Drug-Drug Interactions Among Pediatric Intensive Care Unit: Risk Factors and Clinical Outcomes

Document Type : Original Article

Authors

1 Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

2 Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

3 Department of Pediatrics, Division of Intensive Care Unit, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

4 Department of Biostatistics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Abstract

Drug–drug interactions (DDIs) are a common concern in pediatric intensive care units (PICUs) and may increase the risk of medication-related adverse events. This study aimed to determine the frequency, categories, and associated factors of potential DDIs in a PICU. We conducted a cross-sectional study between June 2022 and February 2023 among children admitted for at least 48 hours to medical or surgical PICUs who received two or more prescribed medications. Potential DDIs were identified and classified using Lexi-Interact®️. Demographic and clinical data, as well as medication-related information, were collected prospectively, and severity and reliability ratings were recorded. Associations with potential DDIs were analyzed using univariable and multivariable logistic regression. Among 345 included patients, 1,858 potential DDIs were detected, including 1,248 (67%) category C interactions, 529 (29%) category D interactions, and 81 (4%) category X interactions. Potential DDIs were more frequent in the medical PICU than in the surgical PICU. The most frequent contraindicated (category X) interaction involved linezolid–methadone. In multivariable analysis, the number of prescribed drugs, use of sedative agents, and PICU type were significantly associated with the occurrence of potential DDIs. In conclusion, potential DDIs were common in this PICU cohort. Polypharmacy, particularly involving sedative agents, was an important modifiable factor associated with potential DDIs. Enhanced monitoring and medication review may help identify and manage high-risk potential DDIs in critically ill pediatric patients.

Highlights

Afsaneh Vazin (Google Scholar)
Mojtaba Shafiekhani (Google Scholar)

Keywords

References

1.    Mehrpooya M, Taher A, Golgiri A, Mohammadi Y, Ahmadimoghaddam D. Evaluation of the Drug   Interactions Frequency and Their Related Factors in Hospitalized Patients of the Intensive Care Unit in the Hamadan Besat Hospital. Avicenna J  Nurs Midwifery Care. 2021;29(3):171-180. doi: 10.30699/ajnmc.29.3.171 
2.    Ghasemiyeh P, Borhani-Haghighi A, Karimzadeh I, Mohammadi-Samani S, Vazin A, Safari A, et al. Major Neurologic Adverse Drug Reactions, Potential Drug-Drug Interactions and Pharmacokinetic Aspects of Drugs Used in COVID-19 Patients with Stroke: A Narrative Review. Ther Clin Risk Manag. 2020 Jun 30;16:595-605. doi: 10.2147/TCRM.S259152. PMID: 32669846; PMCID: PMC7335700.
3.    McDonnell PJ, Jacobs MR. Hospital admissions resulting from preventable adverse drug reactions. Ann Pharmacother. 2002;36(9):1331-6. doi: 10.1345/aph.1A333. PMID: 12196047.
4.    Roughead EE, Kalisch LM, Barratt JD, Gilbert AL. Prevalence of potentially hazardous drug interactions amongst Australian veterans. Br J Clin Pharmacol. 2010;70(2):252–7. doi:10.1111/j.1365-2125.2010.03694.x.
5.    Dai D, Feinstein JA, Morrison W, Zuppa AF, Feudtner C. Epidemiology of Polypharmacy and Potential Drug-Drug Interactions Among Pediatric Patients in ICUs of U.S. Children's Hospitals. Pediatr Crit Care Med. 2016;17(5):e218-28. doi: 10.1097/PCC.0000000000000684. PMID: 26959349; PMCID: PMC5243142.
6.    Ismail M, Aziz S, Noor S, Haider I, Shams F, Haq I, et al. Potential drug-drug interactions in pediatric patients admitted to intensive care unit of Khyber Teaching Hospital, Peshawar, Pakistan: A cross-sectional study. J Crit Care. 2017;40:243-250. doi: 10.1016/j.jcrc.2017.04.028. Epub 2017 Apr 22. PMID: 28458171.
7.    Choi YH, Lee IH, Yang M, Cho YS, Jo YH, Bae HJ, et al. Clinical significance of potential drug-drug interactions in a pediatric intensive care unit: A single-center retrospective study. PLoS One. 2021;16(2):e0246754. doi: 10.1371/journal.pone.0246754. PMID: 33556128; PMCID: PMC7870058.
8.    World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191-4. doi: 10.1001/jama.2013.281053. PMID: 24141714.
9.    Malfará M, Pernassi M, Aragon D, Carlotti A. Impact of the clinical pharmacist interventions on prevention of pharmacotherapy related problems in the paediatric intensive care unit. Int J Clin Pharm. 2018;40(3):513-519. doi: 10.1007/s11096-018-0632-x. Epub 2018 Mar 30. PMID: 29603074.
10.    Medina-Barajas F, Vázquez-Méndez E, Pérez-Guerrero EE, Sánchez-López VA, Hernández-Cañaveral II, Gabriel A RO, et al. Pilot study: Evaluation of potential drug-drug interactions in hospitalized pediatric patients. Pediatr Neonatol. 2020;61(3):279-289. doi: 10.1016/j.pedneo.2019.11.006. Epub 2019 Nov 22. PMID: 31866496.
11.    Nabovati E, Vakili-Arki H, Taherzadeh Z, Hasibian MR, Abu-Hanna A, Eslami S. Drug-drug interactions in inpatient and outpatient settings in Iran: a systematic review of the literature. Daru. 2014;22:52. doi:10.1186/2008-2231-22-52.
12.    Rao C, Shenoy V, Udaykumar P. Potential drug-drug interactions in the pediatric intensive care unit of a tertiary care hospital. J Pharmacol Pharmacother. 2019;10(2):63-8. doi:10.4103/jpp.JPP_27_19.
13.    Lima EDC, Camarinha BD, Ferreira Bezerra NC, Panisset AG, Belmino de Souza R, Silva MT, et al. Severe Potential Drug-Drug Interactions and the Increased Length of Stay of Children in Intensive Care Unit. Front Pharmacol. 2020;11:555407. doi: 10.3389/fphar.2020.555407. PMID: 33343344; PMCID: PMC7744879.
14.    Getachew H, Assen M, Dula F, Bhagavathula AS. Potential drug–drug interactions in pediatric wards of Gondar University Hospital, Ethiopia: A cross sectional study. Asian Pac J Trop Biomed. 2016;6(6):534-8. doi: 10.1016/j.apjtb.2016.04.002
15.    Gagne JJ, Maio V, Rabinowitz C. Prevalence and predictors of potential drug-drug interactions in Regione Emilia-Romagna, Italy. J Clin Pharm Ther. 2008;33(2):141-51. doi:10.1111/j.1365-2710.2007. 00891.x
16.    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.
17.    Cremades J, Gonzalo M, Arrebola I. Relationship between drug interactions and drug-related negative clinical outcomes. Pharm Pract (Granada). 2009;7(1):34-9. doi: 10.4321/s1886-36552009000100005. Epub 2009 Mar 15. PMID: 25147590; PMCID: PMC4139754.
18.    Huang J, Edrees H, Lee G. A Case Series on Serotonin Syndrome from Concomitant use of linezolid With Methadone, Buprenorphine, and/or Dextroamphetamine. J Pharm Pract. 2024;37(3):780-785. doi: 10.1177/08971900231182772. Epub 2023 Jun 9. PMID: 37295073.
19.    Masbough F, Roshanzamiri S, Rahimi M, Sahraei Z, Evini PET. Serotonin syndrome due to concomitant use of linezolid and methadone. Clin Case Rep. 2022;10(11):e6341. doi: 10.1002/ccr3.6341. 
Trends in Pharmaceutical Sciences and Technologies
Volume 12, Issue 1
March 2026
Pages 93-102

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