RISK FACTORS FOR POTENTIAL DRUG-DRUG INTERACTIONS OF ANALGESICS IN HOSPITALIZED UROLOGICAL PATIENTS

  • Ivan Milovanović 1. University of Kragujevac, Faculty of Medical Sciences, Kragujevac, Serbia; 2. University Clinical Centre Kragujevac, Clinic of Urology, Kragujevac, Serbia
  • Ana Pejčić University of Kragujevac, Faculty of Medical Sciences, Department of Pharmacology and Toxicology, Kragujevac, Serbia
  • Zoran Kovačević University Clinical Centre Kragujevac, Clinic of Nephrology, Kragujevac, Serbia
  • Katarina Janićijević University of Kragujevac, Faculty of Medical Sciences, Department of Social Medicine, Kragujevac, Serbia
Keywords: analgesics, drug-drug interactions, urology, hospitalized patients

Abstract


Objective: To evaluate potential drug–drug interactions (pDDIs) involving analgesics in hospitalized urological patients and identify risk factors influencing their number.

Methods: This study involved a post hoc analysis based on data obtained from a retrospective observational cohort clinical study conducted at the Clinic of Urology, University Clinical Centre Kragujevac, Serbia. Of the original 220 patients, 191 who received analgesics were included. Daily pharmacotherapy data, along with demographic and clinical characteristics, were collected, while pDDIs were identified and classified using the Lexicomp Interaction Checker. Descriptive statistics were used to summarize the data. Multiple linear regression with backward elimination was used to identify independent predictors of the number of pDDIs.

Results: Analgesic-related pDDIs were detected in 175 patients (91.6%). Non-steroidal anti-inflammatory drugs (NSAIDs) were prescribed to 173 patients (90.6%), opioids to 53 (27.7%), and paracetamol to 54 (28.3%). The mean number of pDDIs per patient was 5.5 ± 5.5 (range 0–30). Category X interactions most frequently included NSAID combinations (diclofenac + ketorolac, ketorolac + metamizole), while category D interactions frequently involved enoxaparin + ketorolac and opioid–benzodiazepine pairs. Category C interactions were dominated by NSAID + potassium chloride and tramadol + ondansetron or atropine combinations. Multiple regression analysis identified diabetes, a higher number of prescribed drugs, and the use of NSAIDs or opioids as positive predictors of the number of pDDIs, whereas a cancer diagnosis was associated with a lower number.

Conclusion: Analgesic-related pDDIs affect the majority of hospitalized urological patients. Avoiding high-risk combinations, close monitoring, and multidisciplinary medication review in patients with risk factors may help reduce preventable harm.

References

Staudt MD. The multidisciplinary team in pain management. Neurosurg Clin N Am. 2022;33(3):241-9. doi: 10.1016/j.nec.2022.02.002.

Scheife RT, Hines LE, Boyce RD, Chung SP, Momper JD, Sommer CD, et al. Consensus recommendations for systematic evaluation of drug-drug interaction evidence for clinical decision support. Drug Saf. 2015;38(2):197-206. doi: 10.1007/s40264-014-0262-8.

Milovanovic IR, Pejcic AV. Drug-drug interactions in hospitalized urological patients: a retrospective cohort study. Pharmacology. 2025;110(1):15-25. doi: 10.1159/000540427.

Buğday MS, Öksüz E. Drug-drug interactions in the risky population: elderly, urological patients admitted to the intensive care unit. East J Med. 2021;26(2):236-41. doi: 10.5505/ejm.2021.04864.

Varghese J, Chang DL, Mirman BD, Capodice J, Shehebar M. Acute and chronic pain management of the urologic patient. Int J Anesth Crit Care. 2024;3(1):6-16. doi: 10.33696/Anesthesia.3.008.

Khan SA, Afridi R, Afridi UK, Sadozai S. Prescribing pattern and drug–drug interactions of analgesics prescribed for pain management in a Pakistani tertiary hospital. J Appl Pharm. 2016;8(4):1-4. doi: 10.21065/1920-4159.1000230.

Chu F, Yao Y, Gao B, Huang M, Kong L. Incidence and risk factors for potential drug-drug interactions in outpatients receiving opioid analgesics. Expert Opin Drug Saf. 2025;24(2):167-75. doi: 10.1080/14740338.2024.2346101.

Kotlinska-Lemieszek A, Klepstad P, Haugen DF. Clinically significant drug–drug interactions involving opioid analgesics used for pain treatment in patients with cancer: a systematic review. Drug Des DevelTher. 2015;9:5255-67. doi: 10.2147/DDDT.S86983.

Kardas P, Urbański F, Lichwierowicz A, Chudzyńska E, Czech M, Makowska K, et al. The prevalence of selected potential drug-drug interactions of analgesic drugs and possible methods of preventing them: lessons learned from the analysis of the Real-World National Database of 38 million citizens of Poland. Front Pharmacol. 2021;11:607852. doi: 10.3389/fphar.2020.607852

Doubova (Dubova) SV, Reyes-Morales H, del Pilar Torres-Arreola L, Suárez-Ortega M. Potential drug-drug and drug-disease interactions in prescriptions for ambulatory patients over 50 years of age in family medicine clinics in Mexico City. BMC Health Serv Res. 2007;7(1):147. doi: 10.1186/1472-6963-7-147

Mehuys E, De Backer T, De Keyser F, Christiaens T, Van Hees T, Demarche S, et al. Prevalence and management of drug interactions between nonsteroidal anti-inflammatory drugs and antithrombotics in ambulatory care. Br J Clin Pharmacol. 2022;88(8):3896-902. doi: 10.1111/bcp.15288.

Lanas A, Benito P, Alonso J, Hernández-Cruz B, Barón-Esquivias G, Perez-Aísa Á, et al. Safe prescription recommendations for non steroidal anti-inflammatory drugs: consensus document elaborated by nominated experts of three scientific associations (SER-SEC-AEG). Reumatol Clin. 2014;10(2):68-84. doi: 10.1016/j.reuma.2013.10.004. [Article in English, Spanish]

Tai FWD, McAlindon ME. Non-steroidal anti-inflammatory drugs and the gastrointestinal tract. Clin Med. 2021;21(2):131-4. doi: 10.7861/clinmed.2021-0039.

Clinard F, Sgro C, Bardou M, Hillon P, Dumas M, Kreft-Jais C, et al. Association between concomitant use of several systemic NSAIDs and an excess risk of adverse drug reaction. A case/non-case study from the French Pharmacovigilance system database. Eur J Clin Pharmacol. 2004;60(4):279-83. doi: 10.1007/s00228-004-0761-0.

García Rodríguez LA, Cattaruzzi C, Troncon MG, Agostinis L. Risk of hospitalization for upper gastrointestinal tract bleeding associated with ketorolac, other nonsteroidal anti-inflammatory drugs, calcium antagonists, and other antihypertensive drugs. Arch Intern Med. 1998;158(1):33-9. doi: 10.1001/archinte.158.1.33.

Schaffer D, Florin T, Eagle C, Marschner I, Singh G, Grobler M, et al. Risk of serious NSAID-related gastrointestinal events during long-term exposure: a systematic review. Med J Aust. 2006;185(9):501-6. doi: 10.5694/j.1326-5377.2006.tb00665.x.

Klomjit N, Ungprasert P. Acute kidney injury associated with non-steroidal anti-inflammatory drugs. Eur J Intern Med. 2022;101:21-8. doi: 10.1016/j.ejim.2022.05.003.

Zheng Y, Zhang N, Tse G, Li G, Lip GYH, Liu T. Co-administered oral anticoagulants with nonsteroidal anti-inflammatory drugs and the risk of bleeding: A systematic review and meta-analysis. Thromb Res. 2023;232:15-26. doi: 10.1016/j.thromres.2023.10.011.

Harężlak T, Religioni U, Szymański FM, Hering D, Barańska A, Neumann-Podczaska A, et al. Drug interactions affecting kidney function: beware of health threats from triple whammy. Adv Ther. 2021;39(1):140-7. doi: 10.1007/s12325-021-01939-9.

Dreischulte T, Morales DR, Bell S, Guthrie B. Combined use of nonsteroidal anti-inflammatory drugs with diuretics and/or renin-angiotensin system inhibitors in the community increases the risk of acute kidney injury. Kidney Int. 2015;88(2):396-403. doi: 10.1038/ki.2015.101.

Whelton A. Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications. Am J Med. 1999;106(5B):13S-24S. doi: 10.1016/s0002-9343(99)00113-8.

Moore N, Pollack C, Butkerait P. Adverse drug reactions and drug–drug interactions with over-the-counter NSAIDs. Ther Clin Risk Manag. 2015;11:1061-75. doi: 10.2147/TCRM.S79135.

Sahil F, Kumar J, Raiz G, Bhutto NS, Tahir H, Anjum Z, et al Association between long-term use of non-steroidal anti-inflammatory drugs and hyperkalemia in diabetic patients. Cureus. 2021;13(6):e15648. doi: 10.7759/cureus.15648.

Sun EC, Dixit A, Humphreys K, Darnall BD, Baker LC, Mackey S. Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. BMJ. 2017;356:j760. doi: 10.1136/bmj.j760.

Tobias JD, Leder M. Procedural sedation: A review of sedative agents, monitoring, and management of complications. Saudi J Anaesth. 2011;5(4):395-410. doi: 10.4103/1658-354X.87270.

Ranković A, Milentijevic I, Jankovic S. Factors associated with potential drug-drug interactions in psychiatric inpatients. Eur J Hosp Pharm. 2024;31(2):127-34. doi: 10.1136/ejhpharm-2022-003262.

Ayenew W, Asmamaw G, Issa A. Prevalence of potential drug-drug interactions and associated factors among outpatients and inpatients in Ethiopian hospitals: a systematic review and meta-analysis of observational studies. BMC PharmacolToxicol. 2020;21(1):63. doi: 10.1186/s40360-020-00441-2.

Aleksić DZ, Milosavljević MN, Stefanović SM, Bukonjić A, Milosavljević JZ, Janković SM, et al. Risk factors for potential drug–drug interactions in patients with myasthenia gravis. Neurol Res. 2021;43(12):1023-30. doi: 10.1080/01616412.2021.1948767.

Milosavljevic MN, Kocovic AG, Jankovic SM, Radovanovic DM, Milisavljevic SS, Stefanovic SM. Risk factors for the occurrence of potential drug-drug interactions in surgical patients. Ser J Exp Clin Res. 2021;22(3):213-23. doi: 10.2478/sjecr-2019-0032.

Pergolizzi JV. Quantifying the impact of drug-drug interactions associated with opioids. Am J Manag Care. 2011;17(Suppl 11):S288-92.

Hezam AAM, Shaghdar HBM, Chen L. The connection between hypertension and diabetes and their role in heart and kidney disease development. J Res Med Sci. 2024;29:22. doi: 10.4103/jrms.jrms_470_23.

Jafarova Demirkapu M, Cavdar E. Potential drug-drug interactions in outpatient lung cancer patients in a university hospital. Pharmacology. 2024;109(4):231-6. doi: 10.1159/000538742.

Cao L, Zhang L, Chen B, Yan L, Shi X, Tian L. Application of multimodal standardized analgesia under the concept of enhanced recovery after surgery in laparoscopic radical colorectal cancer surgery. Front Oncol. 2024;14:1381809. doi: 10.3389/fonc.2024.1381809.

Published
2026/01/26
Section
Original article