Combining simvastatin with which agent can increase the risk of myalgias?

The combination of simvastatin and gemfibrozil significantly increases the risk of myalgias, largely due to the way both drugs are metabolized in the body. Simvastatin is primarily processed by the liver enzyme CYP3A4, and gemfibrozil can inhibit this enzyme, leading to higher concentrations of simvastatin in the blood. This elevated level can enhance the potential side effects of simvastatin, including muscle-related issues such as myopathy or myalgias.

While atorvastatin, fenofibrate, and ezetimibe can interact with simvastatin, these interactions do not lead to the same pronounced risk of myopathy as seen with gemfibrozil. Atorvastatin is another statin, and while combining statins can lead to increased side effects, they are not specifically known to cause a significant rise in myalgia when used together. Fenofibrate, when combined with statins, has a more favorable profile and is often used cautiously due to the potential for increased muscle effects, but gemfibrozil is the known culprit. Ezetimibe works differently in lipid lowering by reducing intestinal absorption of cholesterol and does not have the same enzyme-inhibiting effect as gemfibrozil.