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Identification
NameTacrolimus
Accession NumberDB00864  (APRD00276, EXPT01437)
TypeSmall Molecule
GroupsApproved, Investigational
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 interacts with and inhibits calcineurin thus inhibiting both T-lymphocyte signal transduction and IL-2 transcription.

Structure
Thumb
Synonyms
(-)-FK 506
8-DEETHYL-8-[but-3-enyl]-ascomycin
FK 506
FK506
Prograf
Tacrolimus anhydrous
External Identifiers
  • FK-506
  • FK5
  • K506
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Advagrafcapsule (extended release)3 mgoralAstellas Pharma Canada Inc2010-04-05Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Advagrafcapsule (extended release)5 mgoralAstellas Pharma Canada Inc2008-04-09Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Advagrafcapsule (extended release)1 mgoralAstellas Pharma Canada Inc2008-04-09Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Advagrafcapsule (extended release)0.5 mgoralAstellas Pharma Canada Inc2008-04-09Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Astagraf XLcapsule, coated, extended release5 mg/1oralAstellas Pharma US, Inc.2013-07-19Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Astagraf XLcapsule, coated, extended release1 mg/1oralAstellas Pharma US, Inc.2013-07-19Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Astagraf XLcapsule, coated, extended release.5 mg/1oralAstellas Pharma US, Inc.2013-07-19Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Envarsus XRtablet, extended release1 mg/1oralVeloxis Pharmaceuticals, Inc2015-09-01Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Envarsus XRtablet, extended release.75 mg/1oralVeloxis Pharmaceuticals, Inc2015-09-01Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Envarsus XRtablet, extended release4 mg/1oralVeloxis Pharmaceuticals, Inc2015-09-01Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Prografcapsule5 mgoralAstellas Pharma Canada Inc1996-08-14Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Prografcapsule, gelatin coated.5 mg/1oralAstellas Pharma US, Inc.1998-08-24Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Prografinjection, solution5 mg/mLintravenousAstellas Pharma US, Inc.1994-04-08Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Prografcapsule, gelatin coated1 mg/1oralCardinal Health1994-04-08Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Prografcapsule0.5 mgoralAstellas Pharma Canada Inc2001-04-02Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Prografcapsule, gelatin coated5 mg/1oralAstellas Pharma US, Inc.1994-04-08Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Prografsolution5 mgintravenousAstellas Pharma Canada Inc1996-08-14Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Prografcapsule, gelatin coated1 mg/1oralAphena Pharma Solutions Tennessee, Llc1994-04-08Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Prografcapsule1 mgoralAstellas Pharma Canada Inc1996-08-14Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Prografcapsule, gelatin coated1 mg/1oralAstellas Pharma US, Inc.1994-04-08Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Protopicointment.3 mg/gtopicalAstellas Pharma US Inc.2000-12-08Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Protopicointment0.03 %topicalAstellas Pharma Canada Inc2001-09-06Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Protopicointment1 mg/gtopicalPhysicians Total Care, Inc.2008-05-08Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Protopicointment0.1 %topicalAstellas Pharma Canada Inc2001-09-06Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Protopicointment1 mg/gtopicalAstellas Pharma US Inc.2000-12-08Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sandoz Tacrolimuscapsule (immediate release)5 mgoralSandoz Canada Incorporated2013-11-25Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Sandoz Tacrolimuscapsule (immediate release)1 mgoralSandoz Canada Incorporated2013-11-25Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Sandoz Tacrolimuscapsule (immediate release)0.5 mgoralSandoz Canada Incorporated2014-06-11Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Tacrolimusointment1 mg/gtopicalPerrigo New York Inc2014-11-20Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimusointment.3 mg/gtopicalPerrigo New York Inc2014-11-20Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Hecoriacapsule.5 mg/1oralNovartis Pharmaceuticals Corporation2011-12-20Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Hecoriacapsule5 mg/1oralNovartis Pharmaceuticals Corporation2011-12-20Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Hecoriacapsule1 mg/1oralNovartis Pharmaceuticals Corporation2011-12-20Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule, gelatin coated.5 mg/1oralKremers Urban Pharmaceuticals Inc.2015-07-30Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule.5 mg/1oralAccord Healthcare Inc.2011-08-31Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule.5 mg/1oralMylan Institutional Inc.2010-11-15Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule1 mg/1oralMylan Pharmaceuticals Inc.2012-07-23Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule.5 mg/1oralAmerican Health Packaging2013-07-17Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule1 mg/1oralCardinal Health2013-07-17Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule1 mg/1oralSandoz Inc2012-01-15Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule5 mg/1oralMylan Institutional Inc.2010-11-01Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule.5 mg/1oralMylan Pharmaceuticals Inc.2012-07-23Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule5 mg/1oralStrides Arcolab Limited2014-08-13Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule.5 mg/1oralCardinal Health2011-06-15Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule.5 mg/1oralSandoz Inc2012-01-15Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule5 mg/1oralIngenus Pharmaceuticals, LLC2012-09-28Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule1 mg/1oralKAISER FOUNDATION HOSPITALS2010-12-10Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule1 mg/1oralStrides Arcolab Limited2014-08-13Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule1 mg/1oralCardinal Health2011-06-15Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule5 mg/1oralSandoz Inc2009-08-10Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule1 mg/1oralIngenus Pharmaceuticals, LLC2012-09-28Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimusointment.3 mg/gtopicalE. Fougera & Co. a division of Fougera Pharmaceuticals Inc.2014-09-09Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule.5 mg/1oralStrides Arcolab Limited2014-08-13Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule5 mg/1oralDr. Reddy's Laboratories Limited2010-05-14Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule1 mg/1oralSandoz Inc2009-08-10Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule.5 mg/1oralIngenus Pharmaceuticals, LLC2012-09-28Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimusointment1 mg/gtopicalE. Fougera & Co. a division of Fougera Pharmaceuticals Inc.2014-09-09Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule, gelatin coated1 mg/1oralbryant ranch prepack2012-10-30Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule1 mg/1oralDr. Reddy's Laboratories Limited2010-05-14Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule.5 mg/1oralSandoz Inc2009-08-10Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule5 mg/1oralAccord Healthcare Inc.2011-08-31Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule, gelatin coated5 mg/1oralKremers Urban Pharmaceuticals Inc.2015-07-30Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule5 mg/1oralAmerican Health Packaging2013-07-17Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule.5 mg/1oralDr. Reddy's Laboratories Limited2010-05-14Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule5 mg/1oralWatson Laboratories, Inc.2010-07-06Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule1 mg/1oralCardinal Health2009-08-10Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule1 mg/1oralMajor Pharmaceuticals2015-01-05Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule, gelatin coated1 mg/1oralKremers Urban Pharmaceuticals Inc.2015-07-30Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule1 mg/1oralAccord Healthcare Inc.2011-08-31Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule1 mg/1oralMylan Institutional Inc.2010-11-01Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule5 mg/1oralMylan Pharmaceuticals Inc.2012-07-23Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule1 mg/1oralAmerican Health Packaging2013-07-17Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule1 mg/1oralCardinal Health2009-08-10Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tacrolimuscapsule5 mg/1oralSandoz Inc2012-01-15Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Tacrolimus Hydrate
Thumb
  • InChI Key: NWJQLQGQZSIBAF-MLAUYUEBSA-N
  • Monoisotopic Mass: 821.492541363
  • Average Mass: 822.0334
DBSALT000167
CategoriesNot Available
UNIIWM0HAQ4WNM
CAS number104987-11-3
WeightAverage: 804.0182
Monoisotopic: 803.481976677
Chemical FormulaC44H69NO12
InChI KeyInChIKey=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
CO[C@@H]1C[C@@H](CC[C@H]1O)\C=C(/C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@H](C[C@@H](C)C\C(C)=C\[C@@H](CC=C)C(=O)C[C@H](O)[C@H]1C)OC
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassMacrolide lactams
Sub ClassNot Available
Direct ParentMacrolide lactams
Alternative Parents
Substituents
  • Macrolide lactam
  • Macrolide
  • Alpha-amino acid ester
  • Cyclohexanol
  • Piperidine
  • Oxane
  • Tertiary carboxylic acid amide
  • Cyclic alcohol
  • Cyclic ketone
  • Tertiary amine
  • Secondary alcohol
  • Lactone
  • Lactam
  • Ketone
  • Hemiacetal
  • Carboxylic acid ester
  • Carboxamide group
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Ether
  • Dialkyl ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor use after allogenic organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection. It was first approved by the FDA in 1994 for use in liver transplantation, this has been extended to include 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.
PharmacodynamicsTacrolimus is a macrolide antibiotic. It 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. Although this activity is similar to cyclosporine studies have shown that the incidence of acute rejection is reduced by tacrolimus use over cyclosporine. 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 actionThe 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.
AbsorptionAbsorption 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

Hepatic, extensive, primarily by CYP3A4. The major metabolite identified in incubations with human liver microsomes is 13-demethyl tacrolimus. In in vitro studies, a 31-demethyl metabolite has been reported to have the same activity as tacrolimus.

SubstrateEnzymesProduct
Tacrolimus
31-O-DemethyltacrolimusDetails
Tacrolimus
Not Available
13-demethyl tacrolimusDetails
Route of eliminationIn 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 lifeThe 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]
ToxicitySide 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug Reactions
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
Multidrug resistance protein 1
Gene symbol: ABCB1
UniProt: P08183
rs2032582 Not AvailableT Allele (G2677T)Increased risk of neurotoxicity12352921
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Astellas pharma us inc
  • Dr reddys laboratories ltd
  • Sandoz inc
  • Watson laboratories inc
  • Astellas Pharma US
Packagers
Dosage forms
FormRouteStrength
Capsule (extended release)oral0.5 mg
Capsule (extended release)oral1 mg
Capsule (extended release)oral3 mg
Capsule (extended release)oral5 mg
Capsule, coated, extended releaseoral.5 mg/1
Capsule, coated, extended releaseoral1 mg/1
Capsule, coated, extended releaseoral5 mg/1
Tablet, extended releaseoral.75 mg/1
Tablet, extended releaseoral1 mg/1
Tablet, extended releaseoral4 mg/1
Capsuleoral.5 mg/1
Capsuleoral1 mg/1
Capsuleoral5 mg/1
Capsuleoral0.5 mg
Capsuleoral1 mg
Capsuleoral5 mg
Capsule, gelatin coatedoral.5 mg/1
Capsule, gelatin coatedoral1 mg/1
Capsule, gelatin coatedoral5 mg/1
Injection, solutionintravenous5 mg/mL
Solutionintravenous5 mg
Ointmenttopical0.03 %
Ointmenttopical0.1 %
Capsule (immediate release)oral0.5 mg
Capsule (immediate release)oral1 mg
Capsule (immediate release)oral5 mg
Ointmenttopical.3 mg/g
Ointmenttopical1 mg/g
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
CountryPatent NumberApprovedExpires (estimated)
Canada13384911996-07-302013-07-30
Canada20374082002-12-172011-03-01
United States52603011994-02-282011-02-28
United States56657271994-09-092014-09-09
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point126 °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 FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
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
  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
  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
  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
  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
  6. FDA label
External Links
ATC CodesD11AH01L04AD02
AHFS Codes
  • 84:92.00
  • 92:00.00
PDB Entries
FDA labelDownload (144 KB)
MSDSDownload (54.9 KB)
Interactions
Drug Interactions
Drug
AbataceptThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Abatacept.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Tacrolimus.
AdalimumabThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Adalimumab.
ado-trastuzumab emtansineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with ado-trastuzumab emtansine.
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Tacrolimus.
AlemtuzumabThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Alemtuzumab.
AlogliptinThe therapeutic efficacy of Alogliptin can be decreased when used in combination with Tacrolimus.
AltretamineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Altretamine.
AmilorideAmiloride may increase the hyperkalemic activities of Tacrolimus.
AmlodipineThe serum concentration of Tacrolimus can be increased when it is combined with Amlodipine.
AmsacrineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Amsacrine.
AnakinraThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Anakinra.
Anti-thymocyte Globulin (Rabbit)The risk or severity of adverse effects can be increased when Tacrolimus is combined with Anti-thymocyte Globulin (Rabbit).
AprepitantThe serum concentration of Tacrolimus can be increased when it is combined with Aprepitant.
AtazanavirThe metabolism of Tacrolimus can be decreased when combined with Atazanavir.
AzacitidineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Azacitidine.
AzathioprineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Azathioprine.
AzithromycinThe serum concentration of Tacrolimus can be increased when it is combined with Azithromycin.
BasilThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Basil.
BasiliximabThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Basiliximab.
BatimastatThe metabolism of Tacrolimus can be decreased when combined with Batimastat.
BelataceptThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Belatacept.
BelimumabThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Belimumab.
BetamethasoneThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Betamethasone.
BexaroteneThe serum concentration of Tacrolimus can be decreased when it is combined with Bexarotene.
BleomycinThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Bleomycin.
BlinatumomabThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Blinatumomab.
BoceprevirThe serum concentration of Tacrolimus can be increased when it is combined with Boceprevir.
BosentanThe serum concentration of Tacrolimus can be decreased when it is combined with Bosentan.
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Tacrolimus.
Brentuximab vedotinThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Brentuximab vedotin.
BudesonideThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Budesonide.
BusulfanThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Busulfan.
CabazitaxelThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Cabazitaxel.
CanagliflozinThe therapeutic efficacy of Canagliflozin can be decreased when used in combination with Tacrolimus.
CanakinumabThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Canakinumab.
CapecitabineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Capecitabine.
CarboplatinThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Carboplatin.
CarmustineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Carmustine.
CaspofunginThe serum concentration of Tacrolimus can be decreased when it is combined with Caspofungin.
CelecoxibCelecoxib may increase the nephrotoxic activities of Tacrolimus.
Certolizumab pegolThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Certolizumab pegol.
ChlorambucilThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Chlorambucil.
ChloramphenicolThe serum concentration of Tacrolimus can be increased when it is combined with Chloramphenicol.
ChlorpropamideThe therapeutic efficacy of Chlorpropamide can be decreased when used in combination with Tacrolimus.
Choline fenofibrateTacrolimus may increase the nephrotoxic activities of Choline fenofibrate.
CinacalcetThe serum concentration of Tacrolimus can be decreased when it is combined with Cinacalcet.
CisplatinThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Cisplatin.
CitalopramTacrolimus may increase the QTc-prolonging activities of Citalopram.
CladribineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Cladribine.
ClarithromycinThe serum concentration of Tacrolimus can be increased when it is combined with Clarithromycin.
ClofarabineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Clofarabine.
ClotrimazoleThe serum concentration of Tacrolimus can be increased when it is combined with Clotrimazole.
ClozapineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Clozapine.
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Tacrolimus.
ConivaptanThe serum concentration of Tacrolimus can be increased when it is combined with Conivaptan.
CorticotropinThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Corticotropin.
Cortisone acetateThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Cortisone acetate.
CrizotinibThe serum concentration of Tacrolimus can be increased when it is combined with Crizotinib.
CyclophosphamideThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Cyclophosphamide.
CyclosporineTacrolimus may increase the nephrotoxic activities of Cyclosporine.
CytarabineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Cytarabine.
Dabigatran etexilateThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Tacrolimus.
DabrafenibThe serum concentration of Tacrolimus can be decreased when it is combined with Dabrafenib.
DacarbazineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Dacarbazine.
DactinomycinThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Dactinomycin.
DanazolThe serum concentration of Tacrolimus can be increased when it is combined with Danazol.
DarunavirThe metabolism of Tacrolimus can be decreased when combined with Darunavir.
DasatinibThe serum concentration of Tacrolimus can be increased when it is combined with Dasatinib.
DaunorubicinThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Daunorubicin.
DeferasiroxThe serum concentration of Tacrolimus can be decreased when it is combined with Deferasirox.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Tacrolimus.
DexamethasoneThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Dexamethasone.
DiclofenacDiclofenac may increase the nephrotoxic activities of Tacrolimus.
DiflunisalDiflunisal may increase the nephrotoxic activities of Tacrolimus.
DiltiazemThe metabolism of Tacrolimus can be decreased when combined with Diltiazem.
DinutuximabThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Dinutuximab.
DocetaxelThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Docetaxel.
DofetilideTacrolimus may increase the QTc-prolonging activities of Dofetilide.
DoxorubicinThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Doxorubicin.
DronedaroneTacrolimus may increase the QTc-prolonging activities of Dronedarone.
EculizumabThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Eculizumab.
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Tacrolimus.
EfavirenzThe serum concentration of Tacrolimus can be decreased when it is combined with Efavirenz.
EfonidipineThe serum concentration of Tacrolimus can be increased when it is combined with Efonidipine.
EnzalutamideThe serum concentration of Tacrolimus can be decreased when it is combined with Enzalutamide.
EpirubicinThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Epirubicin.
EplerenoneEplerenone may increase the hyperkalemic activities of Tacrolimus.
ErtapenemThe serum concentration of Tacrolimus can be increased when it is combined with Ertapenem.
ErythromycinThe serum concentration of Tacrolimus can be increased when it is combined with Erythromycin.
EsomeprazoleThe serum concentration of Tacrolimus can be increased when it is combined with Esomeprazole.
EstramustineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Estramustine.
EtanerceptThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Etanercept.
EthanolEthanol can cause an increase in the absorption of Tacrolimus resulting in an increased serum concentration and potentially a worsening of adverse effects.
EtodolacEtodolac may increase the nephrotoxic activities of Tacrolimus.
EtoposideThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Etoposide.
EverolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Everolimus.
FelodipineThe serum concentration of Tacrolimus can be increased when it is combined with Felodipine.
FenofibrateTacrolimus may increase the nephrotoxic activities of Fenofibrate.
FenoprofenFenoprofen may increase the nephrotoxic activities of Tacrolimus.
FingolimodThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Fingolimod.
FloctafenineFloctafenine may increase the nephrotoxic activities of Tacrolimus.
FloxuridineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Floxuridine.
FluconazoleThe metabolism of Tacrolimus can be decreased when combined with Fluconazole.
FludarabineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Fludarabine.
FludrocortisoneThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Fludrocortisone.
FluorouracilThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Fluorouracil.
FlurbiprofenFlurbiprofen may increase the nephrotoxic activities of Tacrolimus.
Fluticasone PropionateThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Fluticasone Propionate.
FosamprenavirThe metabolism of Tacrolimus can be decreased when combined with Fosamprenavir.
FosaprepitantThe serum concentration of Tacrolimus can be increased when it is combined with Fosaprepitant.
FoscarnetFoscarnet may increase the nephrotoxic activities of Tacrolimus.
FosphenytoinThe serum concentration of Tacrolimus can be decreased when it is combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Tacrolimus can be increased when it is combined with Fusidic Acid.
GemcitabineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Gemcitabine.
Gemtuzumab ozogamicinThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Gemtuzumab ozogamicin.
Glatiramer AcetateThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Glatiramer Acetate.
GliclazideThe therapeutic efficacy of Gliclazide can be decreased when used in combination with Tacrolimus.
GlimepirideThe therapeutic efficacy of Glimepiride can be decreased when used in combination with Tacrolimus.
GliquidoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Tacrolimus.
GlyburideThe therapeutic efficacy of Glyburide can be decreased when used in combination with Tacrolimus.
golimumabThe risk or severity of adverse effects can be increased when Tacrolimus is combined with golimumab.
GoserelinTacrolimus may increase the QTc-prolonging activities of Goserelin.
HydrocortisoneThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Hydrocortisone.
HydroxyureaThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Hydroxyurea.
IbritumomabThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Ibritumomab.
IbrutinibThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Ibrutinib.
IbuprofenIbuprofen may increase the nephrotoxic activities of Tacrolimus.
IdarubicinThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Idarubicin.
IdelalisibThe serum concentration of Tacrolimus can be increased when it is combined with Idelalisib.
IfosfamideThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Ifosfamide.
ImatinibThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Imatinib.
ImiquimodThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Imiquimod.
IndinavirThe metabolism of Tacrolimus can be decreased when combined with Indinavir.
IndomethacinIndomethacin may increase the nephrotoxic activities of Tacrolimus.
InfliximabThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Infliximab.
Insulin AspartThe therapeutic efficacy of Insulin Aspart can be decreased when used in combination with Tacrolimus.
Insulin DetemirThe therapeutic efficacy of Insulin Detemir can be decreased when used in combination with Tacrolimus.
Insulin GlargineThe therapeutic efficacy of Insulin Glargine can be decreased when used in combination with Tacrolimus.
Insulin GlulisineThe therapeutic efficacy of Insulin Glulisine can be decreased when used in combination with Tacrolimus.
Insulin LisproThe therapeutic efficacy of Insulin Lispro can be decreased when used in combination with Tacrolimus.
Insulin RegularThe therapeutic efficacy of Insulin Regular can be decreased when used in combination with Tacrolimus.
Insulin, isophaneThe therapeutic efficacy of Insulin, isophane can be decreased when used in combination with Tacrolimus.
IrinotecanThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Irinotecan.
IsoflurophateThe metabolism of Tacrolimus can be decreased when combined with Isoflurophate.
IsradipineThe serum concentration of Tacrolimus can be increased when it is combined with Isradipine.
ItraconazoleThe metabolism of Tacrolimus can be decreased when combined with Itraconazole.
IvacaftorThe serum concentration of Tacrolimus can be increased when it is combined with Ivacaftor.
KetoconazoleThe metabolism of Tacrolimus can be decreased when combined with Ketoconazole.
KetoprofenKetoprofen may increase the nephrotoxic activities of Tacrolimus.
KetorolacKetorolac may increase the nephrotoxic activities of Tacrolimus.
L-PhenylalanineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with L-Phenylalanine.
LansoprazoleThe serum concentration of Tacrolimus can be increased when it is combined with Lansoprazole.
LedipasvirThe serum concentration of Ledipasvir can be increased when it is combined with Tacrolimus.
LeflunomideThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Leflunomide.
LenalidomideThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Lenalidomide.
LeuprolideTacrolimus may increase the QTc-prolonging activities of Leuprolide.
LevofloxacinLevofloxacin may increase the QTc-prolonging activities of Tacrolimus.
LinagliptinThe therapeutic efficacy of Linagliptin can be decreased when used in combination with Tacrolimus.
LomustineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Lomustine.
LopinavirThe metabolism of Tacrolimus can be decreased when combined with Lopinavir.
LuliconazoleThe serum concentration of Tacrolimus can be increased when it is combined with Luliconazole.
MechlorethamineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Mechlorethamine.
Mefenamic acidMefenamic acid may increase the nephrotoxic activities of Tacrolimus.
MeloxicamMeloxicam may increase the nephrotoxic activities of Tacrolimus.
MelphalanThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Melphalan.
MercaptopurineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Mercaptopurine.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Tacrolimus.
MetforminThe therapeutic efficacy of Metformin can be decreased when used in combination with Tacrolimus.
MethotrexateThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Methotrexate.
MethylprednisoloneThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Methylprednisolone.
MifepristoneMifepristone may increase the QTc-prolonging activities of Tacrolimus.
MitomycinThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Mitomycin.
MitotaneThe serum concentration of Tacrolimus can be decreased when it is combined with Mitotane.
MitoxantroneThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Mitoxantrone.
Mycophenolate mofetilThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Mycophenolate mofetil.
Mycophenolic acidThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Mycophenolic acid.
NabumetoneNabumetone may increase the nephrotoxic activities of Tacrolimus.
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Tacrolimus.
NaproxenNaproxen may increase the nephrotoxic activities of Tacrolimus.
NatalizumabThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Natalizumab.
NefazodoneThe metabolism of Tacrolimus can be decreased when combined with Nefazodone.
NelarabineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Nelarabine.
NelfinavirThe metabolism of Tacrolimus can be decreased when combined with Nelfinavir.
NetupitantThe serum concentration of Tacrolimus can be increased when it is combined with Netupitant.
NicardipineThe serum concentration of Tacrolimus can be increased when it is combined with Nicardipine.
NifedipineThe serum concentration of Tacrolimus can be increased when it is combined with Nifedipine.
NilotinibThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Nilotinib.
NimodipineThe serum concentration of Tacrolimus can be increased when it is combined with Nimodipine.
NisoldipineThe serum concentration of Tacrolimus can be increased when it is combined with Nisoldipine.
ObinutuzumabThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Obinutuzumab.
OmeprazoleThe serum concentration of Tacrolimus can be increased when it is combined with Omeprazole.
OsimertinibThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Osimertinib.
OxaliplatinThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Oxaliplatin.
OxaprozinOxaprozin may increase the nephrotoxic activities of Tacrolimus.
PaclitaxelThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Paclitaxel.
PalbociclibThe serum concentration of Tacrolimus can be increased when it is combined with Palbociclib.
PanobinostatThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Panobinostat.
PantoprazoleThe serum concentration of Tacrolimus can be increased when it is combined with Pantoprazole.
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Tacrolimus.
PegaspargaseThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Pegaspargase.
PemetrexedThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Pemetrexed.
PentostatinThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Pentostatin.
PhenytoinThe serum concentration of Tacrolimus can be decreased when it is combined with Phenytoin.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Tacrolimus.
PiroxicamPiroxicam may increase the nephrotoxic activities of Tacrolimus.
PomalidomideThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Pomalidomide.
PosaconazoleThe metabolism of Tacrolimus can be decreased when combined with Posaconazole.
PralatrexateThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Pralatrexate.
PrednisoloneThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Prednisolone.
PrednisoneThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Prednisone.
ProcarbazineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Procarbazine.
PrucaloprideThe serum concentration of Prucalopride can be increased when it is combined with Tacrolimus.
RabeprazoleThe serum concentration of Tacrolimus can be increased when it is combined with Rabeprazole.
RanolazineThe serum concentration of Tacrolimus can be increased when it is combined with Ranolazine.
RepaglinideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Tacrolimus.
Repository corticotropinThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Repository corticotropin.
RifabutinThe serum concentration of Tacrolimus can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Tacrolimus can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Tacrolimus can be decreased when it is combined with Rifapentine.
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Tacrolimus.
RilonaceptThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Rilonacept.
RitonavirThe metabolism of Tacrolimus can be decreased when combined with Ritonavir.
RituximabThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Rituximab.
RoflumilastRoflumilast may increase the immunosuppressive activities of Tacrolimus.
RuxolitinibThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Ruxolitinib.
SaquinavirThe metabolism of Tacrolimus can be decreased when combined with Saquinavir.
SaxagliptinThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Tacrolimus.
SecukinumabThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Secukinumab.
SevelamerThe serum concentration of Tacrolimus can be decreased when it is combined with Sevelamer.
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Tacrolimus.
SiltuximabThe serum concentration of Tacrolimus can be decreased when it is combined with Siltuximab.
SimeprevirThe metabolism of Tacrolimus can be decreased when combined with Simeprevir.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Tacrolimus.
SirolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Sirolimus.
SorafenibThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Sorafenib.
SpironolactoneSpironolactone may increase the hyperkalemic activities of Tacrolimus.
St. John's WortThe serum concentration of Tacrolimus can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Tacrolimus can be increased when it is combined with Stiripentol.
StreptozocinThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Streptozocin.
SulfisoxazoleThe serum concentration of Tacrolimus can be increased when it is combined with Sulfisoxazole.
SulindacSulindac may increase the nephrotoxic activities of Tacrolimus.
SunitinibThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Sunitinib.
TelaprevirThe serum concentration of Tacrolimus can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Tacrolimus can be increased when it is combined with Telithromycin.
TemozolomideThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Temozolomide.
TemsirolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Temsirolimus.
TeniposideThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Teniposide.
TeriflunomideThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Teriflunomide.
TesmilifeneThe serum concentration of Tacrolimus can be decreased when it is combined with Tesmilifene.
ThalidomideThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Thalidomide.
ThiotepaThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Thiotepa.
Tiaprofenic acidTiaprofenic acid may increase the nephrotoxic activities of Tacrolimus.
TioguanineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Tioguanine.
TipranavirThe metabolism of Tacrolimus can be decreased when combined with Tipranavir.
TocilizumabThe serum concentration of Tacrolimus can be decreased when it is combined with Tocilizumab.
TofacitinibTacrolimus may increase the immunosuppressive activities of Tofacitinib.
TolbutamideThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Tacrolimus.
TolmetinTolmetin may increase the nephrotoxic activities of Tacrolimus.
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Tacrolimus.
TositumomabThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Tositumomab.
TrabectedinThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Trabectedin.
TrastuzumabTrastuzumab may increase the neutropenic activities of Tacrolimus.
TretinoinThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Tretinoin.
TriamcinoloneThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Triamcinolone.
TriamtereneTriamterene may increase the hyperkalemic activities of Tacrolimus.
UstekinumabThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Ustekinumab.
VedolizumabThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Vedolizumab.
VerapamilThe metabolism of Tacrolimus can be decreased when combined with Verapamil.
VilanterolThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Vilanterol.
VildagliptinThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Tacrolimus.
VinblastineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Vinblastine.
VincristineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Vincristine.
VindesineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Vindesine.
VinorelbineThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Vinorelbine.
VoriconazoleThe metabolism of Tacrolimus can be decreased when combined with Voriconazole.
Food Interactions
  • Food, especially food with a high-fat content, decreases the rate and extent of absorption.
  • The time of the meal affects tacrolimus bioavailability. Take tacrolimus capsules consistently everyday either with or without food.

Targets

1. Peptidyl-prolyl cis-trans isomerase FKBP1A

Kind: Protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Peptidyl-prolyl cis-trans isomerase FKBP1A P62942 Details

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
  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

Enzymes

1. Cytochrome P450 3A4

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  3. 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

2. Cytochrome P450 3A5

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A7

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

Carriers

1. Serum albumin

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. FDA label

2. Alpha-1-acid glycoprotein 1

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Alpha-1-acid glycoprotein 1 P02763 Details

References:

  1. FDA label

Transporters

1. Multidrug resistance protein 1

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor inducer

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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
  2. Saeki T, Ueda K, Tanigawara Y, Hori R, Komano T: Human P-glycoprotein transports cyclosporin A and FK506. J Biol Chem. 1993 Mar 25;268(9):6077-80. Pubmed
  3. 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
  4. Hashida T, Masuda S, Uemoto S, Saito H, Tanaka K, Inui K: Pharmacokinetic and prognostic significance of intestinal MDR1 expression in recipients of living-donor liver transplantation. Clin Pharmacol Ther. 2001 May;69(5):308-16. Pubmed
  5. Collett A, Tanianis-Hughes J, Hallifax D, Warhurst G: Predicting P-glycoprotein effects on oral absorption: correlation of transport in Caco-2 with drug pharmacokinetics in wild-type and mdr1a(-/-) mice in vivo. Pharm Res. 2004 May;21(5):819-26. Pubmed
  6. 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

2. ATP-binding cassette sub-family A member 5

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
ATP-binding cassette sub-family A member 5 Q8WWZ7 Details

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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12