Statins Nicotinic acid

Clinically important, potentially hazardous interactions with dicumarol, ezetimibe, lovastatin, nicotinic acid, statins, warfarin... 

Specific concomitant medications or consumptions (check specific statin package insert for warnings) fibrates (especially gemfibrozil, but other fibrates too), nicotinic acid (rarely), cyclosporine, azole antifungals such as itraconazole and ketoconazole, macrolide antibiotics such as erythromycin and clarithromycin, protease inhibitors used to treat Acquired Immune Deficiency Syndrome, nefazodone (antidepressant), verapamil, amiodarone, large quantities of grapefruit juice (usually more than 1 quart per day), and alcohol abuse (independently predisposes to myopathy)... 

Rhabdomyolysis is the destruction of skeletal muscle tissues and may be associated with lipid-regulating drugs such as the fibrates and the statins. The risk of this side-effect is increased in patients with renal impairment and with hypothyroidism. Rhabdomyolysis may also occur with nicotinic acid, the antipsychotic aripiprazole, and the anaesthetic propofol. 

Drugs used to increase HDL levels (fibrates, nicotinic acid, and statins) in otherwise normal people do not have the same effect in patients with Tangier disease. Therefore, it is necessary to identify and treat other risk factors associated with CAD. Exercise, weight reduction, dietary cholesterol and saturated fat reduction, and smoking cessation are the first line in management of low HDL cholesterol. Dietary management with low fat intake is beneficial in reducing the risk for CAD, as well... 

The British National Formulary (BNF) recommends that fibrates or nicotinic acid should not be combined with statins because of the potential for myopathy and rhabdomyolysis with this combination [54]. This is widely discussed in the medical literature. Numerous deaths have been reported and the high mortality associated with concurrent use of cerivastatin and gemfibrozil was partly instrumental in the decision to withdraw cerivastatin from the market in 2001 [34]. It appears that the high mortality in patients using concurrent gemfibrozil and cerivastatin was due to interactions at the level of glucuronidation, CYP2C8 inhibition and OATP inhibition [17, 55]. 

STATINS NICOTINIC ACID Slight risk of rhabdomyolysis Uncertain at present Monitor LFTs and CK closely warn patients to report any features of rhabdomyolysis... 

The fibrates act at the level of the liver to decrease VLDL-TG substantially and to increase HDLc secretion. Nicotinic acid also decreases TG and is considered to the most potent agent to increase HDL. The effects of fibrates and nicotinic acid on TG and HDL are generally greater than those observed with statins, which are generally the most effective LDLc-lowering agents. 

Drugs used in treatment statins fibric acid derivatives anion-exchange resins nicotinic acid and derivatives... 

Familial combined hjrperlipidaemia should be treated with dietary modification and weight reduction (above) together with a statin nicotinic acid and/or a fibrate may be added in resistant cases. 

Familial or polygenic hypercholesterolaemia is treated by dietary modification and a statin an anion-exchange resin and/or a fibrate and/or nicotinic acid may be added. 

Familial hypoalphalipoproteinaemia may respond to exercise, weight loss, and nicotinic acid a fibrate and/or a statin may be added for a small HDL-raising effect but primarily to lower triglycerides and LDL. 

Statins are well absorbed after administration orally, and are metabolised in the liver. They are well tolerated, the commonest adverse effect being transient, and usually minor abnormality of liver function tests in some 1% of patients. Asymptomatic elevation of muscle enzymes (creatine phos-phokinase, CPK) and myositis (with a generalised muscle discomfort) occur more rarely, but is more frequent when statins are combined with other anti-hyperlidaemic drugs such as fibrates and nicotinic acid patients should be counseled about myositis when these drugs are co-administered. Myositis is also more likely with co-administered anti-HIV protease inhibitors, and with drugs that interfere with metabolism of some statins, e.g. ciclosporin. 

HMC-CoA reductase (the "statins"), nicotinic acid, and bile-acid binding resins (cholestyramine). 

Four main classes of lipid-lowering medications are available HMG CoA reductase inhibitors (otherwise known as statins), bile acid sequestrants, nicotinic acid, and fibric acids. 

Clinically important, potentially hazardous interactions with atorvastatin, bexarotene, cyclosporine, dicumarol, ezetimibe, fluvastatin, interferon alfa, lovastatin, nicotinic acid, pioglitazone, pravastatin, repaglinide, rosuvastatin, roxithromycin, simvastatin, statins, warfarin... 

Currently available treatments against atherosclerosis include cholesterol-lowering drugs such as statins, fibrates, nicotinic acid (NA) [8-13] and the cholesterol intestinal absorption inhibitor, ezetimibe (Fig. 1) [14]. 

Statins Ezitimibe Omega-3 triglycerides Bile acid sequestrants Fibrates Nicotinic acid derivatives Inhibit HMG-CoA reductase Inhibits absorption of cholesterol from the intestine Inhibit VLDL synthesis in the liver Bind bile acids in the intestine Lower levels of circulating VLDLs and LDLs by unknown mechanism Reduce the release of VLDLs from the liver... 

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