OBJECTIVES:

Clarithromycin increases the oral bioavailability of colchicine and decreases its hepatic metabolism and clearance by acting as an inhibitor of CYP3A4, producing a life-threatening drug-drug interaction (DDI). The aim of this study is to explore the evidence and clinical implications of the concomitant use of colchicine and clarithromycin.

METHODS:

The US Food and Drug Administration’s Adverse Event Reporting System (FAERS) database was searched in November 2019, and PubMed, EMBASE, and Web of Science were searched in August 2019 using “colchicine” and “clarithromycin” as search terms. The resulting articles were reviewed to identify attributes of interest for case reports of DDI, including dosage, days to onset and offset, symptoms, evidence of renal disease, liver function, and DIPS (Drug Interaction Probability Scale) rating.

RESULTS:

In FAERS, 117 cases of DDI were identified, with a mean age of 66 ± 2 years and 73 (49%) occurring in females. Patients were most commonly diagnosed with gout (n=80, 54%), followed by Familial Mediterranean Fever (n=24, 16%), hyperuricemia (n=7, 5%), Behcet’s Syndrome (n=11, 7%) and amyloidosis (n=4, 3%). Of the 117 patients, 73 expired (male=36, female=36, not specified=1), of whom 46 were treated for gout and pneumonia, 8 for gout and H. pylori infection or dental abscess, and 4 for amyloidosis or upper respiratory infections. Pancytopenia, bone marrow failure and general drug toxicity were also reported. From the published literature, 20 case reports of DDI were identified, of which nineteen were rated “probable” and one “possible” according to DIPS. Four of these patients expired, and the average onset of colchicine toxicity was within five days of starting clarithromycin (range: <2 to 9 days).

CONCLUSIONS: Persons exposed to colchicine and clarithromycin concomitantly are at high risk of dying due to colchicine toxicity. In over 50% of cases of this interaction reported to FAERS, the patient expired.