Simvastatin 4- Repaglinide

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 treatment with the CYP3A4 substrate simvastatin altered the mean AUC and mean Cmax of repaglinide by 2 and 27% respectively (64). 

Clinically important, potentially hazardous interactions with alprazolam, aprepitant, astemizole, atorvastatin, benzodiazepines, carbamazepine, chlordiazepoxide, cilostazol, clonazepam, clorazepate, colchicine, conivaptan, cyclosporine, dabigatran, dasatinib, diazepam, digoxin, dihydroergotamine, disopyramide, ergot alkaloids, fesoterodine, fluoxetine, flurazepam, fluvastatin, HMG-CoA reductase inhibitors, imatinib, ixabepilone, lapatinib, lopinavir, lorazepam, lovastatin, methylprednisolone, methysergide, midazolam, nilotinib, oxazepam, paroxetine, pimozide, pravastatin, prednisone, quazepam, repaglinide, rimonabant, rivaroxaban, sertraline, silodosin, simvastatin, solifenacin, temazepam, temsirolimus, tolvaptan, trabectedin, triazolam, warfarin, zidovudine... 

Clinically important, potentially hazardous interactions with atorvastatin, bexarotene, cyclosporine, dicumarol, ezetimibe, fluvastatin, interferon alfa, lovastatin, nicotinic acid, pioglitazone, pravastatin, repaglinide, rosuvastatin, roxithromycin, simvastatin, statins, warfarin... 

No clinically relevant adverse interactions appear to have been reported between the statins and the sulphonylureas. One study reported an increased incidence of adverse effects with repaglinide and simvastatin, the clinical relevance of which is unclear. Most studies have shown no pharmacokinetic interaction or increased incidence of adverse effects when pioglitazone or rosiglitazone were used with atorvastatin or simvastatin. Subcutaneous exenatide modestly decreased the AUC of lovastatin, but no clear pattern of altered efficacy of statins was noted in exenatide clinical trials. 

A three-period, erossover, open-label study in healthy subjects found that simvastatin 20 mg daily increased the maximum plasma level of repaglinide 2 mg three times daily by 26%, although there was high variability and the mean bioavailability of repaglinide was increased by 8%. There was a higher ineidenee of adverse effeets during concurrent use. ... 

The clinical significance of the increased incidence of adverse effects with repaglinide and simvastatin is unclear and so an element of caution would seem prudent. 

---