Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

The aim of this study was to determine the pattern as well as associated factors of moderate and major potential drug-drug interactions (PDDIs) in both the pre- and early post-transplantation stages at a referral hematopoietic stem cell transplantation (HSCT) center. All adolescents and adults undergone HSCT within a 3-year period were screened retrospectively for potential moderate or severe PDDIs by the Lexi-Interact On-Desktop software. Among 384 patients, a total of 13,600 PDDIs were detected. The median (interquartile range) cumulative PDDIs burden was 41 (28). All (100 %) individuals experienced at least one PDDI. More than four fifths (81.8 %) of detected PDDIs were moderate. The predominant mechanism of PDDIs was pharmacokinetics (54.3 %). Interaction between sulfamethoxazole-trimethoprim and fluconazole was the most common PDDIs involving 95.3 % of the study population. More than three fifths (61.5 %) of detected PDDIs were caused by HSCT-related medications. No interaction was identified between two anticancer agents. Interactions of cyclophosphamide with phenytoin, busulfan with metronidazole, dexamethasone, or clarithromycin were the only detected PDDI between anticancer and non-anticancer medications. Type of HSCT and the numbers of administered medications were significantly associated with major PDDIs. The epidemiology, real clinical consequence, and economic burden of DDIs on patients undergone HSCT particularly around the transplantation period should be assessed further by prospective, multicenter studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Fuhr U (2008) Improvement in the handling of drug-drug interactions. Eur J Clin Pharmacol 64:167–171

    Article  PubMed  Google Scholar 

  2. Riechelmann RP, Del Giglio A (2009) Drug interactions in oncology: how common are they? Ann Oncol 20:1907–1912

    Article  PubMed  CAS  Google Scholar 

  3. Köhler GI, Bode-Böger SM, Busse R, Hoopmann M, Welte T, Böger RH (2000) Drug-drug interactions in medical patients: effects of in-hospital treatment and relation to multiple drug use. Int J Clin Pharmacol Ther 38:504–513

    Article  PubMed  Google Scholar 

  4. Copelan EA (2006) Hematopoietic stem-cell transplantation. N Engl J Med 354:1813–1826

    Article  PubMed  CAS  Google Scholar 

  5. Appelbaum FR (2007) Hematopoietic-cell transplantation at 50. N Engl J Med 357:1472–1475

    Article  PubMed  CAS  Google Scholar 

  6. Gratwohl A, Baldomero H, Aljurf M, Pasquini MC, Bouzas LF, Yoshimi A et al (2010) Hematopoietic stem cell transplantation: a global perspective. JAMA 303:1617–1624

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. Ghavamzadeh A, Alimoghaddam K, Ghaffari F, Derakhshandeh R, Jalali A, Jahani M (2013) Twenty years of experience on stem cell transplantation in Iran. Iran Red Crescent Med J 15:93–100

    Article  PubMed  PubMed Central  Google Scholar 

  8. Guastaldi RB, Reis AM, Figueras A, Secoli SR (2011) Prevalence of potential drug-drug interactions in bone marrow transplant patients. Int J Clin Pharm 33:1002–1009

    Article  PubMed  CAS  Google Scholar 

  9. Jaklič A, Collins CJ, Mrhar A, Sorror ML, Sandmaier BM, Bemer MJ, Locatelli I, McCune JS (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

    PubMed  PubMed Central  Google Scholar 

  10. Barrons R (2004) Evaluation of personal digital assistant software for drug interactions. Am J Health Syst Pharm 61:380–385

    PubMed  Google Scholar 

  11. Vonbach P, Dubied A, Krähenbühl S, Beer JH (2008) Evaluation of frequently used drug interaction screening programs. Pharm World Sci 30:367–374

    Article  PubMed  Google Scholar 

  12. Reis AM, Cassiani SH (2010) Evaluation of three brands of drug interaction software for use in intensive care units. Pharm World Sci 32:822–828

    Article  PubMed  CAS  Google Scholar 

  13. 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

    Article  PubMed  Google Scholar 

  14. World Health Organization. Collaborating Center for Drug Statistics Methodology. ATC/DDD Index 2013. http://www.whocc.no/atc_ddd_index/. Accessed 17 October 2013

  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 71:1619–1627

    Article  PubMed  CAS  Google Scholar 

  16. 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 57:206–210

    Article  PubMed  CAS  Google Scholar 

  17. de Jonge ME, Huitema AD, van Dam SM, Beijnen JH, Rodenhuis S (2005) Significant induction of cyclophosphamide and thiotepa metabolism by phenytoin. Cancer Chemother Pharmacol 55:507–510

    Article  PubMed  Google Scholar 

  18. Choi SW, Levine JE, Ferrara JL (2010) Pathogenesis and management of graft-versus-host disease. Immunol Allergy Clin North Am 30:75–101

    Article  PubMed  PubMed Central  Google Scholar 

  19. Guastaldi RB, Secoli SR (2011) Drug interactions of anti-microbial agents used in hematopoietic stem cell transplantation. Rev Lat Am Enfermagem 19:960–967

    Article  PubMed  Google Scholar 

  20. Cronin S, Chandrasekar PH (2010) Safety of triazole antifungal drugs in patients with cancer. J Antimicrob Chemother 65:410–416

    Article  PubMed  CAS  Google Scholar 

  21. van der Ven AJ, Schoondermark-van de Ven EM, Camps W, Melchers WJ, Koopmans PP, van der Meer JW, Galama JM (1996) Anti-toxoplasma effect of pyrimethamine, trimethoprim and sulphonamides alone and in combination: implications for therapy. J Antimicrob Chemother 38:75–80

    Article  PubMed  Google Scholar 

  22. Kowalsky SF, Dixon DM (1991) Fluconazole: a new antifungal agent. Clin Pharm 10:179–194

    PubMed  CAS  Google Scholar 

  23. Schmidt H, Naumann R, Jaschonek K, Einsele H, Dopfer R, Ehninger G (1989) Drug interaction between cyclosporin and phenytoin in allogeneic bone marrow transplantation. Bone Marrow Transplant 4:212–213

    PubMed  CAS  Google Scholar 

  24. Keown PA, Laupacis A, Carruthers G, Stawecki M, Koegler J, McKenzie FN, Wall W, Stiller CR (1984) Interaction between phenytoin and cyclosporine following organ transplantation. Transplantation 38:304–306

    PubMed  CAS  Google Scholar 

  25. Freeman DJ, Laupacis A, Keown PA, Stiller CR, Carruthers SG (1984) Evaluation of cyclosporin-phenytoin interaction with observations on cyclosporin metabolites. Br J Clin Pharmacol 18:887–893

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  26. Thompson PA, Mosley CA (1996) Tacrolimus-phenytoin interaction. Ann Pharmacother 30:544

    PubMed  CAS  Google Scholar 

  27. Green KGE, Rogosheske JR (2012) Hematopoietic cell transplantation. In: Alldredge BK, Corelli RL, Ernst ME, Guglielmo BJ, Jacobson PA, Kradjan WA, Williams BR (eds) Koda-Kimble and Young’s applied therapeutics: The clinical use of drugs. Lippincott Williams & Wilkins, Philadelphia, p 2248

    Google Scholar 

  28. Boddy AV, Yule SM (2000) Metabolism and pharmacokinetics of oxazaphosphorines. Clin Pharmacokinet 38:291–304

    Article  PubMed  CAS  Google Scholar 

  29. Slattery JT, Kalhorn TF, McDonald GB, Lambert K, Buckner CD, Bensinger WI, Anasetti C, Appelbaum FR (1996) Conditioning regimen-dependent disposition of cyclophosphamide and hydroxycyclophosphamide in human marrow transplantation patients. J Clin Oncol 14:1484–1494

    PubMed  CAS  Google Scholar 

  30. McCune JS, Batchelder A, Deeg HJ, Gooley T, Cole S, Phillips B, Schoch HG, McDonald GB (2007) Cyclophosphamide following targeted oral busulfan as conditioning for hematopoietic cell transplantation: pharmacokinetics, liver toxicity, and mortality. Biol Blood Marrow Transplant 13:853–862

    Article  PubMed  CAS  Google Scholar 

  31. Eberly AL, Anderson GD, Bubalo JS, McCune JS (2008) Optimal prevention of seizures induced by high-dose busulfan. Pharmacotherapy 28:1502–1510

    Article  PubMed  CAS  Google Scholar 

  32. Krivoy N, Hoffer E, Lurie Y, Bentur Y, Rowe JM (2008) Busulfan use in hematopoietic stem cell transplantation: pharmacology, dose adjustment, safety and efficacy in adults and children. Curr Drug Saf 3:60–66

    Article  PubMed  CAS  Google Scholar 

  33. McCune JS, Holmberg LA (2009) Busulfan in hematopoietic stem cell transplant setting. Expert Opin Drug Metab Toxicol 5:957–969

    Article  PubMed  CAS  Google Scholar 

  34. Kebriaei P, Basset R, Ledesma C, Ciurea S, Parmar S, Shpall EJ, Hosing C, Khouri I, Qazilbash M, Popat U, Alousi A, Nieto Y, Jones RB, de Lima M, Champlin RE, Andersson BS (2012) Clofarabine combined with busulfan provides excellent disease control in adult patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 18:1819–1826

    Article  PubMed  CAS  Google Scholar 

  35. Nilsson C, Aschan J, Hentschke P, Ringdén O, Ljungman P, Hassan M (2003) The effect of metronidazole on busulfan pharmacokinetics in patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant 31:429–435

    Article  PubMed  CAS  Google Scholar 

  36. Gulbis AM, Culotta KS, Jones RB, Andersson BS (2011) Busulfan and metronidazole: an often forgotten but significant drug interaction. Ann Pharmacother 45:e39

    Article  PubMed  Google Scholar 

  37. Levy RH (1995) Cytochrome P450isozymes and antiepileptic drug interactions. Epilepsia 36:S8–S13

    Article  PubMed  Google Scholar 

  38. Larsson P, Cybulski W, Tjalve H (1997) Binding of 3H-metronidazole in olfactory, respiratory and alimentary epithelia in rats. Pharmacol Toxicol 81:65–73

    Article  PubMed  CAS  Google Scholar 

  39. Gibbs JP, Yang JS, Slattery JT (1998) Comparison of human liver and small intestinal glutathione S-transferase-catalyzed busulfan conjugation in vitro. Drug Metab Dispos 26:52–55

    PubMed  CAS  Google Scholar 

  40. 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 Transplant 18:989–1006

    Article  PubMed  CAS  Google Scholar 

  41. 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

    Article  PubMed  CAS  Google Scholar 

  42. Egger SS, Meier S, Leu C, Christen S, Gratwohl A, Krähenbühl S, Haschke M (2010) Drug interactions and adverse events associated with antimycotic drugs used for invasive aspergillosis in hematopoietic SCT. Bone Marrow Transplant 45:1197–1203

    Article  PubMed  CAS  Google Scholar 

  43. Miranda V, Fede A, Nobuo M, Ayres V, Giglio A, Miranda M, Riechelmann RP (2011) Adverse drug reactions and drug interactions as causes of hospital admission in oncology. J Pain Symptom Manag 42:342–353

    Article  Google Scholar 

  44. Nagamura F, Takahashi T, Takeuchi M, Iseki T, Ooi J, Tomonari A, Uchimaru K, Takahashi S, Tojo A, Tani K, Asano S (2003) Effect of cyclophosphamide on serum cyclosporine levels at the conditioning of hematopoietic stem cell transplantation. Bone Marrow Transplant 32:1051–1058

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank all the staff of the adult HSCT wards at the Hematology-Oncology and Stem Cell Transplantation Research Center of the Dr Shariati Hospital for their kind cooperation.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Safoora Gholaminezhad

  2. Research Center for Rational Use of Drugs and Faculty of Pharmacy, Tehran University of Medical Sciences, 4th Floor, No. 92, Karimkhan Zand Avenue, Hafte Tir Square, Tehran, 1584775311, Iran

    Molouk Hadjibabaie, Kheirollah Gholami, Mohammad Reza Javadi, Mania Radfar & Iman Karimzadeh

  3. Hematology-Oncology and Stem Cell Transplantation Research Center, Department of Hematology-Oncology, Dr Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Ardeshir Ghavamzadeh

Authors
  1. Safoora Gholaminezhad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Molouk Hadjibabaie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kheirollah Gholami
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mohammad Reza Javadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mania Radfar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Iman Karimzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ardeshir Ghavamzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Iman Karimzadeh.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gholaminezhad, S., Hadjibabaie, M., Gholami, K. et al. 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 (2014). https://doi.org/10.1007/s00277-014-2122-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-014-2122-0

Keywords

Search

Navigation