Tacrolimus drug interactions

Moreno M, Latorre A, Manzanares C, Morales E, Herrero JC, Dominguez-Gil B, Carreno A, Cubas A, Delgado M, Andres A, Morales JM. Clinical management of tacrolimus drug interactions in renal transplant patients. Transplant Proc 1999 31(6) 2252-3. 

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... 

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. 

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. 

Posaconazole is the newest triazole to be licensed in the USA. It is available only in a liquid oral formulation and is used at a dosage of 800 mg/d, divided into two or three doses. Absorption is improved when taken with meals high in fat. Posaconazole is rapidly distributed to the tissues, resulting in high tissue levels but relatively low blood levels. Visual changes have not been reported, but drug interactions with increased levels of CYP3A4 substrates such as tacrolimus and cyclosporine have been documented. 

Tacrolimus can be administered orally or intravenously. The half-life of the intravenous form is approximately 9-12 hours. Like cyclosporine, tacrolimus is metabolized primarily by P450 enzymes in the liver, and there is potential for drug interactions. The dosage is determined by trough blood level at steady state. Its toxic effects are similar to those of cyclosporine and include nephrotoxicity, neurotoxicity, hyperglycemia, hypertension, hyperkalemia, and gastrointestinal complaints. 

Better compliance than with nystatin. Currently, the drug of choice for prophylaxis. A recent report suggested that clotrimazole troche can increase tacrolimus blood levels. (Vasquez E, Poliak R, Benedetti E. Clotrimazole increases tacrolimus blood levels a drug interaction in kidney transplant patients. Clin Transplant. 2001 15(2) 95-9.)... 

Drug Interactions Increased prothrombin time after warfarin administration Phenytoin Cyclosporine Tolbutamide Tacrolimus Glyburide Glipizide Rifampin Cisapride Terfenadine Astemizole Theophylline ... 

Drug Interactions Inducers of drug clearance and/or mixed inducers/inhibitors Cyclosporine Tacrolimus... 

Lampen A, Christians U, Guengerich FP, et al. Metabolism of the immunosuppressant tacrolimus in the small intestine cytochrome P450, drug interactions, and interindividual variability. Drug Metab Dispos 1995 23 1315-1324. 

TACROLIMUS CO-TRIMOXAZOLE Exacerbates hyperkalaemia induced by tacrolimus Additive hyperkalaemic effects Monitor electrolytes closely >- For signs and symptoms of hyperkalaemia, see Qinical Features of Some Adverse Drug Interactions, Hyperkalaemia... 

Christians U, Jacobsen W, Benet LZ, Lampen A. Mechanisms of clinically relevant drug interactions associated with tacrolimus. Clin Pharmacokinet 2002 41 813-51. 

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. 

Hubner GI, Eismann R, Sziegoleit W. Drug interaction between mycophenolate mofetil and tacrolimus detectable within therapeutic mycophenolic acid monitoring in renal transplant patients. Ther Drug Monit 1999 21(5) 536-9. 

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