Tacrolimus Amiodarone

Drugs that may affect nelfinavir include anticonvulsants, azithromycin, azole antifungals, efavirenz, delavirdine, HMG-CoA reductase inhibitors, indinavir, interleukins, nevirapine, rifabutin, rifampin, ritonavir, saquinavir, St. John s wort. Drugs that may be affected by nelfinavir include amiodarone, antiarrhythmics (amiodarone, quinidine), azithromycin, benzodiazepines, efavirenz, ergot alkaloids, delavirdine, didanosine, fentanyl, indinavir, lamivudine methadone, nonsedating antihistamines, oral contraceptives, phenytoin, pimozide, quinidine, rifabutin, saquinavir, sildenafil, sirolimus, tacrolimus, zidovudine. 

Drugs that may be affected by fosamprenavir include the following Amiodarone, amitriptyline, benzodiazepines, calcium channel blockers, cisapride, contraceptives (oral), cyclosporine, ergot derivatives, HMG-CoA reductase inhibitors, imipramine, itraconazole, ketoconazole, lidocaine (systemic), methadone, pimozide, quinidine, rifabutin, sildenafil, tacrolimus, vardenafil, warfarin. 

The catabolism of lovastatin, simvastatin, and atorvastatin proceeds chiefly through CYP3A4, whereas that of fluvastatin and rosuvastatin is mediated by CYP2C9. Pravastatin is catabolized through other pathways, including sulfation. The 3A4-dependent reductase inhibitors tend to accumulate in plasma in the presence of drugs that inhibit or compete for the 3A4 cytochrome. These include the macrolide antibiotics, cyclosporine, ketoconazole and its congeners, HIVprotease inhibitors, tacrolimus, nefazodone, fibrates, and others (see Chapter 4). Concomitant use of reductase inhibitors with amiodarone or verapamil also causes an increased risk of myopathy. 

Lopinavir/Ritonavir (Kaletra) [Anrirelroviral/Protease Inhibitor] Uses HIV Infxn Action Protease inhibitor Dose Adults. Tx naive 2 tab PO daily or 1 tab PO bid Tx experiencedpt 1 tab PO bid (T dose if w/ amprenavir, efavirenz, fosamprenavir, nelfinavir, nevirapine) Peds. 7-15 kg 12/3 mg/kg PO bid 15-40 kg 10/2.5 mg/kg PO bid >40 kg Adult dose w/ food Caution [C, /-] Numerous interactions Contra w/drugs dependent on CYP3A/CYP2D6 (Table VI-8) Disp Tab, soln SE Avoid disulfiram (soln has EtOH), metronidazole GI upset, asthenia, T cholesterol/triglycerides, pancreatitis protease metabolic synd Interactions T Effects Wl clarithromycin, erythromycin T effects OF amiodarone, amprenavir, azole andfungals, bepridil, cisapride, cyclosporine, CCBs, ergot alkaloids, flecainide, flurazepam, HMG-CoA reductase inhibitors, indinavir, lidocaine, meperidine, midazolam, pimozide, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, tacrolimus, terfenadine, triazolam, zolpidem 1 effects Wl barbiturates, carbamazepine, dexamethasone, didanosine, efavirenz, nevirapine, phenytoin, rifabutin, rifampin, St. John s wort 1 effects OF OCPs, warfarin EMS Use andarrhythmics and benzodiazepines... 

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... 

The calcium channel blocker mibefradil (Posicor ) was removed from the market in 1998. The headline for the Pink Sheets article describing this action was "Posicor Withdrawal Reflects Complexity of Interaction Profile" (59). Products identified as potentially dangerous in combination with mibefradil included cardiac drugs, such as amiodarone, flecainide, and propafenone oncologic products, such as tamoxifen, cyclophosphamide, etoposide, ifosfamide, and vinblastine and the immunosuppressant medications cyclosporine and tacrolimus. The sponsor s decision to withdraw mibefradil was based on the complexity of the drug interaction information that would have to be communicated to ensure safe usage. 

Clinically important, potentially hazardous interactions with amiodarone, anisindione, anticoagulants, azithromycin, corticosteroids, cyclosporine, dapsone, delavirdine, dicumarol, fosamprenavir, lapatinib, lopinavir, midazolam, oral contraceptives, ritonavir, solifenacin, tacrolimus, temsirolimus, tolvaptan, voriconazole... 

Clinically important, potentially hazardous interactions with amiodarone, amprenavir, anisindione, antacids, anticoagulants, aprepitant, atazanavir, atovaquone, beclomethasone, buprenorphine, corticosteroids, cortisone, cyclosporine, cyproterone, dabigatran, dapsone, darunavir, delavirdine, dexamethasone, dicumarol, digoxin, eszopiclone, flunisolide, fosamprenavir, gadoxetate, gestrinone, halothane, imatinib, isoniazid, itraconazole, ketoconazole, lapatinib, lorcainide, methylprednisolone, midazolam, nelfinavir, nifedipine, oral contraceptives, phenylbutazone, prednisone, protease inhibitors, pyrazinamide, ramelteon, ritonavir, saquinavir, solifenacin, sunitinib, tacrolimus, telithromycin, temsirolimus, tipranavir, tolvaptan, trabectedin, triamcinolone, triazolam, voriconazole, warfarin, zaleplon... 

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... 

Transporter efflux transporter effects predominant Examples Amiodarone Atorvastatin Azithromycin Carbamazepine Carvediioi Chlorpromazine Ciprofloxacin Cisapride Cyciosporine Danazoi Dapsone Diclofenac Diflunisal Digoxin Erythromycin Flurbiprofen Glipizide Glyburide Griseofulvin Ibuprofen Indinavir Indomethacin Itraconazole Ketoconazole Lansoprazole Lovastatin Mebendazole Naproxen Nelfinavir Ofloxacin Oxaprozin Phenazopyridine Phenytoin Piroxicam Raloxifene Ritonavir Saquinavir Saquinavir Sirolimus Sirolimus Spironolactone Spironolactone Tacrolimus Tacrolimus ... 

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... 

A4 Amiodarone, azole antifungals, cimetidine, clarithromycin, cyclosporine, erythromycin, fluoroquinolones, grapefruit juice, HIV protease inhibitors, metronidazole, quinine. SSRIs, tacrolimus Antiarrhythmics, antidepressants, azole antifungals, benzodiazepines, calcium channel blockers, cyclosporine, delavirdine, doxorubicin, efavirenz, erythromycin, estrogens, HIV protease inhibitors, nefazodone. paclitaxel, proton pump inhibitors, HMG-CoA reductase inhibitors, rifabutin, rifampin, sildenafil, SSRIs, tamoxifen, trazodone, vinca anticancer agents... 

There is an isolated case report of increased sirolimus and tacrolimus levels associated with the concurrent use of amiodarone in a paediatric patient. 

A 2-year-old heart transplant patient given tacrolimus 0.02 mg/kg daily was given amiodarone to control ventricular arrhythmias. Her tacrolimus trough levels were reported as within target range of 8 to 10 micrograms/L on both day 1 and day 3 after starting the amiodarone. She was then switched from tacrolimus to sirolimus 0.06 mg/kg daily, increased to... 

The authors of this report advise that, because of the long half-life of sirolimus, and the difficulty in reducing elevated levels quickly, prescrib-ers should consider reducing the sirolimus and tacrolimus doses before starting amiodarone rather than waiting for the interaction to occur. They also advise more frequent monitoring of sirolimus and tacrolimus levels if amiodarone is also given. This appears to be the only published report of this interaction at present. 

Nalli N, Stewart-Texeira L, Dipchand AI. Amiodarone-sirolimus/tacrolimus interaction in a pediatric heart transplant patient Pediatr Transplant (2006) 10, 736-739. 

A 65-year-old man who had taken amiodarone 200 mg/day for 5 years for atrial fibrillation with a preoperative QTc interval of 440 ms underwent renal transplantation and was given tacrolimus 3 mg bd [47 ]. After 1 day, the QTc interval increased to 535 ms and the tacrolimus concentration was far beyond the usual target range of 12-15 ng/ml. After withdrawal of amiodarone the QTc interval slowly shortened to 493 ms on day 5. 

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