Rosuvastatin Gemfibrozil

OATPIBI (SLCO) Gemfibrozil Rosuvastatin Pravastatin Simvastatin Lovastatin 2-fold increase in AUC Inhibition of hepatic sinusoidal OATPIBI and also inhibition of MRP2 , BCRP ... 

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... 

Concomitant lipid-lowering therapy-The effect of rosuvastatin on LDL-C and total-C may be enhanced when used in combination with a bile acid-binding resin. If rosuvastatin is used in combination with gemfibrozil, limit the dose of rosuvastatin to 10 mg once daily. 

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... 

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... 

Vittal, S., Shitut, N.R., Kumar, T.R. et al. (2006) Simultaneous quantitation of rosuvastatin and gemfibrozil in human plasma by high-performance liquid chromatography and its application to a pharmacokinetic study. Biomed Chrom, 20 (11), 1252-1259. 

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. 

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. 

In a randomised, crossover study 20 healthy subjeets were given gemfibrozil 600 mg twice daily for 7 days, with a single 80-mg dose of rosuvastatin on day 4. The AUC of rosuvastatin was increased 1.88-fold (11 subjects assessed) and the maximum levels of rosuvastatin were increased 2.21-fold. Three subjects had asymptomatic increases in ALT levels (less than 2.5 times upper limit of normd). ... 

Schneck DW, Birmingham BK, ZaUkowski JA, Mitchell PD, Wmig Y, Martin PD, Lasseter KC, Brown CDA, Windass AS, Raza A. The effect of gemfibrozil on the pharmacokinetics of rosuvastatin. Clin Pharmacol Ther (2004) 75, 455-63. 

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