Statins Fibrates

FIBRATES STATINS Gemfibrozil may t atorvastatin, rosuvastatin and simvastatin levels (risk of myopathy with simvastatin) Uncertain Avoid co-administration of simvastatin and gemfibrozil. When using other statins, warn patients to watch for the features of myopathy... 

DAPTOMYCIN LIPID-LOWERING DRUGS -FIBRATES, STATINS Risk of myopathy Additive effect Avoid co-administration... 

Clinically important, potentially hazardous interactions with fibrates, statins... 

ACCORD (Action for Central CV-risk in Diabetes) ACCORD investigators NIH/NHLBI/ NIDDK (a) Better Hbalc, and/or (b) better SBP, and/or (c) use of feno-fibrate + statin vs. statin alone. T2 DM patients (10,251) 2010... 

Schelleman H, Bilker WB, Brensinger CM, Wan F, Yang YX, Hennessy S. Fibrate/ statin initiation in warfarin users and gastrointestinal bleeding risk. Am J Med 2010 123(2) 151-7. 

Combination drug therapy is an effective means to achieve greater reductions in LDL cholesterol (statin + ezetimibe or bile acid resin, bile acid resin + ezetimibe, or three-drug combinations) as well as raising HDL cholesterol and lowering serum triglycerides (statin + niacin or fibrate). 

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)... 

Fibrates are the most effective triglyceride-lowering agents and also raise HDL cholesterol levels. Combination therapy with a fibrate, particularly gemfibrozil, and a statin has been found to increase the risk for myopathy. Of the 31 rhabdomyolysis deaths reported with cerivastatin use, 12 involved concomitant gemfibrozil.25 Therefore, more frequent monitoring, thorough patient education, and consideration of factors that increase the risk as reviewed previously should be considered. 

Familial combined hyperlipidemia may respond better to a fibrate and a statin than to a fibrate and a BAR. 

Dosingof selected agents by class fibrate (gemfibrozil 600 mg twice a day) niacin (1.5-3 g/day of immediate-release product) statin (simvastatin 10-40 mg/day if glomerular filtration rate [GFR] <30 mL/min, 20-80 mg/day if GFR >30 mL/min) bile acid sequestrant (cholestyramine 4-16 g/day). 

Fibrates are being combined with statins to expand their potential in the dyslipidemia market. A recent clinical study examined the effects of rosuvastatin (10) and fenofibrate as mono and combination therapy in hyperlipidemic diabetic patients [43]. In late 2006, large scale Phase III clinical trials of rosuvastatin in combination with a next-generation fibrate, ABT 335, were initiated for evaluation of safety and efficacy in patients with mixed dyslipidemia. 

Reports about the influence of HMG-CoA-reductase inhibitors are conflicting (F7, H42, J8, K22, K29, L15, M3, S33, T5). In general, the effect is minimal or nonexistent some statins, such as simvastatin and lovastatin, are even reported to have an increasing influence (H42, J8, S33, Ul). Fibrates and derivatives are reported to exert a lowering effect (B13, F4, M3). 

As discussed above, obesity is associated with dyslipidemia, a condition where high levels of low-density lipoprotein cholesterol (LDL-C) is common. Elevated LDL-C is strongly associated with an elevated risk of coronary artery disease and for this reason a number of lipid-lowering therapies that target LDL-C have been developed. These include bile-acid sequestrants (BAS), statins (HMG-CoA reductase inhibitors), cholesterol absorption inhibitors, and fibrates. ... 

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. 

Action HMG-CoA reductase inhibitor Dose 5-40 mg PO daily max 5 mg/d w/cyclosporine, 10 mg/d w/gemfibrozil or CrCl <30 mL/min (avoid Al-/Mg-based antacids for 2 h after) Caution [X, /-] Contra Active Uvct Dz, unej lained t LFT Disp Tabs SE Myalgia, constipation, asthenia, abd pain, N, myopathy, rarely rhabdomyolysis Interactions t Effects OF warfarin t risk of myopathy W/ cyclosporine, fibrates, niacin, statins EMS t Effects of warfarin concurrent EtOH use can t risk of liver tox Asian pts have an t risk of advise effects OD Unlikely to cause life-threatening Sxs... 

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