Tacrolimus diltiazem

Drugs that may affect tacrolimus include nephrotoxic agents (aminoglycosides, amphotericin B, cisplatin, cyclosporine), antifungals, bromocriptine, calcium channel blockers, cimetidine, clarithromycin, danazol, diltiazem, erythromycin, methylprednisolone, metoclopramide, carbamazepine, phenobarbital, phenytoin, rifamycins, cisapride, chloramphenicol, metronidazole, nefazodone, omeprazole, protease inhibitors, macrolide antibiotics, fosphenytoin, and St. John s wort. 

Tacrolimus [P] Decreased tacrolimus metabolism with diltiazem, nicardipine, verapamil. 

A4 Acetaminophen, alfentanil, amiodarone, astemizole, cocaine, cortisol, cyclosporine, dapsone, diazepam, dihydroergotamine, dihydropyridines, diltiazem, ethinyl estradiol, gestodene, indinavir, lidocaine, lovastatin, macrolides, methadone, miconazole, midazolam, mifepristone (RU 486), paclitaxel, progesterone, quinidine, rapamycin, ritonavir, saquinavir, spironolactone, sulfamethoxazole, sufentanil, tacrolimus, tamoxifen, terfenadine, testosterone, tetrahydro-cannabinol, triazolam, troleandomycin, verapamil Barbiturates, carbamazepine, macrolides, glucocorticoids, pioglitazone, phenytoin, rifampin Erythromycin, 613-hydroxy cortisol... 

Acyclovir Erythromycin Ivermectin Itraconazole Rifampin Actinomycin D Daunorubicin Doxorubicin Docetaxel Epirubicin Etoposide Imatinib Irinotecan Paclitaxel Vinblastine Vincristine Amprenavir Indinavir Nelfinavir Ritonavir Saquinavir Cyclosporine A Tacrolimus Digoxin Quinidine Verapamil Diltiazem Aldosterone Cortisol Corticosterone Dexamethasone Hydrocortisone Cyclosporine Metkephamid Enkephalin... 

CALCIUM CHANNEL BLOCKERS TACROLIMUS Plasma concentrations of tacrolimus are t when given with diltiazem, felodipine or nifedipine however, they appear to protect renal function Uncertain, but presumed to be due to inhibition of CYP3A4-mediated tacrolimus metabolism Watch for side-effects of tacrolimus monitor ECG, blood count and renal and hepatic function... 

Diltiazem can increase the blood concentration of the macrolide immunosuppressant tacrolimus (38). 

A 68-year-old man developed diarrhea, dehydration, and atrial fibrillation 4 months after liver transplantation. He was taking tacrolimus (blood concentration 13 ng/ml) and was given a continuous infusion of diltiazem for 1 day followed by oral therapy. Three days later he became delirious, confused, and agitated, and the blood concentration of tacrolimus was 55 ng/ml. His mental statns gradnally improved after withdrawal of both dmgs. 

Hebert ME, Lam AY. Diltiazem increases tacrolimus concentrations. Ann Pharmacother 1999 33(6) 680-2. 

A 3-day course of diltiazem 90 mg/day produced a four-fold increase in tacrolimus trough concentrations in a 68-year-old patient with a liver transplant (113). 

Jones TE, Morris RG. Pharmacokinetic interaction between tacrolimus and diltiazem dose-response relationship in kidney and liver transplant recipients. Clin Pharmacokinet 2002 41(5) 381-8. 

Tada H, Yanagiwara S, Ito K, Suzuki T. Role of diltiazem on tacrolimus pharmacokinetics in tacrolimus-induced nephrotoxic rats. Pharmacol Toxicol 1999 84 241 -246. 

Clinically important, potentially hazardous interactions with abarelix, acenocoumarol, amisulpride, amprenavir, anisindione, anticoagulants, arsenic, astemizole, carbimazole, celiprolol, ciprofloxacin, dabigatran, degarelix, dicumarol, digoxin, diltiazem, enoxacin, fentanyl, fosamprenavir, gatifloxacin, grapefruit juice, lomefloxacin, methotrexate, moxifloxacin, nilotinib, norfloxacin, ofloxacin, oxprenolol, quinidine, quinolones, rifabutin, rifampin, rifapentine, ritonavir, simvastatin, sparfloxacin, sulpiride, tacrolimus, tipranavir, verapamil, warfarin, zuclopenthixol... 

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 alfentanil, aminophylline, amisulpride, amoxicillin, ampicillin, anticonvulsants, astemizole, atorvastatin, benzodiazepines, bromocriptine, buprenorphine, bupropion, carbamazepine, cilostazol, ciprofloxacin, cisapride, clindamycin, colchicine, cyclosporine, dasatinib, digoxin, dihydroergotamine, diltiazem, disopyramide, enoxacin, eplerenone, ergotamine, eszopiclone, everolimus, fluconazole, fluoxetine, fluvastatin, gatifloxacin, HMG-CoA reductase inhibitors, imatinib, itraconazole, ketoconazole, lomefloxacin, lorazepam, lovastatin, methadone, methylprednisolone, methysergide, midazolam, mizolastine, moxifloxacin, nitrazepam, norfloxacin, ofloxacin, paroxetine, pimozide, pravastatin, quinolones, ranolazine, repaglinide, rupatadine, sertraline, sildenafil, simvastatin, sparfloxacin, sulpiride, tacrolimus, terfenadine, triazolam, troleandomycin, vardenafil, verapamil, vinblastine, warfarin, zaleplon, zolpidem, zuclopenthixol... 

Clinically important, potentially hazardous interactions with amiodarone, atazanavir, azithromycin, bosentan, ciprofibrate, clarithromycin, clopidogrel, cyclosporine, darunavir, delavirdine, diltiazem, erythromycin, fosamprenavir, fusidic acid, gemfibrozil, grapefruit juice, imatinib, itraconazole, lopinavir, rabeprazole, ranolazine, red rice yeast, ritonavir, roxithromycin, selenium, St John s wort, tacrolimus, telithromycin, tipranavir, verapamil, warfarin... 

CYP3A4 Alfentanil Alprazolam Astern izole Carbamazepine Cisapride Cyclosporine Diltiazem Erythromycin Felodipine Fluconazole Itraconazole Ketoconazole Lidocaine Lova statin Midazolam Nifedipine Quinidine Simvastatin Tacrolimus Terfenadine Verapamil... 

Acetaminophen, aldrin, alfentanil, amiodarone, aminopyrine, amitriptyline, amprenavir, androstenedione,antipyrine, astemizole, benzphetamine, budesonide, carbamazepine, celecoxib, chlorpromazine, chlorzoxazone, cisapride, clarithromycin, clozapine, cocaine, codeine, cortisol, cyclophosphamide,cyclosporin, dapsone, delavirdine, dextromethorphan, digitoxin, diltiazem, diazepam, erythromycin, 17j3-estradiol, ethinylestradiol, etoposide, felbamate, fentanyl, flutamide, hydroxyarginine, ifosphamide, imipramine, indinavir, ketoconazole, lansoprazole, loratidine, losartan, lovastatin, (iS)"mephen3d in, methadone, mianserin, miconazole, mifepristone, nelfinavir, nevirapine, nicardipine, nifedipine, odansetron, omeprazole, orphenadrine, proguanil, propafenone, quinidine, quinine, rapamycin, retinoic acid, ritonavir, saquinavir, selegiline, serindole, sufentanil, sulfinpyrazone, tacrolimus, tamoxifen, tamsulosin, taxol, teniposide, terfenadine, tetrahydrocannabinol, theophylline, toremifene, triazolam, trimethadone, trimethoprim, troleandomycin, verapamil, warfarin, zatosetron, Zolpidem, zonisamide... 

Nifedipine causes a moderate rise in tacrolimus blood levels and also appears to be kidney protective. Case reports surest that diltiazem and felodipine also elevate tacrolimus levels nicardipine, nilvadipine and verapamil are predicted to interact similarly. 

A study in 2 liver and 2 kidney transplant patients found that diltiazem increased the AUC of tacrolimus. In the kidney transplant patients the increase appeared to be dose related a 20-mg dose of diltiazem caused a 26% and 67% rise, while a 180-mg dose caused a 48% and 177% rise in each patient, respectively. The liver transplant patients did not have any alteration in the AUC of tacrolimus until they were given higher doses of diltiazem one patient had an 18% rise following a 120-mg dose, the other a 22% rise following a 180-mg dose. ... 

Jones TE, Maris RG. Fbannacokinetic interacticn between tacrolimus and diltiazem dose-respcnse relaticnship in kidney and Liver transplant recipients. Clin Pharmacokinet (2002) 41,381-8. 

In the case of nifedipine, this seems to be an established and clinically important interaction. However, the increase seems slow, and it seems likely that any decrease in the dose requirements of tacrolimus will be detected by routine monitoring. Although the information about diltiazem is less conclusive it would seem wise to follow the same precautions, as the effect... 

Hardy G, Stanke-Labesque F, ODntamin C, Serre-Debeauvais F, Bayle F, Zaoui P, Bessard G. Protease inhibitors and diltiazem increase tacrolimus blood ccncentraticn in a patient with renal transplantation a case repeat. EurJ Clin Pharmacol (2004) 60,603-5. 

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