| アブストラクト | BACKGROUND: Colchicine has a narrow therapeutic index. Its toxicity can be increased due to concomitant exposure to drugs inhibiting its metabolic pathway; these are cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp). OBJECTIVE: To examine clinical outcomes associated with colchicine drug interactions using the spontaneous reports of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). METHODS: We conducted a disproportionality analysis using FAERS data from January 2004 through June 2020. The reporting odds ratio (ROR) and observed-to-expected ratio (O/E) with shrinkage for adverse events related to colchicine's toxicity (ie, rhabdomyolysis/myopathy, agranulocytosis, hemorrhage, acute renal failure, hepatic failure, arrhythmias, torsade de pointes/QT prolongation, and cardiac failure) were compared between FAERS reports. RESULTS: A total of 787 reports included the combined mention of colchicine, an inhibitor of both CYP3A4 and P-gp drug, and an adverse event of interest. Among reports that indicated the severity, 61% mentioned hospitalization and 24% death. A total of 37 ROR and 34 O/E safety signals involving colchicine and a CYP3A4/P-gp inhibitor were identified. The strongest ROR signal was for colchicine + atazanavir and rhabdomyolysis/myopathy (ROR = 35.4, 95% CI: 12.8-97.6), and the strongest O/E signal was for colchicine + atazanavir and agranulocytosis (O/E = 3.79, 95% credibility interval: 3.44-4.03). CONCLUSION AND RELEVANCE: This study identifies numerous safety signals for colchicine and CYP3A4/P-gp inhibitor drugs. Avoiding the interaction or monitoring for toxicity in patients when co-prescribing colchicine and these agents is highly recommended. |
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| ジャーナル名 | The Annals of pharmacotherapy |
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| 投稿日 | 2023/01/24 |
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| 投稿者 | Gomez-Lumbreras, Ainhoa; Boyce, Richard D; Villa-Zapata, Lorenzo; Tan, Malinda S; Hansten, Philip D; Horn, John; Malone, Daniel C |
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| 組織名 | Department of Pharmacotherapy, College of Pharmacy, The University of Utah, Salt;Lake City, UT, USA.;Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA,;USA.;Department of Pharmacy Practice, College of Pharmacy, Mercer University, Atlanta,;GA, USA.;Department of Pharmacy, School of Pharmacy, University of Washington, Seattle,;WA, USA. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/36688283/ |
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