Rhabdomyolysis fenofibrate

Skeletal muscle effects The use of fibrates alone, including fenofibrate, may occasionally be associated with myopathy. Treatment with drugs of the fibrate class has been associated on rare occasions with rhabdomyolysis, usually in patients with impaired renal function. Consider myopathy in any patient with diffuse myalgias, muscle tenderness or weakness, or marked elevations of creatine phosphokinase levels. 

Rare adverse effects of fibrates include rashes, gastrointestinal symptoms, myopathy, arrhythmias, hypokalemia, and high blood levels of aminotransferases or alkaline phosphatase. A few patients show decreases in white blood count or hematocrit. Both agents potentiate the action of coumarin and indanedione anticoagulants, and doses of these agents should be adjusted. Rhabdomyolysis has occurred rarely. Risk of myopathy increases when fibrates are given with reductase inhibitors. The use of fenofibrate with rosuvastatin appears to minimize this risk. Fibrates should be avoided in patients with hepatic or renal dysfunction. There appears to be a modest increase in the risk of cholesterol gallstones. 

It is possible that the combination of rosiglitazone with fenofibrate was responsible for the severe myopathy, although the possibility of a single drug cannot be excluded. Raised creatine kinase activity has been reported with troglitazone, and there has been a report of rhabdomyolysis in a patient with type 2 diabetes taking pioglitazone when fenofibrate was added. 

Hypothyroidism predisposes to rhabdomyolysis (53,54) and screening of thyroid function has been advocated before starting hypolipidemic drugs (SEDA-21, 458). This notion has been supported by observations in a 69-year-old man taking fenofibrate 200 mg daily (55). The muscular syndrome appears to be a special risk in patients with nephrotic syndrome (SEDA-13,1325 56). 

Two women, 55 and 57 years old, with renal insufficiency, had rhabdomyolysis after taking micronized fenofibrate in dosages a little higher than recommended (57). Both had mild hypothyroidism. 

Clouatre Y, Leblanc M, Ouimet D, Pichette V. Fenofibrate-induced rhabdomyolysis in two dialysis patients with hypothyroidism. Nephrol Dial Transplant 1999 14(4) 1047-8. 

Soyoral YU, Canbaz ET, Erdur MF, Emre H, Begenik H, Erkoc R (2012) Fenofibrate -induced rhabdomyolysis in a patient with stage 4 chronic renal failure due to diabetes mellitus. J Pak Med Assoc 62 849-851... 

A single-dose study in 23 healthy subjects found that the eoneurrent use of pravastatin 40 mg and fenofibrate 201 mg had no effeet on the pharmaeokinetics of either drug, but a moderate increase in the formation of a non-toxic pravastatin metabolite was seen. This was not thought to be clin-ieally important. In a multiple-dose study pravastatin 40 mg daily was given to 23 healthy subjects with fenofibrate 160 mg daily. Fenofibrate increased the maximum levels and AUC of pravastatin by about 40% and 30%, respectively. Similar increases were seen for the main pravastatin metabolite. The combination was well tolerated, and the inereases were eonsidered to be modest." However, a case report describes a patient taking fenofibrate 300 mg daily, who developed rhabdomyolysis after starting pravastatin 10 mg daily. ... 

Combination studies In an open extension of a phase III study, in which fenofibrate 135 mg/day was combined with either simvastatin 40 mg/day or rosuvastatin 20 mg/day or atorvastatin 40 mg/day, 287 patients completed the 2-year study [11 ]. There were no cases of rhabdomyolysis and the discontinuation rate due to adverse reactions was 2.9%, with no differences between the three treatments. None of the adverse events was considered serious they generally occurred early during treatment and the most common were myalgia (2.9%), muscle spasms (3.9%), and increased creatine kinase activity (3.5%), the latter being highest with the rosuvastatin combination. 

A combination therapy of rosuvastatin (Crestor) (156) and fenofibrate (Tricor) (154) has been gaining popularity among vascular physicians and cardiologists. Rosuvastatin can keep LDL very low and can also increase the plasma levels of HDL (97,156). Fenofibrate (94) m the morning can bring a remarkable reduction of the serum triglycerides. Rosuvastatin and fenofibrate is a safe combination therapy with regards to liver toxicity and rhabdomyolysis (154,156). 

Adverse effects due to fenofibrate use often relate to the skeletal muscle, kidney or liver. A 51-year-old female patient who was on fenofibrate therapy for 2 years developed rhabdomyolysis complicated with acute renal failure after discontinuation of the drug for a short period of time [27]. 

Kiskac M, Zorlu M, Yavuz E. A case of rhabdomyolysis complicated with acute renal failure after resumption of fenofibrate therapy a first report. Indian J Pharmacol 2013 45 305-6. 

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