Cholesterol-lowering statins are among the most prescribed medications in the United States. These drugs lower levels of low-density lipoprotein (LDL) cholesterol (the bad cholesterol) by up to 30 to 50 percent.
A high level of LDL cholesterol can lead to atherosclerosis (hardening and narrowing of the arteries) and cardiovascular disease. Statins stabilize the plaques that many people already have in their arteries, making them less likely to rupture. They also have anti-inflammatory and antioxidant effects. Through these measures, statins ultimately reduce the risk of heart attack and stroke.
Many people who take statins also take other drugs to reduce the risk for heart attack, stroke, and other cardiovascular conditions. These drugs include fibrates (for lowering triglycerides), blood thinners (for reducing clots), calcium channel blockers (for high blood pressure and other conditions), and others.
Whenever multiple drugs are taken, there is a risk for drug-drug interactions (DDI). Statin-related DDIs can range from mild muscle aches or weakness to a severe form of muscle damage known as rhabdomyolysis. Rhabdomyolysis is the breakdown of muscle tissue. It results in the release of a protein, called myoglobin, into the blood. Myoglobin can damage the kidneys. Symptoms include dark, reddish urine, a decreased amount of urine, muscles aches and weakness
Talk to your physician about how to minimize side effects if you take any of the following combinations of drugs:
Patients with high triglycerides or complex lipid disorders—such as metabolic syndrome, obesity, and/or diabetes are sometimes are treated with both a statin and a fibrate drug. The fibrates include gemfibrozil (Lopid) and fenofibrate (Tricor). Gemfibrozil is particularly risky when combined with some statins.
Blood levels of lovastatin (Mevacor) and simvastatin (Zocor) can double or triple when combined with gemfibrozil. Gemfibrozil plus pravastatin (Pravachol) can increase statin concentrations in the blood by more than 200 percent. When blood levels of a statin you’re taking reach such high levels, it can increase the risk for rhabdomyolysis.
To be safer, choose the fibrate fenofibrate. According to the FDA’s Adverse Event Reporting System, reports of rhabdomyolysis are 15 times lower with this drug than with gemfibrozil. However, fenofibrate is much more expensive, and not all patients will tolerate it.
Another option is the statin fluvastatin (Lescol). Unlike the three statins mentioned above, fluvastatin doesn’t interact with gemfibrozil.
For patients who must take one of the higher-intensity statins, such as atorvastatin (Lipitor), rosuvastatin (Crestor), or pitavastatin (Livalo) along with gemfibrozil, a lower statin dose can help minimize the risk for side effects.
People who are candidates for statins may also require a blood thinner. Warfarin (Coumadin) is often prescribed for patients with a high risk for stroke, heart attack, or blood clots (including those leading to a pulmonary embolism). It’s also used in people who have had a previous stroke or damage to a heart valve.
Statins may increase the effects of warfarin. When doses of warfarin are too high, it can lead to bleeding. Warning signs include bleeding gums when brushing your teeth, bloody urine or dark stools due to internal bleeding, or sudden, unexplained fatigue (possibly due to anemia).
Some reports have found that warfarin plus simvastatin can cause up to a 30 percent change in a patient’s international normalized ratio (INR), a standard measure of how quickly blood clots. Patients who show a marked change in INR might be advised to take pitavastatin or atorvastatin. They appear less likely to affect the INR than other statin drugs.
When you first combine warfarin with a statin, or when you change a statin dose, you should have frequent blood tests to check your INR so the warfarin dose can be adjusted if needed.
Once the drug effects have stabilized and you have good clotting control, testing can be scaled back to once or twice a month.
In some cases, patients may be able to switch to rivaroxaban (Xarelto) or another one of the newer blood thinners instead of warfarin.
Many patients with high cholesterol also have high blood pressure, stable angina, or arrhythmias, all of which may be treated with a calcium channel blocker drug.
One drug in this class, amlodipine (Norvasc), may increase risk for muscle damage when combined with simvastatin or lovastatin. Other calcium channel blockers, such as diltiazem (Cardizem) and verapamil (Verelan), increase blood levels of simvastatin, atorvastatin, and lovastatin.
The degree of interaction is lower when amlodipine is combined with atorvastatin or pravastatin. Some patients may report occasional fatigue or muscle pain, but the dose of one drug could be lowered to avoid the side effects.
The combinations of diltiazem with lovastatin or simvastatin, or verapamil with the same statins, can cause moderate increases in statin levels. However, lowering the statin dose might be all that’s needed to prevent side effects, such as muscle pain and fatigue.
