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.CO[C@@H]1C[C@@H](CC[C@H]1O)\C=C(/C)[C@H]2OC(=O)[C@@H]3CCCCN3C(=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 8504

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 8583	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 64 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28512670	Primary		Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
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 blood	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
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 blood	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
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 blood	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
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 blood	Homo sapiens population: UNHEALTHY 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	unhealthy, 1.9 years (range: 3-15 years) Health Status: unhealthy Age Group: 1.9 years (range: 3-15 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf	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
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 Health Status: unhealthy Age Group: adult 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 Health Status: unhealthy Age Group: adult 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 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 Health Status: unhealthy Age Group: adult 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 Health Status: unhealthy 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	unhealthy, 1.9 years (range: 3-15 years) Health Status: unhealthy Age Group: 1.9 years (range: 3-15 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf
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	unhealthy, 1.9 years (range: 3-15 years) Health Status: unhealthy Age Group: 1.9 years (range: 3-15 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf
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	unhealthy, 1.9 years (range: 3-15 years) Health Status: unhealthy Age Group: 1.9 years (range: 3-15 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf
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	unhealthy, 1.9 years (range: 3-15 years) Health Status: unhealthy Age Group: 1.9 years (range: 3-15 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf
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	unhealthy, 1.9 years (range: 3-15 years) Health Status: unhealthy Age Group: 1.9 years (range: 3-15 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf
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	unhealthy, 1.9 years (range: 3-15 years) Health Status: unhealthy Age Group: 1.9 years (range: 3-15 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf
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	unhealthy, 1.9 years (range: 3-15 years) Health Status: unhealthy Age Group: 1.9 years (range: 3-15 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf
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	unhealthy, 1.9 years (range: 3-15 years) Health Status: unhealthy Age Group: 1.9 years (range: 3-15 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210115Orig1s000MedR.pdf
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 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 1946 inhibitor 2252	substrate 1193 inhibitor 2438	substrate 1388 inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2A6 879 CYP2C19 2057 CYP2E1 1060 UGT1A1 246 UGT1A3 89 UGT1A6 136 UGT1A9 148 UGT2B4 23 UGT2B7 197 UGT2B15 84 UGT1A8 37	CYP3A5 446 CYP1A2 1197 CYP2A6 626 CYP2B6 776 CYP2C8 810 CYP2E1 729 P-gp 2052 UGT1A4 399

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	no
CYP2A6 911	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	no
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	no
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	no
CYP2E1 1146	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	no
UGT1A9 155	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	no
UGT1A3 99	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	yes [IC50 0.4 uM]
UGT2B15 84	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	yes [IC50 16.5 uM]
UGT2B7 210	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	yes [IC50 23.5 uM]
UGT1A1 303	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	yes [IC50 3.2 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17202802/ Page: -	yes [Ki 0.36 uM]
UGT1A8 49	inhibitor 4027 Sources: http://sedici.unlp.edu.ar/handle/10915/20208 Page: -	yes [Ki 6.1 uM]
UGT1A6 171	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	yes
UGT2B4 23	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23016456/ Page: -	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A2 1197	substrate 4014 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
CYP2A6 626	substrate 4014 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
CYP2B6 776	substrate 4014 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
CYP2C8 810	substrate 4014 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
CYP2C9 1193	substrate 4014 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
CYP2D6 1388	substrate 4014 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
CYP2E1 729	substrate 4014 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	no
P-gp 2052	substrate 4014 Sources: https://www.jstage.jst.go.jp/article/dmpk/22/5/22_5_328/_pdf/-char/ja Page: -	yes
UGT1A4 399	substrate 4014 Sources: https://dmd.aspetjournals.org/content/39/7/1127.short Page: -	yes
CYP3A4 1946	substrate 4014 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 446	substrate 4014 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
Speech disorder related to tacrolimus-induced pontine myelinolysis after orthotopic liver transplantation.	2003-08	12819864
Steroid-free immunosuppression during and after liver transplantation--a 3-yr follow-up report.	2003-06	12780665
Microangiopathic haemolytic anaemia and thrombocytopenia following lung volume reduction surgery in a single lung transplant recipient on maintenance tacrolimus (FK506) therapy.	2003-06	12753543
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+.	2003-05	12709020
MR imaging with quantitative diffusion mapping of tacrolimus-induced neurotoxicity in organ transplant patients.	2003-05	12695819
Neuropsychologic side-effects of tacrolimus in pediatric renal transplantation.	2003-04	12709079
Delayed graft function and cast nephropathy associated with tacrolimus plus rapamycin use.	2003-04	12660339
Tacrolimus-induced hemolytic uremic syndrome case presentation in a lung transplant recipient.	2003-03	12644073
The immunophilin-ligands FK506 and V-10,367 mediate neuroprotection by the heat shock response.	2003-03	12642403
Kidney function and morphology after short-term combination therapy with cyclosporine A, tacrolimus and sirolimus in the rat.	2003-03	12584269
Treatment of human T cells with bisperoxovanadium phosphotyrosyl phosphatase inhibitors leads to activation of cyclooxygenase-2 gene.	2003-02-28	12493747
Tacrolimus (FK506)-induced mutism after liver transplant.	2003-02	12699871
Severe acute renal failure after exposure to sirolimus-tacrolimus in two living donor kidney recipients.	2003-01-15	12544890
Tacrolimus.	2003-01	12488279
Inhibition of nuclear factor-kappaB activation by pyrrolidine dithiocarbamate prevents chronic FK506 nephropathy.	2003-01	12472797
Renin mRNA expression and renal dysfunction in tacrolimus-induced acute nephrotoxicity.	2003-01	12469222
Expression of TGF-beta and fibrogenic genes in transplant recipients with tacrolimus and cyclosporine nephrotoxicity.	2002-12	12427154
Tacrolimus-induced life-threatening arrhythmia in a pediatric liver-transplant patient.	2002-11	12583382
Tacrolimus-induced pain syndrome in a pediatric orthotopic liver transplant patient.	2002-10	12390434
Oxidative stress in kidney transplant patients with calcineurin inhibitor-induced hypertension: effect of ramipril.	2002-10	12352326
Asymmetric cardiac hypertrophy at autopsy in patients who received FK506 (tacrolimus) or cyclosporine A after liver transplant.	2002-09-27	12364862
Long-term comparison of tacrolimus- and cyclosporine-induced nephrotoxicity in pediatric heart-transplant recipients.	2002-09	12243498
Neurotoxicity induced by tacrolimus after liver transplantation: relation to genetic polymorphisms of the ABCB1 (MDR1) gene.	2002-08-27	12352921
Calcineurin inhibitors, cyclosporin A and tacrolimus inhibit expression of inducible nitric oxide synthase in colon epithelial and macrophage cell lines.	2002-07-19	12144947
Recurrent reversible cerebral edema after long term immunosuppression with tacrolimus.	2002-06	12173578
FK 506-induced fulminant leukoencephalopathy after kidney transplantation: case report.	2002-06	12072309
Downregulation of both interleukin-12 and interleukin-2 in heart allografts by pretransplant host treatment with granulocyte colony-stimulating factor and tacrolimus.	2002-05-07	12126653
Tacrolimus is a class II low-solubility high-permeability drug: the effect of P-glycoprotein efflux on regional permeability of tacrolimus in rats.	2002-03	11920757
[A case of FK 506-induced leukoencephalopathy].	2002-01	11868353
End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment.	2001-12-27	11773892
Severe neurotoxicity of tacrolimus (FK506) after renal transplantation: two case reports.	2001-12-26	11750573
Severe axonal polyneuropathy after a FK506 overdosage in a lung transplant recipient.	2001-12-15	11740402
Calcineurin inhibitor attenuates cardiac hypertrophy due to energy metabolic disorder.	2001-12	11773940
Posttransplantation diabetes mellitus in FK-506-treated renal transplant recipients: analysis of incidence and risk factors.	2001-11-27	11726827
Targeting keratinocyte apoptosis in the treatment of atopic dermatitis and allergic contact dermatitis.	2001-11	11692113
Cyclosporin A-induced encephalopathy after allogeneic bone marrow transplantation with prevention of graft-versus-host disease by tacrolimus.	2001-10	11704797
Sirolimus and mycophenolate mofetil for calcineurin-free immunosuppression in renal transplant recipients.	2001-10	11583940
Changes in lipid metabolism and effect of simvastatin in renal transplant recipients induced by cyclosporine or tacrolimus.	2001-10	11583721
Calcineurin-inhibitor related nephrotoxicity- reversibility in paediatric liver transplant recipients.	2001-08-27	11544444
Renal cholesterol accumulation: a durable response after acute and subacute renal insults.	2001-08	11485932
Reversible encephalopathy associated with tacrolimus in pediatric renal transplants.	2001-07	11465799
Beneficial effects of converting liver transplant recipients from cyclosporine to tacrolimus on blood pressure, serum lipids, and weight.	2001-06	11443583
Echocardiographic findings of hypertrophic cardiomyopathy in children after orthotopic liver transplantation.	2001-06	11422821
Tacrolimus suppressed the production of cytokines involved in atopic dermatitis by direct stimulation of human PBMC system. (Comparison with steroids).	2001-06	11407316
Clinical utility of monitoring tacrolimus blood concentrations in liver transplant patients.	2001-05	11361051
[Blood concentrations and side effects of tacrolimus in a living renal transplantation].	2001-03	11296433
Mycophenolate mofetil monotherapy in liver transplantation.	2001-02-24	11558493
[Acute peripheral demyelinating polyneuropathy and acute renal failure after administration of FK506].	2001	11563175
Nephrotoxicity after orthotopic liver transplantation in cyclosporin A and FK 506-treated patients.	1994	11271297
Neurotoxicity after orthotopic liver transplantation in cyclosporin A- and FK 506-treated patients.	1994	11271254

Patents

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 `Mon Mar 31 18:08:23 GMT 2025` Edited by `admin` on `Mon Mar 31 18:08:23 GMT 2025`
Record UNII	WM0HAQ4WNM
Record Status	`Validated (UNII)`
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Name

Type

Language

TACROLIMUS MONOHYDRATE

Preferred Name

English

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 [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-3H-

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