Detail for FK506
Basic Information
DrugID 49
DrugName FK506
DrugDetail Tacrolimus (also FK-506 or fujimycin, trade names Prograf, Advagraf, Protopic) is an immunosuppressive drug that is mainly used after allogeneic organ transplant to reduce the activity of the patient's immune system and so lower the risk of organ rejection. It is also used in a topical preparation in the treatment of atopic dermatitis (eczema), severe refractory uveitis after bone marrow transplants, exacerbations of minimal change disease, and the skin condition vitiligo. It is a 23-membered macrolide lactone discovered in 1984 from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis. It reduces interleukin-2 (IL-2) production by T-cells.

http://en.wikipedia.org/wiki/Tacrolimus

Indication For use after allogenic organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection. It was first approved by the FDA in 1994 for use in liver transplantation, this has been extended to include kidney, heart, small bowel, pancreas, lung, trachea, skin, cornea, and limb transplants. It has also been used in a topical preparation in the treatment of severe atopic dermatitis.

http://www.drugbank.ca/drugs/DB00864

Structure Click to see the orginal picture.
Interaction
Drug Name PMIDLink Reference
Amphotericin B Kontoyiannis DP, Lewis RE, Alexander BD, Lortholary O, Dromer F, Gupta KL, John GT, Del Busto R, Klintmalm GB, Somani J, Lyon GM, Pursell K, Stosor V, Munoz P, Limaye AP, Kalil AC, Pruett TL, Garcia-Diaz J, Humar A, Houston S, House AA, Wray D, Orloff S, Dowdy LA, Fisher RA, Heitman J, Albert ND, Wagener MM, Singh N. (2008) Calcineurin inhibitor agents interact synergistically with antifungal agents in vitro against Cryptococcus neoformans isolates: correlation with outcome in solid organ transplant recipients with cryptococcosis. Antimicrob Agents Chemother. 52(2):735-8.
Bafilomycin A1 Del Poeta M, Cruz MC, Cardenas ME, Perfect JR, Heitman J. (2000) Synergistic antifungal activities of bafilomycin A(1), fluconazole, and the pneumocandin MK-0991/caspofungin acetate (L-743,873) with calcineurin inhibitorsand L-685,818 against Cryptococcus neoformans. Antimicrob Agents Chemother. 44(3):739-46.
Caspofungin Steinbach WJ, Schell WA, Blankenship JR, Onyewu C, Heitman J, Perfect JR. (2004) In vitro interactions between antifungals and immunosuppressants against Aspergillus fumigatus. Antimicrob Agents Chemother. 48(5):1664-9.
Caspofungin acetate Del Poeta M, Cruz MC, Cardenas ME, Perfect JR, Heitman J. (2000) Synergistic antifungal activities of bafilomycin A(1), fluconazole, and the pneumocandin MK-0991/caspofungin acetate (L-743,873) with calcineurin inhibitorsand L-685,818 against Cryptococcus neoformans. Antimicrob Agents Chemother. 44(3):739-46.
Fluconazole Kontoyiannis DP, Lewis RE, Alexander BD, Lortholary O, Dromer F, Gupta KL, John GT, Del Busto R, Klintmalm GB, Somani J, Lyon GM, Pursell K, Stosor V, Munoz P, Limaye AP, Kalil AC, Pruett TL, Garcia-Diaz J, Humar A, Houston S, House AA, Wray D, Orloff S, Dowdy LA, Fisher RA, Heitman J, Albert ND, Wagener MM, Singh N. (2008) Calcineurin inhibitor agents interact synergistically with antifungal agents in vitro against Cryptococcus neoformans isolates: correlation with outcome in solid organ transplant recipients with cryptococcosis. Antimicrob Agents Chemother. 52(2):735-8.
Amphotericin B Dannaoui E., Schwarz P., Lortholary O. (2009) In Vitro Interactions between Antifungals and Immunosuppressive Drugs against Zygomycetes. Antimicrobial Agents and Chemotherapy 53:3549-3551. DOI: 10.1128/aac.00184-09
Fenpropimorph Onyewu C., Blankenship J.R., Del Poeta M., Heitman J. (2003) Ergosterol biosynthesis inhibitors become fungicidal when combined with calcineurin inhibitors against Candida albicans, Candida glabrata, and Candida krusei. Antimicrobial Agents and Chemotherapy 47:956-964. DOI: 10.1128/aac.47.3.956-964.2003.
Fluconazole Jansen G., Lee A.Y., Epp E., Fredette A., Surprenant J., Harcus D., Scott M., Tan E., Nishimura T., Whiteway M., Hallett M., Thomas D.Y. (2009) Chemogenomic profiling predicts antifungal synergies. Molecular Systems Biology 5. DOI: 10.1038/msb.2009.95.
Itraconazole Sun S., Li Y., Guo Q.J., Shi C.W., Yu J.L., Ma L. (2008) In vitro interactions between tacrolimus and Azoles against Candida albicans determined by different methods. Antimicrobial Agents and Chemotherapy 52:409-417. DOI: 10.1128/aac.01070-07.
Terbinafine Onyewu C., Blankenship J.R., Del Poeta M., Heitman J. (2003) Ergosterol biosynthesis inhibitors become fungicidal when combined with calcineurin inhibitors against Candida albicans, Candida glabrata, and Candida krusei. Antimicrobial Agents and Chemotherapy 47:956-964. DOI: 10.1128/aac.47.3.956-964.2003.
Tunicamycin Jansen G., Lee A.Y., Epp E., Fredette A., Surprenant J., Harcus D., Scott M., Tan E., Nishimura T., Whiteway M., Hallett M., Thomas D.Y. (2009) Chemogenomic profiling predicts antifungal synergies. Molecular Systems Biology 5. DOI: 10.1038/msb.2009.95.
Voriconazole Sun S., Li Y., Guo Q.J., Shi C.W., Yu J.L., Ma L. (2008) In vitro interactions between tacrolimus and Azoles against Candida albicans determined by different methods. Antimicrobial Agents and Chemotherapy 52:409-417. DOI: 10.1128/aac.01070-07.
Ravuconazole Dannaoui E., Schwarz P., Lortholary O. (2009) In Vitro Interactions between Antifungals and Immunosuppressive Drugs against Zygomycetes. Antimicrobial Agents and Chemotherapy 53:3549-3551. DOI: 10.1128/aac.00184-09
Target
PathWay
PathWay Name Path Picture
Type I polyketide structures - Reference pathway