What is niacin and lovastatin, and how does it work (mechanism of action)?
Advicor is an oral drug that is used for lowering cholesterol levels in the blood. It is a combination of extended-release niacin and lovastatin. It reduces blood levels of total cholesterol, low density lipoprotein (LDL) cholesterol, and triglycerides and increases blood levels of high density lipoprotein (HDL) cholesterol.
Niacin (nicotinic acid, vitamin B3) is a part of the normal diet that is essential for various chemical reactions in the body. Doses of niacin larger than normal dietary needs reduce cholesterol and triglyceride levels in the blood. Niacin reduces bad cholesterol (LDL cholesterol) and increases good cholesterol (HDL cholesterol). It is not clear how niacin causes its effects on cholesterol and triglyceride levels, but it may be by reducing the production of proteins that transport cholesterol and triglycerides in the blood.
Lovastatin belongs to a class of cholesterol-lowering drugs called HMG-CoA reductase inhibitors, or, more commonly, "statins." Other statins include simvastatin (Zocor), atorvastatin (Lipitor), fluvastatin (Lescol), and rosuvastatin (Crestor). Statins reduce cholesterol by inhibiting an enzyme in the liver (HMG-CoA reductase) that is necessary for the production of cholesterol. In the blood, statins lower LDL cholesterol and triglycerides. LDL cholesterol is believed to be an important cause of coronary artery disease. Lowering LDL cholesterol levels slows and may even reverse coronary artery disease. Statins also increase HDL cholesterol. Raising HDL cholesterol levels, like lowering LDL cholesterol may slow coronary artery disease.The combination of niacin and lovastatin is better than either drug alone in reducing cholesterol, reducing triglycerides and increasing HDL. The FDA approved Advicor in December 2001.
What are the side effects of niacin and lovastatin?
The most common side effects are:
- flushing,
- redness,
- warm sensation,
- rash,
- itching,
- headache,
- stomach upset,
- nausea,
- vomiting,
- muscle pain, and
- tingling in extremities.
Drinking hot liquids or alcohol shortly before or after niacin is taken may increase the occurrence of flushing.
Other important side effects include:
- liver test abnormalities,
- rhabdomyolisis,
- kidney failure,
- muscle pain,
- weakness,
- muscle tenderness,
- increases in HbA1c and fasting serum glucose
- memory loss,
- forgetfulness,
- amnesia,
- confusion, and
- memory impairment
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 lovastatin 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 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.
What is the dosage for niacin and lovastatin?
The recommended starting dose for Advicor is one tablet (500/20 mg). Doses can be increased by 500 mg of niacin every 4 weeks based on the response of the blood cholesterol level. Doses greater than 2000/40 mg are not recommended. Individuals already stabilized on niacin extended-release tablets can be directly switched to the niacin equivalent dose of Advicor. Individuals taking extended-release niacin and lovastatin separately can be switched to an equivalent dose of Advicor.
Other forms of niacin (for example, sustained-release, timed-release or immediate-release) are not equivalent to extended-release niacin in Advicor. Therefore, Advicor is not interchangeable with these niacin preparations, and patients taking these preparations should be switched and stabilized on extended-release niacin before switching to Advicor.
Advicor should be administered at bedtime with a low fat snack. Since there is evidence that at least some drugs in the same class as lovastatin lower cholesterol more when taken at night than in the morning. If Advicor is discontinued for longer than 7 days, therapy should be resumed at the lowest dose.
Which drugs or supplements interact with niacin and lovastatin?
Decreased elimination of lovastatin could increase the levels of lovastatin in the body and increase the risk of muscle toxicity from lovastatin. Examples of drugs that decrease elimination of lovastatin include erythromycin (E-Mycin), ketoconazole (Nizoral), itraconazole (Sporanox), clarithromycin (Biaxin), telithromycin (Ketek), cyclosporine (Sandimmune), nefazodone (Serzone), boceprevir (Victrelis), telaprevir (incivek), voriconazole (Vfend), and protease inhibitors such as indinavir (Crixivan) and ritonavir (Norvir). They should not be combined with lovastatin.
Large quantities of grape fruit juice (>1 quart daily) also will increase blood levels of lovastatin and should be avoided.
Amiodarone (Cordarone), verapamil (Calan, Verelan, Isoptin), diltiazem (Cardizem), danazol (Danocrine), niacin (Niacor, Niaspan, Slo-Niacin), colchicine, ranolazine (Ranexa), gemfibrozil (Lopid), and fenofibrate (Tricor) also may increase the risk of muscle toxicity when combined with lovastatin. Cyclosporine or gemfibrozil should not be combined with lovastatin. Patients taking amiodarone (Cordarone) should not exceed 40 mg daily of lovastatin. Patients taking verapamil, diltiazem, or danazol should start with 10 mg and should not exceed 20 mg of lovastatin daily. Patients taking niacin (greater than or equal to 1 g/day), fenofibrate (Tricor) or cyclosporine (Gengraf, Neoral) should not take more than 20 mg of lovastatin.
Lovastatin may increase the effect of warfarin (Coumadin), a blood thinner. Patients taking lovastatin and warfarin (Coumadin) should be monitored carefully for toxic effects of warfarin.
Niacin may increase blood glucose levels in individuals with diabetes. Therefore, medications for controlling blood glucose may need to be adjusted when niacin is taken by those with diabetes.
Bile acid sequestrants (for example, cholestyramine [Questran]) bind and prevent absorption of niacin. Administration of bile acid sequestrants and niacin should be separated by 4-6 hours. Alcohol or hot drinks may increase flushing and itching caused by niacin and should not be used when Advicor is ingested. Vitamins and nutritional supplements containing niacin or related compounds (for example, nicotinamide) will increase adverse effects of niacin and should not be combined with Advicor.
Is niacin and lovastatin safe to take if I'm pregnant or breastfeeding?
Advicor should not be administered to pregnant women because lovastatin can be harmful to the fetus. Niacin has not been evaluated in pregnant women at doses used for treating levels of cholesterol and triglycerides.
Niacin in Advicor is excreted in breast milk and may cause side effects if ingested by the infant.
No comments:
Post a Comment