Gemfibrozil with statins

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... 

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]. 

Rosuvastatin (crestor) is available in doses ranging between 5 and 40 mg. It has a t of 20—30 hours and may be taken at any time of day. Since experience with rosuvastatin is more limited, treatment should be initiated with 5-10 mg daily, increasing stepwise if needed. If the combination of gemfibrozil with rosuvastatin is used, the dose of rosuvastatin should not exceed 10 mg. Rosuvastatin at a dose of 80 mg (dose not approved by the FDA) was noted to cause proteinuria and hematuria and isolated cases of renal failure. Other statins have also been observed to cause proteinuria, apparently by inhibiting tubular protein reabsorption. Whether statin-induced proteinuria is harmful or beneficial, especially in patients with chronic kidney disease, remains to be determined. 

It has been an attractive option to use combination therapy of statin and fibrate when HDL remains low but there is no data from RCTs to support this approach. It is ironic that gemfibrozil with the best outcome data should not be used in this context given drug interactions. The results of the FIELD trial with fenofibrate as sole therapy were disappointing [59] however, a combination trial with fenofibrate and statin in type 2 diabetes, the ACCORD study, is in progress. 

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. 

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. 

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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