Colchicine-Induced Acute Myopathy in a Patient With Concomitant Use of Simvastatin

Abstract

Colchicine and 3-hydroxy-3-methy-glutaryl coenzyme A (HMG-CoA) reductase inhibitors are well known to cause myopathy. Myotoxicity is dose-dependent in both drugs; therefore, the onset of symptoms usually takes months or years. We report the case of a patient with chronic renal failure who had been taking simvastatin for 2 years and developed acute weakness 2 weeks after the start of treatment with colchicines for recurrent gout. The electromyography and elevated muscle enzymes indicated that his symptoms were caused by myopathy. When this patient stopped taking both drugs, his weakness resolved rapidly. Acute myopathy induced by combination therapy with colchicines and simvastatin is rare. In patients with chronic renal failure, co-administration of colchicine with simvastatin may accelerate the onset of myopathy because CYP3A4 (part of cytochrome P450) is crucial in the breakdown of both drugs. When adding colchicine to a medication regimen that includes a HMG-CoA reductase inhibitor for patients with renal insufficiency, drugs that are metabolized outside the CYP3A4 system (e.g., fluvastatin and pravastatin) should be selected instead.

Recommendations for Management of Clinically Significant Drug-Drug Interactions With Statins and Select Agents Used in Patients With Cardiovascular Disease: A Scientific Statement From the American Heart Association

“…However, clinically significant DDIs have been reported with atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin when used in combination with colchicine. [170][171][172][173][174][175][176][177][178][179][180][181][182] The DDI between colchicine and simvastatin is the most frequently reported in the literature, having been the subject of 6 cases. In each case, simvastatin-colchicine combination therapy resulted in myopathy, and 1 case progressed to rhabdomyolysis, multiorgan failure, and death.…”

Increased autophagy accelerates colchicine-induced muscle toxicity

“…10 In fact, many acute cases of muscle toxicity have been reported in patients concomitantly taking statins and colchicine. [11][12][13][14][15][16][17][18][19][20] Statins reportedly induce colchicine treatment is associated with an autophagic vacuolar myopathy in human patients. The presumed mechanism of colchicine-induced myotoxicity is the destabilization of the microtubule system that leads to impaired autophagosome-lysosome fusion and the accumulation of autophagic vacuoles.…”

Patient awareness, knowledge and use of colchicine: an exploratory qualitative study in the Counties Manukau region, Auckland, New Zealand

“…8 The combination of colchicine and a statin poses a theoretical increased risk of myopathy and rhabdomyolysis. 18,19 Some participants in this study were taking this drug combination, and although clinicians are expected to regularly monitor creatinine kinase, another NZ study claimed that a quarter of all patients with renal impairment who are at high risk of colchicineinduced myopathy did not actually receive adequate safety monitoring. 37 Other drugs of concern taken by the participants in this study were thiazide diuretics and low dose aspirin, both known to elevate serum urate levels and increase the risk of an acute gouty attack.…”

“…14 Unintentional overdoses are most likely attributed to interacting medicines, as reported by study in a US hospital where 46% of colchicine fatalities were attributed to a likely interaction. 15 Interactions occur most often with clarithromycin, [15][16][17][18] and statins [19][20][21] which requires routine creatinine kinase levels to gauge the incidence and severity of these rare complications.…”