A 68-year-old man comes to the office with a 6-week history of muscle pain and fatigue. He has achy pain that is not related to activity. The patient has tried warm compresses and over-the-counter analgesics without relief. Past medical history is significant for hypertension, mixed hyperlipidemia, and coronary artery disease with an acute myocardial infarction 2 years ago. Physical examination shows diffuse tenderness in the proximal muscles of the upper and lower extremities. Serum creatine kinase activity is elevated. Which of the following drug combinations is most likely responsible for this patient's condition?

Question

A 68-year-old man comes to the office with a 6-week history of muscle pain and fatigue.  He has achy pain that is not related to activity.  The patient has tried warm compresses and over-the-counter analgesics without relief.  Past medical history is significant for hypertension, mixed hyperlipidemia, and coronary artery disease with an acute myocardial infarction 2 years ago.  Physical examination shows diffuse tenderness in the proximal muscles of the upper and lower extremities.  Serum creatine kinase activity is elevated.  Which of the following drug combinations is most likely responsible for this patient's condition?

Quizplus · Accepted Answer

Statins (eg, atorvastatin) are the first-line therapy for most patients with hypercholesterolemia and are useful in primary and secondary prevention of acute coronary events. Statins inhibit HMG-CoA reductase, the enzyme responsible for the rate-limiting step in synthesis of cholesterol. Statins lower total cholesterol, LDL, and triglyceride levels. The primary side effects of statins include myopathy and hepatitis. Statin-associated myopathy is usually characterized by mild muscular pain and resolves with discontinuation of the medication. However, some patients will develop severe myopathy with striking elevations in creatine kinase levels and occasional rhabdomyolysis. The risk of severe myopathy is increased when statins are given concurrently with fibrates (particularly gemfibrozil), which impair the hepatic clearance of statins and lead to excessive blood levels. An increased risk of statin myopathy is also likely with concurrent use of niacin or ezetimibe, but to a lesser extent (Choice B). (Choice A) Concurrent use of bile acid sequestrants (eg, cholestyramine) with statins does not increase the risk of myopathy. However, bile acid sequestrants can reduce the gastrointestinal absorption of statins. (Choice D) Fibrates can increase drug levels of ezetimibe but this does not have a significant impact on its side effects, which are generally mild and not dose-related. Ezetimibe does not alter the pharmacokinetics of fibrates and does not substantially influence their adverse effects. (Choices E and F) The primary adverse effects of niacin include flushing, hyperglycemia, and hepatotoxicity. There are no significant interactions with the concurrent use of niacin and ezetimibe or gemfibrozil. Educational objective: The primary side effects of statins include myopathy and hepatitis. Fibrates such as gemfibrozil can impair hepatic clearance of statins, increasing the risk of severe myopathy. __________ References: Effect of gemfibrozil and fenofibrate on the pharmacokinetics of atorvastatin. (http://www.ncbi.nlm.nih.gov/pubmed/20413454)

A 68-Year-Old Man Comes to the Office with a 6-Week