Abstract
Patients undergoing hematopoietic stem cell transplantation (HSCT) are at risk of developing potential drug–drug interactions (PDDIs). The aim of this study was to assess the prevalence of PDDIs that occur in HSCT patients on the day of hematopoietic stem cell infusion. We performed a cross-sectional study based on the evaluation of prescriptions to HSCT patients on the day of infusion (day 0). The PDDIs were analyzed using the DRUG-REAX® system and classified according to the severity level, available scientific evidence, time of onset, and potential clinical impact. Forty patients undergoing HSCT were included in this study; 33 patients (82.5 %) were exposed to at least one major and one contraindicated PDDI in a concomitant manner. All patients exposed to PDDIs had an increased risk of cardiotoxicity. Most cases of PDDIs were classified as being of major severity (80.9 %), with time of onset not specified (61.9 %), and with good or excellent scientific evidence (52.4 %). HSCT patients have a high prevalence of clinically significant PDDIs. The management of PDDIs requires an approach that includes biochemical tests, installation of cardiac monitors, periodic electrocardiograms, implementation of electronic prescriptions with a PDDI alert system, and availability of the PDDI databases.
Similar content being viewed by others
References
Guastaldi RBF, Secoli SR (2011) Drug interactions of anti-microbial agents used in hematopoietic stem cell transplantation. Rev Lat Am Enfermagem 19:960–967
Glotzbecker B, Duncan C, Alyea E, Campbell B, Soiffer R (2012) Important drug interactions in hematopoietic stem cell transplantation: what every physician should know. Biol Blood Marrow Transplant 18:989–1006
Guastaldi RBF, Reis AMM, Figueras A, Secoli SR (2011) Prevalence of potential drug–drug interactions in bone marrow transplant patients. Int J Clin Pharm 33:1002–1009
Antin JH, Raley DY (2013) Manual of stem cell and bone marrow transplantation. Cambrigde University Press, New York
Riechelmann RP, Tannock IF, Wang L, Saad ED, Taback NA, Krzyzanowska MK (2007) Potential drug interactions and duplicate prescriptions among cancer patients. J Natl Cancer Inst 99:592–600
Beijnen JH, Schellens JH (2004) Drug interactions in oncology. Lancet Oncol 5:489–496
Tatro DS (2011) Drug interactions facts. Wolters Kluwer Health/Facts & Comparisons, St Louis
Bachmann KA (2003) Drug interactions handbook. Lexi-Comp, Hudson
van Leeuwen RWF, Brundel DHS, Neef C et al (2013) Prevalence of potential drug–drug interactions in cancer patients treated with oral anticancer drugs. Br J Cancer 108:1071–1078
Lu C, Liao M, Cohen L, Xia CQ (2010) Emerging in vitro tools to evaluate cytochrome P450 and transporter-mediated drug–drug interactions. Curr Drug Discov Technol 7:199–222
Buajordet I, Ebbesen J, Erikssen J, Brørs O, Hilberg T (2001) Fatal adverse drug events: the paradox of drug treatment. J Intern Med 250:327–341
Gholaminezhad S, Hadjibabaie M, Gholami K et al (2014) Pattern and associated factors of potential drug–drug interactions in both pre- and early post-hematopoietic stem cell transplantation stages at a referral center in the middle east. Ann Hematol 93:1913–1922
Egger SS, Meier S, Leu C et al (2010) Drug interactions and adverse events associated with antimycotic drugs used for invasive aspergillosis in hematopoietic SCT. Bone Marrow Transplant 45:1197–1203
Jaklič A, Collins CJ, Mrhar A et al (2013) High prevalence of potential drug interactions affecting mycophenolic acid pharmacokinetics in nonmyeloablative hematopoietic stem cell transplant recipients. Int J Clin Pharmacol Ther 51:711–717
Micromedex Healthcare Series. http://www.micromedexsolutions.com. Accessed 5 Jan 2014
World Health Organization. Collaborating Center for Drug Statistics Methodology. ATC/DDD Index (2012). http://www.whocc.no/atcddd/index. Accessed 16 Nov 2013
Lexi-interact. http://webstore.lexi.com/Lexi-Interact. Accessed 29 Nov 2014
Drugs.com. http://www.drugs.com/drug_interactions.html. Accessed 30 Nov 2014
CredibleMeds. http://reference.medscape.com/drug-interactionchecker. Accessed 30 Nov 2014
Ruping MJ, Vehreschild JJ, Cornely OA (2008) Patients at high risk of invasive fungal infections: when and how to treat. Drugs 68:1941–1962
Singh N, Paterson DL (2005) Aspergillus infections in transplant recipients. Clin Microbiol Rev 18:44–69
McCoy D, Depestel DD, Carver PL (2009) Primary antifungal prophylaxis in adult hematopoietic stem cell transplant recipients: current therapeutic concepts. Pharmacotherapy 29:1306–1325
Nivoix Y, Ubeaud-Sequier G, Engel P, Leveˆque D, Herbrecht R (2009) Drug–drug interactions of triazole antifungal agents in multimorbid patients and implications for patient care. Curr Drug Metab 10:395–409
Bow EJ (2011) Fluoroquinolones, antimicrobial resistance and neutropenic cancer patients. Curr Opin Infect Dis 24:545–553
Lopes LA, Veroneze I, Burgardt CI, Niebel Stier CJ (2014) Prophylaxis with levofloxacin: impact on bacterial susceptibility and epidemiology in a hematopoietic stem cell transplant unit. Rev Bras Hematol Hemoter 36:35–42
Hadjibabaie M, Badri S, Ataei S et al (2013) Potential drug–drug interactions at a referral hematology–oncology ward in Iran: a cross-sectional study. Cancer Chemother Pharmacol 71:1619–1627
U.S. Department of Health and Human Services Food and Drug Administration (FDA) (2011). FDA drug safety communication: abnormal heart rhythms may be associated with use of Zofran (ondansetron). http://www.fda.gov/Drugs/DrugSafety/ucm271913.htm. Accessed 27 Nov 2014
Freedman SB, Uleryk E, Rumantir M, Finkelstein Y (2014) Ondansetron and the risk of cardiac arrhythmias: a systematic review and postmarketing analysis. Ann Emerg Med 64:19–25
Koeller JM, Aapro MS, Gralla RJ et al (2002) Antiemetic guidelines: creating a more practical treatment approach. Support Care Cancer 10:519–522
Robinson RF, Nahata MC, Olshefski RS (2000) Syncope associated with concurrent amitriptyline and fluconazole therapy. Ann Pharmacother 34:1406–1409
Blower PR (2002) 5-HT3-receptor antagonists and the cytochrome P450 system: clinical implications. Cancer J 8:405–414
de Bruijn KM (1992) Tropisetron. A review of the clinical experience. Drugs 43:11–22
Neuvonen PJ, Kantola T, Kivistö KT (1998) Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole. Clin Pharmacol Ther 63:332–341
Hazin R, Abuzetun JY, Suker M, Porter J (2008) Rhabdomyolysis induced by simvastatin–fluconazole combination. J Natl Med Assoc 100:444–446
Shaukat A, Benekli M, Vladutiu GD, Slack JL, Wetzler M, Baer MR (2003) Simvastatin–fluconazole causing rhabdomyolysis. Ann Pharmacother 37:1032–1035
Jamal SM, Eisenberg MJ, Christopoulos S (2004) Rhabdomyolysis associated with hydroxymethylglutaryl-coenzyme a reductase inhibitors. Am Heart J 147:956–965
Kashani A, Phillips CO, Foody JM et al (2006) Risks associated with statin therapy: a systematic overview of randomized clinical trials. Circulation 114:2788–2797
Chatzizisis YS, Koskinas KC, Misirli G, Vaklavas C, Hatzitolios A, Giannoglou GD (2010) Risk factors and drug interactions predisposing to statin-induced myopathy: implications for risk assessment, prevention and treatment. Drug Saf 33:171–187
Scripture CD, Sparreboom A, Figg WD (2005) Modulation of cytochrome P450 activity: implications for cancer therapy. Lancet Oncol 6:780–789
Evans WE, McLeod HL (2003) Pharmacogenomics-drug disposition, drug targets, and side effects. N Engl J Med 348:538–549
Scripture CD, Figg WD (2006) Drug interactions in cancer therapy. Nat Rev Cancer 6:546–558
Peterson JF, Kuperman GJ, Shek C, Bates DW (2001) Physician responses to life-threatening drug–drug interaction alerts. J Gen Intern Med 16(Suppl 1):212
Abookire SA, Teich JM, Sandige H, et al (2000) Improving allergy alerting in a computerized physician order entry system. In: Proceedings of the AMIA symposium, 2–6
Paterno MD, Maviglia SM, Gorman PN et al (2009) Tiering drug–drug interaction alerts by severity increases compliance rates. J Am Med Inform Assoc 16:40–46
Acknowledgments
This work was supported by grants from CNPq.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Trevisan, D.D., Silva, J.B., Oliveira, H.C. et al. Prevalence and clinical significance of potential drug–drug interaction in hematopoietic stem cell transplantation. Cancer Chemother Pharmacol 75, 393–400 (2015). https://doi.org/10.1007/s00280-014-2657-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00280-014-2657-8