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Identification
NameTofacitinib
Accession NumberDB08895
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionTofacitinib 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 Identifiers
  • CP 690550
  • CP-690 free base
  • CP-690-550
  • CP-690,550
  • CP-690,550 free base
  • CP-690550
  • CP-690550 free base
  • CP690,550
  • CP690550
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
XeljanzTablet, film coated5 mg/1OralU.S. Pharmaceuticals2012-11-08Not applicableUs
XeljanzTablet5 mgOralPfizer Canada Inc2014-06-03Not applicableCanada
XeljanzTablet, film coated5 mg/1OralPfizer Laboratories Div Pfizer Inc2012-11-09Not applicableUs
Xeljanz XRTablet, film coated, extended release11 mg/1OralPfizer Laboratories Div Pfizer Inc2016-03-07Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Tofacitinib citrate
540737-29-9
Thumb
  • InChI Key: SYIKUFDOYJFGBQ-YLAFAASESA-N
  • Monoisotopic Mass: 504.196861902
  • Average Mass: 504.4931
DBSALT000180
Categories
UNIINot Available
CAS number477600-75-2
WeightAverage: 312.3696
Monoisotopic: 312.169859292
Chemical FormulaC16H20N6O
InChI KeyUJLAWZDWDVHWOW-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
IndicationFor 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.
Structured Indications
PharmacodynamicsTofacitinib 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 actionRheumatoid 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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Tyrosine-protein kinase JAK2Proteinyes
antagonist
inhibitor
HumanO60674 details
Tyrosine-protein kinase JAK1Proteinyes
inhibitor
HumanP23458 details
Tyrosine-protein kinase JAK3Proteinyes
inhibitor
HumanP52333 details
Related Articles
Absorption74% 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 binding40%, mostly bound to albumin.
Metabolism

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

Route of elimination70% metabolized in the liver by CYP3A4 (major) and CYP2C19 (minor). Metabolites produced are inactive. 30% renally eliminated as unchanged drug.
Half life~3 hours
ClearanceNot Available
ToxicityMinimum 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
2-Methoxyethanol2-Methoxyethanol may increase the immunosuppressive activities of Tofacitinib.Experimental
9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine may increase the immunosuppressive activities of Tofacitinib.Investigational
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
ABR-215757ABR-215757 may increase the immunosuppressive activities of Tofacitinib.Investigational
AcebutololTofacitinib may increase the bradycardic activities of Acebutolol.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
Adefovir DipivoxilAdefovir Dipivoxil may increase the immunosuppressive activities of Tofacitinib.Approved, 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, Withdrawn
AlemtuzumabAlemtuzumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
alicaforsenalicaforsen may increase the immunosuppressive activities of Tofacitinib.Investigational
ALT-110The risk or severity of adverse effects can be increased when Tofacitinib is combined with ALT-110.Investigational
AltretamineAltretamine may increase the immunosuppressive activities of Tofacitinib.Approved
Amg 827Amg 827 may increase the immunosuppressive activities of Tofacitinib.Investigational
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
AnakinraThe risk or severity of adverse effects can be increased when Anakinra is combined with Tofacitinib.Approved
Anti-thymocyte Globulin (Rabbit)Anti-thymocyte Globulin (Rabbit) may increase the immunosuppressive activities of Tofacitinib.Approved
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
BasiliximabBasiliximab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
BcgThe therapeutic efficacy of Bcg can be decreased when used in combination with Tofacitinib.Investigational
BelataceptBelatacept may increase the immunosuppressive activities of Tofacitinib.Approved
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.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
BexaroteneThe serum concentration of Tofacitinib can be decreased when it is combined with Bexarotene.Approved, Investigational
BisoprololTofacitinib may increase the bradycardic activities of Bisoprolol.Approved
BleomycinBleomycin may increase the immunosuppressive activities of Tofacitinib.Approved
BlinatumomabBlinatumomab may increase the immunosuppressive activities of Tofacitinib.Approved
BoceprevirThe serum concentration of Tofacitinib can be increased when it is combined with Boceprevir.Approved
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
BriakinumabBriakinumab may increase the immunosuppressive activities of Tofacitinib.Investigational
BudesonideBudesonide may increase the immunosuppressive activities of Tofacitinib.Approved
BusulfanBusulfan may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
C1 Esterase Inhibitor (Human)C1 Esterase Inhibitor (Human) may increase the immunosuppressive activities of Tofacitinib.Approved
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
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
CDX-110The risk or severity of adverse effects can be increased when Tofacitinib is combined with CDX-110.Investigational
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
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
ClofarabineClofarabine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
ClonidineTofacitinib may increase the bradycardic activities of Clonidine.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 Tofacitinib can be increased when it is combined with Conivaptan.Approved, Investigational
CorticotropinCorticotropin may increase the immunosuppressive activities of Tofacitinib.Approved, Vet Approved
Cortisone acetateCortisone acetate may increase the immunosuppressive activities of Tofacitinib.Approved
CrizotinibTofacitinib may increase the bradycardic activities of Crizotinib.Approved
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
DacarbazineDacarbazine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
DaclizumabDaclizumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
DactinomycinDactinomycin may increase the immunosuppressive activities of Tofacitinib.Approved
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
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
DiltiazemTofacitinib may increase the bradycardic activities of Diltiazem.Approved
Dimethyl fumarateDimethyl fumarate may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
DinutuximabDinutuximab may increase the immunosuppressive activities of Tofacitinib.Approved
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 serum concentration of Tofacitinib can be decreased when it is 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, Vet Approved
Eslicarbazepine acetateThe serum concentration of Tofacitinib can be decreased when it is 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
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 serum concentration of Tofacitinib can be decreased when it is 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
FludarabineFludarabine may increase the immunosuppressive activities of Tofacitinib.Approved
FludrocortisoneFludrocortisone may increase the immunosuppressive activities of Tofacitinib.Approved
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
Fusidic AcidThe serum concentration of Tofacitinib can be increased when it is combined with Fusidic Acid.Approved
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, Withdrawn
GI-5005The risk or severity of adverse effects can be increased when Tofacitinib is combined with GI-5005.Investigational
Glatiramer AcetateGlatiramer 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
GuanfacineTofacitinib may increase the bradycardic activities of Guanfacine.Approved, Investigational
GusperimusGusperimus may increase the immunosuppressive activities of Tofacitinib.Investigational
HydrocortisoneHydrocortisone may increase the immunosuppressive activities of Tofacitinib.Approved, Vet Approved
HydroxyureaHydroxyurea may increase the immunosuppressive activities of Tofacitinib.Approved
Ibritumomab tiuxetanIbritumomab tiuxetan may increase the immunosuppressive activities of Tofacitinib.Approved
IbrutinibIbrutinib may increase the immunosuppressive activities of Tofacitinib.Approved
IcatibantIcatibant may increase the immunosuppressive activities of Tofacitinib.Approved
IdarubicinIdarubicin may increase the immunosuppressive activities of Tofacitinib.Approved
IdelalisibThe serum concentration of Tofacitinib can be increased when it is combined with Idelalisib.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
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
IsradipineThe metabolism of Tofacitinib can be decreased when combined with Isradipine.Approved
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
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, 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
LisofyllineLisofylline may increase the immunosuppressive activities of Tofacitinib.Investigational
LomustineLomustine may increase the immunosuppressive activities of Tofacitinib.Approved
LopinavirThe serum concentration of Tofacitinib can be increased when it is combined with Lopinavir.Approved
LovastatinThe metabolism of Tofacitinib can be decreased when combined with Lovastatin.Approved, Investigational
LucinactantTofacitinib may increase the bradycardic activities of Lucinactant.Approved
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
Lx211Lx211 may increase the immunosuppressive activities of Tofacitinib.Investigational
MechlorethamineMechlorethamine may increase the immunosuppressive activities of Tofacitinib.Approved
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 adverse effects can be increased when Metamizole is combined with Tofacitinib.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
ModafinilThe serum concentration of Tofacitinib can be decreased when it is 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.Investigational
NafcillinThe serum concentration of Tofacitinib can be decreased when it is combined with Nafcillin.Approved
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
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
NilotinibNilotinib may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
ObinutuzumabObinutuzumab may increase the immunosuppressive activities of Tofacitinib.Approved
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
PanobinostatPanobinostat may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
PantoprazoleThe metabolism of Tofacitinib can be decreased when combined with Pantoprazole.Approved
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, 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
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
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.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
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
PropafenoneTofacitinib may increase the bradycardic activities of Propafenone.Approved
PropranololTofacitinib may increase the bradycardic activities of Propranolol.Approved, Investigational
Rabies vaccineThe risk or severity of adverse effects can be increased when Tofacitinib is combined with Rabies vaccine.Approved
Rabies vaccineThe therapeutic efficacy of Rabies vaccine can be decreased when used in combination with Tofacitinib.Approved
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
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
RilonaceptRilonacept may increase the immunosuppressive activities of Tofacitinib.Approved
RitonavirThe serum concentration of Tofacitinib can be increased when it is combined with Ritonavir.Approved, 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
RuxolitinibRuxolitinib may increase the immunosuppressive activities of Tofacitinib.Approved
SaquinavirThe serum concentration of Tofacitinib can be increased when it is combined with Saquinavir.Approved, Investigational
SecukinumabSecukinumab may increase the immunosuppressive activities of Tofacitinib.Approved
SeocalcitolSeocalcitol may increase the immunosuppressive activities of Tofacitinib.Experimental
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
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
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.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
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
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Tofacitinib.Approved, Investigational
TelaprevirThe serum concentration of Tofacitinib can be increased when it is combined with Telaprevir.Approved
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
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
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
TrabectedinTrabectedin may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TranylcypromineThe metabolism of Tofacitinib can be decreased when combined with Tranylcypromine.Approved
TrastuzumabTrastuzumab may increase the neutropenic activities of Tofacitinib.Approved, Investigational
Trastuzumab emtansineTrastuzumab emtansine may increase the immunosuppressive activities of Tofacitinib.Approved
TretinoinTretinoin may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational, Nutraceutical
TriamcinoloneTriamcinolone may increase the immunosuppressive activities of Tofacitinib.Approved, Vet Approved
TrofosfamideTrofosfamide may increase the immunosuppressive activities of Tofacitinib.Investigational
UstekinumabUstekinumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
VedolizumabVedolizumab may increase the immunosuppressive activities of Tofacitinib.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
VinorelbineVinorelbine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
VoriconazoleThe serum concentration of Tofacitinib can be increased when it is combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Tofacitinib can be decreased when combined with Ziprasidone.Approved
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesL04AA29
AHFS Codes
  • 92:36
PDB Entries
FDA labelDownload (722 KB)
MSDSDownload (44.7 KB)
ADMET
Predicted ADMET featuresNot Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral5 mg
Tablet, film coatedOral5 mg/1
Tablet, film coated, extended releaseOral11 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6956027 No2003-03-252023-03-25Us
US6956041 No2000-12-082020-12-08Us
US6965027 No2003-03-252023-03-25Us
US7091208 No2000-12-082020-12-08Us
US7265221 No2000-12-082020-12-08Us
US7301023 No2002-05-232022-05-23Us
USRE41783 No2000-12-082020-12-08Us
Properties
StateSolid
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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as pyrrolopyrimidines. These are compounds containing a pyrrolopyrimidine moiety, which consists of a pyrrole ring fused to a pyrimidine. Pyrrole is 5-membered ring consisting of four carbon atoms and one nitrogen atom. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyrrolopyrimidines
Sub ClassNot Available
Direct ParentPyrrolopyrimidines
Alternative Parents
Substituents
  • Pyrrolopyrimidine
  • N-acyl-piperidine
  • Dialkylarylamine
  • Aminopyrimidine
  • 3-aminopiperidine
  • Imidolactam
  • Pyrimidine
  • Piperidine
  • Heteroaromatic compound
  • Tertiary carboxylic acid amide
  • Pyrrole
  • Tertiary amine
  • Carboxamide group
  • Azacycle
  • Nitrile
  • Carbonitrile
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonistinhibitor
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 adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR)...
Gene Name:
JAK2
Uniprot ID:
O60674
Molecular Weight:
130672.475 Da
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
Molecular Weight:
133275.995 Da
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 crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such...
Gene Name:
JAK3
Uniprot ID:
P52333
Molecular Weight:
125097.565 Da

Enzymes

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
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 imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
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 colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
Comments
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Drug created on June 03, 2013 14:44 / Updated on December 03, 2016 03:21