Evaluation of drug-drug interactions and their clinical importance in a pediatric hematopoietic stem cell transplantation unit

Background and Aims: Many drugs with narrow therapeutic range and high toxicity risk are used in hematopoietic stem cell transplantation (HSCT) Units. The increase in the number of drugs raises the likelihood of interactions. This is particularly important in pediatric patients and may adversely affect the treatment process. In this study, we aimed to determine the potential drug interactions and to evaluate the clinical significance of them in terms of physician’s and pharmacist’s perceptions. Methods: The study was conducted as a prospective descriptive study over a six-month period in a tertiary care hospital’s Pediatric HSCT Unit. A pharmacist evaluated inpatients’ drugs for drug interactions by using a drug interaction checker program and the clinical significance of the interactions were evaluated by the physician and the pharmacist separately. Results: Drugs used in 20 patients (median age= 8 years, range= 0.6–17 years) were evaluated. A total of 525 potential drugdrug interactions were identified. Two hundred and forty seven interactions (47.05%) were major; 238 (45.33%) were moderate; 23 (4.38%) were contraindicated. The number of the interactions considered “clinically significant” by the pharmacist and “clinically insignificant” by the physician at the preparative regimen and post-transplant period were 15 (35.7%) and 37 (29.4%), respectively. Conclusion: The management of drug interactions is important in pediatric HSCT patients as a vulnerable group. Drug interactions should be interpreted according to the patient's clinical presentation, not only theoretically. Cooperation between physicians and pharmacists in the management of interactions will contribute to optimize the patient's treatment.

___

  • • Aljadani, R., & Aseeri, M. (2018). Prevalence of drug-drug interactions in geriatric patients at an ambulatory care pharmacy in a tertiary care teaching hospital. BMC Research Notes, 11(1). http:// dx.doi.org 10.1186/s13104-018-3342-5
  • • Ament, P. W., Bertolino, J.G., & Liszewski, J.L. (2000). Clinically significant drug interactions. American Family Physician, 61(6), 1745–1754.
  • • Balk, T. E., Van-der-Sijs, I. H., Van-Gelder, T., Janssen, J. J. B., Van-der Sluis IM, Van-Leeuwen, R. W. F., & Engels, F. K. (2017). Drug-drug interactions in pediatric oncology patients. Pediatric Blood Cancer. 64(7). https://doi.org/10.1002/pbc.26410
  • • Bernard, E., Goutelle, S., Bertrand, Y., & Bleyzac, N. (2014). Pharmacokinetic drug-drug interaction of calcium channel blockers with cyclosporine in hematopoietic stem cell transplant children. Annals of Pharmacotherapy, 48(12), 1580–1584. https://doi. org/ 10.1177/1060028014550644
  • • Campana, C., Regazzi, M. B, Buggia, I., & Molinaro, M. (1996). Clinically significant drug interactions with cyclosporin - An update. Clinical Pharmacokinetics, 30(2), 141–179.
  • • Chan, A., Tan, S. H., Wong, C. M., Yap, K. Y., & Ko, Y. (2009). Clinically significant drug-drug interactions between oral anticancer agents and nonanticancer agents: a Delphi survey of oncology pharmacists. Clinical Therapeutics, 31(2), 2379–2386. https://doi. org/10.1016/j.clinthera.2009.11.008
  • • Deeg, H. J. (2005). Optimization of transplant regimens for patients with myelodysplastic syndrome (MDS). Hematology American Society of Hematology Education Program, 167–173.
  • • Eldesouky, H. E., Li, X., Abutaleb, N. S., Mohammad, H., & Seleem, M. N. (2018). Synergistic interactions of sulfamethoxazole and azole antifungal drugs against emerging multidrug-resistant Candida auris. International Journal of Antimicrobial Agents, 52(6), 754–761. https://doi.org/10.1016/j.ijantimicag.2018.08.016
  • • Gholaminezhad, S., Hadjibabaie, M., Gholami, K., Javadi, M. R., Radfar, M., Karimzadeh, I., & Ghavamzadeh, A. (2014). Pattern and associated factors of potential drug-drug interactions in both preand early post-hematopoietic stem cell transplantation stages at a referral center in the Middle East. Annals of Hematology, 93(11), 1913–1922.
  • • Glotzbecker, B., Duncan, C., Alyea, E., Campbell, B., & Soiffer, R. (2012). Important drug interactions in hematopoietic stem cell transplantation: what every physician should know. Biology of Blood and Marrow Transplantation, 18(7), 989–1006. https://doi. org/ 10.1016/j.bbmt.2011.11.029
  • • Leather, H. L. (2004). Drug interactions in the hematopoietic stem cell transplant (HSCT) recipient: what every transplanter needs to know. Bone Marrow Transplantation, 33(2), 137–152.
  • • Marcath, L. A., Coe, T. D., Hoylman, E. K., Redman, B. G., & Hertz, D. L. (2018). Prevalence of drug-drug interactions in oncology patients enrolled on National Clinical Trials Network oncology clinical trials. BMC Cancer, 18(1), 1155-1163. http://dx.doi.org/10.1186/ s12885-018-5076-0
  • • Metzke, B., Hug, M. J., Fink, G., Hieke, S., Jung, M., & Engelhardt, M. (2012). Drug-drug interactions in the hematology and oncology department: a real-life assessment of frequency and severity. Blood, 120(21), 4250–4250. Retrieved from https://www.researchgate. net/publication
  • • Myers, A. L., Kawedia, J. D., Champlin, R. E., Kramer, M. A., Nieto, Y., Ghose, R., & Andersson, B. S. (2017). Clarifying busulfan metabolism and drug interactions to support new therapeutic drug monitoring strategies: a comprehensive review. Expert Opinion on Drug Metabolism& Toxicology, 13(9), 901–923. https://doi.org/ 10. 1080/17425255.2017.1360277
  • • Prot-Labarthe, S., Therrien, R., Demanche, C., Larocque, D., & Bussieres, J. F. (2008). Pharmaceutical care in an inpatient pediatric hematopoietic stem cell transplant service. Journal of Oncology Pharmacy Practice, 14(3), 147–152. https://doi. org/ 10.1177/1078155208093929
  • • Rodrigues, A. T., Stahlschmidt, R., Granja, S., Pilger, D., Falcao, A. L. E., & Mazzola, P. G. (2017). Prevalence of potential drug-drug interactions in the intensive care unit of a Brazilian teaching hospital. Brazilian Journal of Pharmaceutical Science, 53(1), e16109- e16117. https://doi.org/10.1590/s2175-97902017000116109
  • • Sadaba, B., Lopez-de-Ocariz, A., Azanza, J. R., Quiroga, J., & Cienfuegos, J. A. (1998). Concurrent clarithromycin and cyclosporin A treatment. Journal of Antimicrobial Chemotherapy, 42(3), 393–395.
  • • Sanchez, L., Bacle, A., Lamy, T., & Le-Corre, P. (2019) Potential drugdrug interactions and nephrotoxicity in hematopoietic stem cell transplant adult recipients during bone marrow transplantation unit stay. Cancer Chemotherapy and Pharmacology, 83(5), 827– 835. https://doi.org/10.1007/s00280-019-03791-9.
  • • Tavousi, F., Sadeghi, A., Darakhshandeh, A., & Moghaddas, A. (2019). Potential drug-drug interactions at a referral pediatric oncology ward in Iran: A cross-sectional study. Journal of Pediatric Hematology Oncology, 41(3), e146–e151. https://doi.org/10.1097/ MPH.0000000000001346
  • • Trevisan, D. D., Silva, J. B., Oliveira, H. C., Secoli, S. R., & Lima, M. H. (2015). Prevalence and clinical significance of potential drugdrug interaction in hematopoietic stem cell transplantation. Cancer Chemotherapy and Pharmacology, 75(2), 393–400. https://doi. org/10.1007/s00280-014-2657-8
  • • Valenzuela, R., Torres, J. P., Salas, C., Gajardo, I., Palma, J., Catalan, P. … Morales, J. (2017). Drug interaction of voriconazole-cyclosporine in children undergoing hematopoietic stem cell transplantation (2013-2014). Revista Chilena de Infectologia, 34(1), 14–18. https://doi.org/ 10.4067/s0716-10182017000100002
  • • Zeighami, S., Hadjibabaie, M., Ashouri, A., Sarayani, A., Khoee, S. H., Mousavi, S. … Ghavamzadeh, A. (2014). Assessment of cyclosporine serum concentrations on the incidence of acute graft versus host disease post hematopoietic stem cell transplantation. Iranian Journal of Pharmaceutical Research, 13(1), 305–312.