Colchicine and macrolides: a cohort study of the risk of adverse outcomes associated with concomitant exposure

Abstract

Colchicine is increasingly used as the number of potential indications expands. However, it also has a narrow therapeutic index that is associated with bothersome to severe side effects. When concomitantly use with medications inhibiting its metabolism, higher plasma levels will result and increase likelihood of colchicine toxicity. We conducted a cohort study using electronic health records comparing encounters with colchicine plus a macrolide and colchicine with an antibiotic non-macrolide. We assessed the relationship between the two groups using adjusted multivariate logistic regression models and the risk of rhabdomyolysis, pancytopenia, muscular weakness, heart failure, acute hepatic failure and death. 12670 patients on colchicine plus an antibiotic non-macrolide were compared to 2199 patients exposed to colchicine plus a macrolide. Patients exposed to colchicine and a macrolide were majority men ( n = 1329, 60.4%) and white ( n = 1485, 67.5%) in their late sixties (mean age in years 68.4, SD 15.6). Heart failure was more frequent in the colchicine plus a macrolide cohort ( n = 402, 18.3%) vs the colchicine non-macrolide one ( n = 1153, 9.1%) ( p < 0.0001) and also had a higher mortality rate [(85 (3.87%) vs 289 (2.28%), p < 0.0001 macrolides vs non-macrolides cohorts, respectively]. When the sample was limited to individuals exposed to either clarithromycin or erythromycin and colchicine, the adjusted OR for acute hepatic failure was 2.47 (95% CI 1.04–5.91) and 2.06 for death (95% CI 1.07–3.97). There is a significant increase in the risk of hepatic failure and mortality when colchicine is concomitantly administered with a macrolide. Colchicine should not be used concomitantly with these antibiotics or should be temporarily discontinued to avoid toxic levels of colchicine. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-022-05201-5.

Literature Review of Safety Event Reporting in Observational Studies: Challenges Extrapolating across Comparable Products

“…Specifically, study populations included patients with chronic rhinosinusitis [10], type 2 diabetes [17], kidney transplant recipients [9], hemodialysisdependent kidney failure [16], or coronary heart disease [21], older adults with advanced chronic kidney disease [18], pregnant women [7,8,15], patients with Helicobacter pylori infection [4], urinary tract infection [1,20], or pneumonia [20]. The remaining studies included patient populations drawn from the general population [2,3,5,6,[11][12][13][14]19].…”

“…Of the seven studies with a single safety outcome of interest, the outcomes included tendon rupture [11], major bleeding events [12], sudden cardiac death [16], hypoglycemic emergency [17], cardiovascular death [2], suicidality [20], or a composite outcome of nervous system or psychiatric disorders, hypoglycemia, or collagen-associated events [18]. The remaining 13 studies included 2-6 endpoints per paper [1,[5][6][7][8][9][10][13][14][15]19].…”

Traditional Chinese Medicine is Associated with the Reduction in Endpoint Events in Patients with Gouty Arthritis: Cohort Study and Association Rule Analysis

“…21,22 The existing therapeutic drugs such as NSAIDs, colchicine, and glucocorticoids provide rapid pain relief in GA patients but also cause significant side effects. [23][24][25] Uric acid-lowering drugs such as febuxostat and allopurinol can inhibit uric acid production, but long-term use tends to overwhelm the liver and kidney. 26,27 GA patients may experience liver and kidney function reduction after years of recurrent attacks and medications.…”

Antibiotic–Drug Interactions in the Intensive Care Unit: A Literature Review

“…When prescribing macrolides, it is important to remember possible drug–drug interactions that may appear. First of all, colchicine combined with macrolides is more likely to induce heart or liver failure or even lead to death than drug combinations from other groups of antibiotics [ 40 , 41 ]. Co-administration of macrolides with digoxin may increase its serum level and lead to serious cardiac adverse effects.…”