Colchicine Drug Interaction Errors and Misunderstandings: Recommendations for Improved Evidence-Based Management

Abstract

Colchicine is useful for the prevention and treatment of gout and a variety of other disorders. It is a substrate for CYP3A4 and P-glycoprotein (P-gp), and concomitant administration with CYP3A4/P-gp inhibitors can cause life-threatening drug–drug interactions (DDIs) such as pancytopenia, multiorgan failure, and cardiac arrhythmias. Colchicine can also cause myotoxicity, and coadministration with other myotoxic drugs may increase the risk of myopathy and rhabdomyolysis. Many sources of DDI information including journal publications, product labels, and online sources have errors or misleading statements regarding which drugs interact with colchicine, as well as suboptimal recommendations for managing the DDIs to minimize patient harm. Furthermore, assessment of the clinical importance of specific colchicine DDIs can vary dramatically from one source to another. In this paper we provide an evidence-based evaluation of which drugs can be expected to interact with colchicine, and which drugs have been stated to interact with colchicine but are unlikely to do so. Based on these evaluations we suggest management options for reducing the risk of potentially severe adverse outcomes from colchicine DDIs. The common recommendation to reduce the dose of colchicine when given with CYP3A4/P-gp inhibitors is likely to result in colchicine toxicity in some patients and therapeutic failure in others. A comprehensive evaluation of the almost 100 reported cases of colchicine DDIs is included in table form in the electronic supplementary material. Colchicine is a valuable drug, but improvements in the information about colchicine DDIs are needed in order to minimize the risk of serious adverse outcomes. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-022-01265-1.

Colchicine’s Role in Cardiovascular Disease Management

“…76,77 Nonfibrate therapy for triglyceride lowering should be preferred for concomitant use with colchicine. 78 Other cardiovascular medications that interact with colchicine include amiodarone, dronedarone, quinidine, and propafenone. 7,75 Concomitant use of these antiarrhythmic agents with colchicine should involve collaborative monitoring with an electrophysiologist.…”

CYP3A4/P-glycoprotein inhibitors related colchicine toxicity mimicking septic shock

“…There is no recommendation for dose adjustment in mild to moderate renal impairment (estimated creatinine clearance 30–80 mL/min); however, close monitoring for adverse outcomes in these groups is advised 24 25. Lastly, (3) drug interactions,13 14 23 26 particularly when co-administered with CYP3A4 or P-gp inhibitors 6 27. Both transporter (P-gp) and metabolising enzyme (CYP3A) share an extensive range of substrates; therefore, the disposition of drugs is influenced by both mechanisms simultaneously 28.…”

Gout Management Using Nanocarrier Systems: A Review

“…109 In addition, when CYP3A4 inhibitors are used in combination with colchicine, it may promote the intracellular accumulation of colchicine, eventually leading to toxic effects such as muscle pain, vomiting, diarrhea, exacerbated infections, and abnormal bleeding. 110 Glucocorticoids. The word glucocorticoid is a portmanteau from a combination of words glucose, cortex, and steroid, owing to its function in regulating glucose metabolism and synthesis in the zona fasciculate of the adrenal cortex, and is a class of steroid hormones.…”

“…Studies have shown that concurrent administration of interacting drugs or use of colchicine in patients who have renal impairment possess myopathy or rhabdomyolysis . In addition, when CYP3A4 inhibitors are used in combination with colchicine, it may promote the intracellular accumulation of colchicine, eventually leading to toxic effects such as muscle pain, vomiting, diarrhea, exacerbated infections, and abnormal bleeding …”