Identification

Name
Tofacitinib
Accession Number
DB08895  (DB08183)
Type
Small Molecule
Groups
Approved, Investigational
Description

Tofacitinib is an inhibitor of Janus kinases, a group of intracellular enzymes involved in signalling pathways that affect hematopoiesis and immune cell function. It is approved by the FDA for treatment of moderate to severe rheumatoid arthritis that responds inadequately to methotrexate or in those who are intolerant to methotrexate. Besides rheumatoid arthritis, tofacitinib has also been studied in clinical trials for the prevention of organ transplant rejection, and is currently under investigation for the treatment of psoriasis. Known adverse effects include nausea and headache as well as more serious immunologic and hematological adverse effects. Tofacitinib is marketed under the brand name Xeljanz by Pfizer.

Structure
Thumb
Synonyms
  • Tasocitinib
  • Tofacitinibum
External IDs
CP 690550 / CP- 690 550 / CP-690 free base / CP-690-550 / CP-690,550 / CP-690,550 free base / CP-690550 / CP-690550 free base / CP690,550 / CP690550
Product Ingredients
IngredientUNIICASInChI Key
Tofacitinib citrateO1FF4DIV0D540737-29-9SYIKUFDOYJFGBQ-YLAFAASESA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
XeljanzTablet, film coated10 mg/1OralU.S. Pharmaceuticals2018-07-02Not applicableUs
XeljanzTablet5 mgOralPfizer2014-06-03Not applicableCanada
XeljanzTablet, film coated5 mg/1OralU.S. Pharmaceuticals2012-11-08Not applicableUs
XeljanzTablet, film coated10 mg/1OralPfizer Laboratories Div Pfizer Inc.2018-07-02Not applicableUs
XeljanzTablet, film coated5 mg/1OralPfizer Laboratories Div Pfizer Inc.2012-11-09Not applicableUs
Xeljanz XRTablet, film coated, extended release11 mg/1OralPfizer Laboratories Div Pfizer Inc.2016-03-07Not applicableUs
Xeljanz XRTablet, extended release11 mgOralPfizer2018-03-29Not applicableCanada
Xeljanz XRTablet, extended release11 mg/1OralU.S. Pharmaceuticals2016-03-07Not applicableUs
Categories
UNII
87LA6FU830
CAS number
477600-75-2
Weight
Average: 312.3696
Monoisotopic: 312.169859292
Chemical Formula
C16H20N6O
InChI Key
UJLAWZDWDVHWOW-YPMHNXCESA-N
InChI
InChI=1S/C16H20N6O/c1-11-5-8-22(14(23)3-6-17)9-13(11)21(2)16-12-4-7-18-15(12)19-10-20-16/h4,7,10-11,13H,3,5,8-9H2,1-2H3,(H,18,19,20)/t11-,13+/m1/s1
IUPAC Name
3-[(3R,4R)-4-methyl-3-[methyl({7H-pyrrolo[2,3-d]pyrimidin-4-yl})amino]piperidin-1-yl]-3-oxopropanenitrile
SMILES
[H][C@@]1(C)CCN(C[C@]1([H])N(C)C1=NC=NC2=C1C=CN2)C(=O)CC#N

Pharmacology

Indication

For the treatment of moderate to severe rheumatoid arthritis which is resistant or intolerant to methotrexate therapy. It may also be used as an adjunct to methotrexate therapy, or other non-biologic disease-modifying antirheumatic drugs (DMARDS), when methotrexate alone is not sufficient.

Tofacitinib has also been investigated as a preventative therapy for kidney transplant rejections, and as a treatment for psoriasis, ulcerative colitis, and ankylosing spondylitis.

It is not to be initiated in patients with a history of chronic or recurrent infections, or in the presence of active infection, even if localized, due to reports of serious and sometimes fatal infections (commonly pneumonia, herpes zoster and urinary tract infections). Use of tofacitinib is also discouraged in those who have been, or are likely to be, exposed to TB. An increased likelihood of exposure may be encountered by traveling to certain areas. In addition, tofacitinib is not to be used in patients with severe hepatic impairment, or low hemoglobin (less than 9g/dL). Cautioned is advised when using tofacitinib in patients at risk of gastrointestinal perforation, and in the elderly who are more susceptible to infection.

Associated Conditions
Pharmacodynamics

Tofacitinib targets inflammation present in rheumatoid arthritis by inhibiting the janus kinases involved in the inflammatory response pathway.

In placebo controlled trials of rheumatoid arthritis patients receiving 5mg or 10mg of tofacitinib twice daily, higher ACR20 responses were observed within 2 weeks in some patients (with ACR20 being defined as a minimum 20% reduction in joint pain or tenderness and 20% reduction in arthritis pain, patient disability, inflammatory markers, or global assessments of arthritis by patients or by doctors, according to the American College of Rheumatology (ACR) response criteria list), and improvements in physical functioning greater than placebo were also noted.

Common known adverse effects of tofacitinib include headaches, diarrhea, nausea, nasopharyngitis and upper respiratory tract infection. More serious immunologic and hematological adverse effects have also been noted resulting in lymphopenia, neutropenia, anemia, and increased risk of cancer and infection.

Before initiations of tofacitinib patients should be tested for latent infections of tuberculosis, and should be closely monitored for signs and symptoms of infection (fungal, viral, bacterial, or mycobacterial) during therapy. Therapy is not to be started in the presence of active infection, systemic or localized, and is to be interrupted if a serious infection occurs.

Tofacitinib has been associated with an increased risk of lymphomas, such as Epstein-Barr virus associated lymphomas, and other malignancies (including lung, breast, gastric, and colorectal cancers). It is recommended to monitor lymphocytes, neutrophils, hemoglobin, liver enzymes, and lipids.

Tofacitinib use is associated with a rapid decrease in C-reactive protein (CRP), dose dependent decreases in natural killer cells, and dose dependent increases in B cells. Depression in C-reactive protein levels continue after 2 weeks of tofacitinib discontinuation and suggest that pharmacodynamic activity last longer than pharmacokinetic half life.

Mechanism of action

Rheumatoid arthritis is an autoimmune disease characterized by a dysregulation of pro-inflammatory cytokines including IL7, IL15, IL21, IL6, IFN-alpha, and IFN-beta. (3) Cytokines signalling results in tissue inflammation and joint damage by stimulating the recruitment and activation of immune cells via the janus kinase signalling pathway.

Tofacitinib is a partial and reversible janus kinase (JAK) inihibitor that will prevent the body from responding to cytokine signals. By inhibiting JAKs, tofacitinib prevents the phosphorylation and activation of STATs. The JAK-STAT signalling pathway is involved in the transcription of cells involved in hematopoiesis, and immune cell function. Tofacitinib works therapeutically by inhibiting the JAK-STAT pathway to decrease the inflammatory response. However, there is evidence to suggest that it may also achieve efficacy via other pathways as well.

TargetActionsOrganism
ATyrosine-protein kinase JAK1
inhibitor
Human
ATyrosine-protein kinase JAK2
antagonist
inhibitor
Human
ATyrosine-protein kinase JAK3
inhibitor
Human
UNon-receptor tyrosine-protein kinase TYK2Not AvailableHuman
Absorption

74% oral absorption (absolute bioavailability), with peak plasma concentrations (T max) achieved in 0.5-1 hour.

Administration with fatty meals does not alter AUC but reduces Cmax by 32%.

Volume of distribution

Vd= 87L after intravenous administration. Distribution is equal between red blood cells and plasma.

Protein binding

40%, mostly bound to albumin.

Metabolism

Metabolized in the liver by CYP3A4 and CYP2C19. Metabolites produced are inactive.

Route of elimination

70% metabolized in the liver by CYP3A4 (major) and CYP2C19 (minor). Metabolites produced are inactive. 30% renally eliminated as unchanged drug.

Half life

~3 hours

Clearance
Not Available
Toxicity

Minimum lethal dose in rat: 500 mg/kg. Maximum asymptomatic dose in non human primate: 40 mg/kg.

Lymphatic, immune system, bone marrow and erythroid cell toxicity was seen in animal studies involving rate and monkeys. Doses used in these studies ranged from 1mg/kg/day to 10mg/kg/day, over a duration of 6 weeks to 6 months. Lymphopenia, neutropenia, and anemia is seen in human subjects and may call for an interruption or discontinuation of therapy if severe.

Reduced female fertility in rats was seen at exposures 17 times the maximum recommended human dose. Fertility may be impaired in human females and harm may be caused to unborn child. Carcinogenic potential is seen, however evidence for dose dependency is lacking.

Because the janus kinase pathway plays a role in stimulating the production of red blood cells and is involved in immune cell function, inhibition of this pathway leads to increased risk of anemia, neutropenia, lymphopenia, cancer and infection.

Lymphopenia, neutropenia, and anemia in human subjects may call for an interruption or discontinuation of therapy if severe.

Role of JAK inhibition in the development of gastrointestinal perforation is not known.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
2-Methoxyethanol2-Methoxyethanol may increase the immunosuppressive activities of Tofacitinib.Experimental
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Tofacitinib.Approved
AbetimusAbetimus may increase the immunosuppressive activities of Tofacitinib.Investigational
AbirateroneThe metabolism of Tofacitinib can be decreased when combined with Abiraterone.Approved
AcebutololTofacitinib may increase the bradycardic activities of Acebutolol.Approved, Investigational
Acetyl sulfisoxazoleThe metabolism of Tofacitinib can be decreased when combined with Acetyl sulfisoxazole.Approved, Vet Approved
ActeosideActeoside may increase the immunosuppressive activities of Tofacitinib.Investigational
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Tofacitinib.Approved
AdefovirAdefovir may increase the immunosuppressive activities of Tofacitinib.Investigational
AfelimomabThe risk or severity of adverse effects can be increased when Afelimomab is combined with Tofacitinib.Investigational
AlefaceptAlefacept may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational, Withdrawn
AlemtuzumabAlemtuzumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
AlicaforsenAlicaforsen may increase the immunosuppressive activities of Tofacitinib.Investigational
AltretamineAltretamine may increase the immunosuppressive activities of Tofacitinib.Approved
AmiodaroneThe serum concentration of Tofacitinib can be increased when it is combined with Amiodarone.Approved, Investigational
AmsacrineAmsacrine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
AnakinraThe risk or severity of adverse effects can be increased when Anakinra is combined with Tofacitinib.Approved
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Tofacitinib is combined with Anthrax immune globulin human.Approved
Antilymphocyte immunoglobulin (horse)Antilymphocyte immunoglobulin (horse) may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
Antithymocyte immunoglobulin (rabbit)Antithymocyte immunoglobulin (rabbit) may increase the immunosuppressive activities of Tofacitinib.Approved
ApalutamideThe serum concentration of Tofacitinib can be decreased when it is combined with Apalutamide.Approved, Investigational
ApremilastApremilast may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
AprepitantThe serum concentration of Tofacitinib can be increased when it is combined with Aprepitant.Approved, Investigational
ArmodafinilThe metabolism of Tofacitinib can be decreased when combined with Armodafinil.Approved, Investigational
AtazanavirThe serum concentration of Tofacitinib can be increased when it is combined with Atazanavir.Approved, Investigational
AtenololTofacitinib may increase the bradycardic activities of Atenolol.Approved
AtomoxetineThe metabolism of Tofacitinib can be decreased when combined with Atomoxetine.Approved
AzacitidineAzacitidine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
AzathioprineAzathioprine may increase the immunosuppressive activities of Tofacitinib.Approved
Bacillus calmette-guerin substrain connaught live antigenThe risk or severity of adverse effects can be increased when Tofacitinib is combined with Bacillus calmette-guerin substrain connaught live antigen.Approved, Investigational
Bacillus calmette-guerin substrain tice live antigenThe risk or severity of adverse effects can be increased when Tofacitinib is combined with Bacillus calmette-guerin substrain tice live antigen.Approved
BasiliximabBasiliximab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Tofacitinib.Investigational
BegelomabBegelomab may increase the immunosuppressive activities of Tofacitinib.Experimental, Investigational
BelataceptBelatacept may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
BelimumabBelimumab may increase the immunosuppressive activities of Tofacitinib.Approved
BendroflumethiazideTofacitinib may increase the bradycardic activities of Bendroflumethiazide.Approved
BenznidazoleBenznidazole may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
BeractantTofacitinib may increase the bradycardic activities of Beractant.Approved
BetamethasoneBetamethasone may increase the immunosuppressive activities of Tofacitinib.Approved, Vet Approved
BetaxololTofacitinib may increase the bradycardic activities of Betaxolol.Approved, Investigational
BisoprololTofacitinib may increase the bradycardic activities of Bisoprolol.Approved
BleomycinBleomycin may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
BlinatumomabBlinatumomab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
BoceprevirThe serum concentration of Tofacitinib can be increased when it is combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Tofacitinib can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Tofacitinib can be decreased when it is combined with Bosentan.Approved, Investigational
Brentuximab vedotinBrentuximab vedotin may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
BriakinumabBriakinumab may increase the immunosuppressive activities of Tofacitinib.Investigational
BrodalumabBrodalumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
BudesonideBudesonide may increase the immunosuppressive activities of Tofacitinib.Approved
BusulfanBusulfan may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
CabazitaxelCabazitaxel may increase the immunosuppressive activities of Tofacitinib.Approved
CalfactantTofacitinib may increase the bradycardic activities of Calfactant.Approved
CanakinumabCanakinumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
CapecitabineCapecitabine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
CarbamazepineThe serum concentration of Tofacitinib can be decreased when it is combined with Carbamazepine.Approved, Investigational
CarboplatinCarboplatin may increase the immunosuppressive activities of Tofacitinib.Approved
CarmustineCarmustine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
CarteololTofacitinib may increase the bradycardic activities of Carteolol.Approved
CarvedilolTofacitinib may increase the bradycardic activities of Carvedilol.Approved, Investigational
CastanospermineCastanospermine may increase the immunosuppressive activities of Tofacitinib.Experimental
CeritinibThe serum concentration of Tofacitinib can be increased when it is combined with Ceritinib.Approved
Certolizumab pegolThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Tofacitinib.Approved
ChlorambucilChlorambucil may increase the immunosuppressive activities of Tofacitinib.Approved
ChloramphenicolThe metabolism of Tofacitinib can be decreased when combined with Chloramphenicol.Approved, Vet Approved
CholecalciferolThe metabolism of Tofacitinib can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Tofacitinib can be decreased when combined with Cimetidine.Approved, Investigational
CisplatinCisplatin may increase the immunosuppressive activities of Tofacitinib.Approved
CitalopramThe metabolism of Tofacitinib can be decreased when combined with Citalopram.Approved
CladribineCladribine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
ClarithromycinThe serum concentration of Tofacitinib can be increased when it is combined with Clarithromycin.Approved
ClemastineThe metabolism of Tofacitinib can be decreased when combined with Clemastine.Approved, Investigational
ClofarabineClofarabine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
ClonidineTofacitinib may increase the bradycardic activities of Clonidine.Approved
Clostridium tetani toxoid antigen (formaldehyde inactivated)The risk or severity of adverse effects can be increased when Tofacitinib is combined with Clostridium tetani toxoid antigen (formaldehyde inactivated).Approved
ClotrimazoleThe metabolism of Tofacitinib can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe risk or severity of adverse effects can be increased when Tofacitinib is combined with Clozapine.Approved
CobicistatThe serum concentration of Tofacitinib can be increased when it is combined with Cobicistat.Approved
ConivaptanThe serum concentration of Conivaptan can be increased when it is combined with Tofacitinib.Approved, Investigational
CorticotropinCorticotropin may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational, Vet Approved
Cortisone acetateCortisone acetate may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The risk or severity of adverse effects can be increased when Tofacitinib is combined with Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated).Approved
CrizotinibTofacitinib may increase the bradycardic activities of Crizotinib.Approved
CurcuminThe serum concentration of Tofacitinib can be increased when it is combined with Curcumin.Approved, Investigational
CyclophosphamideCyclophosphamide may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
CyclosporineCyclosporine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational, Vet Approved
CytarabineCytarabine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
DabrafenibThe serum concentration of Tofacitinib can be decreased when it is combined with Dabrafenib.Approved, Investigational
DacarbazineDacarbazine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
DaclizumabDaclizumab may increase the immunosuppressive activities of Tofacitinib.Investigational, Withdrawn
DactinomycinDactinomycin may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
DarunavirThe serum concentration of Tofacitinib can be increased when it is combined with Darunavir.Approved
DasatinibDasatinib may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
DaunorubicinDaunorubicin may increase the immunosuppressive activities of Tofacitinib.Approved
DeferasiroxThe serum concentration of Tofacitinib can be decreased when it is combined with Deferasirox.Approved, Investigational
DeflazacortDeflazacort may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
DelavirdineThe metabolism of Tofacitinib can be decreased when combined with Delavirdine.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Tofacitinib.Approved
DeoxyspergualinDeoxyspergualin may increase the immunosuppressive activities of Tofacitinib.Investigational
DexamethasoneDexamethasone may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational, Vet Approved
DexmedetomidineTofacitinib may increase the bradycardic activities of Dexmedetomidine.Approved, Vet Approved
DigoxinTofacitinib may increase the bradycardic activities of Digoxin.Approved
DihydroergotamineThe metabolism of Tofacitinib can be decreased when combined with Dihydroergotamine.Approved, Investigational
DiltiazemTofacitinib may increase the bradycardic activities of Diltiazem.Approved, Investigational
Dimethyl fumarateDimethyl fumarate may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
DinutuximabDinutuximab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
DocetaxelDocetaxel may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
DonepezilTofacitinib may increase the bradycardic activities of Donepezil.Approved
DoxifluridineDoxifluridine may increase the immunosuppressive activities of Tofacitinib.Investigational
DoxorubicinDoxorubicin may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
DoxycyclineThe metabolism of Tofacitinib can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneTofacitinib may increase the bradycardic activities of Dronedarone.Approved
EculizumabEculizumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
EfalizumabEfalizumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
EfavirenzThe metabolism of Tofacitinib can be decreased when combined with Efavirenz.Approved, Investigational
EnzalutamideThe serum concentration of Tofacitinib can be decreased when it is combined with Enzalutamide.Approved
EpirubicinEpirubicin may increase the immunosuppressive activities of Tofacitinib.Approved
ErythromycinThe metabolism of Tofacitinib can be decreased when combined with Erythromycin.Approved, Investigational, Vet Approved
Eslicarbazepine acetateThe metabolism of Tofacitinib can be decreased when combined with Eslicarbazepine acetate.Approved
EsmololTofacitinib may increase the bradycardic activities of Esmolol.Approved
EsomeprazoleThe metabolism of Tofacitinib can be decreased when combined with Esomeprazole.Approved, Investigational
EstramustineEstramustine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
EtanerceptThe risk or severity of adverse effects can be increased when Etanercept is combined with Tofacitinib.Approved, Investigational
EtoposideEtoposide may increase the immunosuppressive activities of Tofacitinib.Approved
EtravirineThe metabolism of Tofacitinib can be decreased when combined with Etravirine.Approved
EverolimusEverolimus may increase the immunosuppressive activities of Tofacitinib.Approved
FingolimodFingolimod may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
FloxuridineFloxuridine may increase the immunosuppressive activities of Tofacitinib.Approved
FluconazoleThe serum concentration of Tofacitinib can be increased when it is combined with Fluconazole.Approved, Investigational
FludarabineFludarabine may increase the immunosuppressive activities of Tofacitinib.Approved
FludrocortisoneFludrocortisone may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
FluorouracilFluorouracil may increase the immunosuppressive activities of Tofacitinib.Approved
FluoxetineThe metabolism of Tofacitinib can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvoxamineThe metabolism of Tofacitinib can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Tofacitinib can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Tofacitinib can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe serum concentration of Tofacitinib can be decreased when it is combined with Fosphenytoin.Approved, Investigational
Fusidic AcidThe serum concentration of Tofacitinib can be increased when it is combined with Fusidic Acid.Approved, Investigational
G17DTThe risk or severity of adverse effects can be increased when Tofacitinib is combined with G17DT.Investigational
GalantamineTofacitinib may increase the bradycardic activities of Galantamine.Approved
Gallium nitrateGallium nitrate may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
GemcitabineGemcitabine may increase the immunosuppressive activities of Tofacitinib.Approved
GemfibrozilThe metabolism of Tofacitinib can be decreased when combined with Gemfibrozil.Approved
Gemtuzumab ozogamicinGemtuzumab ozogamicin may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
GI-5005The risk or severity of adverse effects can be increased when Tofacitinib is combined with GI-5005.Investigational
GlatiramerGlatiramer Acetate may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
GlimepirideGlimepiride may increase the immunosuppressive activities of Tofacitinib.Approved
GolimumabThe risk or severity of adverse effects can be increased when Golimumab is combined with Tofacitinib.Approved
GS 0573GS 0573 may increase the immunosuppressive activities of Tofacitinib.Investigational
GuanfacineTofacitinib may increase the bradycardic activities of Guanfacine.Approved, Investigational
GusperimusGusperimus may increase the immunosuppressive activities of Tofacitinib.Investigational
Hepatitis A VaccineThe risk or severity of adverse effects can be increased when Tofacitinib is combined with Hepatitis A Vaccine.Approved
Hepatitis B Vaccine (Recombinant)The risk or severity of adverse effects can be increased when Tofacitinib is combined with Hepatitis B Vaccine (Recombinant).Approved, Withdrawn
Human C1-esterase inhibitorHuman C1-esterase inhibitor may increase the immunosuppressive activities of Tofacitinib.Approved
Human rabies virus immune globulinThe risk or severity of adverse effects can be increased when Tofacitinib is combined with Human rabies virus immune globulin.Approved
HydrocortisoneHydrocortisone may increase the immunosuppressive activities of Tofacitinib.Approved, Vet Approved
HydroxyureaHydroxyurea may increase the immunosuppressive activities of Tofacitinib.Approved
HypericinHypericin may increase the immunosuppressive activities of Tofacitinib.Investigational
Ibritumomab tiuxetanIbritumomab tiuxetan may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
IbrutinibIbrutinib may increase the immunosuppressive activities of Tofacitinib.Approved
IcatibantIcatibant may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
IdarubicinIdarubicin may increase the immunosuppressive activities of Tofacitinib.Approved
IdelalisibIdelalisib may increase the immunosuppressive activities of Tofacitinib.Approved
IfosfamideIfosfamide may increase the immunosuppressive activities of Tofacitinib.Approved
ImatinibImatinib may increase the immunosuppressive activities of Tofacitinib.Approved
ImiquimodImiquimod may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
IndinavirThe serum concentration of Tofacitinib can be increased when it is combined with Indinavir.Approved
InfliximabThe risk or severity of adverse effects can be increased when Infliximab is combined with Tofacitinib.Approved
INGN 201The risk or severity of adverse effects can be increased when Tofacitinib is combined with INGN 201.Investigational
INGN 225The risk or severity of adverse effects can be increased when Tofacitinib is combined with INGN 225.Investigational
IrinotecanIrinotecan may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
IsavuconazoleThe serum concentration of Tofacitinib can be increased when it is combined with Isavuconazole.Approved, Investigational
IsavuconazoniumThe metabolism of Tofacitinib can be decreased when combined with Isavuconazonium.Approved, Investigational
IsoniazidThe metabolism of Tofacitinib can be decreased when combined with Isoniazid.Approved, Investigational
IsradipineThe metabolism of Tofacitinib can be decreased when combined with Isradipine.Approved, Investigational
ItraconazoleThe serum concentration of Tofacitinib can be increased when it is combined with Itraconazole.Approved, Investigational
IvabradineTofacitinib may increase the bradycardic activities of Ivabradine.Approved
IvacaftorThe serum concentration of Tofacitinib can be increased when it is combined with Ivacaftor.Approved
Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated)The risk or severity of adverse effects can be increased when Tofacitinib is combined with Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated).Approved
KetoconazoleThe serum concentration of Tofacitinib can be increased when it is combined with Ketoconazole.Approved, Investigational
L-PhenylalanineL-Phenylalanine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational, Nutraceutical
LabetalolTofacitinib may increase the bradycardic activities of Labetalol.Approved
LanreotideTofacitinib may increase the bradycardic activities of Lanreotide.Approved
LeflunomideLeflunomide may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
LenalidomideLenalidomide may increase the immunosuppressive activities of Tofacitinib.Approved
LevobunololTofacitinib may increase the bradycardic activities of Levobunolol.Approved
LipegfilgrastimTofacitinib may increase the myelosuppressive activities of Lipegfilgrastim.Approved, Investigational
LisofyllineLisofylline may increase the immunosuppressive activities of Tofacitinib.Investigational
LobeglitazoneThe metabolism of Tofacitinib can be decreased when combined with Lobeglitazone.Approved, Investigational
LomustineLomustine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
LopinavirThe serum concentration of Tofacitinib can be increased when it is combined with Lopinavir.Approved
LorpiprazoleThe serum concentration of Tofacitinib can be increased when it is combined with Lorpiprazole.Approved
LovastatinThe metabolism of Tofacitinib can be decreased when combined with Lovastatin.Approved, Investigational
LucinactantTofacitinib may increase the bradycardic activities of Lucinactant.Approved, Investigational
LuliconazoleThe serum concentration of Tofacitinib can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Tofacitinib can be decreased when it is combined with Lumacaftor.Approved
MechlorethamineMechlorethamine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
MelphalanMelphalan may increase the immunosuppressive activities of Tofacitinib.Approved
MepolizumabMepolizumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
MercaptopurineMercaptopurine may increase the immunosuppressive activities of Tofacitinib.Approved
MetamizoleThe risk or severity of myelosuppression can be increased when Metamizole is combined with Tofacitinib.Approved, Investigational, Withdrawn
MethotrexateMethotrexate may increase the immunosuppressive activities of Tofacitinib.Approved
MethyldopaTofacitinib may increase the bradycardic activities of Methyldopa.Approved
MethylprednisoloneMethylprednisolone may increase the immunosuppressive activities of Tofacitinib.Approved, Vet Approved
MetipranololTofacitinib may increase the bradycardic activities of Metipranolol.Approved
MetoprololTofacitinib may increase the bradycardic activities of Metoprolol.Approved, Investigational
MifepristoneThe serum concentration of Tofacitinib can be increased when it is combined with Mifepristone.Approved, Investigational
MitomycinMitomycin may increase the immunosuppressive activities of Tofacitinib.Approved
MitotaneThe serum concentration of Tofacitinib can be decreased when it is combined with Mitotane.Approved
MitoxantroneMitoxantrone may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
MizoribineMizoribine may increase the immunosuppressive activities of Tofacitinib.Investigational
MoclobemideThe metabolism of Tofacitinib can be decreased when combined with Moclobemide.Approved, Investigational
ModafinilThe metabolism of Tofacitinib can be decreased when combined with Modafinil.Approved, Investigational
MuromonabMuromonab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
Mycophenolate mofetilMycophenolate mofetil may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
Mycophenolic acidMycophenolic acid may increase the immunosuppressive activities of Tofacitinib.Approved
NadololTofacitinib may increase the bradycardic activities of Nadolol.Approved
NafamostatNafamostat may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
NatalizumabThe risk or severity of adverse effects can be increased when Tofacitinib is combined with Natalizumab.Approved, Investigational
NebivololTofacitinib may increase the bradycardic activities of Nebivolol.Approved, Investigational
NefazodoneThe serum concentration of Tofacitinib can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelarabineNelarabine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
NelfinavirThe serum concentration of Tofacitinib can be increased when it is combined with Nelfinavir.Approved
NetupitantThe serum concentration of Tofacitinib can be increased when it is combined with Netupitant.Approved, Investigational
NevirapineThe serum concentration of Tofacitinib can be decreased when it is combined with Nevirapine.Approved
NicardipineThe metabolism of Tofacitinib can be decreased when combined with Nicardipine.Approved, Investigational
NilotinibNilotinib may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
ObinutuzumabObinutuzumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
OcrelizumabOcrelizumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
OctreotideTofacitinib may increase the bradycardic activities of Octreotide.Approved, Investigational
OlaparibThe metabolism of Tofacitinib can be decreased when combined with Olaparib.Approved
OmeprazoleThe metabolism of Tofacitinib can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
OsimertinibThe serum concentration of Tofacitinib can be increased when it is combined with Osimertinib.Approved
OxaliplatinOxaliplatin may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
PaclitaxelPaclitaxel may increase the immunosuppressive activities of Tofacitinib.Approved, Vet Approved
PalbociclibPalbociclib may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
PanobinostatPanobinostat may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
PantoprazoleThe metabolism of Tofacitinib can be decreased when combined with Pantoprazole.Approved
PaquinimodPaquinimod may increase the immunosuppressive activities of Tofacitinib.Investigational
PasireotideTofacitinib may increase the bradycardic activities of Pasireotide.Approved
PazopanibPazopanib may increase the immunosuppressive activities of Tofacitinib.Approved
PegaspargasePegaspargase may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
PemetrexedPemetrexed may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
PenbutololTofacitinib may increase the bradycardic activities of Penbutolol.Approved, Investigational
PentobarbitalThe serum concentration of Tofacitinib can be decreased when it is combined with Pentobarbital.Approved, Investigational, Vet Approved
PentostatinPentostatin may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
PhenobarbitalThe serum concentration of Tofacitinib can be decreased when it is combined with Phenobarbital.Approved, Investigational
PhenytoinThe serum concentration of Tofacitinib can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Tofacitinib.Approved, Investigational
PindololTofacitinib may increase the bradycardic activities of Pindolol.Approved, Investigational
PirarubicinPirarubicin may increase the immunosuppressive activities of Tofacitinib.Investigational
PirfenidoneThe risk or severity of adverse effects can be increased when Pirfenidone is combined with Tofacitinib.Approved, Investigational
PitolisantThe serum concentration of Tofacitinib can be decreased when it is combined with Pitolisant.Approved, Investigational
PomalidomidePomalidomide may increase the immunosuppressive activities of Tofacitinib.Approved
Poractant alfaTofacitinib may increase the bradycardic activities of Poractant alfa.Approved
PosaconazoleThe serum concentration of Tofacitinib can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PralatrexatePralatrexate may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
PrednisolonePrednisolone may increase the immunosuppressive activities of Tofacitinib.Approved, Vet Approved
PrednisonePrednisone may increase the immunosuppressive activities of Tofacitinib.Approved, Vet Approved
PrimidoneThe serum concentration of Tofacitinib can be decreased when it is combined with Primidone.Approved, Vet Approved
ProcarbazineProcarbazine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
PropafenoneTofacitinib may increase the bradycardic activities of Propafenone.Approved
PropranololTofacitinib may increase the bradycardic activities of Propranolol.Approved, Investigational
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Tofacitinib is combined with Rabies virus inactivated antigen, A.Approved, Investigational
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Tofacitinib.Approved, Investigational
RanolazineThe metabolism of Tofacitinib can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe serum concentration of Tofacitinib can be decreased when it is combined with Rifabutin.Approved, Investigational
RifampicinThe serum concentration of Tofacitinib can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Tofacitinib can be decreased when it is combined with Rifapentine.Approved, Investigational
RilonaceptRilonacept may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
RindopepimutThe risk or severity of adverse effects can be increased when Tofacitinib is combined with Rindopepimut.Investigational
RituximabThe risk or severity of adverse effects can be increased when Rituximab is combined with Tofacitinib.Approved
RivastigmineTofacitinib may increase the bradycardic activities of Rivastigmine.Approved, Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Tofacitinib.Approved
Rotavirus VaccineThe risk or severity of adverse effects can be increased when Tofacitinib is combined with Rotavirus Vaccine.Approved
Rubella virus vaccineThe risk or severity of adverse effects can be increased when Tofacitinib is combined with Rubella virus vaccine.Approved, Investigational
RucaparibThe metabolism of Tofacitinib can be decreased when combined with Rucaparib.Approved, Investigational
RuxolitinibRuxolitinib may increase the immunosuppressive activities of Tofacitinib.Approved
Salmonella typhi ty2 vi polysaccharide antigenThe risk or severity of adverse effects can be increased when Tofacitinib is combined with Salmonella typhi ty2 vi polysaccharide antigen.Approved
Salmonella typhi ty21a live antigenThe risk or severity of adverse effects can be increased when Tofacitinib is combined with Salmonella typhi ty21a live antigen.Approved
SaquinavirThe serum concentration of Tofacitinib can be increased when it is combined with Saquinavir.Approved, Investigational
SarilumabThe therapeutic efficacy of Tofacitinib can be decreased when used in combination with Sarilumab.Approved, Investigational
SecukinumabSecukinumab may increase the immunosuppressive activities of Tofacitinib.Approved
SemapimodSemapimod may increase the immunosuppressive activities of Tofacitinib.Investigational
SeocalcitolSeocalcitol may increase the immunosuppressive activities of Tofacitinib.Experimental, Investigational
SertralineThe metabolism of Tofacitinib can be decreased when combined with Sertraline.Approved
SildenafilThe metabolism of Tofacitinib can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabSiltuximab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
SimeprevirThe serum concentration of Tofacitinib can be increased when it is combined with Simeprevir.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Tofacitinib.Approved, Investigational
SirolimusSirolimus may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
SitaxentanThe serum concentration of Tofacitinib can be increased when it is combined with Sitaxentan.Approved, Investigational, Withdrawn
SorafenibSorafenib may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
SotalolTofacitinib may increase the bradycardic activities of Sotalol.Approved
SRP 299The risk or severity of adverse effects can be increased when Tofacitinib is combined with SRP 299.Investigational
St. John's WortThe serum concentration of Tofacitinib can be decreased when it is combined with St. John's Wort.Approved, Investigational, Nutraceutical
SteproninStepronin may increase the immunosuppressive activities of Tofacitinib.Approved
StiripentolThe serum concentration of Tofacitinib can be increased when it is combined with Stiripentol.Approved
StreptozocinStreptozocin may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
SufentanilTofacitinib may increase the bradycardic activities of Sufentanil.Approved, Investigational
SulfisoxazoleThe metabolism of Tofacitinib can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
SunitinibSunitinib may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TacrolimusTacrolimus may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TecemotideThe risk or severity of adverse effects can be increased when Tofacitinib is combined with Tecemotide.Investigational
TelaprevirThe serum concentration of Tofacitinib can be increased when it is combined with Telaprevir.Approved, Withdrawn
TelithromycinThe serum concentration of Tofacitinib can be increased when it is combined with Telithromycin.Approved
TemozolomideTemozolomide may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TemsirolimusTemsirolimus may increase the immunosuppressive activities of Tofacitinib.Approved
TeniposideTeniposide may increase the immunosuppressive activities of Tofacitinib.Approved
TepoxalinTepoxalin may increase the immunosuppressive activities of Tofacitinib.Vet Approved
TeriflunomideTeriflunomide may increase the immunosuppressive activities of Tofacitinib.Approved
TG4010The risk or severity of adverse effects can be increased when Tofacitinib is combined with TG4010.Investigational
ThalidomideThalidomide may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational, Withdrawn
ThiotepaThiotepa may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TiclopidineThe metabolism of Tofacitinib can be decreased when combined with Ticlopidine.Approved
TimololTofacitinib may increase the bradycardic activities of Timolol.Approved
TioguanineTioguanine may increase the immunosuppressive activities of Tofacitinib.Approved
TizanidineTofacitinib may increase the bradycardic activities of Tizanidine.Approved, Investigational
TocilizumabThe risk or severity of adverse effects can be increased when Tocilizumab is combined with Tofacitinib.Approved
TopiramateThe metabolism of Tofacitinib can be decreased when combined with Topiramate.Approved
TopotecanTopotecan may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TositumomabTositumomab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrabectedinTrabectedin may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TranylcypromineThe metabolism of Tofacitinib can be decreased when combined with Tranylcypromine.Approved, Investigational
TrastuzumabTrastuzumab may increase the neutropenic activities of Tofacitinib.Approved, Investigational
Trastuzumab emtansineTrastuzumab emtansine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TretinoinTretinoin may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational, Nutraceutical
TriamcinoloneTriamcinolone may increase the immunosuppressive activities of Tofacitinib.Approved, Vet Approved
TriptolideTriptolide may increase the immunosuppressive activities of Tofacitinib.Investigational
TrofosfamideTrofosfamide may increase the immunosuppressive activities of Tofacitinib.Investigational
Typhoid VaccineThe risk or severity of adverse effects can be increased when Tofacitinib is combined with Typhoid Vaccine.Approved
UstekinumabUstekinumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
Varicella Zoster Vaccine (Live/Attenuated)The risk or severity of adverse effects can be increased when Tofacitinib is combined with Varicella Zoster Vaccine (Live/Attenuated).Approved
VedolizumabVedolizumab may increase the immunosuppressive activities of Tofacitinib.Approved
VemurafenibThe serum concentration of Tofacitinib can be decreased when it is combined with Vemurafenib.Approved
VenlafaxineThe metabolism of Tofacitinib can be decreased when combined with Venlafaxine.Approved
VerapamilTofacitinib may increase the bradycardic activities of Verapamil.Approved
VilanterolVilanterol may increase the immunosuppressive activities of Tofacitinib.Approved
VinblastineVinblastine may increase the immunosuppressive activities of Tofacitinib.Approved
VincristineVincristine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
VindesineVindesine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
VinorelbineVinorelbine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
VoclosporinVoclosporin may increase the immunosuppressive activities of Tofacitinib.Investigational
VoriconazoleThe serum concentration of Tofacitinib can be increased when it is combined with Voriconazole.Approved, Investigational
WortmanninWortmannin may increase the immunosuppressive activities of Tofacitinib.Experimental
Yellow Fever VaccineThe risk or severity of adverse effects can be increased when Tofacitinib is combined with Yellow Fever Vaccine.Approved, Investigational
ZiprasidoneThe metabolism of Tofacitinib can be decreased when combined with Ziprasidone.Approved
ZucapsaicinThe metabolism of Tofacitinib can be decreased when combined with Zucapsaicin.Approved, Investigational
Food Interactions
Not Available

References

General References
  1. Papp KA, Krueger JG, Feldman SR, Langley RG, Thaci D, Torii H, Tyring S, Wolk R, Gardner A, Mebus C, Tan H, Luo Y, Gupta P, Mallbris L, Tatulych S: Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: Long-term efficacy and safety results from 2 randomized phase-III studies and 1 open-label long-term extension study. J Am Acad Dermatol. 2016 May;74(5):841-850. doi: 10.1016/j.jaad.2016.01.013. Epub 2016 Feb 19. [PubMed:26899199]
  2. Link [Link]
External Links
KEGG Drug
D09970
PubChem Compound
9926791
PubChem Substance
347827811
ChemSpider
8102425
BindingDB
50193995
ChEBI
71200
ChEMBL
CHEMBL221959
HET
MI1
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Tofacitinib
ATC Codes
L04AA29 — Tofacitinib
AHFS Codes
  • 92:36.00 — Disease-modifying Antirheumatic Agents
PDB Entries
3eyg / 3fup / 3lxk / 3lxn / 4oti
FDA label
Download (722 KB)
MSDS
Download (44.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentDiscoid Lupus Erythematosus (DLE) / Systemic Lupus Erythematosus (SLE)1
1CompletedNot AvailableHealthy Volunteers2
1CompletedNot AvailableHepatic Insufficiency1
1CompletedBasic ScienceEnd-Stage Renal Disease (ESRD) / Hemodialysis-dependent patients1
1CompletedBasic ScienceHealthy Volunteers2
1CompletedBasic ScienceImpaired Renal Function1
1CompletedBasic ScienceJuvenile Idiopathic Arthritis (JIA)1
1CompletedBasic ScienceRheumatoid Arthritis3
1CompletedOtherRheumatoid Arthritis1
1CompletedOtherSystemic Lupus Erythematosus (SLE)1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentImmunomodulation / Psoriasis1
1RecruitingTreatmentDermatomyositis1
1, 2CompletedTreatmentDry Eye Syndromes1
1, 2RecruitingTreatmentCutaneous Lupus / Systemic Lupus Erythematosus (SLE)1
1, 2RecruitingTreatmentScleroderma / Sclerosis, Progressive Systemic1
2Active Not RecruitingTreatmentAlopecia Areata (AA)1
2CompletedPreventionTransplantation, Kidney4
2CompletedTreatmentAlopecia Areata (AA) / Alopecia Totalis (AT) / Alopecia Universalis (AU)1
2CompletedTreatmentAnkylosing Spondylitis (AS)1
2CompletedTreatmentCrohn's Disease (CD)4
2CompletedTreatmentPsoriasis2
2CompletedTreatmentRheumatoid Arthritis8
2CompletedTreatmentUlcerative Colitis (UC)1
2Not Yet RecruitingTreatmentScleritis / Uveitis1
2RecruitingTreatmentRheumatoid Arthritis1
2WithdrawnTreatmentKeratoconjunctivitis Sicca1
3Active Not RecruitingTreatmentPsoriatic Arthritis1
3Active Not RecruitingTreatmentRheumatoid Arthritis2
3Active Not RecruitingTreatmentUlcerative Colitis (UC)1
3CompletedTreatmentPsoriasis5
3CompletedTreatmentPsoriatic Arthritis1
3CompletedTreatmentRheumatoid Arthritis8
3CompletedTreatmentUlcerative Colitis (UC)3
3RecruitingTreatmentAnkylosing Spondylitis (AS)1
3RecruitingTreatmentArthritis Juvenile Idiopathic1
3RecruitingTreatmentJuvenile Idiopathic Arthritis (JIA)2
3RecruitingTreatmentUlcerative Colitis (UC)1
3TerminatedTreatmentPsoriasis1
4RecruitingPreventionSpondyloarthritis1
4RecruitingTreatmentRheumatoid Arthritis2
Not AvailableActive Not RecruitingNot AvailableRheumatoid Arthritis1
Not AvailableCompletedNot AvailableRheumatoid Arthritis1
Not AvailableCompletedNot AvailableTransplantation, Kidney1
Not AvailableCompletedTreatmentAlopecia Areata (AA) / Alopecia Totalis (AT) / Alopecia Universalis (AU)1
Not AvailableRecruitingNot AvailableRheumatoid Arthritis3

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral5 mg
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral5 mg/1
Tablet, extended releaseOral11 mg
Tablet, extended releaseOral11 mg/1
Tablet, film coated, extended releaseOral11 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7091208No2000-12-082020-12-08Us
US6965027No2003-03-252023-03-25Us
USRE41783No2000-12-082020-12-08Us
US7265221No2000-12-082020-12-08Us
US6956041No2000-12-082020-12-08Us
US7301023No2002-05-232022-05-23Us
US6956027No2003-03-252023-03-25Us
US9937181No2014-03-142034-03-14Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP1.808 MSDS, Tofacitinib Citrate
Predicted Properties
PropertyValueSource
Water Solubility0.299 mg/mLALOGPS
logP1.58ALOGPS
logP1.24ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)8.46ChemAxon
pKa (Strongest Basic)7.13ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area88.91 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity87.8 m3·mol-1ChemAxon
Polarizability32.65 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9897
Blood Brain Barrier+0.9568
Caco-2 permeable+0.5154
P-glycoprotein substrateSubstrate0.6524
P-glycoprotein inhibitor IInhibitor0.7609
P-glycoprotein inhibitor IIInhibitor0.8898
Renal organic cation transporterInhibitor0.6368
CYP450 2C9 substrateNon-substrate0.8246
CYP450 2D6 substrateNon-substrate0.723
CYP450 3A4 substrateSubstrate0.7649
CYP450 1A2 substrateNon-inhibitor0.734
CYP450 2C9 inhibitorNon-inhibitor0.8014
CYP450 2D6 inhibitorNon-inhibitor0.9537
CYP450 2C19 inhibitorNon-inhibitor0.8036
CYP450 3A4 inhibitorNon-inhibitor0.9307
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7937
Ames testNon AMES toxic0.5492
CarcinogenicityNon-carcinogens0.9032
BiodegradationNot ready biodegradable0.9956
Rat acute toxicity2.7249 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5995
hERG inhibition (predictor II)Inhibitor0.7324
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as n-acylpiperidines. These are compounds containing an N-acyethanolamine moiety, which is characterized by an acyl group is linked to the nitrogen atom of a piperidine.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Piperidines
Sub Class
N-acylpiperidines
Direct Parent
N-acylpiperidines
Alternative Parents
Pyrrolo[2,3-d]pyrimidines / Dialkylarylamines / Aminopyrimidines and derivatives / Aminopiperidines / Imidolactams / Tertiary carboxylic acid amides / Pyrroles / Heteroaromatic compounds / Nitriles / Azacyclic compounds
show 4 more
Substituents
N-acyl-piperidine / Pyrrolo[2,3-d]pyrimidine / Pyrrolopyrimidine / Dialkylarylamine / 3-aminopiperidine / Aminopyrimidine / Pyrimidine / Imidolactam / Pyrrole / Tertiary carboxylic acid amide
show 15 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tertiary amino compound, N-acylpiperidine, nitrile, pyrrolopyrimidine (CHEBI:71200)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ubiquitin protein ligase binding
Specific Function
Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor.
Gene Name
JAK1
Uniprot ID
P23458
Uniprot Name
Tyrosine-protein kinase JAK1
Molecular Weight
133275.995 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Inhibitor
General Function
Sh2 domain binding
Specific Function
Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptiv...
Gene Name
JAK2
Uniprot ID
O60674
Uniprot Name
Tyrosine-protein kinase JAK2
Molecular Weight
130672.475 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a...
Gene Name
JAK3
Uniprot ID
P52333
Uniprot Name
Tyrosine-protein kinase JAK3
Molecular Weight
125097.565 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein tyrosine kinase activity
Specific Function
Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain.
Gene Name
TYK2
Uniprot ID
P29597
Uniprot Name
Non-receptor tyrosine-protein kinase TYK2
Molecular Weight
133648.77 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Human
Pharmacological action
No
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
Details
2. Cytochrome P450 2C19
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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

Drug created on June 03, 2013 14:44 / Updated on July 16, 2018 21:25