Drug Interaction Between Febuxostat and Thiopurine Antimetabolites: A Review of the FDA Adverse Event Reporting System and Medical Literature.
azathioprine
drug interactions
drug-related side effects and adverse reactions
immunosuppression
mercaptopurine
pancytopenia
xanthine oxidase
Journal
Pharmacotherapy
ISSN: 1875-9114
Titre abrégé: Pharmacotherapy
Pays: United States
ID NLM: 8111305
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
pubmed:
31
12
2019
medline:
18
12
2020
entrez:
31
12
2019
Statut:
ppublish
Résumé
There is a known drug interaction (DI) between xanthine oxidase (XO) inhibitors and the thiopurine immunosuppressants, azathioprine (AZA) and mercaptopurine (6-MP). Xanthine oxidase inhibition increases concentrations of AZA and 6-MP active metabolites, possibly resulting in myelosuppression. When allopurinol is used with AZA or 6-MP, dose reduction of AZA or 6-MP is recommended. Febuxostat is a newer XO inhibitor approved for the treatment of gout. To determine the clinical impact of the febuxostat-thiopurine DI. Case series derived from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and published medical literature. Nineteen patients who received concomitant febuxostat and either AZA or 6-MP. Laboratory and clinical data. Nineteen cases reporting myelosuppressive events were identified in patients receiving febuxostat with AZA or 6-MP. Eighteen cases were treated with the combination of AZA and febuxostat. A median of 1.6 months elapsed from initiation of the drug combination until discovery of the event. Sixteen cases required hospitalization; 15 reported administration of blood products. Thirteen cases reported resolution of the event with discontinuation of both drugs, two reported discontinuation of the thiopurine only, and one reported discontinuation of febuxostat only. Thiopurine monotherapy may cause myelosuppression. Complications of immunosuppression that may contribute to the real-world morbidity and mortality associated with the febuxostat-thiopurine DI were not examined. Finally, FAERS data are limited by the voluntary nature of reporting. Current febuxostat labeling contraindicates concomitant administration of febuxostat with either AZA or 6-MP. This case series demonstrates that the DI can result in clinically significant adverse events and is supportive of current febuxostat labeling.
Sections du résumé
BACKGROUND
There is a known drug interaction (DI) between xanthine oxidase (XO) inhibitors and the thiopurine immunosuppressants, azathioprine (AZA) and mercaptopurine (6-MP). Xanthine oxidase inhibition increases concentrations of AZA and 6-MP active metabolites, possibly resulting in myelosuppression. When allopurinol is used with AZA or 6-MP, dose reduction of AZA or 6-MP is recommended. Febuxostat is a newer XO inhibitor approved for the treatment of gout.
OBJECTIVE
To determine the clinical impact of the febuxostat-thiopurine DI.
DESIGN AND SETTING
Case series derived from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and published medical literature.
PATIENTS
Nineteen patients who received concomitant febuxostat and either AZA or 6-MP.
MEASUREMENTS
Laboratory and clinical data.
RESULTS
Nineteen cases reporting myelosuppressive events were identified in patients receiving febuxostat with AZA or 6-MP. Eighteen cases were treated with the combination of AZA and febuxostat. A median of 1.6 months elapsed from initiation of the drug combination until discovery of the event. Sixteen cases required hospitalization; 15 reported administration of blood products. Thirteen cases reported resolution of the event with discontinuation of both drugs, two reported discontinuation of the thiopurine only, and one reported discontinuation of febuxostat only.
LIMITATIONS
Thiopurine monotherapy may cause myelosuppression. Complications of immunosuppression that may contribute to the real-world morbidity and mortality associated with the febuxostat-thiopurine DI were not examined. Finally, FAERS data are limited by the voluntary nature of reporting.
CONCLUSION
Current febuxostat labeling contraindicates concomitant administration of febuxostat with either AZA or 6-MP. This case series demonstrates that the DI can result in clinically significant adverse events and is supportive of current febuxostat labeling.
Substances chimiques
Antimetabolites
0
Gout Suppressants
0
Febuxostat
101V0R1N2E
Mercaptopurine
E7WED276I5
Azathioprine
MRK240IY2L
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
125-132Informations de copyright
Published 2019. This article is a U.S. Government work and is in the public domain in the USA.
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