A systematic review of the drug–drug interaction between statins and colchicine: Patient characteristics, etiologies, and clinical management strategies

Abstract

Colchicine and statins are frequently co-prescribed for prevention and treatment of cardiovascular diseases, auto-inflammatory diseases, and gout. Both are substrates and inhibitors of the cytochrome P-450 (CYP) 3A4 isozyme and P-glycoprotein so that taken together, they represent a clinically significant interaction. Data suggest the interaction may be associated with potentially life-threatening myopathies and rhabdomyolysis. The purposes of this systematic review (SR) were to gather and appraise evidence surrounding the statin-colchicine drug interaction and discuss related risk-mitigation strategies. An electronic literature search was performed. Twenty-one articles met the protocol to be included in the qualitative analysis: 18 case reports/ series, 2 retrospective observational cohort studies, and 1 retrospective case-control study. Thirty-eight patients developed an adverse drug event (ADE) receiving statincolchicine combination therapy; 25 (66%) patients developed myopathy; 10 (26%) patients developed rhabdomyolysis, and three (8%) patients developed neuromyopathy. Over 70% of patients developed ADEs on simvastatin or atorvastatin, and 80% of studies reported moderate-to-high intensity statins. Colchicine dosing varied but ranged between 0.5 to 1.5 mg daily. Sixty-two percent of patients in the case reports/series had comorbid renal disease. Seven studies (33% of all included studies) reported patients taking concomitant interacting medications at the CYP3A4 and/ or P-glycoprotein efflux pump. Seventeen studies (81% of all included studies) reported ADEs leading to hospitalization. A multivariate analysis from one case-control study identified risk factors prognosticating myopathy ADEs in patients taking statincolchicine therapy: comorbid renal disease and/or cirrhosis, colchicine doses 1.2 mg daily or greater, and concomitant interacting medications. Clinicians must be cognizant that the statin-colchicine drug interaction may lead to patient harm and thus should employ risk-mitigation strategies for statin-associated muscle symptoms. Future studies are warranted to validate clinically relevant risk factors that are strongly associated with the complications owing to the statin-colchicine drug interaction.

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

“…7 case reports of myopathy with combination b ; additive myotoxicity? [ 58 , 59 ] ORCA Class 3. Assess risk; take action if needed Concurrent use need not be avoided, especially if the colchicine dose is 0.6 mg/day or less If colchicine dose is > 0.6 mg/day, myopathy risk may be increased in predisposed patients, (i.e.…”

“…c,m Consider alternative: fluvastatin, pravastatin, and rosuvastatin may be less likely to interact Monitor for colchicine toxicity, especially for signs of myopathy Advise patient to report evidence of myopathy (muscle weakness, myalgia, dark urine) Fluvastatin Not expected to affect colchicine AUC; isolated cases of rhabdomyolysis reported with combination, but causality was not established b ; additive myotoxicity? [ 58 , 59 ] ORCA Class 4: Low risk Concurrent use need not be avoided; it is possible that the myopathy risk is increased in predisposed patients, but more data are needed n Normal monitoring for colchicine toxicity, with emphasis on signs of myopathy (muscle weakness, myalgia, dark urine) Lovastatin Possible P-gp inhibitory effect of lovastatin? [ 78 ] Possible additive myotoxicity?…”

“…[ 78 ] Possible additive myotoxicity? [ 58 , 59 ]. Isolated cases of myopathy b ; lovastatin has similar pharmacokinetic properties as simvastatin (see below) ORCA Class 3: Assess risk; take action if needed Concurrent use need not be avoided, especially if the colchicine dose is 0.6 mg/day or less If colchicine dose is > 0.6 mg/day, myopathy risk may be increased with renal impairment or elevated statin levels due to dose, DDIs, etc.)…”

The Role of Colchicine in Atherosclerosis: From Bench to Bedside

“…Dose adjustment is recommended in these situations. Some cases of myopathy and/or rhabdomyolysis have been reported for instances when colchicine was used in conjunction with statins, however, they are in general well tolerated when used simultaneously [ 105 ]. Death due to colchicine administration has been reported when used in conjunction with clarithromycin, particularly in patients with renal insufficiency [ 106 ].…”

IL-1 inhibition in familial Mediterranean fever: clinical outcomes and expectations

“…Mild weakness persisted even 6 months after halting the clarithromycin (unpublished data). While myopathy is a well-known complication of supratherapeutic doses of colchicine ( 77), co-administration with statins may augment this risk (78).…”