Lipitor (atorvastatin) vs. Vytorin (simvastatin and ezetimibe)

• Lipitor (atorvastatin) and Vytorin (simvastatin and ezetimibe) are used to lower cholesterol levels in the blood.
• Lipitor and Vytorin contain HMG-CoA reductase inhibitors (“statins”). Vytorin also contains another cholesterol-lowering drug.
• Side effects of Lipitor and Vytorin that are similar include diarrhea and headache.
• Side effects of Lipitor that are different from Vytorin include constipation, fatigue, gas, heartburn, common cold, joint pain, pain in the extremities, and urinary tract infection (UTI).
• Side effects of Vytorin that are different from Lipitor include nausea, vomiting, muscle pain, and abnormal liver tests.

Lipitor (atorvastatin) is a “statin” drug (an HMG-CoA reductase inhibitor) used to lowers cholesterol levels in the blood. Lipitor reduces total cholesterol and LDL (“bad”) cholesterol, which is mainly responsible for the development of coronary artery disease. Reducing LDL cholesterol slows and may reverse coronary artery disease. Lipitor also raises HDL ("good") cholesterol that protects against coronary artery disease and reduces the concentration of triglycerides in the blood, which also have been associated with coronary artery disease. In individuals with coronary artery disease Lipitor prevents stroke, heart attack, angina, hospitalization for congestive heart failure, and revascularization procedures.

Vytorin (simvastatin and ezetimibe) is a combination of a statin drug and another cholesterol-lowering drug used for treating high levels of cholesterol in the blood. Vytorin reduces total cholesterol and LDL ("bad") cholesterol while increasing HDL ("good") cholesterol. The ezetimibe component of Vytorin lowers blood cholesterol by blocking the absorption of cholesterol, including dietary cholesterol, from the intestine. The simvastatin component of Vytorin reduces cholesterol by blocking an enzyme in the liver (HMG-CoA reductase) that produces cholesterol. Statins lower total and LDL cholesterol in the blood as well as triglycerides. They also increase HDL cholesterol. Lowering LDL cholesterol levels slows and may reverse coronary artery disease. Raising HDL cholesterol levels also may slow coronary artery disease.

Lipitor

Lipitor is generally well tolerated. Minor side effects include:

• Constipation
• Diarrhea
• Fatigue
• Gas
• Heartburn
• Headache

Other commonly reported side effects include:

• Common cold (nasopharyngitis)
• Joint pain (arthralgia)
• Pain in the extremities
• Urinary tract infection

Lipitor may cause liver and muscle damage. Serious liver damage caused by statins is rare. Liver tests should be performed at the beginning of treatment then as needed thereafter.

Inflammation of the muscles caused by statins can lead to serious breakdown of muscle cells called rhabdomyolysis. Rhabdomyolysis causes the release of muscle protein (myoglobin) into the blood, and myoglobin can cause kidney failure and even death. When used alone, statins cause rhabdomyolysis in less than one percent of patients. To prevent the development of serious rhabdomyolysis, patients taking atorvastatin should contact their health-care professional immediately if they develop unexplained muscle pain, weakness, or muscle tenderness.

Statins have been associated with increases in HbA1c and fasting serum glucose levels as seen in diabetes.

Post-marketing reports for atorvastatin of adverse events include:

• Memory loss
• Forgetfulness
• Amnesia
• Confusion
• Memory impairment

Symptoms may start one day to years after starting treatment and resolve within a median of three weeks after stopping the statin.

Vytorin

The most common side effects of Vytorin are:

• headache,
• nausea,
• vomiting,
• diarrhea,
• muscle pain, and
• abnormal liver tests.

Hypersensitivity reactions also have been reported. The most serious potential side effects are liver damage and muscle inflammation or breakdown. The simvastatin component of Vytorin is a statin. Therefore it shares side effects, such as liver and muscle damage associated with statins. Serious liver damage caused by statins is rare. More often, statins cause abnormalities of liver tests, and, therefore, periodic measurement of liver tests in the blood is recommended for all statins. Abnormal tests usually return to normal even if a statin is continued, but if the abnormal test value is greater than three times the upper limit of normal, the statin usually is stopped. Liver tests should be measured before Vytorin is started and periodically thereafter or if there is a medical concern about liver damage.

Inflammation of the muscles caused by statins can lead to a serious breakdown of muscle cells called rhabdomyolysis. Rhabdomyolysis causes the release of muscle protein (myoglobin) into the blood. Myoglobin can cause kidney failure and even death. When used alone, statins cause rhabdomyolysis in less than one percent of patients. To prevent the development of rhabdomyolysis, patients taking Vytorin should contact their health care professional immediately if they develop unexplained muscle pain, weakness, or muscle tenderness.

Statins have been associated with increases in HbA1c and fasting serum glucose levels that are seen in diabetes. There are also post-marketing reports of memory loss, forgetfulness, amnesia, confusion, and memory impairment. Symptoms may start 1 day to years after starting treatment and resolve within a median of 3 weeks after stopping the statin.

Lipitor

• Lipitor is prescribed once daily.
• The usual starting dose for adults is 10-20 mg per day, and the maximum dose is 80 mg per day. Adults who need more than a 45% reduction in LDL cholesterol may be started at 40 mg daily.
• Pediatric patients should receive 10 mg once daily up to a maximum dose of 20 mg daily.

Lipitor may be taken with or without food and at any time of day

Vytorin

The recommended dose range of Vytorin is 10/10 mg to 10/40 mg, and it is administered once daily in the evening with or without food. Therapy usually is initiated with 10/10 or 10/20 mg daily, but individuals who need more than a 55% reduction in LDL cholesterol can be started on 10/40 mg daily.

Vytorin 10/80 mg is restricted to patients who have been taking Vytorin 10/80 mg chronically (for example, for 12 months or more) without evidence of muscle toxicity because the 10/80 mg dose is associated with increased risk of muscle toxicity, including rhabdomyolysis. Patients who are currently tolerating the 10/80-mg dose of Vytorin and who need an interacting drug that should not be taken with high doses of simvastatin should be switched to an alternative statin or statin-based regimen with less potential for the drug-drug interaction. Patients new to treatment with Vytorin who require more than the 10/40 mg dose should be switched to alternative agents.

Lipitor

Decreased elimination of Lipitor could increase levels of Lipitor in the body and increase the risk of muscle toxicity from Lipitor. Therefore, Lipitor should not be combined with drugs that decrease its elimination. Examples of such drugs includes:

• erythromycin (E-Mycin),
• ketoconazole (Nizoral),
• itraconazole (Sporanox),
• clarithromycin (Biaxin),
• telithromycin (Ketek),
• cyclosporine (Sandimmune),
• nefazodone (Serzone), and
• HIV protease inhibitors such as indinavir (Crixivan) and ritonavir (Norvir).

Large quantities of grape fruit juice (>1.2 liters daily) also will increase blood levels of Lipitor and should not be taken.

The following drugs also may increase the risk of muscle toxicity when combined with Lipitor.

• amiodarone (Cordarone)
• verapamil (Calan Verelan, Isoptin)
• cyclosporine (Sandimmune)
• niacin (Niacor, Niaspan, Slo-Niacin)
• gemfibrozil (Lopid)
• fenofibrate (Tricor)

Lipitor increases the effect of warfarin (Coumadin) and the concentration in blood of digoxin (Lanoxin). Patients taking Lipitor and warfarin or digoxin should be monitored carefully. Cholestyramine (Questran) decreases the absorption of Lipitor. Lipitor should be given at least two hours before and at least four hours after cholestyramine.

Rifampin increases breakdown of Lipitor. To reduce the likelihood of this interaction both drugs should be given at the same time. Lipitor should not be given after rifampin.

Vytorin

Vytorin contains simvastatin (Zocor), and numerous drugs block the elimination of simvastatin by the liver. Decreased elimination of simvastatin could increase the levels of simvastatin in the body and increase the risk of muscle toxicity from simvastatin. Vytorin should not be combined with drugs that decrease its elimination. Examples of these drugs include erythromycin (E-Mycin), ketoconazole (Nizoral), itraconazole (Sporanox), clarithromycin (Biaxin), telithromycin (Ketek), cyclosporine (Sandimmune), nefazodone (Serzone), boceprevir (Victrelis), telaprevir (incivek), voriconazole (Vfend), posaconazole (Noxafil), and HIV protease inhibitors such as indinavir (Crixivan) and ritonavir (Norvir).

Large quantities of grape fruit juice (>1 quart daily) also will increase blood levels of simvastatin and should be avoided.\

Amiodarone (Cordarone), verapamil (Calan Verelan, Isoptin), diltiazem, amlodipine (Norvasc), danazol (Danocrine), ranolazine (Ranexa) cyclosporine (Gengraf, Neoral), niacin (Niacor, Niaspan, Slo-Niacin), gemfibrozil (Lopid) and fenofibrate (Tricor) also may increase the risk of muscle toxicity when combined with simvastatin.

Patients taking amiodarone, amlodipine, or ranolazine should not exceed 10/20 mg, and those taking verapamil or diltiazem should not exceed 10/10 mg of of Vytorin daily.

Patients taking gemfibrozil or danazol should not take Vytorin.

Simvastatin increases the effect of warfarin (Coumadin) and the blood concentration of digoxin (Lanoxin). Patients taking simvastatin and warfarin or digoxin should be monitored carefully. Cholestyramine (Questran) decreases the absorption of ezetimibe, and, therefore, Vytorin should be administer two hours before or at least four hours after cholestyramine is administered.

Chinese patients taking more than 1 gram of niacin daily in combination with simvastatin, 40 mg, have an increased risk of muscle-related side effects. Therefore, these patients should not receive Vytorin 10/80 mg combined with niacin doses greater than 1 gram daily. Other doses of Vytorin should be administered cautiously when combined with niacin, 1 gram daily.

Lipitor

• Lipitor should not be taken during pregnancy because the developing fetus requires cholesterol for development, and Lipitor reduces the production of cholesterol. Lipitor should only be administered to women of childbearing age if they are not likely to become pregnant.
• It is not known if Lipitor is secreted in breast milk. Because of the potential risk of adverse events, breastfeeding mothers should not use Lipitor.

Vytorin

• Vytorin should not be taken during pregnancy because the developing fetus requires cholesterol for development, and Vytorin, due to the simvastatin component, reduces the production of cholesterol. Vytorin should only be administered to women of child bearing age if they are not likely to become pregnant.
• Because of the risk of adverse effects to the developing infant, Vytorin should not be administered to nursing mothers.