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Pharmacoepidemiological study of drug–drug interactions in onco-hematological pediatric patients

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Abstract

Background Onco-hematological patients are particularly susceptible to drug–drug interactions (DDIs) because they often undergo multiple combined treatments. Some studies have analyzed the frequency of DDIs in adult patients with cancer; however, the prevalence of DDIs in children, and especially among pediatric cancer patients, remains unknown. Objective To determine the prevalence of DDIs in treatment sheets comparing two commonly used drug interaction databases, to describe the most common clinically relevant DDIs (CR-DDIs) and to investigate the risk factors associated with them. Setting An onco-hematological pediatric unit from a tertiary hospital in Spain. Method A prospective, observational and descriptive study was carried out from November 2012 to February 2013. Twice a week, every patient’s treatment sheet was collected. Each medication list was screened through two databases: Thomson Micromedex™ and Drug Interaction Facts™. All identified DDIs were graded by their level of severity. Summary statistics were used to describe patient and disease characteristics, most often prescribed drugs, and frequency, types and classification of CR-DDIs. Multivariate analysis was used to identify risk factors associated with CRDDIs. Main outcome measure Prevalence of CR-DDIs was measured as percentage. Results A total of 506 potential DDIs were detected in 150 treatment sheets. The prevalence of CR-DDIs by Micromedex database and Drug Interaction Facts database were 44.7 and 51.3 % respectively. Amikacin, azole antifungals, antiemetics and cyclosporine were the most frequent drugs involved in CR-DDIs. In multivariate analysis, the main risk factor associated with increased odds for CR-DDIs was a higher number of drugs. Conclusion The frequency of potential DDIs was related to a higher number of drugs, being immunosuppressant and azole antifungal agents the most commonly involved drugs. The lack of agreement between different databases enhances the complexity to detect drug interactions in clinical practice.

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References

  1. Stockley BK. General considerations and an outline survey of some basic interaction mechanisms. In: Stockley’s drug interactions. 8th ed. London: Pharmaceutical Press; 2008. p. 1–11. ISBN: 978-0-85369-754-1.

  2. Riechelmann RP, Saad ED. A systematic review on drug interactions in oncology. Cancer Investig. 2006;24:704–12.

    Article  CAS  Google Scholar 

  3. 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;20:402–8.

    Article  PubMed  Google Scholar 

  4. Galindo-Ocaña J, Gil-Navarro MV, García-Morillo JS, Bernabeu-Wittel M, Ollero-Baturonea M, Ortiz-Camúñez MA. Drug–drug interactions in a multicentre polypathological polymedicated patients. Rev Clin Esp. 2010;210(6):270–8.

    Article  PubMed  Google Scholar 

  5. Reimche L, Forster AJ, van Walraven C. Incidence and contributors to potential drug–drug interactions in hospitalized patients. J Clin Pharmacol. 2011;51:1043–50.

    Article  CAS  PubMed  Google Scholar 

  6. 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(10):879–88.

    Article  PubMed  Google Scholar 

  7. Reis AMM, Cassiani SHB. Adverse drug events in an intensive care unit of a university hospital. Eur J Clin Pharmacol. 2011;67:625–32.

    Article  PubMed  Google Scholar 

  8. Riechelmann RP, Zimmermann C, Chin SN, Wang L, O’Carroll A, Zarinehbaf S, et al. Potential drug interactions in cancer patients receiving palliative care exclusively. J Pain Symptom Manage. 2008;35:535–43.

    Article  PubMed  Google Scholar 

  9. Riechelmann RP, Tannock IF, Wang L, Saad ED, Taback NA, Krzyzanowska MK. Potential drug interactions and duplicate prescriptions among cancer patients. J Natl Cancer Inst. 2007;99:592–600.

    Article  PubMed  Google Scholar 

  10. Riechelmann RP, Moreira F, Smaletz O, Saad ED. Potential for drug interactions in hospitalized cancer patients. Cancer Chemother Pharmacol. 2005;56:286–90.

    Article  PubMed  Google Scholar 

  11. Haidar C, Jeha S. Drug interactions in childhood cancer. Lancet Oncol. 2011;12:92–9.

    Article  CAS  PubMed  Google Scholar 

  12. Rashed AN, Wong ICK, Cranswick N, Hefele B, Tomlin S, Jackman J, et al. Adverse drug reactions in children—international surveillance and evaluation (ADVISE). A multicenter cohort study. Drug Saf. 2012;35(6):481–96.

    Article  CAS  PubMed  Google Scholar 

  13. Telechea H, Speranza N, Lucas L, Giachetto G, Nanni L, Menchaca A. Adverse drug reactions in a paediatric intensive care unit. Farm Hosp. 2012;36(5):403–9.

    Article  CAS  PubMed  Google Scholar 

  14. Impicciatore P, Choonara I, Clarkson A, Provasi D, Pandolfini C, Bonati M. Incidence of adverse drug reactions in pediatric in/out-patients: a systematic review and meta-analysis of prospective studies. Br J Clin Pharmacol. 2001;52:77–83.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Martínez-Mir I, García-López M, Palop V, Ferrer JM, Rubio E, Morales-Oliva FJ. A prospective study of adverse drug reactions in hospitalized children. Br J Clin Pharmacol. 1999;47:681–8.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Micromedex healthcare series: interactions (updated periodically). Thomson Reuters (Healthcare) Inc. http://www.micromedexsolutions.com/home/dispatch. Accessed March 1 2013.

  17. Tatro DS. Drug interaction facts. The autorithy on drug interactions. St Louis, Missouri: Wolters Kluwer Health, 2012. ISBN: 978-1-57439-331-6.

  18. Ibáñez A, Alcalá M, García J, Puche E. Drug–drug interactions in patients from an internal medicine service. Farm Hosp. 2008;32(5):293–7.

    Article  PubMed  Google Scholar 

  19. Mino-León D, Galván-Plata ME, Doubova SV, Flores-Hernandez S, Reyes-Morales H. A pharmacoepidemiological study of potential drug interactions and their determinant factors in hospitalized patients. Rev Invest Clin. 2011;63(2):170–8.

    PubMed  Google Scholar 

  20. Reis AMM, Cassiani SHB. Prevalence of potential drug interactions in patients in an intensive care unit of a university hospital in Brazil. Clinics. 2011;66(1):9–15.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Martinbiancho J, Zuckermann J, Dos Santos L, Silva MM. Profile of drug interactions in hospitalized children. Pharm Pract. 2007;5(4):157–61.

    Google Scholar 

  22. Zwart-van Rijkom JEF, Uijtendaal EV, ten Berg MJ, van Solinge WW, Egberts ACG. Frequency and nature of drug–drug interactions in a Dutch university hospital. Br J Clin Pharmacol. 2009;68(2):187–93.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Smith CR, Lietman PS. Effect of furosemide on aminoglycoside-induced nephrotoxicity and auditory toxicity in humans. Antimicrob Agents Chemother. 1983;23(1):133–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. DIFLUCAN Product information. http://www.aemps.gob.es/cima/pdfs/es/ft/58817/FT_58817.pdf. Accessed July 20, 2013.

  25. ZOFRAN Product information. http://www.aemps.gob.es/cima/pdfs/es/ft/59071/FT_59071.pdf. Accessed July 20, 2013.

  26. Romero AJ, Le PP, Nilsson LG, Wood N. Effect of voriconazole on the pharmacokinetics of cyclosporine in renal transplant patients. Clin Pharmacol Ther. 2002;71:226–34.

    Article  CAS  PubMed  Google Scholar 

  27. Fanta S, Jonsson S, Backman JT, Karlsson MO, Hoppu K. Developmental pharmacokinetics of ciclosporin—a population pharmacokinetic study in paediatric renal transplant candidates. Br J Clin Pharmacol. 2007;64:772–84.

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Fukudo M, Yano I, Masuda S, Goto M, Uesugi M, Katsura T, et al. Population pharmacokinetic and pharmacogenomic analysis of tacrolimus in pediatric living-donor liver transplant recipients. Clin Pharmacol Ther. 2006;80:331–45.

    Article  CAS  PubMed  Google Scholar 

  29. Chan TYK, Critchley JAJH. Life-threatening hyperkalaemia in an elderly patient receiving captopril, furosemide and potassium supplements. Drug Saf. 1992;7:159–61.

    Article  CAS  PubMed  Google Scholar 

  30. Stoltz ML, Andrews CE. Severe hyperkalemia during very-low-calorie diets and angiotensin converting enzyme use. JAMA. 1990;264:2737–8.

    Article  CAS  PubMed  Google Scholar 

  31. Cagnoni PJ, Matthes S, Day TC, Bearman SI, Shpall EJ, Jones RB. Modification of the pharmacokinetics of high-dose cyclophosphamide and cisplatin by antiemetics. Bone Marrow Transplant. 1999;24(1):1–4.

    Article  CAS  PubMed  Google Scholar 

  32. Gilbert CJ, Petros WP, Vredenburgh J, Hussein A, Ross M, Rubin P, et al. Pharmacokinetic interaction between ondansetron and cyclophosphamide during high-dose chemotherapy for breast cancer. Cancer Chemother Pharmacol. 1998;42(6):497–503.

    Article  CAS  PubMed  Google Scholar 

  33. Balis FM, Holcenberg JS, Zimm S, Tubergen D, Collins JM, Murphy RF, et al. The effect of methotrexate on the bioavailability of oral 6-mercaptopurine. Clin Pharmacol Ther. 1987;41(4):384–7.

    Article  CAS  PubMed  Google Scholar 

  34. Andersen JB, Szumlanski C, Weinshilboum RM, Schmiegelow K. Pharmacokinetics, dose adjustments, and 6-mercaptopurine/methotrexate drug interactions in two patients with thiopurine methyltransferase deficiency. Acta Paediatr. 1998;87(1):108–11.

    Article  CAS  PubMed  Google Scholar 

  35. Abarca J, Malone DC, Armstrong EP, Grizzle AJ, Hansten PD, Van Bergen RC, et al. Concordance of severity ratings provided in four drug interaction compendia. J Am Pharm Assoc. 2004;44(2):136–41.

    Article  Google Scholar 

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Correspondence to M. Angeles Fernández de Palencia Espinosa.

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Fernández de Palencia Espinosa, M.A., Díaz Carrasco, M.S., Fuster Soler, J.L. et al. Pharmacoepidemiological study of drug–drug interactions in onco-hematological pediatric patients. Int J Clin Pharm 36, 1160–1169 (2014). https://doi.org/10.1007/s11096-014-0011-1

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  • DOI: https://doi.org/10.1007/s11096-014-0011-1

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