Mehmet Zafer GÖREN, Özlem SARIKAYA, Filiz ONAT, Esra KÜÇÜKİBRAHİMOĞLU, Mahluga DEMIRKAPU, Atila KARAALP, Medine GÜLÇEBİ İDRİZ OĞLU

Potential drug?drug interactions in a medical intensive care unit of a university hospital

Background/aim: Drug drug interactions (DDIs) can impact patient safety. Occurrence of clinically important DDIs is higher for intensive care unit (ICU) patients. This observational study aimed to evaluate the potential DDIs in medical ICU patients of a university hospital. Materials and methods: The Medical Pharmacology Department organized consultation reports for ICU patients in order to detect the DDIs. To focus on clinically important DDIs, interactions in the C, D, or X risk rating categories of the Lexi-Interact online database were analyzed. Frequency and clinical risk rating categories of DDIs were detected. Relationship between number of prescriptions and DDIs were assessed. The most frequent drug/drug groups were identified. Results: Of 101 ICU patients, 45.5% were found to have DDIs. We detected 125 C (72.2%), 37 D (21.4%), and 11 X (6.4%) risk category interactions. A statistically significant increase in the number of DDIs was shown with the number of prescriptions (P = 0.002). The most frequent DDIs were between agents acting on the cardiovascular system and corticosteroids (12.8%). Conclusion: Results of this study show that pharmacological consultation plays a critical role in the recognition of DDIs for improvement of medication management and effective therapeutic endpoints without any adverse or toxic reactions.

PDF

___

1. Doucet J, Chassagne P, Trivalle C, Landrin I, Pauty MD, Kadri N, Ménard JF, Bercoff E. Drug-drug interactions related to hospital admissions in older adults: a prospective study of 1000 patients. J Am Geriatr Soc 1996; 44: 944-948.
2. Classen DC, Pestotnik SL, Evans RS, Lloyd JF, Burke JP. Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality. JAMA 1997; 277: 301-306.
3. 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: 343- 355.
4. Lima RE, De Bortoli Cassiani SH. Potential drug interactions in intensive care patients at a teaching hospital. Rev Lat Am Enfermagem 2009; 17: 222-227.
5. Gosney M, Tallis R. Prescription of contraindicated and interacting drugs in elderly patients admitted to hospital. Lancet 1984; 2: 564-567.
6. Rosas-Carrasco O, García-Peña C, Sánchez-García S, VargasAlarcón G, Gutiérrez-Robledo LM, Juárez-Cedillo T. The relationship between potential drug-drug interactions and mortality rate of elderly hospitalized patients. Rev Invest Clin 2011; 63: 564-573.
7. Smithburger PL, Kane-Gill SL, Seybert AL. Drug-drug interactions in the medical intensive care unit: an assessment of frequency, severity and the medications involved. Int J Pharm Pract 2012; 20: 402-408.
8. Uijtendaal EV, van Harssel LL, Hugenholtz GW, Kuck EM, Zwart-van Rijkom JE, Cremer OL, Egberts TC. Analysis of potential drug-drug interactions in medical intensive care unit patients. Pharmacotherapy 2014; 34: 213-219.
9. Heininger-Rothbucher D, Bischinger S, Ulmer H, Pechlaner C, Speer G, Wiedermann CJ. Incidence and risk of potential adverse drug interactions in the emergency room. Resuscitation 2001; 49: 283-288.
10. UpToDate, Inc. Lexi-Interact Online. www.uptodate.com/ crlsql/interact/frameset.jsp, 2014.
11. Rivkin A, Yin H. Evaluation of the role of the critical care pharmacist in identifying and avoiding or minimizing significant drug-drug interactions in medical intensive care patients. J Crit Care 2011; 26: 104e1-104e6.
12. Smithburger PL, Kane-Gill SL, Seybert Al. Drug-drug interactions in cardiac and cardiothoracic intensive care units: an analysis of patients in an academic medical centre in the US. Drug Saf 2010; 33: 879-888.
13. Askari M, Eslami S, Louws M, Wierenga PC, Dongelmans DA, Kuiper RA, Abu-Hanna A. Frequency and nature of drug-drug interactions in the intensive care unit. Pharmacoepidemiol Drug Saf 2013; 22: 430-437.
14. Franceschi A, Tuccori M, Bocci G, Vannozzi F, Di Paolo A, Barbara C, Lastella M, Blandizzi C, Del Tacca M. Drug therapeutic failures in emergency department patients. A university hospital experience. Pharmacol Res 2004; 49: 85-91.
15. Johnell K, Klarin I. The relationship between number of drugs and potential drug-drug interactions in the elderly: a study of over 600,000 elderly patients from the Swedish Prescribed Drug Register. Drug Saf 2007; 30: 911-918.
16. Lavery S, Himabindu R, McDaniel W, Pushkin Y. Linezolid and serotonin syndrome. Psychosomatics 2001; 42: 432-434.
17. DeBellis RJ, Schaefer OP, Liquori M, Volturo GA. Linezolidassociated serotonin syndrome after concomitant treatment with citalopram and mirtazepine in a critically ill bone marrow transplant recipient. J Intensive Care Med 2005; 20: 351-353.
18. Vieweg WV, Wood MA, Fernandez A, Beatty-Brooks M, Hasnain M, Pandurangi AK. Proarrhythmic risk with antipsychotic and antidepressant drugs: implications in the elderly. Drugs Aging 2009; 26: 997-1012.
19. Imani S, Jusko WJ, Steiner R. Diltiazem retards the metabolism of oral prednisone with effects on T-cell markers. Pediatr Transplant 1999; 3: 1-5.
20. Booker BM, Magee MH, Blum RA, Lates CD, Jusko WJ. Pharmacokinetic and pharmacodynamic interactions between diltiazem and methylprednisolone in healthy volunteers. Clin Pharmacol Ther 2002; 72: 370-382.
21. Widmer P, Maibach R, Kunzi UP. Diuretic-related hypokalaemia: the role of diuretics, potassium supplements, glucocorticoids and beta 2-adrenoceptor agonists. Results from the Comprehensive Hospital Drug Monitoring Programme, Berne (CHDM). Eur J Clin Pharmacol 1995; 49: 31-36.
22. Stubbs DF. Positive synergism between diuretics and methylprednisolone following acute myocardial infarction. J Int Med Res 1986; 14: 21-24.
23. Centeno RF, Yu YL. The propanolol-epinephrine interaction revisited: a serious and potentially catastrophic adverse drug interaction in facial plastic surgery. Plast Reconstr Surg 2003; 111: 944-945.
24. van Herwaarden CL. Effects of adrenaline during treatment with propranolol and metoprolol. Br Med J 1977; 2: 029.
25. Levy B, Perez P, Perny J, Thivilier C, Gerard A. Comparison of norepinephrine-dobutamine to epinephrine for hemodynamics, lactate metabolism, and organ function variables in cardiogenic shock. A prospective, randomized pilot study. Crit Care Med 2011; 39: 450-455.
26. Annane D, Vignon P, Renault A, Bollaert PE, Charpentier C, Martin C, Troché G, Ricard JD, Nitenberg G, Papazian L et al. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet 2007; 370: 676-684.
27. Lawrence KR, Adra M, Gillman PK. Serotonin toxicity associated with the use of linezolid: a review of postmarketing data. Clin Infect Dis 2006; 42: 1578-1583.
28. Meyer-Massetti C, Cheng CM, Sharpe BA, Meier CR, Guglielmo BJ. The FDA extended warning for intravenous haloperidol and torsades de pointes: how should institutions respond? J Hosp Med 2010; 5: E8-16.
29. Kannankeril P, Roden DM, Darbar D. Drug-induced long QT syndrome. Pharmacol Rev 2010; 62: 760-781.
30. Letsas KP, Sideris A, Kounas SP, Efremidis M, Korantzopoulos P, Kardaras F. Drug-induced QT interval prolongation after ciprofloxacin administration in a patient receiving olanzapine. Int J Cardiol 2006; 109: 273-274.
31. Castro VM, Clements CC, Murphy SN, Gainer VS, Fava M, Weilburg JB, Erb JL, Churchill SE, Kohane IS, Iosifescu DV et al. QT interval and antidepressant use: a cross sectional study of electronic health records. BMJ 2013; 346: f288.
32. Watanabe H, Hasegawa A, Shinozaki T, Arita S, Chigira M. Possible cardiac side effects of granisetron, an antiemetic agent, in patients with bone and soft-tissue sarcomas receiving cytotoxic chemotherapy. Cancer Chemother Pharmacol 1995; 35: 278-282.
33. McMahon FG, Ryan JR, Akdamar K, Ertan A. Effect of potassium chloride supplements on upper gastrointestinal mucosa. Clin Pharmacol Ther 1984; 35: 852-855.
34. Hanania NA, Mannava B, Franklin AE, Lipworth BJ, Williamson PA, Garner WJ, Dickey BF, Bond RA. Response to salbutamol in patients with mild asthma treated with nadolol. Eur Respir J 2010; 36: 963-965.