TACROLIMUS

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C44H69NO12.H2O
Molecular Weight	822.0334
Optical Activity	( - )
Defined Stereocenters	14 / 14
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.[H][C@]1(CC[C@@H](O)[C@@H](C1)OC)\C=C(/C)[C@@]2([H])OC(=O)[C@]3([H])CCCCN3C(=O)C(=O)[C@]4(O)O[C@@]([H])([C@H](C[C@H]4C)OC)[C@H](C[C@@H](C)C\C(C)=C\[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)OC

InChI

InChIKey=NWJQLQGQZSIBAF-MLAUYUEBSA-N

InChI=1S/C44H69NO12.H2O/c1-10-13-31-19-25(2)18-26(3)20-37(54-8)40-38(55-9)22-28(5)44(52,57-40)41(49)42(50)45-17-12-11-14-32(45)43(51)56-39(29(6)34(47)24-35(31)48)27(4)21-30-15-16-33(46)36(23-30)53-7;/h10,19,21,26,28-34,36-40,46-47,52H,1,11-18,20,22-24H2,2-9H3;1H2/b25-19+,27-21+;/t26-,28+,29+,30-,31+,32-,33+,34-,36+,37-,38-,39+,40+,44+;/m0./s1

HIDE SMILES / InChI

Molecular Formula	C44H69NO12
Molecular Weight	804.0182
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	14 / 14
E/Z Centers	1
Optical Activity	UNSPECIFIED

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050708s045,050709s038lbl.pdf

Tacrolimus, previously known as FK506, is the active ingredient in Prograf. Tacrolimus is a macrolide immunosuppressant produced by Streptomyces tsukubaensis. It reduces peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP-12 (FK506 binding protein) creating a new complex. This FKBP12-FK506 complex interacts with and inhibits calcineurin thus inhibiting both T-lymphocyte signal transduction and IL-2 transcription. Tacrolimus inhibits T-lymphocyte activation, although the exact mechanism of action is not known. Experimental evidence suggests that tacrolimus binds to an intracellular protein, FKBP-12. A complex of tacrolimus-FKBP-12, calcium, calmodulin, and calcineurin is then formed and the phosphatase activity of calcineurin inhibited. This effect may prevent the dephosphorylation and translocation of nuclear factor of activated T-cells (NF-AT), a nuclear component thought to initiate gene transcription for the formation of lymphokines (such as interleukin-2, gamma interferon). The net result is the inhibition of T-lymphocyte activation (i.e., immunosuppression). Prograf is indicated for the prophylaxis of organ rejection in patients receiving allogeneic liver transplants, kidney transplants, heart transplants. It has also been used in a topical preparation in the treatment of severe atopic dermatitis.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
FK506-binding protein 1A 9 Target ID: CHEMBL1902 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16289353	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Organ rejection 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050708s045,050709s038lbl.pdf	Preventing		Approved 8429	PROGRAF Approved Use Prograf is a calcineurin-inhibitor immunosuppressant indicated for: Prophylaxis of organ rejection in patients receiving allogeneic liver, kidney or heart transplants. Use concomitantly with adrenal corticosteroids; in kidney and heart transplant, use in conjunction with azathioprine or mycophenolate mofetil (MMF) Launch Date 1994
Atopic dermatitis 43 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28512670	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
26 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204096s000lbl.pdf	0.2 mg/kg 1 times / day multiple, oral dose: 0.2 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered:		TACROLIMUS unknown	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
6.2 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204096s000lbl.pdf	4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered:		TACROLIMUS unknown	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
372 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204096s000lbl.pdf	0.2 mg/kg 1 times / day multiple, oral dose: 0.2 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered:		TACROLIMUS unknown	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
74 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204096s000lbl.pdf	4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered:		TACROLIMUS unknown	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.15 mg/kg 2 times / day steady, oral Dose: 0.15 mg/kg, 2 times / day Route: oral Route: steady Dose: 0.15 mg/kg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf Page: p. 79	unhealthy, 1.9 years (range: 3-15 years) n = 91 Health Status: unhealthy Condition: Primary Liver Transplantation Age Group: 1.9 years (range: 3-15 years) Sex: M+F Population Size: 91 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf Page: p. 79	Disc. AE: Anemia, Edema lung... AEs leading to discontinuation/dose reduction: Anemia Edema lung Allergic reaction Abnormal liver function tests Bilirubinemia Lymphoma like reaction Diarrhea Intestinal obstruction Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf Page: p. 79
5.2 mg 1 times / day multiple, oral Highest studied dose Dose: 5.2 mg, 1 times / day Route: oral Route: multiple Dose: 5.2 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204096s000lbl.pdf	unhealthy, adult n = 60 Health Status: unhealthy Condition: kidney transplantation Age Group: adult Population Size: 60 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204096s000lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204096s000lbl.pdf
8 mg single, oral Highest studied dose Dose: 8 mg Route: oral Route: single Dose: 8 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050708s052,050709s044,210115s004lbl.pdf	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050708s052,050709s044,210115s004lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050708s052,050709s044,210115s004lbl.pdf
0.1 mg/kg 2 times / day multiple, oral Recommended Dose: 0.1 mg/kg, 2 times / day Route: oral Route: multiple Dose: 0.1 mg/kg, 2 times / day Co-administed with:: Azathioprine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050708s052,050709s044,210115s004lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050708s052,050709s044,210115s004lbl.pdf	Other AEs: Infection... Other AEs: Infection (serious) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050708s052,050709s044,210115s004lbl.pdf
0.02 mg/kg single, intravenous Dose: 0.02 mg/kg Route: intravenous Route: single Dose: 0.02 mg/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050708s052,050709s044,210115s004lbl.pdf	unhealthy, adult n = 12 Health Status: unhealthy Condition: Renal Impairment Age Group: adult Population Size: 12 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050708s052,050709s044,210115s004lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050708s052,050709s044,210115s004lbl.pdf
0.03 % 1 times / day multiple, topical Dose: 0.03 %, 1 times / day Route: topical Route: multiple Dose: 0.03 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/33657259	unhealthy n = 31 Health Status: unhealthy Condition: non-segmental vitiligo Population Size: 31 Sources: https://pubmed.ncbi.nlm.nih.gov/33657259	Sources: https://pubmed.ncbi.nlm.nih.gov/33657259

AEs

AE	Significance	Dose	Population
Abnormal liver function tests	Disc. AE	0.15 mg/kg 2 times / day steady, oral Dose: 0.15 mg/kg, 2 times / day Route: oral Route: steady Dose: 0.15 mg/kg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf Page: p. 79	unhealthy, 1.9 years (range: 3-15 years) n = 91 Health Status: unhealthy Condition: Primary Liver Transplantation Age Group: 1.9 years (range: 3-15 years) Sex: M+F Population Size: 91 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf Page: p. 79
Allergic reaction	Disc. AE	0.15 mg/kg 2 times / day steady, oral Dose: 0.15 mg/kg, 2 times / day Route: oral Route: steady Dose: 0.15 mg/kg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf Page: p. 79	unhealthy, 1.9 years (range: 3-15 years) n = 91 Health Status: unhealthy Condition: Primary Liver Transplantation Age Group: 1.9 years (range: 3-15 years) Sex: M+F Population Size: 91 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf Page: p. 79
Anemia	Disc. AE	0.15 mg/kg 2 times / day steady, oral Dose: 0.15 mg/kg, 2 times / day Route: oral Route: steady Dose: 0.15 mg/kg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf Page: p. 79	unhealthy, 1.9 years (range: 3-15 years) n = 91 Health Status: unhealthy Condition: Primary Liver Transplantation Age Group: 1.9 years (range: 3-15 years) Sex: M+F Population Size: 91 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf Page: p. 79
Bilirubinemia	Disc. AE	0.15 mg/kg 2 times / day steady, oral Dose: 0.15 mg/kg, 2 times / day Route: oral Route: steady Dose: 0.15 mg/kg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf Page: p. 79	unhealthy, 1.9 years (range: 3-15 years) n = 91 Health Status: unhealthy Condition: Primary Liver Transplantation Age Group: 1.9 years (range: 3-15 years) Sex: M+F Population Size: 91 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf Page: p. 79
Diarrhea	Disc. AE	0.15 mg/kg 2 times / day steady, oral Dose: 0.15 mg/kg, 2 times / day Route: oral Route: steady Dose: 0.15 mg/kg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf Page: p. 79	unhealthy, 1.9 years (range: 3-15 years) n = 91 Health Status: unhealthy Condition: Primary Liver Transplantation Age Group: 1.9 years (range: 3-15 years) Sex: M+F Population Size: 91 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf Page: p. 79
Edema lung	Disc. AE	0.15 mg/kg 2 times / day steady, oral Dose: 0.15 mg/kg, 2 times / day Route: oral Route: steady Dose: 0.15 mg/kg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf Page: p. 79	unhealthy, 1.9 years (range: 3-15 years) n = 91 Health Status: unhealthy Condition: Primary Liver Transplantation Age Group: 1.9 years (range: 3-15 years) Sex: M+F Population Size: 91 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf Page: p. 79
Intestinal obstruction	Disc. AE	0.15 mg/kg 2 times / day steady, oral Dose: 0.15 mg/kg, 2 times / day Route: oral Route: steady Dose: 0.15 mg/kg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf Page: p. 79	unhealthy, 1.9 years (range: 3-15 years) n = 91 Health Status: unhealthy Condition: Primary Liver Transplantation Age Group: 1.9 years (range: 3-15 years) Sex: M+F Population Size: 91 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf Page: p. 79
Lymphoma like reaction	Disc. AE	0.15 mg/kg 2 times / day steady, oral Dose: 0.15 mg/kg, 2 times / day Route: oral Route: steady Dose: 0.15 mg/kg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf Page: p. 79	unhealthy, 1.9 years (range: 3-15 years) n = 91 Health Status: unhealthy Condition: Primary Liver Transplantation Age Group: 1.9 years (range: 3-15 years) Sex: M+F Population Size: 91 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf Page: p. 79
Infection	serious	0.1 mg/kg 2 times / day multiple, oral Recommended Dose: 0.1 mg/kg, 2 times / day Route: oral Route: multiple Dose: 0.1 mg/kg, 2 times / day Co-administed with:: Azathioprine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050708s052,050709s044,210115s004lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050708s052,050709s044,210115s004lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2C19 1478 CYP2E1 882 UGT1A1 204 UGT1A3 84 UGT1A6 108 UGT1A9 116 UGT2B4 19 UGT2B7 146 UGT2B15 64 UGT1A8 36	CYP3A5 395 CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2E1 667 P-gp 1537 UGT1A4 347

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	no
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	no
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	no
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	no
UGT1A9 121	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	no
UGT1A3 93	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	yes [IC50 0.4 uM]
UGT2B15 64	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	yes [IC50 16.5 uM]
UGT2B7 157	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	yes [IC50 23.5 uM]
UGT1A1 254	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	yes [IC50 3.2 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	yes [Ki 0.36 uM]
UGT1A8 48	inhibitor 3277 Sources: http://sedici.unlp.edu.ar/handle/10915/20208 Page: -	yes [Ki 6.1 uM]
UGT1A6 141	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	yes
UGT2B4 19	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A2 1054	substrate 3367 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
CYP2A6 543	substrate 3367 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
CYP2B6 664	substrate 3367 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
CYP2C8 693	substrate 3367 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
CYP2C9 1037	substrate 3367 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
CYP2D6 1217	substrate 3367 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
CYP2E1 667	substrate 3367 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
P-gp 1537	substrate 3367 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	yes
UGT1A4 347	substrate 3367 Sources: https://dmd.aspetjournals.org/content/39/7/1127.short Page: -	yes
CYP3A4 1737	substrate 3367 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	yes	yes (co-administration study) Comment: Tacrolimus was metabolized by the cytochrome P450 (CYP) 3A subfamily. Metabolic drug-drug interaction studies were conducted to provide information regarding the optimal usage of tacrolimus, and its metabolism was inhibited by known CYP3A inhibitors such as ketoconazole, cyclosporine A, and nifedipine. Recent reports on clinical pharmacokinetics indicate that dose levels of tacrolimus need to be adjusted in transplant patients with CYP3A5 polymorphism. Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -
CYP3A5 395	substrate 3367 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	yes	yes (pharmacogenomic study) Comment: Tacrolimus was metabolized by the cytochrome P450 (CYP) 3A subfamily. Metabolic drug-drug interaction studies were conducted to provide information regarding the optimal usage of tacrolimus, and its metabolism was inhibited by known CYP3A inhibitors such as ketoconazole, cyclosporine A, and nifedipine. Recent reports on clinical pharmacokinetics indicate that dose levels of tacrolimus need to be adjusted in transplant patients with CYP3A5 polymorphism. Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -

PubMed

Title	Date	PubMed
Neurological complications in the European multicentre study of FK 506 and cyclosporin in primary liver transplantation.	1994	11271222
Tacrolimus toxicity in rhesus monkey: model for clinical side effects.	1999 Dec	10616519
Oscillopsia and pseudonystagmus in kidney transplant patients.	1999 Dec	10612521
Which calcineurin inhibitor is preferred in renal transplantation: tacrolimus or cyclosporine?	1999 Nov	10630811
Leg bone pain syndrome in a kidney transplant patient treated with tacrolimus (FK506).	1999 Oct	10577370
Successful use of cyclosporine in a lung transplant recipient with tacrolimus-associated hemolytic uremic syndrome.	1999 Oct	10561115
Tacrolimus (FK506)-induced severe and late encephalopathy in a renal transplant recipient.	1999 Oct	10528682
FK506 markedly enhances apoptosis of antigen-stimulated peripheral T cells by down-regulation of Bcl-xL.	1999 Oct 15	10532544
Trimetazidine counteracts tacrolimus nephrotoxicity in a hypertensive liver transplant patient.	1999 Oct 27	10551656
Tacrolimus in acute renal failure: does L-arginine-infusion prevent changes in renal hemodynamics?	2000	11140242
Arteriolopathy in non-episode biopsies of renal transplant allograft.	2000	11092348
Treatment of tacrolimus-related adverse effects by conversion to cyclosporine in liver transplant recipients.	2000	10743694
A case of bilateral optic neuropathy in a patient on tacrolimus (FK506) therapy after liver transplantation.	2000 Apr	10764869
Reversible tacrolimus-induced neurotoxicity isolated to the brain stem.	2000 Aug	10954277
Sirolimus in pediatric gastrointestinal transplantation: the use of sirolimus for pediatric transplant patients with tacrolimus-related cardiomyopathy.	2000 Feb	10731058
FK506-induced intractable leukoencephalopathy following allogeneic bone marrow transplantation.	2000 Feb	10673708
Conversion to neoral for neurotoxicity after primary adult liver transplantation under tacrolimus.	2000 Jan 15	10653398
Tacrolimus (FK506) and methotrexate as prophylaxis for acute graft-versus-host disease in pediatric allogeneic stem cell transplantation.	2000 Jul	10918426
Caspase-mediated proteolytic activation of calcineurin in thapsigargin-mediated apoptosis in SH-SY5Y neuroblastoma cells.	2000 Jul 15	10898953
Effect of aminophylline on urine flow in children with tacrolimus-induced renal insufficiency.	2000 Jun	10856596
Tacrolimus-induced hemolytic uremic syndrome and end-stage renal failure after liver transplantation.	2000 Jun	10831087
Cortical laminar necrosis caused by immunosuppressive therapy and chemotherapy.	2000 Mar	10730638
FK506 inhibition of histamine release and cytokine production by mast cells and basophils.	2000 Mar	10685002
Immunosuppressive drugs: the first 50 years and a glance forward.	2000 May	10878284
Tacrolimus and myocardial hypertrophy.	2000 May 15	10830241
Clinical outcome after conversion to FK 506 (tacrolimus) therapy for acute graft-versus-host disease resistant to cyclosporine or for cyclosporine-associated toxicities.	2000 Nov	11100278
Cyclosporine and tacrolimus-associated thrombotic microangiopathy.	2000 Oct	11007689
Delayed transient neurologic toxicity due to tacrolimus: CT and MRI.	2000 Sep	11071440
Tacrolimus-associated mutism after orthotopic liver transplantation.	2000 Sep 27	11014653
Calcineurin-inhibitor induced pain syndrome (CIPS): a severe disabling complication after organ transplantation.	2001	11263551
Calcineurin inhibitor attenuates cardiac hypertrophy due to energy metabolic disorder.	2001 Dec	11773940
End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment.	2001 Dec 27	11773892
Sirolimus interferes with the innate response to bacterial products in human whole blood by attenuation of IL-10 production.	2001 Feb	11169223
Mycophenolate mofetil monotherapy in liver transplantation.	2001 Feb 24	11558493
Nonclinical and early clinical development of tacrolimus ointment for the treatment of atopic dermatitis.	2001 Jan	11145792
Posttransplantation diabetes mellitus in FK-506-treated renal transplant recipients: analysis of incidence and risk factors.	2001 Nov 27	11726827
Cyclosporin A-induced encephalopathy after allogeneic bone marrow transplantation with prevention of graft-versus-host disease by tacrolimus.	2001 Oct	11704797
Sirolimus and mycophenolate mofetil for calcineurin-free immunosuppression in renal transplant recipients.	2001 Oct	11583940
Changes in lipid metabolism and effect of simvastatin in renal transplant recipients induced by cyclosporine or tacrolimus.	2001 Oct	11583721
[A case of FK 506-induced leukoencephalopathy].	2002 Jan	11868353
Calcineurin inhibitors, cyclosporin A and tacrolimus inhibit expression of inducible nitric oxide synthase in colon epithelial and macrophage cell lines.	2002 Jul 19	12144947
Tacrolimus is a class II low-solubility high-permeability drug: the effect of P-glycoprotein efflux on regional permeability of tacrolimus in rats.	2002 Mar	11920757
Downregulation of both interleukin-12 and interleukin-2 in heart allografts by pretransplant host treatment with granulocyte colony-stimulating factor and tacrolimus.	2002 May 7	12126653
Tacrolimus-induced life-threatening arrhythmia in a pediatric liver-transplant patient.	2002 Nov	12583382
Long-term comparison of tacrolimus- and cyclosporine-induced nephrotoxicity in pediatric heart-transplant recipients.	2002 Sep	12243498
Tacrolimus (FK506)-induced mutism after liver transplant.	2003 Feb	12699871
Severe acute renal failure after exposure to sirolimus-tacrolimus in two living donor kidney recipients.	2003 Jan 15	12544890
Microangiopathic haemolytic anaemia and thrombocytopenia following lung volume reduction surgery in a single lung transplant recipient on maintenance tacrolimus (FK506) therapy.	2003 Jun	12753543
The immunophilin-ligands FK506 and V-10,367 mediate neuroprotection by the heat shock response.	2003 Mar	12642403
Enhanced interleukin-4 production in CD4+ T cells and elevated immunoglobulin E levels in antigen-primed mice by bisphenol A and nonylphenol, endocrine disruptors: involvement of nuclear factor-AT and Ca2+.	2003 May	12709020

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Sample Use Guides

In Vivo Use Guide

Dosage in Adult Kidney, Liver, or Heart Transplant Patients: Adult kidney transplant patients (Oral Dosage: daily doses should be administered as two divided doses, every 12 hours): in combination with azathioprine: 0.2 mg/kg/day; in combination with MMF/IL-2 receptor antagonist: 0.1 mg/kg/day. Adult liver transplant patients: 0.10-0.15 mg/kg/day. Adult heart transplant patients: 0.075 mg/kg/day. Prograf (TACROLIMUS) injection should be used only as a continuous IV infusion and when the patient cannot tolerate oral administration of Prograf capsules. Prograf injection should be discontinued as soon as the patient can tolerate oral administration of Prograf capsules, usually within 2-3 days. In a patient receiving an IV infusion, the first dose of oral therapy should be given 8-12 hours after discontinuing the IV infusion. The recommended starting dose of Prograf injection is 0.03-0.05 mg/kg/day in kidney and liver transplant and 0.01 mg/kg/day in heart transplant given as a continuous IV infusion. Adult patients should receive doses at the lower end of the dosing range. Concomitant adrenal corticosteroid therapy is recommended early post-transplantation. Dosage in Pediatric Liver Transplant Patients: (Oral Dosage): Pediatric liver transplant patients 0.15-0.20 mg/kg/day (daily doses should be administered as two divided doses, every 12 hours)

Route of Administration: Other

In Vitro Use Guide

Tacrolimus at concentration of 0.06 μmol/L could promote collagen induced platelet aggregation, inhibit thrombin induced platelet aggregation, have no effect on ristocetin and vWF induced platelet aggregation function. Tacrolimus at concentration of 120 μmol/L and 240 μmol/L could reduce the platelet mitochondrial membrane potential and induce the expression of apoptosis protein caspase-3. In vitro experimental results showed that high concentration of tacrolimus could lead to platelet apoptosis. But the current therapeutic dose of tacrolimus at 0.06 μmol/L (which is equivalent to 50 ng/ml blood concentration) could have different effects on platelet aggregation function according to different stimulating agents.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:46:51 GMT 2023` Edited by `admin` on `Fri Dec 15 15:46:51 GMT 2023`
Record UNII	WM0HAQ4WNM
Record Status	`Validated (UNII)`
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Name

Type

Language

TACROLIMUS

Official Name

English

FK 506

Code

English

TACROLIMUS [ORANGE BOOK]

Common Name

English

TACROLIMUS [USP-RS]

Common Name

English

TACROLIMUS HYDRATE [JAN]

Common Name

English

NSC-758659

Code

English

MODIGRAF

Brand Name

English

TACROLIMUS MONOHYDRATE

Common Name

English

TACROLIMUS [EMA EPAR]

Common Name

English

PROTOPIC

Brand Name

English

FK-506

Code

English

FK506

Code

English

TACROLIMUS HYDRATE

Common Name

English

TACROLIMUS [VANDF]

Common Name

English

TACROLIMUS MONOHYDRATE [MI]

Common Name

English

TACROLIMUS [USAN]

Common Name

English

PROGRAF

Brand Name

English

ADVAGRAF

Brand Name

English

Tacrolimus monohydrate [WHO-DD]

Common Name

English

15,19-Epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclotricosine-1,7,20,21(4H,23H)-tetrone, 5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5,19-dihydroxy-3-[(1E)-2-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethenyl]-14,16-dimethoxy-4,10,12,18-t

Systematic Name

English

TACROLIMUS MONOHYDRATE [EP MONOGRAPH]

Common Name

English

ENVARSUS XR

Brand Name

English

(−)-(3S,4R,5S,8R,9E,12S,14S,15R,16S,18R,19R,26aS)-8-Allyl-5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5,19-dihydroxy-3-[(E)-2-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylvinyl]-14,16-dimethoxy-4,10,12,18-tetramethyl-15,19-epoxy-3

Systematic Name

English

FR-900506

Code

English

FR900506

Code

English

TACROLIMUS [USP MONOGRAPH]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

472815