbdelMagged O, Abdelaty K, Khalil D, Abdelgaied M (2021). Potential Cardiovascular Drug Interactions in Egypt: Incidence, Outcomes, Mecha-nism, and Management. Kafrelsheikh Vet-erinary Medical Journal, 19(2):22–7.
37. Wongrakpanich S, Wongrakpanich A, Melhado K, Rangaswami J (2018). A comprehensive review of non-steroidal anti-inflammatory drug use in the elder-ly. Aging Dis, 9(1):143-150.
38. Moore N, Pollack C, Butkerait P (2015). Adverse drug reactions and drug–drug interactions with over-the-counter NSAIDs. Ther Clin Risk Manag, 11:1061-75.
39. Pejčić AV, Janković SM, Davidović G (2019). Drug–drug interactions in pa-tients with acute coronary syndrome across phases of treatment. Intern Emerg Med, 14(3):411–22.
40. Andersson ML, Böttiger Y, Kockum H, Ei-ermann B (2018). High Prevalence of Drug–Drug Interactions in Primary Health Care is caused by Prescriptions from other Healthcare Units. Basic Clin Pharmacol Toxicol, 122(5):512–6.
41. Kostić MJ, Zarić RSŽ, Janković SM (2021). Risk factors for potential drug-drug in-teractions in a general neurology ward. Vojnosanit Pregl, 78(6):607–14.
42. Andersson ML, Böttiger Y, Lindh JD, Wet-termark B, Eiermann B (2013). Impact of the drug-drug interaction database SFINX on prevalence of potentially se-rious drug-drug interactions in primary health care. Eur J Clin Pharmacol, 69(3):565–71.
43. Ylä-Rautio H, Siissalo S, Leikola S (2020). Drug-related problems and pharmacy interventions in non-prescription medi-cation, with a focus on high-risk over-the-counter medications. Int J Clin Pharm, 42(2):786–95.
| Files | ||
| Issue | Vol 52 No 7 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v52i7.13248 | |
| Keywords | ||
| Drug-drug interactions Dyslipidemia Interaction checker Risk factors | ||
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How to Cite
1.
Lalatović N, Pantović S, Nedović-Vuković M, Kostić M. Risk Factors for Potential Drug-Drug Interactions in Outpatients with Dyslipidemia. Iran J Public Health. 2023;52(7):1466-1475.
