Colchicine-antimicrobial drug interactions: what pharmacists need to know in treating gout.

Article Details

Citation

Davis MW, Wason S, Digiacinto JL

Colchicine-antimicrobial drug interactions: what pharmacists need to know in treating gout.

Consult Pharm. 2013 Mar;28(3):176-83. doi: 10.4140/TCP.n.2013.176.

PubMed ID
23462027 [ View in PubMed
]
Abstract

OBJECTIVE: Review the magnitude and clinical relevance of drug-drug interactions between a new formulation of colchicine, used to treat gout, and antibiotics. SETTING AND PRACTICE DESCRIPTION: Relevant to community and institutional pharmacists servicing patients with gout. PRACTICE INNOVATION: Pharmacists have clear roles for the identification of drug-drug interactions, providing recommendations for alternative therapy or dose adjustments/modifications, and monitoring for interactionrelated adverse events. MAIN OUTCOME MEASURES: Colchicine is metabolized via cytochrome P450 3A4 (CYP3A4); therefore, coadministration with agents that inhibit this isoenzyme can produce elevated colchicine plasma concentrations, resulting in severe and sometimes fatal adverse events. Knowledge of the potential for drug-drug interactions involving antibiotics (e.g., macrolide antibiotics, azole antifungals) allows pharmacists to help patients avoid serious adverse events. RESULTS: Pharmacokinetic studies have demonstrated that the maximum plasma concentration (C(max)) and drug exposure (as assessed by area under the plasma concentration time curve [AUC]) of colchicine are increased by 277% and 282%, respectively, after coadministration with clarithromycin. Similarly, coadministration with ketoconazole increases colchicine C(max) and AUC by 102% and 212%, respectively. Other antibiotics that are strong CYP3A4 inhibitors include itraconazole and telithromycin, whereas erythromycin and fluconazole are moderate inhibitors of the isoenzyme CYP3A4. Coadministration of CYP3A4 inhibitors (particularly clarithromycin) and colchicine has resulted in acute colchicine toxicity manifested by severe gastrointestional toxicity, bone marrow suppression, multiorgan failure, and death. CONCLUSION: Pharmacist awareness of potentially clinically significant interactions between colchicine and antibiotics that inhibit CYP3A4 can help to ensure the efficacy of colchicine is realized while mitigating serious toxicities and minimizing the risk of adverse events.

DrugBank Data that Cites this Article

Drug Reactions
Reaction
Details
Details
Drug Interactions
DrugsInteraction
Colchicine
Clozapine
The metabolism of Colchicine can be decreased when combined with Clozapine.
Colchicine
Viloxazine
The metabolism of Colchicine can be decreased when combined with Viloxazine.
Colchicine
Aldesleukin
The metabolism of Colchicine can be decreased when combined with Aldesleukin.
Colchicine
Octreotide
The metabolism of Colchicine can be decreased when combined with Octreotide.
Colchicine
Fluvoxamine
The metabolism of Colchicine can be decreased when combined with Fluvoxamine.