Potential Drug–Drug Interactions among Hospitalized COVID-19 Patients Admitted to Medical Wards of a Referral Hospital, North-East of Iran: A Cross Sectional Study
Abstract
Background: Hospitalized corona virus disease 2019 (COVID-19) patients are special population in term of drug-drug interaction (DDI), as they receive various experimental novel medications and also most of them are elderly with various comorbidities and consequently numerous medications. The aim of present study was to assess the prevalence and determinants of potential DDIs in hospitalized COVID-19 patients admitted to the medical ward of a Referral Hospital in North-East of Iran.Methods: A cross-sectional study was conducted among COVID-19 inpatients between March 2020 and April 2020. Prescribed medication being taken concurrently for at least 24 h were included and checked for DDI using Lexicomp® online drug reference. Data were analyzed using SPSS19.Results: A total of 88 patients were evaluated. The cardiovascular disease was the most common comorbidity (30.68%). The median number of medications prescribed for each patient was 5. Hydroxychloroquine was the most common prescribed medication for COVID-19 management (92.05%). About two-third (62.5 %) of patients were exposed to at least one potential C (84.09 %) or D (52.27%) DDI and no X DDIs were found. Patients with at least five prescribed medications were at higher risk of having DDI (P = 0.001).Conclusion: Drug–drug interaction in COVID-19 inpatients was common. Considering these DDIs, clinical pharmacist involvement can be helpful in minimizing the risk of these potentially harmful drug combinations.
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5. Hajibabaie M, Badri S, Ataei S, Moslehi AH, Karimzadeh I, Ghavamzadeh A. Potential drug–drug interactions at a referral hematology–oncology ward in Iran: a cross-sectional study. Cancer Chemother Pharmacol 2013;71(6):1619–27.
6. Dechanont S, Maphanta S, Butthum B, Kongkaew C. Hospital admissions/visits associated with drug–drug interactions: a systematic review and meta-analysis. Pharmacoepidemiol Drug Saf 2014;23:489–97.
7. Riechelmann RP, Del Giglio A. Drug interactions in oncology: how common are they? Ann Oncol 2009;20(12):1907–12.
8. Uijtendaal EV, van Harssel LL, Hugenholtz GW, et al. Analysis of potential drug–drug interactions in medical intensive care unit patients. Pharmacotherapy 2014;34(3):213–9.
9. Saurat JH, Guerin A, Yu AP, et al. High prevalence of potential drug–drug interactions for psoriasis patients prescribed methotrexate or cyclosporine for psoriasis: associated clinical and economic outcomes in real-world practice. Dermatology 2010;220(2):128–37.
10. Moura C, Acurcio F, Belo N. Drug–drug interactions associated with length of stay and cost of hospitalization. J Pharm Pharmaceut Sci 2009;12:266–72.
11. Bjerrum L, Lopez-Valcarcel BG, Petersen G. Risk factors for potential drug interactions in general practice. Eur J Gen Pract 2008;14:23–9.
12. Lexicomp Online, Lexi-Drug Interaction Online, Hudson, Ohio: UpToDate, Inc.; 2020; September 20, 2020.
13. Teka F, Teklay G, Ayalew E, Teshome T. Potential drug–drug interactions among elderly patients admitted to medical ward of Ayder Referral Hospital, Northern Ethiopia: a cross sectional study. BMC Res Notes 2016; 9(1): 431.
14. Lin CF, Wang CY, Bai CH. Polypharmacy, aging and potential drug–drug interactions in outpatients in Taiwan: a retrospective computerized screening study. Drugs Aging 2011;28(3):219–25.
15. Salwe KJ, Kalyansundaram D, Bahurupi Y. A study on polypharmacy and potential drug–drug interactions among elderly patients admitted in Department of Medicine of a Tertiary Care Hospital in Puducherry. J Clin Diagn Res 2016;10(2):FC06–10.
16. Kashyap M, D’Cruz S, Sachdev A, Tiwari P. Drug–drug interactions and their predictors: results from Indian elderly inpatients. Pharm Pract 2013;11(4):191–5.
17. Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis 2020; 94: 91-95.
18. Hu S, Gao R, Liu L, et al. Summary of the 2018 report on cardiovascular diseases in China. Chin Circ J 2019;34:209.
19. Liu M, Liu SW, Wang LJ, et al. Burden of diabetes, hyperglycemia in China from to 2016: findings from the 1990 to 2016, global burden of disease study. Diabetes Metab 2019;45:286–93.
20. Pasina L, Djade CD, Nobili A, et al. Drug–drug interactions in a cohort of hospitalized elderly patients. Pharmacoepidemiol Drug Saf 2013;22:1054–60.
21. Lea M, Roqnan SE, Koristovic R, Wyller TB, Molden E. Severity and management of drug–drug interactions in acute geriatric patients. Drugs Aging 2013;30(9):721–7.
22. Tulner LR, Frankfort SV, Gijsen GJ, van Campen JP, Koks CH, Beijnen JH. Drug–drug interactions in a geriatric outpatient cohort: prevalence and relevance. Drugs Aging 2008;25(4):343–55.
23. Mibielli P, Rozenfeld S, Matos GC, Fde Acurcio A. Potential drug–drug interactions among elderly using antihypertensives from the Brazilian list of essential medicines. Cad Saude Pub 2014;30(9):1947–56.
24. Secoli SR, Figueras A, Lebrão ML, de Lima FD, Santos JL. Risk of potential drug–drug interactions among Brazilian elderly: a population-based, cross-sectional study. Drugs Aging 2010;27(9):759–70.
25. Kumar D, Trivei N. Disease-drug and drug-drug interaction in COVID-19: risk and assessment. Biomed Pharmacother 2021;139: 111642.
26. Grunden JW, Fisher KA. Lovastatin-Induced Rhabdomyolysis Possibly Associated with Clarithromycin and Azithromycin. Ann Pharmacother 1997;31(7-8):859-63.
27. Alreja G, Inayatullah S, Goel S, et al. Rhabdomyolysis Caused by an Unusual Interaction between Azithromycin and Simvastatin. J Cardiovasc Dis Res 2012;3(4):319-22.
28. Strandell J, Bate A, Hagg S, et al. Rhabdomyolysis a Result of Azithromycin and Statins: An Unrecognized Interaction. Br J Clin Pharmacol 2009;68(3):427-34.
29. Polasek TM, Miners JO. Quantitative Prediction of Macrolide Drug-Drug Interaction Potential from in Vitro Studies Using Testosterone as the Human Cytochrome P4503A Substrate. Eur J Clin Pharmacol 2006;62(3):203-8.
30. Greenblatt DJ, von Moltke LL, Harmatz JS, et al. Inhibition of Triazolam Clearance by Macrolide Antimicrobial Agents: In Vitro Correlates and Dynamic Consequences. Clin Pharmacol Ther 1998;64(3):278-85.
31. Seithel A, Eberl S, Singer K, et al. The Influence of Macrolide Antibiotics on the Uptake of Organic Anions and Drugs Mediated by OATP1B1 and OATP1B3. Drug Metab Dispos 2007;35(5):779-86.
32. Mah Ming JB, Gill MJ. Drug-Induced Rhabdomyolysis after Concomitant Use of Clarithromycin, Atorvastatin, and Lopinavir/Ritonavir in a Patient with HIV. AIDS Patient Care STDS 2003; 17:207-10.
33. Yu T, Niu T. Giant inverted T waves and substantial QT interval prolongation induced by azithromycin in an elderly woman with renal insufficiency. Can Fam Physician 2014;60(11):1012-1015.
34. Cocco G, Jerie P. Torsades de pointes induced by the concomitant use of ivabradine and azithromycin: an unexpected dangerous interaction. Cardiovasc Toxicol 2015;15(1):104-106.
35. Amer S, Hassan S, Shariffi M, Chueca L. QT interval prolongation associated with azithromycin/methadone combination. West Indian Med J 2013;62(8):864-865.
36. Giudicessi JR, Ackerman MJ. Azithromycin and risk of sudden cardiac death: guilty as charged or falsely accused? Cleve Clin J Med 2013;80(9):539-544.
37. Sciaccaluga C, Cameli M, Menci D, et al. COVID-19 and the burning issue of drug interaction: never forget the ECG. Postgraduate Med J 2021; 97: 180-184.
38. Brandariz-Nuñez D, Correas-Sanahuja M, Guarc E, Picón R, García B, Gil R. Potential drug–drug interactions in COVID 19 patients in treatment with lopinavir/ritonavir. Medicina Clínica 2020; 155(7): 281-287.
39. Lipitor (atorvastatin) [prescribing information]. New York, NY: Pfizer, Inc; November 2019.
40- Faizah AK, Nurrahman NW, Putra ON. A Mini Review: Clinically Significant Potential Drug-Drug Interactions in COVID-19 and Comorbid Therapy. Pharmaceut Scienc Res 2020; 7(4): 3.
41. Plasencia-García BO, Rodríguez-Menéndez G, Rico-Rangel MI, Rubio-García A, Torelló-Iserte J, Crespo-Facorro. Drug-drug interactions between COVID-19 treatments and antipsychotics drugs: integrated evidence from 4 databases and a systematic review. Psychopharmacology (Berl) 2021; 238: 329-340.
42. Marzolini C, Back D, Weber R, et al. Ageing with HIV: medication use and risk for potential drug–drug interactions. J Antimicrob Chemother 2011;66(9):2107–11.
43. Obreli-Neto PR, Nobili A, de Oliveira Baldoni A, et al. Adverse drug reactions caused by drug–drug interactions in elderly outpatients: a prospective cohort study. Eur J Clin Pharmaco 2012;68(12):1667–76.
44. Mendes-Nett RS, Silva CQ, Oliveira-Filbo AD, Rocha CE, Lyra-Junior DP. Assessment of drug interactions in elderly patients of a family healthcare unit in Aracaju (Brazil): a pilot study. Afr J Pharm Pharmacol 2011;5:812–8.
45. Maher RL, Hanlon JT, Hajjar ER. Clinical Consequences of Polypharmacy in Elderly. Expert Opin Drug Saf 2014;13(1):57–65.
46. Nobili A, Pasina L, Tettamanti M, et al. Potentially severe drug interactions in elderly outpatients: results of an observational study of an administrative prescription database. J Clin Pharm Ther 2009;34(4):377–86.
47. Bogetti-Salazar M, González-González C, Juárez-Cedillo T, Sánchez-García S, Rosas-Carrasco O. Severe potential drug–drug interactions in older people with dementia and associated factors. Clinics 2016;71(1):17–21.
48. Obreli Neto PR, Nobili A, de Lyra DP Jr, et al. Incidence and predictors of adverse drug reactions caused by drug–drug interactions in elderly outpatients: a prospective cohort study. J Pharm Pharm Sci 2012;15(2):332–43.
49. Obreli Neto PR, Nobili A, Marusic S, et al. Prevalence and predictors of potential drug–drug interactions in the elderly: a crosssectional study in the Brazilian primary public health system. J Pharm Pharm Sci 2012;15(2):344–54.
2. Grasselli G, Zangrillo A, Zanella A, et al. Baseline Characteristics and Outcomes of 1591 Patients Infected with SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. JAMA 2020; 323(16):1574‐1581.
3. Wu C, Chen X, Cai Y, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med 2020;e 200994.
4. Bishara D, Kalafatis C, Taylor D. Emerging and experimental treatments for COVID-19 and drug interactions with psychotropic agents. Ther Adv Psychopharmacol 2020; 10: 2045125320935306.
5. Hajibabaie M, Badri S, Ataei S, Moslehi AH, Karimzadeh I, Ghavamzadeh A. Potential drug–drug interactions at a referral hematology–oncology ward in Iran: a cross-sectional study. Cancer Chemother Pharmacol 2013;71(6):1619–27.
6. Dechanont S, Maphanta S, Butthum B, Kongkaew C. Hospital admissions/visits associated with drug–drug interactions: a systematic review and meta-analysis. Pharmacoepidemiol Drug Saf 2014;23:489–97.
7. Riechelmann RP, Del Giglio A. Drug interactions in oncology: how common are they? Ann Oncol 2009;20(12):1907–12.
8. Uijtendaal EV, van Harssel LL, Hugenholtz GW, et al. Analysis of potential drug–drug interactions in medical intensive care unit patients. Pharmacotherapy 2014;34(3):213–9.
9. Saurat JH, Guerin A, Yu AP, et al. High prevalence of potential drug–drug interactions for psoriasis patients prescribed methotrexate or cyclosporine for psoriasis: associated clinical and economic outcomes in real-world practice. Dermatology 2010;220(2):128–37.
10. Moura C, Acurcio F, Belo N. Drug–drug interactions associated with length of stay and cost of hospitalization. J Pharm Pharmaceut Sci 2009;12:266–72.
11. Bjerrum L, Lopez-Valcarcel BG, Petersen G. Risk factors for potential drug interactions in general practice. Eur J Gen Pract 2008;14:23–9.
12. Lexicomp Online, Lexi-Drug Interaction Online, Hudson, Ohio: UpToDate, Inc.; 2020; September 20, 2020.
13. Teka F, Teklay G, Ayalew E, Teshome T. Potential drug–drug interactions among elderly patients admitted to medical ward of Ayder Referral Hospital, Northern Ethiopia: a cross sectional study. BMC Res Notes 2016; 9(1): 431.
14. Lin CF, Wang CY, Bai CH. Polypharmacy, aging and potential drug–drug interactions in outpatients in Taiwan: a retrospective computerized screening study. Drugs Aging 2011;28(3):219–25.
15. Salwe KJ, Kalyansundaram D, Bahurupi Y. A study on polypharmacy and potential drug–drug interactions among elderly patients admitted in Department of Medicine of a Tertiary Care Hospital in Puducherry. J Clin Diagn Res 2016;10(2):FC06–10.
16. Kashyap M, D’Cruz S, Sachdev A, Tiwari P. Drug–drug interactions and their predictors: results from Indian elderly inpatients. Pharm Pract 2013;11(4):191–5.
17. Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis 2020; 94: 91-95.
18. Hu S, Gao R, Liu L, et al. Summary of the 2018 report on cardiovascular diseases in China. Chin Circ J 2019;34:209.
19. Liu M, Liu SW, Wang LJ, et al. Burden of diabetes, hyperglycemia in China from to 2016: findings from the 1990 to 2016, global burden of disease study. Diabetes Metab 2019;45:286–93.
20. Pasina L, Djade CD, Nobili A, et al. Drug–drug interactions in a cohort of hospitalized elderly patients. Pharmacoepidemiol Drug Saf 2013;22:1054–60.
21. Lea M, Roqnan SE, Koristovic R, Wyller TB, Molden E. Severity and management of drug–drug interactions in acute geriatric patients. Drugs Aging 2013;30(9):721–7.
22. Tulner LR, Frankfort SV, Gijsen GJ, van Campen JP, Koks CH, Beijnen JH. Drug–drug interactions in a geriatric outpatient cohort: prevalence and relevance. Drugs Aging 2008;25(4):343–55.
23. Mibielli P, Rozenfeld S, Matos GC, Fde Acurcio A. Potential drug–drug interactions among elderly using antihypertensives from the Brazilian list of essential medicines. Cad Saude Pub 2014;30(9):1947–56.
24. Secoli SR, Figueras A, Lebrão ML, de Lima FD, Santos JL. Risk of potential drug–drug interactions among Brazilian elderly: a population-based, cross-sectional study. Drugs Aging 2010;27(9):759–70.
25. Kumar D, Trivei N. Disease-drug and drug-drug interaction in COVID-19: risk and assessment. Biomed Pharmacother 2021;139: 111642.
26. Grunden JW, Fisher KA. Lovastatin-Induced Rhabdomyolysis Possibly Associated with Clarithromycin and Azithromycin. Ann Pharmacother 1997;31(7-8):859-63.
27. Alreja G, Inayatullah S, Goel S, et al. Rhabdomyolysis Caused by an Unusual Interaction between Azithromycin and Simvastatin. J Cardiovasc Dis Res 2012;3(4):319-22.
28. Strandell J, Bate A, Hagg S, et al. Rhabdomyolysis a Result of Azithromycin and Statins: An Unrecognized Interaction. Br J Clin Pharmacol 2009;68(3):427-34.
29. Polasek TM, Miners JO. Quantitative Prediction of Macrolide Drug-Drug Interaction Potential from in Vitro Studies Using Testosterone as the Human Cytochrome P4503A Substrate. Eur J Clin Pharmacol 2006;62(3):203-8.
30. Greenblatt DJ, von Moltke LL, Harmatz JS, et al. Inhibition of Triazolam Clearance by Macrolide Antimicrobial Agents: In Vitro Correlates and Dynamic Consequences. Clin Pharmacol Ther 1998;64(3):278-85.
31. Seithel A, Eberl S, Singer K, et al. The Influence of Macrolide Antibiotics on the Uptake of Organic Anions and Drugs Mediated by OATP1B1 and OATP1B3. Drug Metab Dispos 2007;35(5):779-86.
32. Mah Ming JB, Gill MJ. Drug-Induced Rhabdomyolysis after Concomitant Use of Clarithromycin, Atorvastatin, and Lopinavir/Ritonavir in a Patient with HIV. AIDS Patient Care STDS 2003; 17:207-10.
33. Yu T, Niu T. Giant inverted T waves and substantial QT interval prolongation induced by azithromycin in an elderly woman with renal insufficiency. Can Fam Physician 2014;60(11):1012-1015.
34. Cocco G, Jerie P. Torsades de pointes induced by the concomitant use of ivabradine and azithromycin: an unexpected dangerous interaction. Cardiovasc Toxicol 2015;15(1):104-106.
35. Amer S, Hassan S, Shariffi M, Chueca L. QT interval prolongation associated with azithromycin/methadone combination. West Indian Med J 2013;62(8):864-865.
36. Giudicessi JR, Ackerman MJ. Azithromycin and risk of sudden cardiac death: guilty as charged or falsely accused? Cleve Clin J Med 2013;80(9):539-544.
37. Sciaccaluga C, Cameli M, Menci D, et al. COVID-19 and the burning issue of drug interaction: never forget the ECG. Postgraduate Med J 2021; 97: 180-184.
38. Brandariz-Nuñez D, Correas-Sanahuja M, Guarc E, Picón R, García B, Gil R. Potential drug–drug interactions in COVID 19 patients in treatment with lopinavir/ritonavir. Medicina Clínica 2020; 155(7): 281-287.
39. Lipitor (atorvastatin) [prescribing information]. New York, NY: Pfizer, Inc; November 2019.
40- Faizah AK, Nurrahman NW, Putra ON. A Mini Review: Clinically Significant Potential Drug-Drug Interactions in COVID-19 and Comorbid Therapy. Pharmaceut Scienc Res 2020; 7(4): 3.
41. Plasencia-García BO, Rodríguez-Menéndez G, Rico-Rangel MI, Rubio-García A, Torelló-Iserte J, Crespo-Facorro. Drug-drug interactions between COVID-19 treatments and antipsychotics drugs: integrated evidence from 4 databases and a systematic review. Psychopharmacology (Berl) 2021; 238: 329-340.
42. Marzolini C, Back D, Weber R, et al. Ageing with HIV: medication use and risk for potential drug–drug interactions. J Antimicrob Chemother 2011;66(9):2107–11.
43. Obreli-Neto PR, Nobili A, de Oliveira Baldoni A, et al. Adverse drug reactions caused by drug–drug interactions in elderly outpatients: a prospective cohort study. Eur J Clin Pharmaco 2012;68(12):1667–76.
44. Mendes-Nett RS, Silva CQ, Oliveira-Filbo AD, Rocha CE, Lyra-Junior DP. Assessment of drug interactions in elderly patients of a family healthcare unit in Aracaju (Brazil): a pilot study. Afr J Pharm Pharmacol 2011;5:812–8.
45. Maher RL, Hanlon JT, Hajjar ER. Clinical Consequences of Polypharmacy in Elderly. Expert Opin Drug Saf 2014;13(1):57–65.
46. Nobili A, Pasina L, Tettamanti M, et al. Potentially severe drug interactions in elderly outpatients: results of an observational study of an administrative prescription database. J Clin Pharm Ther 2009;34(4):377–86.
47. Bogetti-Salazar M, González-González C, Juárez-Cedillo T, Sánchez-García S, Rosas-Carrasco O. Severe potential drug–drug interactions in older people with dementia and associated factors. Clinics 2016;71(1):17–21.
48. Obreli Neto PR, Nobili A, de Lyra DP Jr, et al. Incidence and predictors of adverse drug reactions caused by drug–drug interactions in elderly outpatients: a prospective cohort study. J Pharm Pharm Sci 2012;15(2):332–43.
49. Obreli Neto PR, Nobili A, Marusic S, et al. Prevalence and predictors of potential drug–drug interactions in the elderly: a crosssectional study in the Brazilian primary public health system. J Pharm Pharm Sci 2012;15(2):344–54.
| Files | ||
| Issue | Vol 9, No 2 (Spring 2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/jpc.v9i2.6612 | |
| Keywords | ||
| COVID-19; Drug–Drug Interaction; Clinical Pharmacy | ||
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How to Cite
1.
Saber-Moghaddam N, Hejazi S, Elyasi S. Potential Drug–Drug Interactions among Hospitalized COVID-19 Patients Admitted to Medical Wards of a Referral Hospital, North-East of Iran: A Cross Sectional Study. J Pharm Care. 2021;9(2):88-95.
