Rosuvastatin and Colchicine combined myotoxicity: lessons to be learnt

Abstract

Statins and colchicine co-administration consists of a potentially catastrophic drug-drug interaction since it provokes myotoxicity, myopathy and various degrees of rhabdomyolysis. Lipophilic statins and colchicine are biotransformed in the liver, primarily via CYP3A4 enzyme system leading to elevated blood levels of both agents and resulting in increased potential for combined myotoxicity. Hence, it would be of great clinical importance not only the awareness of this devastating complication but also the more advantageous type of statin that we should choose to achieve the recommended therapeutic goals regarding LDL levels with minimal myopathy risk. Therefore, once colchicine's use is commenced, a hydrophilic statin selection, such as rosuvastatin, seems favorable regarding the risk of myotoxicity. Herein, we aim to describe a patient with chronic kidney disease stage III and nephrotic syndrome that developed acute rhabdomyolysis soon after the administration of rosuvastatin while receiving colchicine. To the best of our knowledge, this is the first report of the combined effect of rosuvastatin and colchicine in the setting of chronic kidney disease leading to myotoxicity.

Rosuvastatin Induces Renal HO-1 Activity and Expression Levels as a Main Protective Mechanism against STZ-Induced Diabetic Nephropathy

“…Administration of RSV was reported to cause proximal tubule damage and renal toxicity in rats [ 35 ] and acute interstitial nephritis in humans [ 36 ]. In addition, RSV caused renal damage associated with severe rhabdomyolysis, whether RSV was given alone [ 37 , 38 , 39 ], or in combination with colchicine [ 40 ], ticagrelor [ 41 ], or cocaine and heroin [ 42 ]. Despite that the results of the current study suggested that RSV had protective effects against DN, long-term follow-up studies are needed to confirm whether RSV improves DN or just delays its progress.…”

Drugs That Interact With Colchicine Via Inhibition of Cytochrome P450 3A4 and P-Glycoprotein: A Signal Detection Analysis Using a Database of Spontaneously Reported Adverse Events (FAERS)

“…15 Published case reports and observational studies of colchicine when given concomitantly with inhibitors of CYP3A4/P-gp point to the clinical relevance of these interactions. 9,16-18 Patients with chronic conditions are often exposed to polypharmacy making relevant drug-drug interaction (DDI) information crucial for safe therapy. 19,20…”

“…15 Published case reports and observational studies of colchicine when given concomitantly with inhibitors of CYP3A4/P-gp point to the clinical relevance of these interactions. 9,[16][17][18] Patients with chronic conditions are often exposed to polypharmacy making relevant drug-drug interaction (DDI) information crucial for safe therapy. 19,20 The purpose of this study analysis was to identify potential clinical implications of exposure to colchicine and CYP3A4/P-gp inhibitors using spontaneously submitted safety reports present in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).…”