Identification

Name
Tacrolimus
Accession Number
DB00864
Description

Tacrolimus (also FK-506 or Fujimycin) is an immunosuppressive drug whose main use is after organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection. It is also used in a topical preparation in the treatment of severe atopic dermatitis, severe refractory uveitis after bone marrow transplants, and the skin condition vitiligo. It was discovered in 1984 from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis. Tacrolimus is chemically known as a macrolide. It reduces peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP-12 (FK506 binding protein) creating a new complex. This FKBP12-FK506 complex inhibits calcineurin which inhibits T-lymphocyte signal transduction and IL-2 transcription.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 804.0182
Monoisotopic: 803.481976677
Chemical Formula
C44H69NO12
Synonyms
  • Anhydrous tacrolimus
  • Tacrolimus
  • Tacrolimus anhydrous
  • Tacrolimus, anhydrous
External IDs
  • FK-506
  • FK5
  • K506

Pharmacology

Indication

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

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Tacrolimus acts by reducing peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP-12 (FK506 binding protein) creating a new complex. This inhibits both T-lymphocyte signal transduction and IL-2 transcription. Tacrolimus has similar activity to cyclosporine but rates of rejection are lower with tacrolimus. Tacrolimus has also been shown to be effective in the topical treatment of eczema, particularly atopic eczema. It suppresses inflammation in a similar way to steroids, but is not as powerful. An important dermatological advantage of tacrolimus is that it can be used directly on the face; topical steroids cannot be used on the face, as they thin the skin dramatically there. On other parts of the body, topical steroid are generally a better treatment.

Mechanism of action

The mechanism of action of tacrolimus in atopic dermatitis is not known. While the following have been observed, the clinical significance of these observations in atopic dermatitis is not known. It has been demonstrated that tacrolimus inhibits T-lymphocyte activation by first binding 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 is inhibited. This prevents 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. Tacrolimus also inhibits the transcription for genes which encode IL-3, IL-4, IL-5, GM-CSF, and TNF-, all of which are involved in the early stages of T-cell activation. Additionally, tacrolimus has been shown to inhibit the release of pre-formed mediators from skin mast cells and basophils, and to downregulate the expression of FceRI on Langerhans cells.

TargetActionsOrganism
APeptidyl-prolyl cis-trans isomerase FKBP1A
inhibitor
Humans
Absorption

Absorption of tacrolimus from the gastrointestinal tract after oral administration is incomplete and variable. The absolute bioavailability in adult kidney transplant patients is 17±10%; in adults liver transplant patients is 22±6%; in healthy subjects is 18±5%. The absolute bioavailability in pediatric liver transplant patients was 31±24%. Tacrolimus maximum blood concentrations (Cmax) and area under the curve (AUC) appeared to increase in a dose-proportional fashion in 18 fasted healthy volunteers receiving a single oral dose of 3, 7, and 10 mg. When given without food, the rate and extent of absorption were the greatest. The time of the meal also affected bioavailability. When given immediately after a meal, mean Cmax was reduced 71%, and mean AUC was reduced 39%, relative to the fasted condition. When administered 1.5 hours following the meal, mean Cmax was reduced 63%, and mean AUC was reduced 39%, relative to the fasted condition.

Volume of distribution
  • 2.6 ± 2.1 L/kg [pediatric liver transplant patients]
  • 1.07 ± 0.20 L/kg [patients with renal impairment, 0.02 mg/kg/4 hr dose, IV]
  • 3.1 ± 1.6 L/kg [Mild Hepatic Impairment, 0.02 mg/kg/4 hr dose, IV]
  • 3.7 ± 4.7 L/kg [Mild Hepatic Impairment, 7.7 mg dose, PO]
  • 3.9 ± 1.0 L/kg [Severe hepatic impairment, 0.02 mg/kg/4 hr dose, IV]
  • 3.1 ± 3.4 L/kg [Severe hepatic impairment, 8 mg dose, PO]
Protein binding

~99% bound to human plasma protein, primarily to albumin and alpha-1-acid glycoprotein. This is independent of concentration over a range of 5-50 ng/mL.

Metabolism

The metabolism of tacrolimus is predominantly mediated by CYP3A4 and secondarily by CYP3A5.6,7 Tacrolimus is metabolized into 8 metabolites: 13-demethyl tacrolimus, 31-demethyl tacrolimus, 15-demethyl tacrolimus, 12-hydroxy tacrolimus, 15,31-didemethyl tacrolimus, 13,31-didemethyl tacrolimus, 13,15-didemethyl tacrolimus, and a final metabolite involving O-demethylation and the formation of a fused ring.6 The major metabolite identified in incubations with human liver microsomes is 13-demethyl tacrolimus.7 In in vitro studies, a 31-demethyl metabolite has been reported to have the same activity as tacrolimus.7

Hover over products below to view reaction partners

Route of elimination

In man, less than 1% of the dose administered is excreted unchanged in urine. When administered IV, fecal elimination accounted for 92.6±30.7%, urinary elimination accounted for 2.3±1.1%.

Half-life

The elimination half life in adult healthy volunteers, kidney transplant patients, liver transplants patients, and heart transplant patients are approximately 35, 19, 12, 24 hours, respectively. The elimination half life in pediatric liver transplant patients was 11.5±3.8 hours, in pediatric kidney transplant patients was 10.2±5.0 (range 3.4-25) hours.

Clearance
  • 0.040 L/hr/kg [healthy subjects, IV]
  • 0.172 ± 0.088 L/hr/kg [healthy subjects, oral]
  • 0.083 L/hr/kg [adult kidney transplant patients, IV]
  • 0.053 L/hr/kg [adult liver transplant patients, IV]
  • 0.051 L/hr/kg [adult heart transplant patients, IV]
  • 0.138 ± 0.071 L/hr/kg [pediatric liver transplant patients]
  • 0.12 ± 0.04 (range 0.06-0.17) L/hr/kg [pediatric kidney transplant patients]
  • 0.038 ± 0.014 L/hr/kg [patients with renal impairment, 0.02 mg/kg/4 hr dose, IV]
  • 0.042 ± 0.02 L/hr/kg [Mild Hepatic Impairment, 0.02 mg/kg/4 hr dose, IV]
  • 0.034 ± 0.019 L/hr/kg [Mild Hepatic Impairment, 7.7 mg dose, PO]
  • 0.017 ± 0.013 L/hr/kg [Severe hepatic impairment, 0.02 mg/kg/4 hr dose, IV]
  • 0.016 ± 0.011 L/hr/kg [Severe hepatic impairment, 8 mg dose, PO]
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Side effects can be severe and include blurred vision, liver and kidney problems (it is nephrotoxic), seizures, tremors, hypertension, hypomagnesemia, diabetes mellitus, hyperkalemia, itching, insomnia, confusion. LD50=134-194 mg/kg (rat).

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Multidrug resistance protein 1---(T;T) / (G;T)T Allele (G2677T)ADR Directly StudiedThe presence of this genotype in ABCB1 may indicate an increased risk of drug-induced neurotoxicity when treated with tacrolimus.Details
Cytochrome P450 3A5CYP3A5*1Not AvailableFunctional geneEffect Directly StudiedPatients with this genotype in CYP3A5 are extensive metabolizers and require higer doses of tacrolimus to attain the therapeutic effect.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirTacrolimus may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbametapirThe serum concentration of Tacrolimus can be increased when it is combined with Abametapir.
AbataceptTacrolimus may increase the immunosuppressive activities of Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Tacrolimus.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Tacrolimus.
AcalabrutinibThe serum concentration of Tacrolimus can be increased when it is combined with Acalabrutinib.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Tacrolimus.
AcebutololThe risk or severity of QTc prolongation can be increased when Tacrolimus is combined with Acebutolol.
AceclofenacThe risk or severity of renal failure can be increased when Aceclofenac is combined with Tacrolimus.
AcemetacinThe risk or severity of renal failure can be increased when Acemetacin is combined with Tacrolimus.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid alcohol. Consuming alcohol may increase the rate of tacrolimus release from extended-release formulations.
  • Avoid grapefruit products.
  • Exercise caution with St. John's Wort. This herb induces the CYP3A4 metabolism of tacrolimus; therefore, monitoring tacrolimus whole blood trough concentrations may be warranted.
  • Take at the same time every day.
  • Take on an empty stomach. Take at least 1 hour before or 2 hours after a meal as coadministration with food decreases the rate and extent of absorption.
  • Take separate from antacids. Coadministration of tacrolimus with aluminum or magnesium hydroxide antacids may increase the serum levels of tacrolimus, which poses a risk for toxicity.

Products

Product Ingredients
IngredientUNIICASInChI Key
Tacrolimus hydrateWM0HAQ4WNM109581-93-3NWJQLQGQZSIBAF-MSLXHMNKSA-N
Product Images
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AdvagrafCapsule, extended release5 mgOralAstellas Pharma Europe Bv2007-04-23Not applicableEU flag
AdvagrafCapsule, extended release1 mgOralAstellas Pharma Europe Bv2007-04-23Not applicableEU flag
AdvagrafCapsule, extended release3 mgOralAstellas Pharma Europe Bv2007-04-23Not applicableEU flag
AdvagrafCapsule, extended release3 mgOralAstellas Pharma Europe Bv2007-04-23Not applicableEU flag
AdvagrafCapsule, extended release3 mgOralAstellas Pharma Europe Bv2007-04-23Not applicableEU flag
AdvagrafCapsule, extended release1 mgOralAstellas Pharma Europe Bv2007-04-23Not applicableEU flag
AdvagrafCapsule, extended release1 mgOralAstellas Pharma Europe Bv2007-04-23Not applicableEU flag
AdvagrafCapsule, extended releaseOralAstellas Pharma Inc2008-04-09Not applicableCanada flag
AdvagrafCapsule, extended release5 mgOralAstellas Pharma Europe Bv2007-04-23Not applicableEU flag
AdvagrafCapsule, extended release0.5 mgOralAstellas Pharma Europe Bv2007-04-23Not applicableEU flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Ach-tacrolimusCapsuleOralAccord Healthcare IncNot applicableNot applicableCanada flag
Ach-tacrolimusCapsuleOralAccord Healthcare IncNot applicableNot applicableCanada flag
Ach-tacrolimusCapsuleOralAccord Healthcare IncNot applicableNot applicableCanada flag
Apo-tacrolimusCapsuleOralApotex CorporationNot applicableNot applicableCanada flag
Apo-tacrolimusCapsuleOralApotex CorporationNot applicableNot applicableCanada flag
Apo-tacrolimusCapsuleOralApotex CorporationNot applicableNot applicableCanada flag
Apo-tacrolimusCapsuleOralApotex CorporationNot applicableNot applicableCanada flag
Apo-tacrolimusCapsuleOralApotex CorporationNot applicableNot applicableCanada flag
HecoriaCapsule0.5 mg/1OralNovartis2011-12-202015-12-31US flag
HecoriaCapsule5 mg/1OralNovartis2011-12-202015-12-31US flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Hyaluronic Acid Sodium Salt 1% / Niacinamide 4% / Tacrolimus 0.1%Tacrolimus hydrate (0.1 g/100g) + Hyaluronic acid (1 g/100g) + Nicotinamide (4 g/100g)CreamTopicalSinceru Florida, LLC2019-05-01Not applicableUS flag
Hyaluronic Acid Sodium Salt 1% / Tacrolimus 0.1% / Urea 20%Tacrolimus hydrate (0.1 g/100g) + Sodium hyaluronate (1 g/100g) + Urea (20 g/100g)CreamTopicalSincerus Florida, LLC2019-05-17Not applicableUS flag
Niacinamide 4% / Tacrolimus 0.03%Tacrolimus hydrate (0.03 g/100g) + Nicotinamide (4 g/100g)OintmentTopicalSincerus Florida, LLC2019-05-17Not applicableUS flag
Niacinamide 4% / Tacrolimus 0.1%Tacrolimus hydrate (0.1 g/100g) + Nicotinamide (4 g/100g)OintmentTopicalSincerus Florida, LLC2019-05-01Not applicableUS flag
Tacrolimus 0.1%Tacrolimus hydrate (0.1 g/100g)SolutionTopicalSincerus Florida, LLC2019-05-10Not applicableUS flag
Tacrolimus 0.1% In PseudocatalaseTacrolimus hydrate (0.1 g/100g)CreamTopicalSincerus Florida, LLC2019-05-01Not applicableUS flag
ValidermTacrolimus hydrate (0.05 g/0.05g) + Calcitriol (0.2 mg/0.2mg) + Fluticasone propionate (0.05 g/0.05g)KitTopicalAccumix Pharmaceuticals2014-12-152015-07-17US flag

Categories

ATC Codes
D11AH01 — TacrolimusL04AD02 — Tacrolimus
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as macrolide lactams. These are cyclic polyketides containing both a cyclic amide and a cyclic ester group.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Macrolide lactams
Sub Class
Not Available
Direct Parent
Macrolide lactams
Alternative Parents
Alpha amino acid esters / Macrolides and analogues / Cyclohexanols / Piperidines / Oxanes / Tertiary carboxylic acid amides / Carboxylic acid esters / Cyclic alcohols and derivatives / Cyclic ketones / Hemiacetals
show 10 more
Substituents
Alcohol / Aliphatic heteropolycyclic compound / Alpha-amino acid ester / Alpha-amino acid or derivatives / Azacycle / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Carboxylic acid ester / Cyclic alcohol
show 24 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
macrolide (CHEBI:61049) / Macrolides and lactone polyketides (C01375) / Macrolides and lactone polyketides (LMPK04000003)

Chemical Identifiers

UNII
Y5L2157C4J
CAS number
104987-11-3
InChI Key
QJJXYPPXXYFBGM-LFZNUXCKSA-N
InChI
InChI=1S/C44H69NO12/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/b25-19+,27-21+/t26-,28+,29+,30-,31+,32-,33+,34-,36+,37-,38-,39+,40+,44+/m0/s1
IUPAC Name
(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-1,14-dihydroxy-12-[(1E)-1-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-17-(prop-2-en-1-yl)-11,28-dioxa-4-azatricyclo[22.3.1.0⁴,⁹]octacos-18-ene-2,3,10,16-tetrone
SMILES

References

Synthesis Reference

Pan Sup Chang, Hoon Cho, "Water soluble polymer-tacrolimus conjugated compounds and process for preparing the same." U.S. Patent US5922729, issued April, 1997.

US5922729
General References
  1. Kino T, Hatanaka H, Hashimoto M, Nishiyama M, Goto T, Okuhara M, Kohsaka M, Aoki H, Imanaka H: FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics. J Antibiot (Tokyo). 1987 Sep;40(9):1249-55. [PubMed:2445721]
  2. Pritchard DI: Sourcing a chemical succession for cyclosporin from parasites and human pathogens. Drug Discov Today. 2005 May 15;10(10):688-91. [PubMed:15896681]
  3. Liu J, Farmer JD Jr, Lane WS, Friedman J, Weissman I, Schreiber SL: Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell. 1991 Aug 23;66(4):807-15. [PubMed:1715244]
  4. Fukatsu S, Fukudo M, Masuda S, Yano I, Katsura T, Ogura Y, Oike F, Takada Y, Inui K: Delayed effect of grapefruit juice on pharmacokinetics and pharmacodynamics of tacrolimus in a living-donor liver transplant recipient. Drug Metab Pharmacokinet. 2006 Apr;21(2):122-5. [PubMed:16702731]
  5. Hanifin JM, Paller AS, Eichenfield L, Clark RA, Korman N, Weinstein G, Caro I, Jaracz E, Rico MJ: Efficacy and safety of tacrolimus ointment treatment for up to 4 years in patients with atopic dermatitis. J Am Acad Dermatol. 2005 Aug;53(2 Suppl 2):S186-94. [PubMed:16021174]
  6. Iwasaki K: Metabolism of tacrolimus (FK506) and recent topics in clinical pharmacokinetics. Drug Metab Pharmacokinet. 2007 Oct;22(5):328-35. [PubMed:17965516]
  7. FDA Approved Drug Products: Tacrolimus Oral Capsules [Link]
Human Metabolome Database
HMDB15002
KEGG Drug
D00107
KEGG Compound
C01375
PubChem Compound
445643
PubChem Substance
46506004
ChemSpider
393220
BindingDB
50079777
RxNav
235991
ChEBI
61049
ChEMBL
CHEMBL269732
ZINC
ZINC000169289411
Therapeutic Targets Database
DAP000162
PharmGKB
PA451578
PDBe Ligand
FK5
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tacrolimus
AHFS Codes
  • 92:44.00 — Immunosuppressive Agents
  • 84:92.00 — Misc. Skin and Mucous Membrane Agents
PDB Entries
1bkf / 1fkf / 1fkj / 1q6i / 1tco / 1yat / 2fke / 2vn1 / 3ihz / 3o5r
show 20 more
FDA label
Download (2.11 MB)
MSDS
Download (54.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingHealth Services ResearchTransplantation, Liver1
4Active Not RecruitingTreatmentCytomegalovirus / Transplantation, Kidney1
4Active Not RecruitingTreatmentEnd Stage Renal Disease (ESRD)1
4Active Not RecruitingTreatmentFunction of Renal Transplant1
4Active Not RecruitingTreatmentHepatocellular Carcinoma1
4Active Not RecruitingTreatmentKidney Transplant Patients1
4Active Not RecruitingTreatmentKidney Transplant Rejection / Other Complications of Kidney Transplant1
4Active Not RecruitingTreatmentLiver Diseases1
4Active Not RecruitingTreatmentPancreas Transplantation / Transplantation, Kidney1
4Active Not RecruitingTreatmentRenal Transplant Patients1

Pharmacoeconomics

Manufacturers
  • Astellas pharma us inc
  • Dr reddys laboratories ltd
  • Sandoz inc
  • Watson laboratories inc
  • Astellas Pharma US
Packagers
  • Astellas Pharma Inc.
  • B&B Pharmaceuticals
  • Cardinal Health
  • Caremark LLC
  • Doctor Reddys Laboratories Ltd.
  • Kaiser Foundation Hospital
  • Mckesson Corp.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Neuman Distributors Inc.
  • Physicians Total Care Inc.
  • Rebel Distributors Corp.
  • Sandoz
  • Watson Pharmaceuticals
Dosage Forms
FormRouteStrength
CapsuleOral0.75 MG
CapsuleOral2 MG
Capsule0.5 mg
Capsule1 mg
Capsule5 mg
Capsule, extended releaseOral
Capsule, extended releaseOral0.5 mg
Capsule, extended releaseOral1 mg
Capsule, extended releaseOral3 mg
Capsule, extended releaseOral5 mg
Tablet, film coated, extended release3 mg
CapsuleOral
Capsule, coated, extended releaseOral0.5 mg/1
Capsule, coated, extended releaseOral1 mg/1
Capsule, coated, extended releaseOral5 mg/1
Ointment0.1 %
Capsule, extended release0.5 MG
Capsule, extended release1 MG
Capsule, extended release2 MG
Capsule, extended release3 MG
Capsule, extended release5 MG
OintmentTopical0.0307 g
Tablet, extended releaseOral0.75 mg
Tablet, extended releaseOral1 mg
Tablet, extended releaseOral4 mg
Tablet, extended release0.75 mg
TabletOral1 mg
TabletOral4 mg
Tablet, extended releaseOral
Tablet, extended releaseOral0.75 mg/1
Tablet, extended releaseOral1 mg/1
Tablet, extended releaseOral4 mg/1
CreamTopical
GranuleOral0.2 mg
GranuleOral1 mg
OintmentTopical
Capsule, coatedOral5 mg
Capsule, gelatin coatedOral1 mg/1
Granule, for suspensionOral0.2 mg/1
Granule, for suspensionOral1 mg/1
Injection, solutionIntravenous5 mg/1mL
Injection, solution, concentrateIntravenous5 MG/ML
Capsule, coatedOral1 mg
SolutionIntravenous5 mg
InjectionIntravenous5 mg/ml
OintmentCutaneous0.03 %
OintmentCutaneous0.1 %
OintmentTopical0.03 %
OintmentTopical0.1 %
OintmentTopical1 mg/1g
Ointment0.03 %
Ointment
OintmentTopical0.1 g
OintmentTopical0.03 g
CapsuleOral0.5 MG
CapsuleOral1 MG
CapsuleOral5 MG
CapsuleOral0.5 mg/1
CapsuleOral1 mg/1
CapsuleOral5 mg/1
Capsule, gelatin coatedOral0.5 mg/1
Capsule, gelatin coatedOral5 mg/1
OintmentTopical0.3 mg/1g
SolutionTopical0.1 g/100g
CreamTopical0.1 g/100g
Capsule, coatedOral0.5 mg
KitTopical
Prices
Unit descriptionCostUnit
Tacrolimus micronized powder2800.0USD g
Protopic 0.1% Ointment 60 gm Tube255.34USD tube
Protopic 0.03% Ointment 60 gm Tube251.17USD tube
Prograf 5 mg/ml ampule163.94USD ml
Protopic 0.03% Ointment 30 gm Tube132.99USD tube
Protopic 0.1% Ointment 30 gm Tube124.42USD tube
Prograf 5 mg capsule24.26USD capsule
Tacrolimus anhydrous 5 mg cap22.3USD each
Prograf 1 mg capsule4.85USD capsule
Tacrolimus 1 mg capsule4.64USD capsule
Tacrolimus anhydrous 1 mg cap4.46USD each
Protopic 0.1% ointment4.17USD g
Protopic 0.03% ointment4.09USD g
Prograf 0.5 mg capsule2.43USD capsule
Tacrolimus anhydrous 0.5 mg cap2.23USD each
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5665727No1997-09-092014-09-09US flag
US5260301No1993-11-092011-02-28US flag
CA2037408No2002-12-172011-03-01Canada flag
CA1338491No1996-07-302013-07-30Canada flag
US6884433No2005-04-262019-03-25US flag
US6576259No2003-06-102019-03-25US flag
US8551522No2013-10-082019-03-25US flag
US6440458No2002-08-272019-03-25US flag
US9161907No2015-10-202024-08-30US flag
US8889186No2014-11-182024-08-30US flag
US8623411No2014-01-072024-08-30US flag
US8486993No2013-07-162024-08-30US flag
US8889185No2014-11-182024-08-30US flag
US8664239No2014-03-042028-05-30US flag
US8586084No2013-11-192024-08-30US flag
US8685998No2014-04-012028-05-30US flag
US8623410No2014-01-072024-08-30US flag
US8617599No2013-12-312024-08-30US flag
US7994214No2011-08-092024-08-30US flag
US8591946No2013-11-262024-08-30US flag
US9549918No2017-01-242028-05-30US flag
US9757362No2017-09-122024-08-30US flag
US9763920No2017-09-192024-08-30US flag
US10166190No2019-01-012028-05-30US flag
US8644239No2014-02-042028-08-30US flag
US10548880No2004-08-302024-08-30US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)126 °CNot Available
water solubilityInsolubleFDA label
logP3.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00402 mg/mLALOGPS
logP3.19ALOGPS
logP5.59ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)9.96ChemAxon
pKa (Strongest Basic)-2.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count11ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area178.36 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity215.62 m3·mol-1ChemAxon
Polarizability87.41 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.8264
Blood Brain Barrier-0.9659
Caco-2 permeable-0.5977
P-glycoprotein substrateSubstrate0.7862
P-glycoprotein inhibitor IInhibitor0.8687
P-glycoprotein inhibitor IIInhibitor0.7974
Renal organic cation transporterNon-inhibitor0.8135
CYP450 2C9 substrateNon-substrate0.9116
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7435
CYP450 1A2 substrateNon-inhibitor0.8874
CYP450 2C9 inhibitorNon-inhibitor0.9053
CYP450 2D6 inhibitorNon-inhibitor0.9402
CYP450 2C19 inhibitorNon-inhibitor0.8969
CYP450 3A4 inhibitorNon-inhibitor0.869
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9807
Ames testNon AMES toxic0.6355
CarcinogenicityNon-carcinogens0.9422
BiodegradationNot ready biodegradable0.9698
Rat acute toxicity2.7541 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9817
hERG inhibition (predictor II)Non-inhibitor0.8733
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Type i transforming growth factor beta receptor binding
Specific Function
Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruites SMAD7 to ACVR1B which prevent...
Gene Name
FKBP1A
Uniprot ID
P62942
Uniprot Name
Peptidyl-prolyl cis-trans isomerase FKBP1A
Molecular Weight
11950.665 Da
References
  1. Labrande C, Velly L, Canolle B, Guillet B, Masmejean F, Nieoullon A, Pisano P: Neuroprotective effects of tacrolimus (FK506) in a model of ischemic cortical cell cultures: role of glutamate uptake and FK506 binding protein 12 kDa. Neuroscience. 2006;137(1):231-9. Epub 2005 Nov 10. [PubMed:16289353]
  2. Masri M, Rizk S, Barbari A, Stephan A, Kamel G, Rost M: An assay for the determination of sirolimus levels in the lymphocyte of transplant patients. Transplant Proc. 2007 May;39(4):1204-6. [PubMed:17524933]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Zheng H, Webber S, Zeevi A, Schuetz E, Zhang J, Bowman P, Boyle G, Law Y, Miller S, Lamba J, Burckart GJ: Tacrolimus dosing in pediatric heart transplant patients is related to CYP3A5 and MDR1 gene polymorphisms. Am J Transplant. 2003 Apr;3(4):477-83. [PubMed:12694072]
  2. Kamdem LK, Streit F, Zanger UM, Brockmoller J, Oellerich M, Armstrong VW, Wojnowski L: Contribution of CYP3A5 to the in vitro hepatic clearance of tacrolimus. Clin Chem. 2005 Aug;51(8):1374-81. doi: 10.1373/clinchem.2005.050047. Epub 2005 Jun 10. [PubMed:15951320]
  3. Op den Buijsch RA, Christiaans MH, Stolk LM, de Vries JE, Cheung CY, Undre NA, van Hooff JP, van Dieijen-Visser MP, Bekers O: Tacrolimus pharmacokinetics and pharmacogenetics: influence of adenosine triphosphate-binding cassette B1 (ABCB1) and cytochrome (CYP) 3A polymorphisms. Fundam Clin Pharmacol. 2007 Aug;21(4):427-35. doi: 10.1111/j.1472-8206.2007.00504.x. [PubMed:17635182]
  4. Zheng H, Zeevi A, Schuetz E, Lamba J, McCurry K, Griffith BP, Webber S, Ristich J, Dauber J, Iacono A, Grgurich W, Zaldonis D, McDade K, Zhang J, Burckart GJ: Tacrolimus dosing in adult lung transplant patients is related to cytochrome P4503A5 gene polymorphism. J Clin Pharmacol. 2004 Feb;44(2):135-40. doi: 10.1177/0091270003262108. [PubMed:14747421]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Ekins S, Bravi G, Wikel JH, Wrighton SA: Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J Pharmacol Exp Ther. 1999 Oct;291(1):424-33. [PubMed:10490933]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  3. Lampen A, Christians U, Guengerich FP, Watkins PB, Kolars JC, Bader A, Gonschior AK, Dralle H, Hackbarth I, Sewing KF: Metabolism of the immunosuppressant tacrolimus in the small intestine: cytochrome P450, drug interactions, and interindividual variability. Drug Metab Dispos. 1995 Dec;23(12):1315-24. [PubMed:8689938]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Schuetz EG, Beck WT, Schuetz JD: Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells. Mol Pharmacol. 1996 Feb;49(2):311-8. [PubMed:8632764]
  2. Wandel C, Kim RB, Kajiji S, Guengerich P, Wilkinson GR, Wood AJ: P-glycoprotein and cytochrome P-450 3A inhibition: dissociation of inhibitory potencies. Cancer Res. 1999 Aug 15;59(16):3944-8. [PubMed:10463589]
  3. Quezada CA, Garrido WX, Gonzalez-Oyarzun MA, Rauch MC, Salas MR, San Martin RE, Claude AA, Yanez AJ, Slebe JC, Carcamo JG: Effect of tacrolimus on activity and expression of P-glycoprotein and ATP-binding cassette transporter A5 (ABCA5) proteins in hematoencephalic barrier cells. Biol Pharm Bull. 2008 Oct;31(10):1911-6. [PubMed:18827354]
  4. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
May play a role in the processing of autolysosomes.
Gene Name
ABCA5
Uniprot ID
Q8WWZ7
Uniprot Name
ATP-binding cassette sub-family A member 5
Molecular Weight
186505.825 Da
References
  1. Quezada CA, Garrido WX, Gonzalez-Oyarzun MA, Rauch MC, Salas MR, San Martin RE, Claude AA, Yanez AJ, Slebe JC, Carcamo JG: Effect of tacrolimus on activity and expression of P-glycoprotein and ATP-binding cassette transporter A5 (ABCA5) proteins in hematoencephalic barrier cells. Biol Pharm Bull. 2008 Oct;31(10):1911-6. [PubMed:18827354]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Kalliokoski A, Niemi M: Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009 Oct;158(3):693-705. doi: 10.1111/j.1476-5381.2009.00430.x. Epub 2009 Sep 25. [PubMed:19785645]

Drug created on June 13, 2005 07:24 / Updated on September 27, 2020 08:17

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