tacrolimus indications/contra

Stem definitionDrug idCAS RN
immunosuppressants, rapamycin derivatives 2552 104987-11-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • FK-506
  • tacrolimus hydrate
  • tacrolimus
  • fujimycin
  • tsukubaenolide
  • anhydrous tacrolimus
  • tacrolimus anhydrous
  • modigraf
  • FR900506
A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.
  • Molecular weight: 804.03
  • Formula: C44H69NO12
  • CLOGP: 5.78
  • LIPINSKI: 3
  • HAC: 13
  • HDO: 3
  • TPSA: 178.36
  • ALOGS: -5.30
  • ROTB: 7

Drug dosage:

DoseUnitRoute
5 mg O
5 mg P

Approvals:

DateAgencyCompanyOrphan
April 8, 1994 FDA ASTELLAS

FDA Adverse Event Reporting System

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MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Transplant rejection 4089.42 31.90 819 21650 1292 3362098
Cytomegalovirus infection 3523.09 31.90 829 21640 3678 3359712
Off label use 2816.58 31.90 1262 21207 52715 3310675
Thrombotic microangiopathy 2660.39 31.90 578 21891 1614 3361776
Acute graft versus host disease 2388.26 31.90 511 21958 1291 3362099
Kidney transplant rejection 2223.07 31.90 474 21995 1169 3362221
Drug ineffective 1925.48 31.90 1269 21200 114821 3248569
Graft versus host disease 1756.00 31.90 424 22045 2123 3361267
Renal impairment 1717.19 31.90 653 21816 17608 3345782
Acute kidney injury 1709.45 31.90 875 21594 48808 3314582
Immunosuppressant drug level increased 1696.77 31.90 339 22130 515 3362875
Sepsis 1646.47 31.90 746 21723 31627 3331763
Liver transplant rejection 1597.04 31.90 314 22155 415 3362975
Polyomavirus-associated nephropathy 1587.69 31.90 287 22182 139 3363251
Blood creatinine increased 1556.41 31.90 639 21830 21179 3342211
Posterior reversible encephalopathy syndrome 1545.60 31.90 402 22067 2852 3360538
Complications of transplanted kidney 1518.53 31.90 306 22163 498 3362892
Post transplant lymphoproliferative disorder 1430.78 31.90 289 22180 479 3362911
Multiple organ dysfunction syndrome 1348.88 31.90 514 21955 13896 3349494
Pyrexia 1262.20 31.90 855 21614 80260 3283130
Diarrhoea 1255.96 31.90 940 21529 103408 3259982
Chronic graft versus host disease 1246.97 31.90 278 22191 900 3362490
Cytomegalovirus viraemia 1192.65 31.90 248 22221 511 3362879
Transplant dysfunction 1191.48 31.90 229 22240 243 3363147
Drug interaction 1137.95 31.90 656 21813 46156 3317234
BK virus infection 1111.89 31.90 221 22248 320 3363070
Respiratory failure 1107.58 31.90 512 21957 22629 3340761
Diabetes mellitus 1099.85 31.90 423 22046 11710 3351680
Pneumonia 1089.03 31.90 739 21730 69404 3293986
Toxicity to various agents 1086.93 31.90 638 21831 46416 3316974

Pharmacologic Action:

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SourceCodeDescription
ATC D11AH01 DERMATOLOGICALS
OTHER DERMATOLOGICAL PREPARATIONS
OTHER DERMATOLOGICAL PREPARATIONS
Agents for dermatitis, excluding corticosteroids
ATC L04AD02 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
IMMUNOSUPPRESSANTS
IMMUNOSUPPRESSANTS
Calcineurin inhibitors
FDA EPC N0000175457 Calcineurin Inhibitor Immunosuppressant
MeSH PA D065095 Calcineurin Inhibitors
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D007155 Immunologic Factors
MeSH PA D007166 Immunosuppressive Agents
CHEBI has role CHEBI:35705 immunosuppressive agent

Drug Use (View source of the data)

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DiseaseRelationSNOMED_IDDOID
Atopic dermatitis indication 24079001 DOID:3310
Transplanted organ rejection indication 213148006
Liver transplant rejection indication 235911006
Renal transplant rejection indication 236570004
Intractable Eczema indication
Prevention of Liver Transplant Rejection indication
Prevention of Kidney Transplant Rejection indication
Prevention of Transplant Rejection indication
Prevention of Cardiac Transplant Rejection indication
Delirium contraindication 2776000
Herpes zoster contraindication 4740000 DOID:8536
Hyperkalemia contraindication 14140009
Progressive multifocal leukoencephalopathy contraindication 22255007 DOID:643
Constitutional aplastic anemia contraindication 28975000 DOID:1342
Lymphadenopathy contraindication 30746006
Torsades de pointes contraindication 31722008
Immunosuppression contraindication 38013005
Hypertensive disorder contraindication 38341003 DOID:10763
Infectious disease contraindication 40733004
Mental handicap contraindication 47437004
Chronic heart failure contraindication 48447003
Left ventricular hypertrophy contraindication 55827005
Hepatic failure contraindication 59927004
Diabetes mellitus contraindication 73211009 DOID:9351
Hyperglycemia contraindication 80394007 DOID:4195
Herpes simplex contraindication 88594005 DOID:8566
Kidney disease contraindication 90708001 DOID:2527
Prolonged QT interval contraindication 111975006
Malignant lymphoma contraindication 118600007 DOID:0060058
Seizure disorder contraindication 128613002 DOID:1826
Eczema herpeticum contraindication 186535001 DOID:9123
Toxic nephropathy contraindication 236514003
Post-transplant lymphoproliferative disorder contraindication 254290004
Infectious mononucleosis contraindication 271558008 DOID:8568
Netherton's syndrome contraindication 312514006 DOID:0050474
Coma contraindication 371632003
Primary malignant neoplasm contraindication 372087000
Neuropathy contraindication 386033004 DOID:870
Breastfeeding (mother) contraindication 413712001
Congenital long QT syndrome contraindication 442917000
Posterior reversible encephalopathy syndrome contraindication 450886002
BK Polyomavirus Reactivation Nephropathy contraindication
Tacrolimus Toxicity contraindication
Tremors contraindication
Prevention of Lung Transplant Rejection off-label use

Acid dissociation constants calculated using MoKa v3.0.0

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Dissociation levelDissociation constantType (acidic/basic)
pKa1 12.4 acidic
pKa2 13.12 acidic

Orange Book patent data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 0.5MG BASE ASTAGRAF XL ASTELLAS N204096 July 19, 2013 RX CAPSULE, EXTENDED RELEASE ORAL 6576259 March 25, 2019 METHOD OF ONCE A DAY ADMINISTRATION
EQ 0.5MG BASE ASTAGRAF XL ASTELLAS N204096 July 19, 2013 RX CAPSULE, EXTENDED RELEASE ORAL 6884433 March 25, 2019 METHOD OF ONCE A DAY ADMINISTRATION
EQ 1MG BASE ASTAGRAF XL ASTELLAS N204096 July 19, 2013 RX CAPSULE, EXTENDED RELEASE ORAL 6576259 March 25, 2019 METHOD OF ONCE A DAY ADMINISTRATION
EQ 1MG BASE ASTAGRAF XL ASTELLAS N204096 July 19, 2013 RX CAPSULE, EXTENDED RELEASE ORAL 6884433 March 25, 2019 METHOD OF ONCE A DAY ADMINISTRATION
EQ 5MG BASE ASTAGRAF XL ASTELLAS N204096 July 19, 2013 RX CAPSULE, EXTENDED RELEASE ORAL 6576259 March 25, 2019 METHOD OF ONCE A DAY ADMINISTRATION
EQ 5MG BASE ASTAGRAF XL ASTELLAS N204096 July 19, 2013 RX CAPSULE, EXTENDED RELEASE ORAL 6884433 March 25, 2019 METHOD OF ONCE A DAY ADMINISTRATION
EQ 0.75MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8486993 Aug. 30, 2024 PROPHYLAXIS OF ORGAN REJECTION
EQ 0.75MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8586084 Aug. 30, 2024 PROPHYLAXIS OF ORGAN REJECTION
EQ 0.75MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8623411 Aug. 30, 2024 PROPHYLAXIS OF ORGAN REJECTION
EQ 0.75MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8889185 Aug. 30, 2024 PROPHYLAXIS OF ORGAN REJECTION
EQ 0.75MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8889186 Aug. 30, 2024 PROPHYLAXIS OF ORGAN REJECTION
EQ 0.75MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 9161907 Aug. 30, 2024 PROPHYLAXIS OF ORGAN REJECTION
EQ 1MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8486993 Aug. 30, 2024 PROPHYLAXIS OF ORGAN REJECTION
EQ 1MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8586084 Aug. 30, 2024 PROPHYLAXIS OF ORGAN REJECTION
EQ 1MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8623411 Aug. 30, 2024 PROPHYLAXIS OF ORGAN REJECTION
EQ 1MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8889185 Aug. 30, 2024 PROPHYLAXIS OF ORGAN REJECTION
EQ 1MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8889186 Aug. 30, 2024 PROPHYLAXIS OF ORGAN REJECTION
EQ 1MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 9161907 Aug. 30, 2024 PROPHYLAXIS OF ORGAN REJECTION
EQ 4MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8486993 Aug. 30, 2024 PROPHYLAXIS OF ORGAN REJECTION
EQ 4MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8586084 Aug. 30, 2024 PROPHYLAXIS OF ORGAN REJECTION
EQ 4MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8623411 Aug. 30, 2024 PROPHYLAXIS OF ORGAN REJECTION
EQ 4MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8889185 Aug. 30, 2024 PROPHYLAXIS OF ORGAN REJECTION
EQ 4MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8889186 Aug. 30, 2024 PROPHYLAXIS OF ORGAN REJECTION
EQ 4MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 9161907 Aug. 30, 2024 PROPHYLAXIS OF ORGAN REJECTION
EQ 0.75MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8664239 May 30, 2028 PROPHYLAXIS OF ORGAN REJECTION
EQ 0.75MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8685998 May 30, 2028 PROPHYLAXIS OF ORGAN REJECTION
EQ 1MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8664239 May 30, 2028 PROPHYLAXIS OF ORGAN REJECTION
EQ 1MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8685998 May 30, 2028 PROPHYLAXIS OF ORGAN REJECTION
EQ 4MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8664239 May 30, 2028 PROPHYLAXIS OF ORGAN REJECTION
EQ 4MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL 8685998 May 30, 2028 PROPHYLAXIS OF ORGAN REJECTION

Orange Book exclusivity data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 0.75MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL July 10, 2022 PROPHYLAXIS OF ORGAN REJECTION IN KIDNEY TRANSPLANT PATIENTS CONVERTED FROM TACROLIMUS IMMEDIATE-RELEASE FORMULATIONS IN COMBINATION WITH OTHER IMMUNOSUPPRESSANTS
EQ 1MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL July 10, 2022 PROPHYLAXIS OF ORGAN REJECTION IN KIDNEY TRANSPLANT PATIENTS CONVERTED FROM TACROLIMUS IMMEDIATE-RELEASE FORMULATIONS IN COMBINATION WITH OTHER IMMUNOSUPPRESSANTS
EQ 4MG BASE ENVARSUS XR VELOXIS PHARMS INC N206406 July 10, 2015 RX TABLET, EXTENDED RELEASE ORAL July 10, 2022 PROPHYLAXIS OF ORGAN REJECTION IN KIDNEY TRANSPLANT PATIENTS CONVERTED FROM TACROLIMUS IMMEDIATE-RELEASE FORMULATIONS IN COMBINATION WITH OTHER IMMUNOSUPPRESSANTS

Bioactivity Summary:

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TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Peptidyl-prolyl cis-trans isomerase FKBP1A Enzyme INHIBITOR Kd 9.40 WOMBAT-PK CHEMBL
Cytochrome P450 3A4 Enzyme IC50 6 DRUG MATRIX
Serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform Enzyme Ki 7.46 WOMBAT-PK
Interleukin-2 Cytokine IC50 9.72 WOMBAT-PK
Interferon gamma Cytokine IC50 10.22 WOMBAT-PK
Interleukin-5 Cytokine IC50 10.22 WOMBAT-PK
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 6 WOMBAT-PK
Peptidyl-prolyl cis-trans isomerase FKBP10 Enzyme IC50 9.02 WOMBAT-PK
Serine/threonine-protein kinase mTOR Kinase IC50 9.02 CHEMBL
Splicing factor 3B subunit 3 Unclassified IC50 7.96 CHEMBL
Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform Enzyme Kd 7.70 CHEMBL
Peptidyl-prolyl cis-trans isomerase FKBP5 Enzyme Ki 7.10 CHEMBL
Peptidyl-prolyl cis-trans isomerase FKBP1B Enzyme Kd 9.40 CHEMBL

External reference:

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IDSource
4020868 VUID
N0000148372 NUI
C0085149 UMLSCUI
6784 IUPHAR_LIGAND_ID
D00107 KEGG_DRUG
CHEMBL269732 ChEMBL_ID
DB00864 DRUGBANK_ID
4020868 VANDF
N0000007302 NDFRT
N0000148372 NDFRT
004446 NDDF
42316 RXNORM
109129008 SNOMEDCT_US
386975001 SNOMEDCT_US
5539 MMSL
d03752 MMSL
66434 MMSL
445643 PUBCHEM_CID
WM0HAQ4WNM UNII
109581-93-3 SECONDARY_CAS_RN
D016559 MESH_DESCRIPTOR_UI
6878 INN_ID
CHEBI:61049 CHEBI

Pharmaceutical products:

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ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
Tacrolimus HUMAN PRESCRIPTION DRUG LABEL 1 0168-0416 OINTMENT 1 mg TOPICAL ANDA 15 sections
Tacrolimus HUMAN PRESCRIPTION DRUG LABEL 1 0168-0417 OINTMENT 0.30 mg TOPICAL ANDA 15 sections
Tacrolimus HUMAN PRESCRIPTION DRUG LABEL 1 0179-0079 CAPSULE 1 mg ORAL ANDA 11 sections
Tacrolimus HUMAN PRESCRIPTION DRUG LABEL 1 0378-2045 CAPSULE 0.50 mg ORAL ANDA 18 sections
Tacrolimus HUMAN PRESCRIPTION DRUG LABEL 1 0378-2046 CAPSULE 1 mg ORAL ANDA 18 sections
Tacrolimus HUMAN PRESCRIPTION DRUG LABEL 1 0378-2047 CAPSULE 5 mg ORAL ANDA 18 sections
Prograf HUMAN PRESCRIPTION DRUG LABEL 1 0469-0607 CAPSULE, GELATIN COATED 0.50 mg ORAL NDA 18 sections
Prograf HUMAN PRESCRIPTION DRUG LABEL 1 0469-0617 CAPSULE, GELATIN COATED 1 mg ORAL NDA 18 sections
ASTAGRAF XL HUMAN PRESCRIPTION DRUG LABEL 1 0469-0647 CAPSULE, COATED, EXTENDED RELEASE 0.50 mg ORAL NDA 18 sections
Prograf HUMAN PRESCRIPTION DRUG LABEL 1 0469-0657 CAPSULE, GELATIN COATED 5 mg ORAL NDA 18 sections
ASTAGRAF XL HUMAN PRESCRIPTION DRUG LABEL 1 0469-0677 CAPSULE, COATED, EXTENDED RELEASE 1 mg ORAL NDA 18 sections
ASTAGRAF XL HUMAN PRESCRIPTION DRUG LABEL 1 0469-0687 CAPSULE, COATED, EXTENDED RELEASE 5 mg ORAL NDA 18 sections
Prograf HUMAN PRESCRIPTION DRUG LABEL 1 0469-3016 INJECTION, SOLUTION 5 mg INTRAVENOUS NDA 18 sections
Protopic HUMAN PRESCRIPTION DRUG LABEL 1 0469-5201 OINTMENT 0.30 mg TOPICAL NDA 13 sections
Protopic HUMAN PRESCRIPTION DRUG LABEL 1 0469-5202 OINTMENT 1 mg TOPICAL NDA 13 sections
Tacrolimus HUMAN PRESCRIPTION DRUG LABEL 1 0781-2102 CAPSULE 0.50 mg ORAL ANDA 18 sections
Tacrolimus HUMAN PRESCRIPTION DRUG LABEL 1 0781-2103 CAPSULE 1 mg ORAL ANDA 18 sections
Tacrolimus HUMAN PRESCRIPTION DRUG LABEL 1 0781-2104 CAPSULE 5 mg ORAL ANDA 18 sections
Tacrolimus HUMAN PRESCRIPTION DRUG LABEL 1 0781-9302 CAPSULE 0.50 mg ORAL ANDA 18 sections
Tacrolimus HUMAN PRESCRIPTION DRUG LABEL 1 0781-9303 CAPSULE 1 mg ORAL ANDA 18 sections
Tacrolimus HUMAN PRESCRIPTION DRUG LABEL 1 0781-9304 CAPSULE 5 mg ORAL ANDA 18 sections
Tacrolimus HUMAN PRESCRIPTION DRUG LABEL 1 0904-6425 CAPSULE 1 mg ORAL ANDA 18 sections
Tacrolimus HUMAN PRESCRIPTION DRUG LABEL 1 0904-6623 CAPSULE 0.50 mg ORAL ANDA 18 sections
Tacrolimus HUMAN PRESCRIPTION DRUG LABEL 1 0904-6624 CAPSULE 5 mg ORAL ANDA 18 sections
Tacrolimus HUMAN PRESCRIPTION DRUG LABEL 1 16729-041 CAPSULE 0.50 mg ORAL ANDA 18 sections
Tacrolimus HUMAN PRESCRIPTION DRUG LABEL 1 16729-042 CAPSULE 1 mg ORAL ANDA 18 sections
Tacrolimus HUMAN PRESCRIPTION DRUG LABEL 1 16729-043 CAPSULE 5 mg ORAL ANDA 18 sections
Prograf HUMAN PRESCRIPTION DRUG LABEL 1 21695-170 CAPSULE, GELATIN COATED 1 mg ORAL NDA 14 sections
Prograf HUMAN PRESCRIPTION DRUG LABEL 1 43353-178 CAPSULE, GELATIN COATED 1 mg ORAL NDA 20 sections
Tacrolimus HUMAN PRESCRIPTION DRUG LABEL 1 43353-317 CAPSULE 1 mg ORAL ANDA 19 sections