Is combination treatment with a statin + a fibrate dangerous? Two case reports

Background: Statins are widely used for reducing serum low-density lipoprotein cholesterol (LDL). Fenofibrate, a fibric acid derivative, is used to treat hypertriglyceridemia. Statins are well known to be associated with muscle disorders ranging from simple asymptomatic elevations of creatine phosphokinase (CPK) to rhabdomyolysis. Fibrates are frequently used together with statins when there are significant triglyceride levels along with high LDL levels. The incidence of myopathy associated with statin and fibrate combination is ≈ 0.5–2.5%. We report two cases of significant myopathy apparently precipitated by fenofibrates in patients already taking low doses of a statin. Case presentations: A 57-year-old patient with ischaemic heart disease, hypertension, and hyperlipidaemia receiving rosuvastatin presented with severe pain in both her upper and lower limbs without any weakness, 3 weeks after starting fenofibrate 200 mg/day for hypertriglyceridaemia. Her CPK level was markedly elevated without any evidence of rhabdomyolysis and muscle biopsy did not reveal any pathology. One week after stopping both rosuvastatin and fenofibrate, her CPK level returned to normal. A 61-year-old patient with diabetes mellitus, chronic kidney disease, hypothyroidism and bronchial asthma who received atorvastatin 10 mg/day for 2 years was started on fenofibrate 200 mg/day to treat high triglyceride levels. Two weeks after commencement of fenofibrate, she presented with generalized body pain with severe tenderness of limb and abdominal muscles. She had a raised CPK level of 7002 U/L with raised creatinine level, but her urine was negative for myoglobin and muscle biopsy showed nonspecific changes. Her CPK level dropped to 260 U/L 2 weeks after stopping the statin and fibrate. Conclusions: Fenofibrate is a safe drug when used as monotherapy. Physicians need to be aware of potentially serious adverse effects such as myopathy and rhabdomyolysis when it is co-administered with statins irrespective of dose. In patients with risk factors for muscle toxicity, such as hepatic impairment, renal insufficiency, diabetes, hypothyroidism and advanced age, CPK levels should be evaluated within 2 weeks and followed more closely. In addition, patients should be instructed to stop statin and fibrate treatment immediately and seek medical advice if significant muscle weakness or pain develops. CPK levels must be monitored and, if tenfold higher than normal, statin treatment should remain discontinued.