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Cancer Chemotherapy and Pharmacology

, Volume 83, Issue 5, pp 827–835 | Cite as

Potential drug–drug interactions and nephrotoxicity in hematopoietic stem cell transplant adult recipients during bone marrow transplantation unit stay

  • Lydia Sanchez
  • Astrid Bacle
  • Thierry Lamy
  • Pascal Le CorreEmail author
Original Article
  • 162 Downloads

Abstract

Purpose

Studies have documented potential drug–drug interactions (pDDIs) occurring in cancer patients mainly with solid malignancies, either in the ambulatory or hospital settings. While hematopoietic stem cell transplant (HSCT) patients during their bone marrow transplantation unit (BMTU) stay have rather complex medical regimens combining chemotherapy, anti-infectious agents, immunosuppressive agents, and supportive-care drugs, studies on potential DDIs are lacking. Our objective was to evaluate the prevalence and the density of pharmacokinetic and pharmacodynamic potential DDIs, and the evolution of the renal function in hematopoietic stem cell transplant (HSCT) adult recipients during their BMTU stay.

Methods

Retrospective study in 31 adult patients consecutively admitted to the BMTU.

Results

Prevalence of pharmacokinetic interactions was ten times lower than the pharmacodynamic interactions. The contraindications were rare, and only of pharmacokinetic origin. The main drugs involved in pharmacokinetic DDIs were ciclosporine, methotrexate, esomeprazole, tramadol, and vincristine. The median number of potential nephrotoxicity-related DDIs per patient was 7 and the median number of days during which nephrotoxicity-related DDIs potentially occurred was 77 days per patient. The decrease in glomerular filtration rate (GFR) throughout the BMTU stay (mean decrease of 13 ml/min) was correlated with the number of days of potential nephrotoxic drug interactions.

Conclusions

Potential DDIs in HCST patients in BMTU were quite common. The DDIs from pharmacokinetic origin were less frequent, but of higher grade, than those of pharmacodynamic origin. The decrease in GFR suggests that the density of potential nephrotoxic drug interactions may be an issue to be considered in these patients.

Keywords

Pharmacokinetic Pharmacodynamic Drug–drug interactions Hematopoietic stem cell transplant Bone marrow transplantation unit stay Nephrotoxicity 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Institutional Ethical committee of our institution with a waiver of patient consent authorization (No. 18.76). Since the design of the study is retrospective, no formal consent is required.

References

  1. 1.
    Leather HL (2004) Drug interactions in the hematopoietic stem cell transplant (HSCT) recipient: what every transplanter needs to know. Bone Marrow Transpl 33:137–152CrossRefGoogle Scholar
  2. 2.
    Glotzbecker B, Duncan C, Alyea E 3rd, Campbell B, Soiffer R (2012) Important drug interactions in hematopoietic stem cell transplantation: what every physician should know. Biol Blood Marrow Transpl 18:989–1006CrossRefGoogle Scholar
  3. 3.
    Gay C, Toulet D, Le Corre P (2017) Pharmacokinetic drug-drug interactions of tyrosine kinase inhibitors: A focus on cytochrome P450, transporters, and acid suppression therapy. Hematol Oncol 35:259–280CrossRefPubMedGoogle Scholar
  4. 4.
    Morival C, Oumari S, Lenglet A, Le Corre P (2017) Clinical pharmacokinetics of oral drugs in the treatment of multiple myeloma. Hematol Oncol.  https://doi.org/10.1002/hon.2485 CrossRefPubMedGoogle Scholar
  5. 5.
    Riechelmann RP, Saad ED (2006) A systematic review on drug interactions in oncology. Cancer Invest 24:704–712CrossRefPubMedGoogle Scholar
  6. 6.
    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 99:592–600CrossRefPubMedGoogle Scholar
  7. 7.
    Riechelmann RP, Zimmermann C, Chin SN, Wang L, O’Carroll A, Zarinehbaf S, Krzyzanowska MK (2008) Potential drug interactions in cancer patients receiving supportive care exclusively. J Pain Symptom Manage 35:535–543CrossRefPubMedGoogle Scholar
  8. 8.
    Riechelmann RP, Del Giglio A (2009) Drug interactions in oncology: how common are they? Ann Oncol 20:1907–1912CrossRefPubMedGoogle Scholar
  9. 9.
    Kannan G, Anitha R, Rani VN, Thennarasu P, Alosh J, Vasantha J, Martin JR, Uma MR (2011) A study of drug-drug interactions in cancer patients of a south Indian tertiary care teaching hospital. J Postgrad Med 57:206–210CrossRefPubMedGoogle Scholar
  10. 10.
    Miranda V, Fede A, Nobuo M, Ayres V, Giglio A (2011) Adverse drug reactions and drug interactions as causes of hospital admission in oncology. J Pain Symptom Manage 42:342–353CrossRefPubMedGoogle Scholar
  11. 11.
    Riechelmann RP, Moreira F, Smaletz O, Saad ED (2005) Potential for drug interactions in hospitalized cancer patients. Cancer Chemother Pharmacol 56:286–290CrossRefPubMedGoogle Scholar
  12. 12.
    Fernández de Espinosa M, Díaz Carrasco MS, Alonso Romero JL, de la Rubia Nieto A, Espuny Miró A (2015) Potential drug-drug interactions in oncological adult inpatients at a Spanish hospital: epidemiology and risk factors. Int J Clin Pharm 37:1021–1027CrossRefGoogle Scholar
  13. 13.
    Vecchia S, Orlandi E, Confalonieri C, Damonti E, Riva A, Sartori A, Cavanna L (2017) Prevalence study on potential drug-drug interaction in cancer patients in Piacenza hospital’s Onco-Haematology department. J Oncol Pharm Pract.  https://doi.org/10.1177/1078155217717324 CrossRefPubMedGoogle Scholar
  14. 14.
    Guastaldi RB, Reis AM, Figueras A, Secoli SR (2011) Prevalence of potential drug–drug interactions in bone marrow transplant patients. Int J Clin Pharm 33:1002–1009CrossRefPubMedGoogle Scholar
  15. 15.
    Hadjibabaie M, Badri S, Ataei S, Moslehi AH, Karimzadeh I, Ghavamzadeh A (2013) Potential drug-drug interactions at a referral hematology–oncology ward in Iran: a cross-sectional study. Cancer Chemother Pharmacol 71:1619–1627CrossRefPubMedGoogle Scholar
  16. 16.
    Gholaminezhad S, Hadjibabaie M, Gholami K, Javadi MR, Radfar M, Karimzadeh I, Ghavamzadeh A (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 93:1913–1922CrossRefPubMedGoogle Scholar
  17. 17.
    Schaefer L, Keinki C, Baron von Osthoff M, Huebner J (2018) Potential interactions of medication prescribed in discharge letters from a clinic for hematology and oncology. Oncol Res Treat 41:200–205.  https://doi.org/10.1159/000486161 CrossRefPubMedGoogle Scholar
  18. 18.
    Trevisan DD, Silva JB, Oliveira HC, Secoli SR, Lima MH (2015) Prevalence and clinical significance of potential drug–drug interaction in hematopoietic stem cell transplantation. Cancer Chemother Pharmacol 75:393–400CrossRefPubMedGoogle Scholar
  19. 19.
    Arnaout K, Patel N, Jain M, El-Amm J, Amro F, Tabbara IA (2014) Complications of allogeneic hematopoietic stem cell transplantation. Cancer Invest 32:349–362CrossRefPubMedGoogle Scholar
  20. 20.
    Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN et al (2015) Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med 41:1411CrossRefGoogle Scholar
  21. 21.
    Hingorani S, Pao E, Stevenson P, Schoch G, Laskin BL, Gooley T, McDonald GB (2018) Changes in glomerular filtration rate and impact on long-term survival among adults after hematopoietic cell transplantation: a prospective cohort study. Clin J Am Soc NephrolGoogle Scholar
  22. 22.
    Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Clinical Practice Guidelines For Chronic Kidney Disease: Evaluation, Classification and Stratification. National Kidney Foundation, Kidney Disease Outcomes Quality Initiative (2002)Google Scholar
  24. 24.
    Farzanegan B, Alehashem M, Bastani M, Baniasadi S (2015) Potential drug-drug interactions in cardiothoracic intensive care unit of a pulmonary teaching hospital. J Clin Pharmacol 55:132–136CrossRefPubMedGoogle Scholar
  25. 25.
    Uijtendaal EV, van Harssel LL, Hugenholtz GW, Kuck EM, Zwart-van Rijkom JE, Cremer OL, Egberts TC (2014) Analysis of potential drug-drug interactions in medical intensive care unit patients. Pharmacotherapy 34:213–219CrossRefPubMedGoogle Scholar
  26. 26.
    Vanham D, Spinewine A, Hantson P, Wittebole X, Wouters D, Sneyers B (2017) Drug-drug interactions in the intensive care unit: do they really matter? J Crit Care 38:97–103CrossRefPubMedGoogle Scholar
  27. 27.
    Ando M, Ohashi K, Akiyama H, Sakamaki H, Morito T, Tsuchiya K, Nitta K (2010) Chronic kidney disease in long-term survivors of myeloablative allogeneic haematopoietic cell transplantation: prevalence and risk factors. Nephrol Dial Transpl 25:278–282CrossRefGoogle Scholar
  28. 28.
    Kogon A, Hingorani S (2010) Acute kidney injury in hematopoietic cell transplantation. Semin Nephrol 30:615–626CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Binnenmars SH, Hijmans RS, Navis G, de Borst MH (2017) Biomarkers of renal function: towards clinical actionability. Clin Pharmacol Ther 102:481–492CrossRefPubMedGoogle Scholar
  30. 30.
    Rewa O, Bagshaw SM (2014) Acute kidney injury-epidemiology, outcomes and economics. Nat Rev Nephrol 10:193–207CrossRefGoogle Scholar
  31. 31.
    Awdishu L, Mehta RL (2017) The 6R’s of drug induced nephrotoxicity. BMC Nephrol 18:124.  https://doi.org/10.1186/s12882-017-0536-3 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    US Food and Drug Administration. Drug development and drug interactions: table of substrates, inhibitors and inducers. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm#4. Accessed 30 may 2018

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Pôle Pharmacie, Service Hospitalo-Universitaire de PharmacieCHU de RennesRennesFrance
  2. 2.Pharmacia Del Carre LópezBilbaoSpain
  3. 3.Pôle Médecines Spécialisées, Service d’Hématologie CliniqueCHU de RennesRennesFrance
  4. 4.Univ Rennes 1, INSERM, EFS Bretagne, UMR U1236RennesFrance
  5. 5.Laboratoire de Biopharmacie et Pharmacie Clinique, Faculté de PharmacieUniversité de Rennes 1Rennes CedexFrance
  6. 6.Univ Rennes, CHU Rennes, Inserm, EHESP, Irset-UMR_S 1085RennesFrance

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