Diltiazem Sirolimus

Drugs that may increase sirolimus blood concentrations include the following Nicardipine, verapamil, clotrimazole, fluconazole, itraconazole, clarithromycin, erythromycin, troleandomycin, cisapride, metoclopramide, bromocriptine, cimetidine, danazol, HIV-protease inhibitors, cyclosporine, diltiazem, azole antifungals. 

Sirolimus [P] Decreased sirolimus metabolism with diltiazem, nicardipine, verapamil. 

BottigerY Sawe J, Brattstrom C, et al. Pharmacokinetic interaction between single oral dose of diltiazem and sirolimus in healthy volunteers. Cli Pharmacol 2001 69 32-40. 

CALCIUM CHANNEL BLOCKERS SIROUMUS Plasma concentrations of sirolimus are t when given with diltiazem. Plasma levels of both drugs are t when verapamil and sirolimus are coadministered Diltiazem and verapamil inhibit intestinal CYP3A4, which is the main site of sirolimus metabolism Watch for side-effects of sirolimus when it is co-administered with diltiazem or verapamil monitor renal and hepatic function. Monitor PR and BP closely when sirolimus is given with verapamil... 

The pharmacokinetic interaction of a single oral dose of diltiazem 120 mg with a single oral dose of sirolimus 10 mg... 

In 18 healthy subjects, in a randomized, crossover study of the pharmacokinetics of a single oral dose of sirolimus 10 mg, a single dose of diltiazem 120 mg, and the combination, diltiazem increased exposure to sirolimus, presumably by inhibiting its first-pass metabolism (13). 

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... 

Drug Interactions Since sirolimus is a substrate for CYP3A4 and is transported by P-glycoprotein, close attention to interactions with other drugs that are metaboUzed or transported by these proteins is required. As noted above, cyclosporine and sirolimus interact, and their administration should be separated by time. Dose adjustment may be required when sirolimus is coadministered with diltiazem or rifampin. 

Diltiazem and verapamil raise sirolimus levels, and dosage adjustments may be necessaiy. Nicardipine is predicted to interact similarly. Nifedipine appears not to interact with sirolimus. 

---