TACROLIMUS

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C44H69NO12.H2O
Molecular Weight	822.0351
Optical Activity	UNSPECIFIED
Defined Stereocenters	14 / 14
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C=CC[C@]1([H])/C(/[H])=C(\C)/C[C@]([H])(C)C[C@@]([H])([C@]2([H])[C@]([H])(C[C@@]([H])(C)[C@@](C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O[C@]([H])(/C(=C(\[H])/[C@]4([H])CC[C@]([H])([C@@]([H])(C4)OC)O)/C)[C@]([H])(C)[C@]([H])(CC1=O)O)(O)O2)OC)OC.O

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	H2O
Molecular Weight	18.0153
Charge	0
Count

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

Molecular Formula	C44H69NO12
Molecular Weight	804.0199
Charge	0
Count

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

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 3 Target ID: CHEMBL1902 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16289353	Inhibitor 3315

Conditions

Condition	Modality	Targets	Highest Phase	Product
Organ rejection 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050708s045,050709s038lbl.pdf	Preventing		Approved 4033	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 7.6576319E11
Atopic dermatitis 17 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28512670	Primary		Phase III 257	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 882 inhibitor 753	substrate 530 inhibitor 825	substrate 610 inhibitor 894

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 725 CYP2A6 334 CYP2C19 700 CYP2E1 424 UGT1A1 90 UGT1A3 46 UGT1A6 50 UGT1A9 53 UGT2B4 13 UGT2B7 67 UGT2B15 27 UGT1A8 14	CYP3A5 203 CYP1A2 526 CYP2A6 266 CYP2B6 338 CYP2C8 354 CYP2E1 332 P-gp 724 UGT1A4 171

Drug as perpetrator

Target	Modality	Activity
CYP1A2 805	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	no
CYP2A6 356	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	no
CYP2C19 738	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	no
CYP2C9 851	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	no
CYP2D6 908	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	no
CYP2E1 467	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	no
UGT1A9 55	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	no
UGT1A3 51	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	yes [IC50 0.4 uM]
UGT2B15 27	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	yes [IC50 16.5 uM]
UGT2B7 71	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	yes [IC50 23.5 uM]
UGT1A1 117	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	yes [IC50 3.2 uM]
CYP3A4 920	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	yes [Ki 0.36 uM]
UGT1A8 20	inhibitor 1612 Sources: http://sedici.unlp.edu.ar/handle/10915/20208 Page: -	yes [Ki 6.1 uM]
UGT1A6 69	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	yes
UGT2B4 13	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A2 526	substrate 1689 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
CYP2A6 266	substrate 1689 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
CYP2B6 338	substrate 1689 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
CYP2C8 354	substrate 1689 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
CYP2C9 530	substrate 1689 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
CYP2D6 610	substrate 1689 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
CYP2E1 332	substrate 1689 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
P-gp 724	substrate 1689 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	yes
UGT1A4 171	substrate 1689 Sources: https://dmd.aspetjournals.org/content/39/7/1127.short Page: -	yes
CYP3A4 882	substrate 1689 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 203	substrate 1689 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
Neurotoxicity after orthotopic liver transplantation in cyclosporin A- and FK 506-treated patients.	1994	11271254
Neurological complications in the European multicentre study of FK 506 and cyclosporin in primary liver transplantation.	1994	11271222
Renal complications and development of hypertension in the European study of FK 506 and cyclosporin in primary liver transplant recipients.	1994	11271207
Hemolytic-uremic syndrome in association with both cyclosporine and tacrolimus.	2000	11140243
Tacrolimus in acute renal failure: does L-arginine-infusion prevent changes in renal hemodynamics?	2000	11140242
[Acute peripheral demyelinating polyneuropathy and acute renal failure after administration of FK506].	2001	11563175
Calcineurin-inhibitor induced pain syndrome (CIPS): a severe disabling complication after organ transplantation.	2001	11263551
Renal cholesterol accumulation: a durable response after acute and subacute renal insults.	2001 Aug	11485932
Calcineurin-inhibitor related nephrotoxicity- reversibility in paediatric liver transplant recipients.	2001 Aug 27	11544444
Calcineurin inhibitor attenuates cardiac hypertrophy due to energy metabolic disorder.	2001 Dec	11773940
Severe axonal polyneuropathy after a FK506 overdosage in a lung transplant recipient.	2001 Dec 15	11740402
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
Reversible encephalopathy associated with tacrolimus in pediatric renal transplants.	2001 Jul	11465799
Beneficial effects of converting liver transplant recipients from cyclosporine to tacrolimus on blood pressure, serum lipids, and weight.	2001 Jun	11443583
Echocardiographic findings of hypertrophic cardiomyopathy in children after orthotopic liver transplantation.	2001 Jun	11422821
Tacrolimus suppressed the production of cytokines involved in atopic dermatitis by direct stimulation of human PBMC system. (Comparison with steroids).	2001 Jun	11407316
[Blood concentrations and side effects of tacrolimus in a living renal transplantation].	2001 Mar	11296433
Targeting keratinocyte apoptosis in the treatment of atopic dermatitis and allergic contact dermatitis.	2001 Nov	11692113
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
Neurotoxicity induced by tacrolimus after liver transplantation: relation to genetic polymorphisms of the ABCB1 (MDR1) gene.	2002 Aug 27	12352921
[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
FK 506-induced fulminant leukoencephalopathy after kidney transplantation: case report.	2002 Jun	12072309
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
Oxidative stress in kidney transplant patients with calcineurin inhibitor-induced hypertension: effect of ramipril.	2002 Oct	12352326
Long-term comparison of tacrolimus- and cyclosporine-induced nephrotoxicity in pediatric heart-transplant recipients.	2002 Sep	12243498
Asymmetric cardiac hypertrophy at autopsy in patients who received FK506 (tacrolimus) or cyclosporine A after liver transplant.	2002 Sep 27	12364862
Neuropsychologic side-effects of tacrolimus in pediatric renal transplantation.	2003 Apr	12709079
Delayed graft function and cast nephropathy associated with tacrolimus plus rapamycin use.	2003 Apr	12660339
Speech disorder related to tacrolimus-induced pontine myelinolysis after orthotopic liver transplantation.	2003 Aug	12819864
Tacrolimus (FK506)-induced mutism after liver transplant.	2003 Feb	12699871
Treatment of human T cells with bisperoxovanadium phosphotyrosyl phosphatase inhibitors leads to activation of cyclooxygenase-2 gene.	2003 Feb 28	12493747
Tacrolimus.	2003 Jan	12488279
Inhibition of nuclear factor-kappaB activation by pyrrolidine dithiocarbamate prevents chronic FK506 nephropathy.	2003 Jan	12472797
Renin mRNA expression and renal dysfunction in tacrolimus-induced acute nephrotoxicity.	2003 Jan	12469222
Severe acute renal failure after exposure to sirolimus-tacrolimus in two living donor kidney recipients.	2003 Jan 15	12544890
Steroid-free immunosuppression during and after liver transplantation--a 3-yr follow-up report.	2003 Jun	12780665
Microangiopathic haemolytic anaemia and thrombocytopenia following lung volume reduction surgery in a single lung transplant recipient on maintenance tacrolimus (FK506) therapy.	2003 Jun	12753543
Tacrolimus-induced hemolytic uremic syndrome case presentation in a lung transplant recipient.	2003 Mar	12644073
The immunophilin-ligands FK506 and V-10,367 mediate neuroprotection by the heat shock response.	2003 Mar	12642403
Kidney function and morphology after short-term combination therapy with cyclosporine A, tacrolimus and sirolimus in the rat.	2003 Mar	12584269
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
MR imaging with quantitative diffusion mapping of tacrolimus-induced neurotoxicity in organ transplant patients.	2003 May	12695819

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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 Jun 25 21:05:16 UTC 2021` Edited by `admin` on `Fri Jun 25 21:05:16 UTC 2021`
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 MONOHYDRATE [WHO-DD]

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 [EP MONOGRAPH]

Common Name

English

ENVARSUS XR

Brand Name

English

FR-900506

Code

English

FR900506

Code

English

TACROLIMUS [USP MONOGRAPH]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

472815