Gemfibrozil Lovastatin

Type IV Endogenous hyperlipemia (T VLDL production -l removal) Increased VLDL Nicotinic acid, gemfibrozil, lovastatin... 

The plasma levels of lovastatin, simvastatin, atorvastatin and pravastatin are increased by gemfibrozil, the levels of fluvastatin are increased by bezaflbrate, and the levels of pravastatin are increased by fenoflbrate. No pharmacokinetic interactions occur with the combinations of fluvastatin with gemfibrozil, lovastatin with bezaflbrate, and pravastatin, rosuvastatin or simvastatin with fenoflbrate. Both statins and fibrates are known to cause rhabdomyolysis, and their concurrent use increases the risk of this reaction. 

Myopathy and rhabdomyolysis associated with lovastatin-gemfibrozil combination therapy. JAMA 1990 264 71. 

Sanllehy C, Casals E, Rodriguez-Vil-lar C, Zambon D, Ojuel J, Ballesta AM, et al. Lack of interaction of apolipo-protein E phenotype with the lipoprotein response to lovastatin or gemfibrozil in patients with primary hypercholesterolemia. Metabolism 1998 47 560-565. 

Gemfibrozil, fenofibrate, and lovastatin are available as generic products. This table does not include all drugs used for treating dyslipidemia. 

Drugs of this series include clofibrate and gemfibrozil, which are derivatives of phenoxy-carboxylic acids—fibrates probucol, which is a substituted fc/y-mercaptophenol and also natural compounds lovastatin, mevastatin, and their analogs. They will be examined separately because it is difficult to explain their action via the entire mechanism. 

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. 

Drugs that may interact with gemfibrozil include oral anticoagulants and lovastatin. 

Fenofibrate (Anatra, Lipofen, Lofibra, TriCor, Triglide) Fluvastatin (Lescol) Gemfibrozil (Lopid) Lovastatin (Mevacor, Altocor)... 

Lovastatin (Mevacor/ Altocor) [Antilipemic/HMG-CoA Reductase Inhibitor] Uses Hypercholesterolemia Action HMG-CoA reductase inhibitor Dose 20 mg/d PO w/ PM meal may T at 4-wk intervals to 80 mg/d max or 60 mg ER tab take w/ meals Caution [X, -] Avoid w/ grapefruit juice, gemfibrozil. Contra Active liver Dz Disp Tabs SE HA GI intolerance common promptly report any unexplained muscle pain, tenderness, or weakness (myopathy) Interactions T Effects W/ grapefruit juice T risk of severe myopathy W/ azole antifungals, cyclosporine, erythromycin, gemfibrozil, HMG-CoA inhibitors, niacin T effects OF warfarin >1 effects W/ isradipine, pectin EMS t Risk of photosensitivity Rxns T effects of warfarin concurrent EtOH use t risk of liver tox diltiazem and verapamil can T risk of lovastatin tox OD Unlikely to cause life-threatening Sxs... 

In 80 patients with primary mixed hyperlipidemia, gemfibrozil used together with lovastatin resulted in 3% discontinuation because of myositis, but none attributable to rhabdomyolysis or myoglobinuria (72). 

In a retrospective series, 4 (5%) out of 80 subjects taking lovastatin and gemfibrozil developed a myopathy. Based on this and on reports to US Food and Drug Administration the combined use of the two drugs is discouraged, especially in patients with compromised renal and/or hepatic function. Elderly women may be at special risk (73,74). 

Kyrklund C, Backman JT, Kivisto KT, Neuvonen M, Laitila J, Neuvonen PJ. Plasma concentrations of active lovastatin acid are markedly increased by gemfibrozil but not by bezafibrate. Clin Pharmacol Ther 2001 69(5) 340-5. 

Goldstein MR. Myopathy and rhabdomyolysis with lovastatin taken with gemfibrozil. JAMA 1990 264(23) 2991-2. 

Lovastatin in combination with gemfibrozil caused a rise in creatine kinase activity 234 000 U/l, with complete remission after both drugs had been withdrawn (15). 

Rhabdomyolysis requiring short-term dialysis occurred in a 57-year-old man with chronic renal insufficiency treated with lovastatin 40 mg/day, gemfibrozil 600 mg bd, and clarithromycin 500 mg tds (18). 

Treatment Weight reduction (if necessary) is of primary Importance. Dietary restriction of controlled carbohydrate, modified fat, low alcohol consumption. If necessary, drug therapy includes niacin and/or gemfibrozil (or clofibrate), or lovastatin (or mevastatin). 

Deltoro MG, Rocati G, CavaniUes CR, CerveUera AG, Catala JC, Belda JE, De Lehs FP, Rodena JV, Gonzalez EO, Ballester AH. Rhabdomyolysis and renal failure due to lovastatin-gemfibrozil. A case report. Endocrinologia 1998 45 35-7. 

---