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Cited by 164Antifungal resistance and susceptibilityCancer Treatment and PharmacologyPharmacogenetics and Drug Metabolism

Adverse interactions between antifungal azoles and vincristine: review and analysis of cases

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Moriyama, Brad, Henning, Stacey A., Leung, Janice, Falade‐Nwulia, Oluwaseun, Jarosinski, Paul, Penzak, Scott R., Walsh, Thomas J.·2012·Mycoses
DOI 10.1111/j.1439-0507.2011.02158.xPMC PMC3345292
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Abstract

Summary: Triazole and imidazole antifungal agents inhibit metabolism of vincristine, leading to excess vinca alkaloid exposure and severe neurotoxicity. Recent reports of debilitating interactions between vincristine and itraconazole, as well as posaconazole, voriconazole and ketoconazole underscore the need to improve medical awareness of this adverse combination. We, therefore, undertook a comprehensive analysis of reports of adverse drug interactions (ADIs) with the combination of vincristine and azole antifungal agents, established a new classification, and provided a detailed summary of these toxicities. In patients who had sufficient data for analysis, 47 individuals were identified who had an ADI with the combination of vincristine and antifungal azoles. Median age was 8 years (1.3–68 years) with 33(70%) having a diagnosis of acute lymphoblastic leukaemia. Median time to ADI with vincristine was 9.5 days with itraconazole, 13.5 days posaconazole and 30 days voriconazole. The median number of vincristine doses preceding the ADI was 2 doses with itraconazole, 3 doses posaconazole and 2 doses voriconazole. The most common severe ADIs included gastrointestinal toxicity, peripheral neuropathy, hyponatremia/SIADH, autonomic neuropathy and seizures. Recovery from these ADIs occurred in 80.6% of patients. We recommend using alternative antifungal agents if possible in patients receiving vincristine to avoid this serious and potentially life‐threatening drug interaction.

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  1. [1]Chan JD Pharmacokinetic drug interactions of vinca alkaloids: summary of case reports Pharmacotherapy 1998 18 1304 1307 9855331
  2. [2]Moore A Pinkerton R Vincristine: Can its therapeutic index be enhanced? Pediatr Blood Cancer 2009 53 1180 1187 19588521
  3. [3]Murphy JA Ross LM Gibson BE Vincristine toxicity in five children with acute lymphoblastic leukaemia Lancet 1995 346 443 7623589
  4. [4]Sathiapalan RK Al-Nasser A El-Solh H Al-Mohsen I Al-Jumaah S Vincristine-itraconazole interaction: cause for increasing concern J Pediatr Hematol Oncol 2002 24 591 12368705
  5. [5]Ariffin H Omar KZ Ang EL Shekhar K Severe vincristine neurotoxicity with concomitant use of itraconazole J Paediatr Child Health 2003 39 638 639 14629538
  6. [7]Bermudez M Fuster JL Llinares E Galera A Gonzalez C Itraconazole-related increased vincristine neurotoxicity: case report and review of literature J Pediatr Hematol Oncol 2005 27 389 392 16012330
  7. [8]Takahashi N Kameoka Y Yamanaka Y Itraconazole oral solution enhanced vincristine neurotoxicity in five patients with malignant lymphoma Intern Med 2008 47 651 653 18379154
  8. [9]Porter CC Carver AE Albano EA Vincristine induced peripheral neuropathy potentiated by voriconazole in a patient with previously undiagnosed CMT1X Pediatr Blood Cancer 2009 52 298 300 18837430
  9. [10]Mantadakis E Amoiridis G Kondi A Kalmanti M Possible increase of the neurotoxicity of vincristine by the concurrent use of posaconazole in a young adult with leukemia J Pediatr Hematol Oncol 2007 29 130 17279013
  10. [11]Eiden C Palenzuela G Hillaire-Buys D Posaconazole-increased vincristine neurotoxicity in a child: a case report J Pediatr Hematol Oncol 2009 31 292 295 19346885
  11. [12]Jain S Kapoor G Severe life threatening neurotoxicity in a child with acute lymphoblastic leukemia receiving posaconazole and vincristine Pediatr Blood Cancer 2010 54 783 20205256
  12. [13]Gomber S Dewan P Chhonker D Vincristine induced neurotoxicity in cancer patients Indian J Pediatr 2010 77 97 100 19936661
  13. [14]Walsh TJ Anaissie EJ Denning DW Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America Clin Infect Dis 2008 46 327 360 18177225
  14. [15]Kobayashi R Suzuki D Yasuda K Kobayashi K Itraconazole for invasive fungal infection with pediatric malignancies Pediatr Int 2010 52 707 710 20337979
  15. [16]Sathiapalan RK El-Solh H Enhanced vincristine neurotoxicity from drug interactions: case report and review of literature Pediatr Hematol Oncol 2001 18 543 546 11764105
  16. [17]Kamaluddin M McNally P Breatnach F Potentiation of vincristine toxicity by itraconazole in children with lymphoid malignancies Acta Paediatr 2001 90 1204 1207 11697438
  17. [18]Jeng MR Feusner J Itraconazole-enhanced vincristine neurotoxicity in a child with acute lymphoblastic leukemia Pediatr Hematol Oncol 2001 18 137 142 11255732
  18. [19]Gillies J Hung KA Fitzsimons E Soutar R Severe vincristine toxicity in combination with itraconazole Clin Lab Haematol 1998 20 123 124 9681224
  19. [20]Bohme A Ganser A Hoelzer D Aggravation of vincristine-induced neurotoxicity by itraconazole in the treatment of adult ALL Ann Hematol 1995 71 311 312 8534764
  20. [21]van Schie RM Bruggemann RJ Hoogerbrugge PM te Loo DM Effect of azole antifungal therapy on vincristine toxicity in childhood acute lymphoblastic leukaemia J Antimicrob Chemother 2011 66 1853 1856 21652620
  21. [22]Pana ZD Roilides E Risk of azole-enhanced vincristine neurotoxicity in pediatric patients with hematological malignancies: Old problem - New Dilemma Pediatr Blood Cancer 2011 57 30 35 21265011
  22. [24]Nelson RL The comparative clinical pharmacology and pharmacokinetics of vindesine, vincristine, and vinblastine in human patients with cancer Med Pediatr Oncol 1982 10 115 127 7070351
  23. [25]Gubbins PO Heldenbrand S Clinically relevant drug interactions of current antifungal agents Mycoses 2010 53 95 113 20002883
  24. [26]Bruggemann RJ Alffenaar JW Blijlevens NM Clinical relevance of the pharmacokinetic interactions of azole antifungal drugs with other coadministered agents Clin Infect Dis 2009 48 1441 1458 19361301
  25. [27]Venkatakrishnan K von Moltke LL Greenblatt DJ Effects of the antifungal agents on oxidative drug metabolism: clinical relevance Clin Pharmacokinet 2000 38 111 180 10709776
  26. [28]Dodds-Ashley E Management of drug and food interactions with azole antifungal agents in transplant recipients Pharmacotherapy 2010 30 842 854 20653361
  27. [29]Harnicar S Adel N Jurcic J Modification of vincristine dosing during concomitant azole therapy in adult acute lymphoblastic leukemia patients J Oncol Pharm Pract 2009 15 175 182 19282418
  28. [30]Gidding CE Kellie SJ Kamps WA de Graaf SS Vincristine revisited Crit Rev Oncol Hematol 1999 29 267 287 10226730
  29. [31]Fedeli L Colozza M Boschetti E Pharmacokinetics of vincristine in cancer patients treated with nifedipine Cancer 1989 64 1805 1811 2790693
  30. [34]Li Y Theuretzbacher U Clancy CJ Nguyen MH Derendorf H Pharmacokinetic/pharmacodynamic profile of posaconazole Clin Pharmacokinet 2010 49 379 396 20481649
  31. [35]Weiss J Ten Hoevel MM Burhenne J CYP2C19 genotype is a major factor contributing to the highly variable pharmacokinetics of voriconazole J Clin Pharmacol 2009 49 196 204 19033450
  32. [36]Scholz I Oberwittler H Riedel KD Pharmacokinetics, metabolism and bioavailability of the triazole antifungal agent voriconazole in relation to CYP2C19 genotype Br J Clin Pharmacol 2009 68 906 915 20002085 PMC2810802
  33. [37]Lei HP Wang G Wang LS Lack of effect of Ginkgo biloba on voriconazole pharmacokinetics in Chinese volunteers identified as CYP2C19 poor and extensive metabolizers Ann Pharmacother 2009 43 726 731 19299322
  34. [38]Wang G Lei HP Li Z The CYP2C19 ultra-rapid metabolizer genotype influences the pharmacokinetics of voriconazole in healthy male volunteers Eur J Clin Pharmacol 2009 65 281 285 18982321
  35. [39]Moriyama B Falade-Nwulia O Leung J Prolonged half-life of voriconazole in a CYP2C19 homozygous poor metabolizer receiving vincristine chemotherapy: avoiding a serious adverse drug interaction Mycoses 2011 PMC3164277 21615537

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Authors
Moriyama, B., Henning, S. A., Leung, J., Falade‐Nwulia, O., Jarosinski, P., Penzak, S. R., & Walsh, T. J.
Affiliations
  • National Institutes of Health (US)
  • Cornell University (US)
Corresponding author
Walsh, Thomas J.
ORCID
Venue
Mycoses
Publisher
Wiley
Published
2011-11-29
Volume
55
Issue
4
Pages
290-297
ISSN
  • 0027-5557 (ISSN-L)
  • 0933-7407
  • 1439-0507
DOI
10.1111/j.1439-0507.2011.02158.x
PMC
PMC3345292
OpenAlex
W2140134181
Cited by
164
References
2
Citations by year
2026: 11 · 2025: 7 · 2024: 8 · 2023: 12 · 2022: 8 · 2021: 17 · 2020: 15 · 2019: 17 · 2018: 14 · 2017: 20 · 2016: 13 · 2015: 9 · 2014: 5 · 2013: 7 · 2012: 1
FWCI
0.52
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Mycoses (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (Z99CL999999)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
vincristine, azole antifungals, drug interactions, itraconazole, posaconazole, voriconazole, ketoconazole, peripheral neuropathy, acute lymphoblastic leukemia, adverse drug interactions, hyponatremia, seizures, autonomic neuropathy
MeSH terms
Adolescent, Antifungal Agents, Antineoplastic Agents, Phytogenic, Azoles, Child, Child, Preschool, Drug Interactions, Female, Humans, Infant, Male, Vincristine, Young Adult

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