Volume 197 - Issue 6
Myopathy and possible intestinal dysfunction in a patient treated with colchicine and simvastatin
Authors: Danielle H J Oh, Shuang Quan Chan and Andrew M Wilson
Med J Aust 2012; 197 (6): 332-333. || doi: 10.5694/mja12.10333
Published online: 17 September 2012
Published online: 17 September 2012
To the Editor: We report a case in which the concurrent administration
of colchicine and simvastatin led to significant morbidity with myopathy and intestinal dysfunction.
An 84-year-old man presented with an acute flare of gout, and was treated with 1 mg of colchicine daily for 3 days, and then 0.5 mg daily. His pain improved over the next 72 hours. He then noticed progressive generalised muscle ache and weakness in ...
To the Editor: We report a case in which the concurrent administration of colchicine and simvastatin led to significant morbidity with myopathy and intestinal dysfunction.
An 84-year-old man presented with an acute flare of gout, and was treated with 1 mg of colchicine daily for 3 days, and then 0.5 mg daily. His pain improved over the next 72 hours. He then noticed progressive generalised muscle ache and weakness in all four limbs, requiring admission 3 weeks later.
The patient’s medical history included stable chronic kidney disease (baseline estimated glomerular filtration rate [eGFR], 37 mL/min; reference interval [RI], > 90 mL/min) and asthma treated with 5 mg of prednisolone daily and a fluticasone-salmeterol inhaler. Other medications were simvastatin (40 mg daily), ezetimibe (20 mg daily), amlodipine, irbesartan, hydrochlorothiazide, clopidogrel, rabeprazole and oxycodone.
A neurological examination showed symmetrical proximal muscle weakness. Reflexes and all sensory modalities were intact. Mild to moderate dysphagia was noted, and a videofluoroscopic swallowing study suggested weak pharyngeal contraction. Laboratory studies showed elevated creatine kinase (CK) of 2837 U/L (RI, 40–200 U/L), serum creatinine of 208 mol/L (RI, 45–80 mol/L), eGFR of 23 mL/min, normal thyroid function test results and myoglobinuria.
The patient was treated with supportive therapy, and colchicine and simvastatin were no longer given. His hospital stay was complicated by acute pseudo-obstruction of the colon, which required a decompressive colonoscopy. His muscle weakness and bowel habit returned to normal over an 8-week period. His CK and renal function returned to baseline over the next 3 weeks.
Colchicine myopathy and statin myopathy are well recognised clinical entities in their own right. Colchicine and statins are drugs that exhibit dose-dependent myotoxicity, which may produce a synergistic effect when combined. Three cases of myopathy associated with concomitant colchicine and simvastatin use in patients with chronic kidney disease have been reported in the literature.1 The United States Food and Drug Administration has recently revised the product label on simvastatin, in particular recommending maximum dosage of 10 mg per day when used together with amiodarone, verapamil and diltiazem.2
The association between dysphagia and medication-induced myopathy has not been previously reported in the English literature.3 Apart from his generalised myopathy, our patient did not have any other concurrent condition that would have contributed to his colonic pseudo-obstruction. Using the Naranjo scale, it is estimated that this association is possible (Naranjo score, 3).4 Intestinal pseudo-obstruction has been described in cerivastatin-induced myopathy, and leiomyolysis of the intestinal muscular wall has been suggested as a potential cause.5
The potential interaction between colchicine and simvastatin resulting in myotoxicity is under-recognised, and such combinations should be avoided in patients with chronic kidney disease.
Competing interests
No relevant disclosures.
References
- Justiniano M, Dold S, Espinoza LR. Rapid onset of muscle weakness (rhabdomyolysis) associated with the combined use of simvastatin and colchicine. J Clin Rheumatol 2007; 13: 266-268. 0_CBBGJGGI
- US Food and Drug Administration. FDA drug safety communication: revised dose limitation for Zocor (simvastatin) when taken with amiodarone. http://www.fda.gov/Drugs/DrugSafety/ucm283137.htm (accessed Apr 2012).
- Edholm B. Statin-induced dysphagia [Danish]. Ugeskr Laeger 2010; 172: 544-545. 0_pgfId-2646992
- Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30: 239-245. 0_CBBEIGBJ
- Marfia GA, Pachatz C, Arciprete F, et al. Intestinal pseudobstruction as presenting event of fatal cerivastatin-induced myopathy. J Neurol 2003; 250: 887-888. 0_i1142883