Statins Gemfibrozil

Because the costs for chronic preventative pharmacotherapy are the same for primary and secondary prevention, while the risk of events is higher with secondary prevention, secondary prevention is more cost effective than primary prevention of CHD. Pharmacotherapy demonstrating cost effectiveness to prevent death in the ACS and post-MI patient includes fibrinolytics ( 2,000 to 33,000 cost per year of life saved), aspirin, glycoprotein Ilb/IIIa receptor blockers ( 13,700 to 16,500 per year of life added), (3-blockers (less than 5,000 to 15,000 cost per year of life saved), ACE inhibitors ( 3,000 to 5,000 cost per year of life saved), eplerenone ( 15,300 to 32,400 per year of life gained), statins ( 4,500 to 9,500 per year of life saved) and gemfibrozil ( 17,000 per year of life saved).49-58 Because cost-effectiveness ratios of less than 50,000 per added life-year are considered economically attractive from a societal perspective,49 pharmacotherapy described above for ACS and secondary prevention are standards of care because of their efficacy and cost attractiveness to payors. 

Gemfibrozil 600 mg tablets 1200 mg/day in two doses, 30 minutes before meals abdominal pain, and rash. Increased risk of rhabdomyolysis when given with a statin. Fibric acids are associated with gallstones, myositis, and hepatitis. 

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. 

Hyperlipidemia Diet HMG-CoA reductase inhibitors (stati ns) Gemfibrozil Ezetemibe CSA greater than TAC consider switch to TAC discontinue or hold SRL CSA/TAC may increase statin levels start at lowest dose Monitor for muscle cramps, CPK levels and LFTs Adjust dose in those with Rl Caution with concomitant statin Often used in combination with a statin... 

Regimens intended to increase HDL levels should include either gemfibrozil or niacin, bearing in mind that statins combined with either of these drugs may result in a greater incidence of hepatotoxicity or myositis. 

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). 

A potential drug-drug interaction has also been described for the combination of gemfibrozil with several statins. Studies in healthy volunteers have demonstrated that gemfibrozil increased the AUC and Cm ix of rosuvastatin by 1.9- and 2.2-fold, respectively [43]. These results could be confirmed in vitro using Xenopus oocytes. In these experiments, gemfibrozil inhibited OATPIBl-mediated rosuvastatin transport... 

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... 

Prueksaritanont T, Zhao JJ, Ma B, et al. Mechanistic studies on metabolic interactions between gemfibrozil and statins. Pharmacol Exp Ther 2002 301(3) 1042-1051. 

The fibrates are another class of antihyperlipidemic drug and are frequently coadministered with a statin. Fibrates act as agonists of the peroxisome proliferator-activated receptors (PPAR), particularly PPAR-a. PPARs are nuclear receptors that influence gene expression and lipid metabolism. Examples of fibrates include gemfibrozil (Lopid, A.110) and fenofibrate (Tricor, A.lll) (Figure A.30). Fenofibrate is hydrolyzed in the body to its active form, fenofibric acid (A.112). Fibrates do not decrease LDL levels as effectively as statins, but fibrates do elevate HDL cholesterol levels. 

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