Niacin with lovastatin

Concomitant lipid-lowering therapy - Generally avoid use of lovastatin with fibrates or niacin. If lovastatin is used in combination with gemfibrozil, other fibrates, or lipid-lowering doses (1 g/day or more) of niacin, the dose of lovastatin should not exceed 20 mg/day. 

Primary hypercholesterolemia/mixed dyslipidemia For the treatment of primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Frederickson Types lla and Mb) in the following Patients treated with lovastatin who require further TG-lowering or FIDL-raising who may benefit from having niacin added to their regimen patients treated with niacin who require further... 

The usual recommended starting dose of lovastatin is 20 mg once/day. Make dose adjustments at intervals of 4 weeks or more. Patients already receiving a stable dose of lovastatin may receive concomitant dosage titration with niacin extended-release tablets, and switch to niacin extended-release/lovastatin tablets once a stable dose of niacin extended-release tablets has been reached. 

F Before initiating statin therapy, it is recommended to have baseline measurements of the lipoprotein profile and LFTs. If the LFTs are more than three times the upper limit of normal (ULN), statins should be avoided. If the LFTs are less than three times the ULN, statin therapy can be initiated, but the patient should be monitored closely. If LFTs become elevated, reversal of the transaminase elevation is common upon discontinuation of the statin. Some experts also recommend obtaining a baseline creatine kinase (CK) level. If the CK level is more than 10 times the ULN while on a statin, the statin should be discontinued. The combination of a statin with niacin or a fibrate should be used cautiously because of an increased risk of myopathy. Although most statins are taken at dinner or bedtime, atorvastatin can be taken at any time of the day due to its longer T /i ( 14 hours). Lovastatin should be taken with food because this increases its bioavailabilty. 

The manufacturer does not recommend use of the fixed combination as initial therapy of primary hypercholesterolemia or mixed dyslipidemia. It is specifically Indicated in patients receiving lovastatin alone plus diet who require an additional reduction in triglyceride levels or increase in HDL cholesterol levels it is also Indicated In those treated with niacin alone who require additional decreases in LDL cholesterol. 

The Familial Atherosclerosis Treatment Study (FATS) randomized 146 men with elevated apolipoprotein B and family history of coronary artery disease to one of three strategies for 2.5 years niacin and colestipol, lovastatin and colestipol, or conventional therapy. Mean stenosis increased by 2.1% in the control group. In contrast, it decreased by 0.9% with niacin and colestipol and 0.7% with lovastatin and colestipol (F<0.003). Although clinical outcomes were not the primary endpoint, there was a 73% reduction in the combined intensive groups versus the conventionally treated group (Brown et al. 1990). 

Brown, B.G., Bardsley, J., Poulin, D., Hillger, L.A., Dowdy, A., Maher, V.M., Zhao, X.Q., Albers, J.J., and Knopp, R.H., 1997. Moderate dose, three-drug therapy with niacin, lovastatin, and colestipol to reduce low-density lipoprotein cholesterol < 100 mg/dl in patients with hyperlipidemia and coronary artery disease. American Journal of Cardiology. 80 111-115. 

Some patients, in particular those with genetic forms of hypercholesterolemia (Table 9-2), will require three or more drugs to manage their disorder. Regimens using a statin, resin, and niacin were found to reduce LDL cholesterol up to 75%.42 These early studies were conducted with lovastatin, so larger reductions would be expected with the more potent statins available today. 

In clinical trials, the combination of niacin with lovastatin (14) afforded significant HDL elevation (30%) and reduced LDL-C (47%) and TG (41%) after 16 weeks of treatment [19]. At 52 weeks of treatment, HDL increased by 41% with this combination therapy [19]. 

Crestor Astra-Zeneca) and lovastatin + niacin (Advicor Kos Pharmaceutical) — that can also cause rhabdomyolysis remain on the market. Although scientists agree that the other statins "seem to have essentially identical safety profiles and benefif-risk rafios," FDA said the ADRs associated with Baycol "have been reported significantly more frequently than for other approved statins." ... 

Take niacin extended-release/lovastatin tablets at bedtime, with a low-fat snack, and individualize dose according to patient response. 

Take whole do not break, chew, or crush before swallowing. Do not increase the dose by more than 500 mg/day (based on the niacin extended release component) every 4 weeks. The lowest dose of niacin extended-release/lovastatin tablets is 500/20 mg. Doses greater than 2000/40 mg/day are not recommended. If therapy is discontinued for an extended period (greater than 7 days), begin reinstitution of therapy with the lowest dose. 

It is clear from Equation (19.4) that saturated fat, not cholesterol, is the single most important factor that raises serum cholesterol. Some cases of hyperlipoproteinemia type IV (high VLDL) respond to low-carbohydrate diets, because the excess of VLDL comes from intestinal cells, where it is produced from dietary carbohydrate. Resins, such as cholestyramine and cholestipol, bind and cause the excretion of bile salts, forcing the organism to use more cholesterol. Lovastatin decreases endogenous cholesterol biosynthesis (see later), and niacin (nicotinic acid) apparently decreases the production of VLDL and, consequently, LDL. It also results in an HDL increase. Antioxidants that inhibit the conversion of LDL to oxidized LDL have also been used with some success. These are high doses of vitamin E and the drug probucol. 

Some combinations of lipid-altering drugs are currently available such as extended-release niacin/lovastatin and ezetimibe/simvastatin, which are more promising for lipid-lowering therapy with stronger effects and decreased adverse reactions. 

All HMGRIs are approved for the treatment of primary hypercholesterolemia and familial combined hyperlipidemia (Fredrickson s type Ha and lib) (Table 30.2) In patients who have not responded to diet, exercise, and other non pharmacological methods (Table 30.6) (15,21). They may be used either alone or In combination with bile acid sequestrants, ezetimibe, or niacin. As previously mentioned, they should be administered at least 1 hour before or 4 to 6 hours after bile acid sequestrants when this combination Is desired. Fluvastatin, lovastatin, pravastatin, and simvastatin have been specifically Indicated to reduce the mortality of CHD and stroke. By reducing plasma LDL levels, these compounds slow the progression of atherosclerosis and reduce the risk of myocardial Infarction and other ramifications of vascular occlusion. Atorvastatin, rosuvastatin, and simvastatin have been shown to be effective In homozygous familial hyperlipidemia and are Indicated for this use. Additionally, atorvastatin, pravastatin, and simvastatin are Indicated for primary dysbetallpoprotelnemla (Fredrickson s type III) (Table 30.2). Finally, atorvastatin, pravastatin, rosuvastatin, and simvastatin are Indicated for the treatment of hypertriglyceridemia. 

Millions of people in the world suffer from cardiovascular disease, and it is a leading cause of death in both men and women. Elevation in plasma low-density lipoprotein (LDL) cholesterol levels is a major risk factor for myocardial infarction (heart attack) in these patients. Drugs to reduce dyslipidemia have included niacin and the fibrate class, but each of these has clinical limitations, such as low efficacy or toxic side effects. The development of HMG-CoA reductase inhibitors, or statins, has had an enormous clinical impact on the treatment of heart disease and prevention of heart attack, and these are taken by tens of millions of patients worldwide [1]. One of the first such drugs, lovastatin, was discovered in the 1970s as a fungal natural product [2] and lowered lipid levels in animals and healthy volunteers. Problems with the development of another early statin, compactin, halted advancement of lovastatin to regular clinical use until the late 1980s. Since then. 

Hiatt WR, Hirsch AT, Creager MA, Rajagopalan S, Mohler ER, Ballantyne CM, Regensteiner JG, Treat-Jacobson D, Dale RA. Effect of niacin ER/lovastatin on claudication symptoms in patients with peripheral artery disease. Vase Med 2010 15 171-9. 

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