Tacrolimus interactions

Chenhsu RY, Loong CC, Chon MH, Lin MF, Yang WC. Renal allograft dysfunction associated tvith rifampin-tacrolimus interaction. Ann Pharmacother 2000 34(1) 27-31. 

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

Chenhsu R-Y, Loong C-C, ChouM-H, Lin M-F, Yang W-C. Renal allograft dysfunction associated witii rifampin-tacrolimus interaction Ann Pharmacoffier 2000) 34, 27-31. 

Pierce DA, Reeves-Daniel AM. Ranola-zine-tacrolimus interaction. Ann Pharmacother 2010 44(11) 1844-9. 

Sirolimus is currently the only FDA-approved ToR inhibitor. One of its derivatives, everolimus, is in phase III clinical trials and has been approved for use in some European countries.30 Sirolimus is a macrolide antibiotic that has no effect on cal-cineurin phosphatase.11,31,32 Sirolimus inhibits T cell activation and proliferation by binding to and inhibiting the activation of the mammalian ToR, which suppresses cellular response to IL-2 and other cytokines (i.e., IL-4 and IL-15J.11,31 Studies have shown that sirolimus may be used safely and effectively with either cyclosporine or tacrolimus as a replacement for either azathioprine or mycophenolate mofetil.33 However, when using both sirolimus and cyclosporine as part of a patient s immunosuppressant therapy, because of a drug interaction between the two resulting in a marked increase in sirolimus concentrations, it is recommended to separate the sirolimus and cyclosporine doses by at least 4 hours. Sirolimus also can be used as an alternative agent for patients who do not tolerate calcineurin inhibitors due to nephrotoxicity or other adverse events.34... 

Most pharmacokinetic interactions in transplantation occur due to interactions with the CYP enzyme system however, several interactions have been shown to occur via alternative mechanisms. One of the most notable is that seen between tacrolimus and some of the prokinetic agents. Cisapride and metoclopramide have been shown to increase the absorption of tacrolimus by enhancing gastric emptying.41... 

Azathioprine, mycophenolate mofetil, and enteric-coated MPA are not metabolized through the CYP isozyme system therefore, they do not experience the same DDI profiles as cyclosporine, tacrolimus, and sirolimus. Azathioprine s major DDIs involve allopurinol, angiotensin-converting enzyme (ACE) inhibitors, aminosalicylates (e.g., mesalamine and sulfasalazine), and warfarin.11 The interaction with allopurinol is seen frequently and has clinical significance. Allopurinol inhibits xanthine oxidase, the enzyme responsible for metabolizing azathioprine. Combination of azathioprine and allopurinol has resulted in severe toxicities, particularly myelosuppression. It is recommended that concomitant therapy with azathioprine and allopurinol be avoided, but if combination therapy is necessary, the azathioprine doses must be reduced to one-third or one-fourth of the current dose. Use of azathioprine with the ACE inhibitors or aminosalicylates also can result in enhanced myelosuppression.11 Some case reports exist demonstrating that warfarin s therapeutic effects may be decreased by azathioprine.43-45... 

Lampen, A., Christians, U., Guengerich, F. P., Watkins, P. B., Koiars, J. C., Bader, A., Dralle, H., Hackbarth, I., Sewing, K. F., Metabolism of the immunosuppressant tacrolimus in the small intestine cytochrome P450 drug interactions, and interindividual variability, Drug Metab. Disp. 1995, 23, 1315-1324. 

Azithromycin Drugs that may interact with azithromycin include antacids, cyclosporine, HMG-CoA reductase inhibitors, pimozide, tacrolimus, theophyllines, and warfarin. Also consider all drug interactions with erythromycin. 

Drugs that may interact with caspofungin include cyclosporine, inducers of drug clearance or mixed inducers/inhibitors, and tacrolimus. 

The following drug interactions were reported for metronidazole, a chemically related nitroimidazole. Therefore, these drug interactions may occur with tinidazole. Drugs that may affect tinidazole include cholestyramine, CYP3A4 inducers and inhibitors and oxytetracycline. Drugs that may be affected by tinidazole include alcohols, anticoagulants, cyclosporine, tacrolimus, disulfiram, fluorouracil, hydantoins, and lithium. 

Drug/Food interactions The presence of food reduced the absorption of tacrolimus (decrease in AUC and C ax > 1 increase in Tmax)- The relative oral bioavailability... 

Echinacea (Echinacea purpurea) Uses immune system stimulant prevention/Rx of colds, flu as supportive th apy for colds chronic infxns of the resp tract lower urinary tract Action Stimulates phagocytosis cytokine production T resp cellular activity topically exerts anesthetic, antimicrobial, anti-inflammatory effects Efficacy Not established may X severity duration of URI Available forms Caps w/ powdered herb equivalent to 300-500 mg, PO, tid pressed juice 6-9 mL, PO, once/d tine 2-4 mL, PO, tid (1 5 dilution) tea 2 tsp (4 g) of powdered herb in 1 cup of boiling water Noles/SE Fever, taste p -version, urticaria, angioedema Contra w/ autoimmune Dz, collagen Dz, progressive systemic Dz (TB, MS, collagen-vascular disorders), HIV, leukemia, may interfere w/ immunosuppressive therapy Interactions t Risk of disulfiram-like reaction W/ disulfiram, metronidazole T risk of exacerbation of HIV or AIDS W/ chinacea amprenavir, other protease inhibitors X effects OF azathioprine, basiliximab, corticosteroids, cyclosporine, daclizumab, econazole vag cream, muromonab-CD3, mycophenolate, prednisone, tacrolimus EMS Possible immunosuppression... 

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