Simvastatin 4- Gemfibrozil

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). 

Drugs that may affect repaglinide include CYP 450 inhibitors (eg, clarithromycin, erythromycin, ketoconazole, miconazole), CYP 450 inducers (eg, barbiturates, carbamazepine, rifampin), beta blockers, calcium channel blockers, chloramphenicol, corticosteroids, coumarins, estrogens, gemfibrozil, isoniazid, itraconazole, levonorgestrel and ethinyl estradiol, MAOIs, nicotinic acid, NSAIDs, oral contraceptives, phenothiazines, phenytoin, probenecid, salicylates, simvastatin, sulfonamides, sympathomimetics, thiazides and other diuretics, and thyroid products. 

Concomitant lipid-lowering therapy- Simvastatin is effective alone or when used concomitantly with bile acid sequestrants. The combined use of simvastatin with gemfibrozil, other fibrates, or lipid-lowering doses (1 g/day or more) of niacin should be avoided unless the benefit of further alteration in lipid levels is likely to outweigh the increased risk of this drug combination. 

Ezetimibe/Simvastatin (Vytorin) [Antilipemic/HMG CoA Reductose Inhibitor] Uses H rp cholest olemia Action X Absorption of cholesterol phytost ol w/ HMG-CoA reductase inhibitor Dose 10/10-10/80 mg/d PO w/ cyclosporine or danazol 10/10 mg/d max w/ amio-darone or verapamil 10/20 mg/d max -1- w/ sev e renal insuff Caution [X, -] w/ CYP3A4 inhibitors (Table VI-8), gemfibrozil, niacin >lg/d, danazol, amiodarone, verapamil Contra PRG/lactation livCT Dz, t LFTs Disp Tabs SE HA, GI upset, myalgia, myopathy (muscle pain, weakness, or tendOTiess w/ CK 10 x ULN, rhab-domyolysis), Hep, Infxn Interactions t Risk of myopathy W7 clarithromycin, erythromycin, itraconazole, ketoconazole EMS None OD Sxs unknown symptomatic and supportive... 

Simvastatin (Zocor) [Anrilipemic/HMG-CoA Reductase Inhibitor] Uses X Cholesterol Action HMG-CoA reductase inhibitor Dose Adults. 5-80 mg PO w/ meals X in renal insuff Peds. 10-17 y 10 mg, 40 mg/daily max Caution [X, —] Avoid concurrent use of gemfibrozil Contra PRG, liver Dz Disp Tabs 5,10, 20, 40, 80 mg SE HA, GI upset, myalgia, myopathy (muscle pain, tenderness or weakness w/ creatine kinase 10 x ULN), Hep Interactions T Effects OF digoxin, warfarin T risk of myopathy/iiiabdomyolysis W/ amiodarone, cyclosporine, CYP3A4 inhibitors, fibrates, HIV protease inhibitors, macrolides, niacin, verapamil, grapefruit juice X effects W/ cholestyramine, colestipol, fluvas-tatin, isradipine, propranolol EMS T Effects of warfarin use amiodarone and... 

Backman JT, Kyrklund C, Kivisto KT, Wang JS, Neuvonen PJ. Plasma concentrations of active simvastatin acid are increased by gemfibrozil. Clin Pharmacol Ther 2000 68(2) 122-9. 

Severe rhabdomyolysis occurred in a 52-year-old woman taking a combination of gemfibrozil and simvastatin (44). 

Tal A, Rajeshawari M, Isley W. Rhabdomyolysis associated with simvastatin-gemfibrozil therapy. South Med J 1997 90(5) 546-7. 

Maxa JL, Melton LB, Ogu CC, Sills MN, Limanni A. Rhabdomyolysis after concomitant use of cyclosporine, simvastatin, gemfibrozil, and itraconazole. Ann Pharmacother 2002 36(5) 820-3. 

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... 

Muggeo M, Travia D, Querena M, Zenti MG, Bagnani M, Branzi P, et al. Long term treatment with pravastatin, simvastatin and gemfibrozil in patients with primary hypercholester-olaemia, a controlled study. Drug Invest 1992 4 376-85. 

Myopathy occurred in a 73-year-old woman taking simvastatin 80 mg/day and gemfibrozil 600 mg bd 4 days after she started to take roxithromycin 300 mg/day (18). 

Clinically important, potentially hazardous interactions with amiloride, aminoglycosides, amphotericin B, ampicillin, anisindione, anticoagulants, armodafinil, atorvastatin, azathioprine, azithromycin, bacampicillin, basiliximab, bezafibrate, bosentan, bupropion, carbenicillin, caspofungin, cholestyramine, clarithromycin, cloxacillin, co-trimoxazole, corticosteroids, cyclophosphamide, daclizumab, danazol, dicloxacillin, dicumarol, digoxin, diltiazem, disulfiram, echinacea, erythromycin, ethotoin, etoposide, ezetimibe, flunisolide, fluoxymesterone, fluvastatin, foscarnet, fosphenytoin, gemfibrozil, hemophilus B vaccine, HMG-CoA reductase inhibitors, imatinib, imipenem/cilastatin, influenza vaccines, ketoconazole, lanreotide, lopinavir, lovastatin, mephenytoin, methicillin, methoxsalen, methylphenidate, methylprednisolone, methyltestosterone, mezlocillin, mizolastine, mycophenolate, nafcillin, nisoldipine, NSAIDs, orlistat, oxacillin, penicillins, phellodendron, phenytoin, pravastatin, prednisolone, prednisone, pristinamycin, ranolazine, red rice yeast, rifabutin, rifampin, rifapentine, ritonavir, rosuvastatin, simvastatin, sirolimus, spironolactone, St John s wort, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfisoxazole, sulfonamides, tacrolimus, telithromycin, tenoxicam, testosterone, ticarcillin, tolvaptan, trabectedin, triamterene, troleandomycin, ursodeoxycholic acid, vaccines, vecuronium, warfarin, zofenopril... 

Clinically important, potentially hazardous interactions with aminophylline, digoxin, disopyramide, ergot alkaloids, gemfibrozil, midazolam, simvastatin, terfenadine, warfarin... 

Hypertriglyceridemia usually responds well to niacin, gemfibrozil, or high-dose/potency statins (e.g., atorvastatin or simvastatin) niacin should be used cautiously in diabetics because of worsening glycemic control. 

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