Repaglinide Gemfibrozil

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. 

In 12 healthy subjects gemfibrozil raised the AUC of repaglinide 8-fold and itraconazole raised it 1.4-fold however, the combination increased it nearly 20-fold (62). 

Niemi M, Backman JT, Neuvonen M, Neuvonen PJ. Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics and pharmacodynamics of repaglinide potentially hazardous interaction between gemfibrozil and repaglinide. Diabetologia 2003 46(3) 347-51. 

REPAGLINIDE FIBRATES-GEMFIBROZIL Nearly eightfold t in repaglinide levels. Risk of severe and prolonged hypoglycaemia Hepatic metabolism inhibited The European Agency for the Evaluation of Medicinal products contraindicated concurrent use in 2003. Bezafibrate and fenofibrate are suitable alternatives if a fibric acid derivative is required... 

CYP2C8 <5 1-2 Disopyramide Amiodarone Clozapine Diclofenac Fluvastatin Nicardipine Paclitaxel Retinoic acid Rosiglitazone Torsemide Repaglinide Amiodarone Celecoxib Felodipine Nicardipine Fluoxetine Ketoconazole Ritonavir Indinavir Troglitazone Zafirlukast Retinoic acid Clotrimazole Phenobarbital Dexamethasone Gemfibrozil Rifampin Phenytoin Ritonavir... 

Repaglinide Gemfibrozil Increased repaglinide plasma concentrations... 

TABLE 7.6 Fold increase in repaglinide exposure by gemfibrozil and itraconazole. 

Note that on the basis of the study, and following five reports of serious hypoglycaemic episodes with gemfibrozil and repaglinide, the European... 

EMEA public statement on repaglinide (NovoNorm/Prandin) contraindication of concomitant use of repaglinide and gemfibrozil, 21 Ivby 2003, London. Available at http //www,emea,eu,int/pdfs/human/press/pus/l 17003en.pdf (accessed 17/08/07). 

Tornio A, Niemi M, Neuvonen M, Laitila J, Kalliokoski A, Neuvonen PJ, Backman JT. The effect of gemfibrozil on repaglinide pharmacokinetics persists for at least 12 h after the dose evidence for mechanism-based inhibition of CYP2C8 in vivo. Chn Pharmacol Ther 2008 84 403-11. 

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