Upadacitinib 45mg modified-release tablets
Prescription only
Requires a prescription from a doctor or prescriber
Tablet
45mg
Oral
Upadacitinib is an oral Janus kinase (JAK)1-selective inhibitor and a disease-modifying antirheumatic drug (DMARD) used in the treatment of rheumatoid arthritis to slow down disease progression.
Active ingredients:
Upadacitinib
No active safety alerts
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Official medicine documents
Source: MHRA Products DatabaseOGL 3.0
Updated 3 months ago(16 Jan 2026)Safety monitoring data
Yellow Card reports
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Suspected adverse reactions reported for Upadacitinib
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Data from the MHRA Yellow Card scheme. A reported reaction does not necessarily mean the medicine caused it. Contains public sector information licensed under the Open Government Licence v3.0.
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Suspected adverse reactions reported for Upadacitinib
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1 branded products available
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Rinvoq 45mg modified-release tablets
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WHO defined daily dose (DDD)
15 mg
Not a recommended dose. The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. It is a statistical measure used for research and comparison purposes only.
Source: WHO Collaborating Centre for Drug Statistics Methodology, distributed via NHS dm+d BNF mapping files. Contains public sector information licensed under the Open Government Licence v3.0.
Therapeutically similar medicines
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Tablet
6mg
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Tofacitinib 1mg/ml oral solution sugar free
Oral solution
1mg
Same therapeutic group
Upadacitinib 30mg modified-release tablets
Tablet
30mg
Same therapeutic group
Filgotinib 200mg tablets
Tablet
200mg
Same therapeutic group
Similarity based on WHO Anatomical Therapeutic Chemical (ATC) classification and NHS BNF section grouping. Source data: NHS dm+d via TRUD (OGL v3.0), WHO ATC/DDD Index.
NHS prescribing volume and spending trends
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Clinical guidelines and formulary information
British National Formulary
Upadacitinib
BNF
Drug monograph — bnf.nice.org.ukSource: British National Formulary, NICE. Joint Formulary Committee. Contains public sector information licensed under the Open Government Licence v3.0.
NICE clinical guidance(13)
Upadacitinib for treating active ankylosing spondylitis (TA829)
TA829
Technology appraisal
Updated Sept 2022Upadacitinib for treating severe rheumatoid arthritis (TA665)
TA665
Technology appraisal
Updated Dec 2020Upadacitinib for treating moderate rheumatoid arthritis (TA744)
TA744
Technology appraisal
Updated Nov 2021Upadacitinib for treating moderately to severely active ulcerative colitis (TA856)
TA856
Technology appraisal
Updated Jan 2023Upadacitinib for treating active non-radiographic axial spondyloarthritis (TA861)
TA861
Technology appraisal
Updated Feb 2023Upadacitinib for previously treated moderately to severely active Crohn's disease (TA905)
TA905
Technology appraisal
Updated Jun 2023Upadacitinib for treating active psoriatic arthritis after inadequate response to DMARDs (TA768)
TA768
Technology appraisal
Updated Feb 2022Abrocitinib, tralokinumab or upadacitinib for treating moderate to severe atopic dermatitis (TA814)
TA814
Technology appraisal
Updated Aug 2022Spondyloarthritis in over 16s: diagnosis and management (NG65)
NG65
NICE guideline
Updated Jun 2017Lebrikizumab for treating moderate to severe atopic dermatitis in people 12 years and over (TA986)
TA986
Technology appraisal
Updated Jul 2024Rheumatoid arthritis in adults: management (NG100)
NG100
NICE guideline
Updated Oct 2020Nemolizumab for treating moderate to severe atopic dermatitis in people 12 years and over (TA1077)
TA1077
Technology appraisal
Updated Jul 2025Ulcerative colitis: management (NG130)
NG130
NICE guideline
Updated May 2019Source: National Institute for Health and Care Excellence (NICE). Contains public sector information licensed under the Open Government Licence v3.0.
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Supply & product information
Official product databases and supply status monitoring
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Codes for healthcare professionals and prescribing systems
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These codes are used by healthcare IT systems and prescribers to identify this medicine.
NHS UK identifiers
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SNOMED CT and dm+d codes from NHS TRUD (Technology Reference data Update Distribution), licensed under the Open Government Licence v3.0. BNF codes from NHS Business Services Authority (NHSBSA). ATC codes from the WHO Collaborating Centre for Drug Statistics Methodology (whocc.no).
Active and completed clinical studies from ClinicalTrials.gov
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Searching UK clinical trials...
Source: ClinicalTrials.gov, a database of the U.S. National Library of Medicine (NLM), National Institutes of Health (NIH). Data accessed via ClinicalTrials.gov API v2. Trial information is provided for research purposes and does not constitute medical advice.
Pharmacology and chemical data from DrugBank
Key facts
Drug status
Approved
Major interactions
None known
Half-life
8 to 14 hours
Mechanism
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that invo…
Food interactions
3 warnings
Human targets
1 target
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
2 to 4 hours
Upadacitinib displays a dose-proportional pharmacokinetic profile over the therapeutic dose range.…
Half-life
8 to 14 hours
The mean terminal elimination half-life of upadacitinib ranged from 8 to 14 hours following administration of the extended-release formulation.
[L10896][L10905]…
[L10896][L10905]…
Protein binding
52%
Upadacitinib is 52% bound to human plasma proteins.
[L10896]
[L10896]
Volume of distribution
224 L
The volume of distribution of upadacitinib in a patient with rheumatoid arthritis and a body weight of 74 kg is estimated to be 224 L following oral administration of an extended-release formula.
[L10905]…
[L10905]…
Metabolism
79%
Upadacitinib predominantly undergoes CYP3A4-mediated metabolism;[L10896] however, upadacitinib is a nonsensitive substrate of CYP3A4.
[A189162]…
[A189162]…
Elimination
53%
Following administration of a single radio-labelled dose from the immediate-release formulation, approximately 53% of the total dose was excreted…
Clearance
53.7 L/h
The apparent oral clearance of upadacitinib in healthy volunteers receiving the extended-release formulation was 53.7 L/h.
[A184043]
[A184043]
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Status:
Approved
Investigational
Small molecule
About this compound
Upadacitinib is an oral Janus kinase (JAK)1-selective inhibitor and a disease-modifying antirheumatic drug (DMARD) used in the treatment of rheumatoid arthritis to slow down disease progression. Rheumatoid arthritis is a chronic autoimmune inflammatory disease affecting the peripheral joints. It is characterized by synovial inflammation and hyperplasia, autoantibody production, cartilage damage and bone destruction, leading to co-morbidities.[A189165] Despite a variety of therapeutic agents available for treatment, up to 40% of the patients do not respond to current therapies, including biological therapies.[A189171] The etiology of the disease is mostly unknown; however, the role of JAK as a driver of immune-mediated conditions was discovered, leading to the use of JAK as therapeutic targets for rheumatoid arthritis.[A189168] To reduce dose-related toxicity (as seen with some pan-JAK inhibitors) without significantly affecting efficacy, more selective JAK1 inhibitors, upadacitinib and [filgotinib], were developed.[A189165]
The FDA approved upadacitinib in August 2019 and it is used for the treatment of active rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, and ankylosing spondylitis.[L10896] In December 2019, it was additionally approved by the European Commission and Health Canada.[L10899][L42540] Upadacitinib is marketed under the brand name RINVOQ for oral administration.[L10896]. More recently, it has also been approved for the treatment of giant cell arteritis in adults and active polyarticular juvenile idiopathic arthritis in patients aged 2 years and older.[L10896]
The FDA approved upadacitinib in August 2019 and it is used for the treatment of active rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, and ankylosing spondylitis.[L10896] In December 2019, it was additionally approved by the European Commission and Health Canada.[L10899][L42540] Upadacitinib is marketed under the brand name RINVOQ for oral administration.[L10896]. More recently, it has also been approved for the treatment of giant cell arteritis in adults and active polyarticular juvenile idiopathic arthritis in patients aged 2 years and older.[L10896]
Properties:
liquid
Avg. mass: 380.38 Da
DrugBank indication
Upadacitinib is indicated for the treatment of moderately to severely active rheumatoid arthritis or active psoriatic arthritis in adult patients who have had an inadequate response or intolerance to one or more disease-modifying anti-rheumatic drugs (DMARDs), such as TNF blockers.
[L10896][L39474]
In Europe, upadacitinib may be used as monotherapy or in combination with [methotrexate] for rheumatoid or psoriatic arthritis.
[L39474]
Upadacitinib is indicated for use in patients 12 years of age and older with refractory, moderate-to-severe atopic dermatitis whose disease is inadequately controlled with other systemic therapies or when other therapies are inadvisable.
[L10896][L39474]
Upadacitinib is indicated for the treatment of active ankylosing spondylitis or radiographic axial spondyloarthritis in adult patients who have an inadequate response to conventional therapy.
[L10896][L39474]
It is also indicated to treat non-radiographic axial spondyloarthritis with objective signs of inflammation in adults who have had an inadequate response or intolerance to TNF blocker therapy.
[L10896]
Upadacitinib is also indicated to treat moderately to severely active ulcerative colitis in adults who have had an inadequate response or intolerance to either conventional therapy or a biologic agent,[L39474] such as to one or more TNF blockers.
[L10896]
Upadacitinib is indicated to treat moderately to severely active Crohn’s disease in adults who have had an inadequate response or intolerance to one or more TNF blockers.
[L46486][L39474]
Upadacitinib is also indicated for the treatment of patients two years of age and older with active polyarticular juvenile idiopathic arthritis who have had an inadequate response or intolerance to one or more TNF blockers, and for the treatment of adults with giant cell arteritis.
[L10896][L54211]
Combining upadacitinib with other JAK inhibitors, biologic DMARDs, or other potent immunosuppressive agents is not recommended.
[L10896]
[L10896][L39474]
In Europe, upadacitinib may be used as monotherapy or in combination with [methotrexate] for rheumatoid or psoriatic arthritis.
[L39474]
Upadacitinib is indicated for use in patients 12 years of age and older with refractory, moderate-to-severe atopic dermatitis whose disease is inadequately controlled with other systemic therapies or when other therapies are inadvisable.
[L10896][L39474]
Upadacitinib is indicated for the treatment of active ankylosing spondylitis or radiographic axial spondyloarthritis in adult patients who have an inadequate response to conventional therapy.
[L10896][L39474]
It is also indicated to treat non-radiographic axial spondyloarthritis with objective signs of inflammation in adults who have had an inadequate response or intolerance to TNF blocker therapy.
[L10896]
Upadacitinib is also indicated to treat moderately to severely active ulcerative colitis in adults who have had an inadequate response or intolerance to either conventional therapy or a biologic agent,[L39474] such as to one or more TNF blockers.
[L10896]
Upadacitinib is indicated to treat moderately to severely active Crohn’s disease in adults who have had an inadequate response or intolerance to one or more TNF blockers.
[L46486][L39474]
Upadacitinib is also indicated for the treatment of patients two years of age and older with active polyarticular juvenile idiopathic arthritis who have had an inadequate response or intolerance to one or more TNF blockers, and for the treatment of adults with giant cell arteritis.
[L10896][L54211]
Combining upadacitinib with other JAK inhibitors, biologic DMARDs, or other potent immunosuppressive agents is not recommended.
[L10896]
Also known as(57)
Upadacitinib
2.7.10.2
JAK-1
JAK1A
JAK1B
Janus kinase 1
1,4-cineole 2-exo-monooxygenase
1,8-cineole 2-exo-monooxygenase
Dosage forms(11)
Tablet (Oral) — 30.700 mg
Solution (Oral) — 1 mg/1mL
Tablet, extended release (Oral) — 15 mg
Tablet, extended release (Oral) — 15 mg/1
Tablet, extended release (Oral) — 30 mg/1
Tablet, extended release (Oral) — 30 mg
Tablet, extended release (Oral) — 45 mg
Tablet, extended release (Oral) — 45 mg/1
Molecular properties(19)
Drug interactions(460)
Known interactions with other medications. Always consult a healthcare professional.
The risk or severity of adverse effects can be increased when Denosumab is combined with Upadacitinib.
Etanercept
Unknown severity
The risk or severity of adverse effects can be increased when Etanercept is combined with Upadacitinib.
Peginterferon alfa-2a
Unknown severity
The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Upadacitinib.
Interferon alfa-n1
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Upadacitinib.
Interferon alfa-n3
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Upadacitinib.
Peginterferon alfa-2b
Unknown severity
The risk or severity of adverse effects can be increased when Peginterferon alfa-2b is combined with Upadacitinib.
The risk or severity of adverse effects can be increased when Anakinra is combined with Upadacitinib.
Interferon gamma-1b
Unknown severity
The risk or severity of adverse effects can be increased when Interferon gamma-1b is combined with Upadacitinib.
Interferon alfa-2a
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfa-2a is combined with Upadacitinib.
Aldesleukin
Unknown severity
The risk or severity of adverse effects can be increased when Aldesleukin is combined with Upadacitinib.
Adalimumab
Unknown severity
The risk or severity of adverse effects can be increased when Adalimumab is combined with Upadacitinib.
Gemtuzumab ozogamicin
Unknown severity
The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Upadacitinib.
Pegaspargase
Unknown severity
The risk or severity of adverse effects can be increased when Pegaspargase is combined with Upadacitinib.
Infliximab
Unknown severity
The risk or severity of adverse effects can be increased when Infliximab is combined with Upadacitinib.
Interferon beta-1b
Unknown severity
The risk or severity of adverse effects can be increased when Interferon beta-1b is combined with Upadacitinib.
Interferon alfacon-1
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Upadacitinib.
The risk or severity of adverse effects can be increased when Rituximab is combined with Upadacitinib.
Basiliximab
Unknown severity
The risk or severity of adverse effects can be increased when Basiliximab is combined with Upadacitinib.
The risk or severity of adverse effects can be increased when Muromonab is combined with Upadacitinib.
Ibritumomab tiuxetan
Unknown severity
The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Upadacitinib.
Tositumomab
Unknown severity
The risk or severity of adverse effects can be increased when Tositumomab is combined with Upadacitinib.
Alemtuzumab
Unknown severity
The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Upadacitinib.
The risk or severity of adverse effects can be increased when Alefacept is combined with Upadacitinib.
Efalizumab
Unknown severity
The risk or severity of adverse effects can be increased when Efalizumab is combined with Upadacitinib.
Antithymocyte immunoglobulin (rabbit)
Unknown severity
The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Upadacitinib.
Interferon alfa-2b
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfa-2b is combined with Upadacitinib.
Daclizumab
Unknown severity
The risk or severity of adverse effects can be increased when Daclizumab is combined with Upadacitinib.
Phenylalanine
Unknown severity
The risk or severity of adverse effects can be increased when Phenylalanine is combined with Upadacitinib.
Flunisolide
Unknown severity
The risk or severity of adverse effects can be increased when Flunisolide is combined with Upadacitinib.
Bortezomib
Unknown severity
The risk or severity of adverse effects can be increased when Bortezomib is combined with Upadacitinib.
Cladribine
Moderate
Upadacitinib may increase the immunosuppressive activities of Cladribine.
Carmustine
Unknown severity
The risk or severity of adverse effects can be increased when Carmustine is combined with Upadacitinib.
The risk or severity of adverse effects can be increased when Amsacrine is combined with Upadacitinib.
The risk or severity of adverse effects can be increased when Bleomycin is combined with Upadacitinib.
Chlorambucil
Unknown severity
The risk or severity of adverse effects can be increased when Chlorambucil is combined with Upadacitinib.
Raltitrexed
Unknown severity
The risk or severity of adverse effects can be increased when Raltitrexed is combined with Upadacitinib.
The risk or severity of adverse effects can be increased when Mitomycin is combined with Upadacitinib.
Bexarotene
Unknown severity
The risk or severity of adverse effects can be increased when Bexarotene is combined with Upadacitinib.
The risk or severity of adverse effects can be increased when Vindesine is combined with Upadacitinib.
Floxuridine
Unknown severity
The risk or severity of adverse effects can be increased when Floxuridine is combined with Upadacitinib.
Fluorometholone
Unknown severity
The risk or severity of adverse effects can be increased when Fluorometholone is combined with Upadacitinib.
Indomethacin
Unknown severity
The risk or severity of adverse effects can be increased when Indomethacin is combined with Upadacitinib.
Tioguanine
Unknown severity
The risk or severity of adverse effects can be increased when Tioguanine is combined with Upadacitinib.
Vinorelbine
Unknown severity
The risk or severity of adverse effects can be increased when Vinorelbine is combined with Upadacitinib.
Dexrazoxane
Unknown severity
The risk or severity of adverse effects can be increased when Dexrazoxane is combined with Upadacitinib.
Beclomethasone dipropionate
Unknown severity
The risk or severity of adverse effects can be increased when Beclomethasone dipropionate is combined with Upadacitinib.
The risk or severity of adverse effects can be increased when Sorafenib is combined with Upadacitinib.
Streptozocin
Unknown severity
The risk or severity of adverse effects can be increased when Streptozocin is combined with Upadacitinib.
Trifluridine
Unknown severity
The risk or severity of adverse effects can be increased when Trifluridine is combined with Upadacitinib.
Gemcitabine
Unknown severity
The risk or severity of adverse effects can be increased when Gemcitabine is combined with Upadacitinib.
Showing 50 of 460 interactions
Food & lifestyle interactions
Avoid Grapefruit
Avoid grapefruit products. Upadacitinib exposure is increased when a strong CYP3A4 inhibitor such as grapefruit is used, which may increase the risk for drug-related adverse events.
Advice
Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of upadacitinib.
Advice
Take with or without food. Food does not significantly affect drug concentrations.
Toxicity & overdose
There is limited clinical information on the overdose from upacitinib: in clinical trials, once-daily administration of 60 mg in extended-release formulations were well tolerated. In case of an overdose, it is recommended that the patient is monitored for signs and symptoms of adverse reactions and treated with appropriate symptomatic treatment.
[L10896]
The oral LD50 in rats is 14500 mg/kg.
[L10911]
[L10896]
The oral LD50 in rats is 14500 mg/kg.
[L10911]
How it works
Mechanism of action
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that involves the interplay of several mediators, including the immune cells (mainly T- and B-lymphocytes) and pro-inflammatory cytokines, such as the tumour necrosis factor (TNF), transforming growth factor (TGF), and interleukin 6 (IL-6).[A189165] The Janus Kinase (JAK) family plays an essential role in the normal physiological functions (such as erythropoiesis), but also the signalling of pro-inflammatory cytokines that are implicated in many immune-mediated diseases.[A189168] The JAK family consists of four isoforms (JAK1, JAK2, JAK3, and Tyrosine Kinase 2) that each interacts with different cytokine receptors and uniquely associates with the intracellular domains of Type I/II cytokine receptors.[A189168] JAK1 is primarily involved in the signalling transduction pathways of IL-6, IFN and the common γ -chain cytokines, including IL-2 and IL-15.[A189180] IL-6 has been closely studied in particular, as it is a major cytokine involved in B- and T-cell differentiation and the acute phase response in inflammation.[A189177]
Upon interaction of cytokines with their cytokine receptors, the JAKs mediate the JAK-STAT signal transduction pathway in response to receptor activation. JAKs are tyrosine kinases that cause phosphorylation of several proteins, including cytokine receptors and JAKs themselves. Phosphorylation of JAKs promotes the phosphorylation and activation of the signalling molecules called STATs, leading to their nuclear translocation, binding to DNA promoters, and target gene transcription. JAK1-mediated signalling pathways ultimately promote pro-inflammatory events, such as increased proliferation and survival of immune cells, T cell differentiation, and macrophage activation.[A189168] Upadacitinib is a selective JAK1 inhibitor that has a negligible effect on JAK3, leading to an improved drug safety profile.[A189165] Upadacitinib blocks the cellular processes that contribute to the inflammatory conditions in rheumatoid arthritis. In human leukocytes cellular assays, upadacitinib inhibited JAK1/3-induced phosphorylation of STAT3/5 mediated by IL-6/7.[L10896]
Upon interaction of cytokines with their cytokine receptors, the JAKs mediate the JAK-STAT signal transduction pathway in response to receptor activation. JAKs are tyrosine kinases that cause phosphorylation of several proteins, including cytokine receptors and JAKs themselves. Phosphorylation of JAKs promotes the phosphorylation and activation of the signalling molecules called STATs, leading to their nuclear translocation, binding to DNA promoters, and target gene transcription. JAK1-mediated signalling pathways ultimately promote pro-inflammatory events, such as increased proliferation and survival of immune cells, T cell differentiation, and macrophage activation.[A189168] Upadacitinib is a selective JAK1 inhibitor that has a negligible effect on JAK3, leading to an improved drug safety profile.[A189165] Upadacitinib blocks the cellular processes that contribute to the inflammatory conditions in rheumatoid arthritis. In human leukocytes cellular assays, upadacitinib inhibited JAK1/3-induced phosphorylation of STAT3/5 mediated by IL-6/7.[L10896]
Pharmacodynamics
Upadacitinib is a DMARD that works by inhibiting the Janus Kinases (JAKs), which are essential downstream cell signalling mediators of pro-inflammatory cytokines. It is believed that these pro-inflammatory cytokines play a role in many autoimmune inflammatory conditions, such as rheumatoid arthritis.[A189171] In clinical trials, upadacitinib decreased the activity of pro-inflammatory interleukins, transiently increased the levels of lymphocytes, and insignificantly decreased the levels of immunoglobulins from the baseline.[L10896]
Pharmacokinetics
How the body processes this drug — absorption, distribution, metabolism, and elimination
Absorption
Upadacitinib displays a dose-proportional pharmacokinetic profile over the therapeutic dose range. Following oral administration, the median time to reach Cmax (Tmax) ranges from 2 to 4 hours. The steady-state plasma concentrations of upadacitinib are reached within 4 days following multiple once-daily administrations, with minimal accumulation.
[L10896]
Food intake has no clinically relevant effect on the AUC, Cmax, and Cmin of upadacitinib from the extended-release formulation.
[A189162]
[L10896]
Food intake has no clinically relevant effect on the AUC, Cmax, and Cmin of upadacitinib from the extended-release formulation.
[A189162]
Half-life
The mean terminal elimination half-life of upadacitinib ranged from 8 to 14 hours following administration of the extended-release formulation.
[L10896][L10905]
In clinical trials, approximately 90% of upadacitinib in the systemic circulation was eliminated within 24 hours of dosing.
[L10896]
[L10896][L10905]
In clinical trials, approximately 90% of upadacitinib in the systemic circulation was eliminated within 24 hours of dosing.
[L10896]
Protein binding
Upadacitinib is 52% bound to human plasma proteins.
[L10896]
[L10896]
Volume of distribution
The volume of distribution of upadacitinib in a patient with rheumatoid arthritis and a body weight of 74 kg is estimated to be 224 L following oral administration of an extended-release formula.
[L10905]
In a pharmacokinetic study consisting of healthy volunteers receiving the extended-release formulation, the steady-state volume of distribution was 294 L.
[A184043]
Upadacitinib partitions similarly between plasma and blood cellular components with a blood to plasma ratio of 1.0.
[L10896]
[L10905]
In a pharmacokinetic study consisting of healthy volunteers receiving the extended-release formulation, the steady-state volume of distribution was 294 L.
[A184043]
Upadacitinib partitions similarly between plasma and blood cellular components with a blood to plasma ratio of 1.0.
[L10896]
Metabolism
Upadacitinib predominantly undergoes CYP3A4-mediated metabolism;[L10896] however, upadacitinib is a nonsensitive substrate of CYP3A4.
[A189162]
It is also metabolized by CYP2D6 to a lesser extent.
[L10896]
In a human radio-labelled study, about 79% of the total plasma radioactivity accounted for the parent drug, and about 13% of the total plasma radioactivity accounted for the main metabolite produced from mono-oxidation, followed by glucuronidation.
[L10896]
There are no known active metabolites of upadacitinib.
[L10905]
[A189162]
It is also metabolized by CYP2D6 to a lesser extent.
[L10896]
In a human radio-labelled study, about 79% of the total plasma radioactivity accounted for the parent drug, and about 13% of the total plasma radioactivity accounted for the main metabolite produced from mono-oxidation, followed by glucuronidation.
[L10896]
There are no known active metabolites of upadacitinib.
[L10905]
Route of elimination
Following administration of a single radio-labelled dose from the immediate-release formulation, approximately 53% of the total dose was excreted in the feces where 38% of the excreted dose was an unchanged parent drug. About 43% of the total dose was excreted in the urine, where 24% of that dose was in the unchanged parent drug form.
[L10905]
Approximately 34% of the total dose of upadacitinib dose was excreted as metabolites.
[L10896]
[L10905]
Approximately 34% of the total dose of upadacitinib dose was excreted as metabolites.
[L10896]
Clearance
The apparent oral clearance of upadacitinib in healthy volunteers receiving the extended-release formulation was 53.7 L/h.
[A184043]
[A184043]
Drug targets(1)
Proteins and enzymes this drug interacts with in the body
Tyrosine-protein kinase JAK1
JAK1
inhibitor
Specific functionATP binding
Cellular location
Endomembrane system
General function & pharmacology
Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway .
PMID:16239216 PMID:28111307 PMID:32750333 PMID:7615558 PMID:8232552
Kinase partner for the interleukin (IL)-2 receptor PMID:11909529 as well as interleukin (IL)-10 receptor .
PMID:12133952
Kinase partner for the type I interferon receptor IFNAR2 .
PMID:16239216 PMID:28111307 PMID:32750333 PMID:7615558 PMID:8232552
In response to interferon-binding to IFNAR1-IFNAR2 heterodimer, phosphorylates and activates its binding partner IFNAR2, creating docking sites for STAT proteins .
PMID:7759950
Directly phosphorylates STAT proteins but also activates STAT signaling through the transactivation of other JAK kinases associated with signaling receptors PMID:16239216 PMID:32750333 PMID:8232552
PMID:16239216 PMID:28111307 PMID:32750333 PMID:7615558 PMID:8232552
Kinase partner for the interleukin (IL)-2 receptor PMID:11909529 as well as interleukin (IL)-10 receptor .
PMID:12133952
Kinase partner for the type I interferon receptor IFNAR2 .
PMID:16239216 PMID:28111307 PMID:32750333 PMID:7615558 PMID:8232552
In response to interferon-binding to IFNAR1-IFNAR2 heterodimer, phosphorylates and activates its binding partner IFNAR2, creating docking sites for STAT proteins .
PMID:7759950
Directly phosphorylates STAT proteins but also activates STAT signaling through the transactivation of other JAK kinases associated with signaling receptors PMID:16239216 PMID:32750333 PMID:8232552
Metabolizing enzymes(2)
Enzymes involved in drug metabolism — important for understanding drug interactions
Enzyme activity key
substrate
inhibitor
inducer
CYP3A4Cytochrome P450 3A4
substrate
CYP2D6Cytochrome P450 2D6
substrate
Transporters(3)
Proteins that transport this drug across cell membranes
ATP-dependent translocase ABCB1
ABCB1
substrate
inhibitor
Specific functionABC-type xenobiotic transporter activity
Cellular location
Cell membrane
General function & pharmacology
Translocates drugs and phospholipids across the membrane .
PMID:2897240 PMID:35970996 PMID:8898203 PMID:9038218 PMID:35507548
Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins .
PMID:8898203
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells PMID:2897240 PMID:35970996 PMID:9038218
PMID:2897240 PMID:35970996 PMID:8898203 PMID:9038218 PMID:35507548
Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins .
PMID:8898203
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells PMID:2897240 PMID:35970996 PMID:9038218
Broad substrate specificity ATP-binding cassette transporter ABCG2
ABCG2
substrate
inhibitor
Specific functionABC-type xenobiotic transporter activity
Cellular location
Cell membrane
General function & pharmacology
Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells .
PMID:11306452 PMID:12958161 PMID:19506252 PMID:20705604 PMID:28554189 PMID:30405239 PMID:31003562
Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme .
PMID:20705604 PMID:23189181
Also mediates the efflux of sphingosine-1-P from cells .
PMID:20110355
Acts as a urate exporter functioning in both renal and extrarenal urate excretion .
PMID:19506252 PMID:20368174 PMID:22132962 PMID:31003562 PMID:36749388
In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates .
PMID:12682043 PMID:28554189 PMID:30405239
Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity).
Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux .
PMID:11306452 PMID:12477054 PMID:15670731 PMID:18056989 PMID:31254042
In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity).
In inflammatory macrophages, exports itaconate from the cytosol to the extracellular compartment and limits the activation of TFEB-dependent lysosome biogenesis involved in antibacterial innate immune response
PMID:11306452 PMID:12958161 PMID:19506252 PMID:20705604 PMID:28554189 PMID:30405239 PMID:31003562
Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme .
PMID:20705604 PMID:23189181
Also mediates the efflux of sphingosine-1-P from cells .
PMID:20110355
Acts as a urate exporter functioning in both renal and extrarenal urate excretion .
PMID:19506252 PMID:20368174 PMID:22132962 PMID:31003562 PMID:36749388
In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates .
PMID:12682043 PMID:28554189 PMID:30405239
Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity).
Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux .
PMID:11306452 PMID:12477054 PMID:15670731 PMID:18056989 PMID:31254042
In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity).
In inflammatory macrophages, exports itaconate from the cytosol to the extracellular compartment and limits the activation of TFEB-dependent lysosome biogenesis involved in antibacterial innate immune response
Solute carrier organic anion transporter family member 1B1
SLCO1B1
inhibitor
Specific functionbile acid transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Mediates the Na(+)-independent uptake of organic anions .
PMID:10358072 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) .
PMID:10358072 PMID:10601278 PMID:10873595 PMID:11159893 PMID:12196548 PMID:12568656 PMID:15159445 PMID:15970799 PMID:16627748 PMID:17412826 PMID:19129463 PMID:26979622
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Involved in the clearance of endogenous and exogenous substrates from the liver .
PMID:10358072 PMID:10601278
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:10601278 PMID:15159445 PMID:15970799
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver .
PMID:16624871 PMID:16627748
Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions PMID:19129463
PMID:10358072 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) .
PMID:10358072 PMID:10601278 PMID:10873595 PMID:11159893 PMID:12196548 PMID:12568656 PMID:15159445 PMID:15970799 PMID:16627748 PMID:17412826 PMID:19129463 PMID:26979622
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Involved in the clearance of endogenous and exogenous substrates from the liver .
PMID:10358072 PMID:10601278
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:10601278 PMID:15159445 PMID:15970799
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver .
PMID:16624871 PMID:16627748
Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions PMID:19129463
Scientific references(8)
Klunder B., Mittapalli R.K., Mohamed M.F., Friedel A., Noertersheuser P., Othman A.A.
Population Pharmacokinetics of Upadacitinib Using the Immediate-Release and Extended-Release Formulations in Healthy Subjects and Subjects with Rheumatoid Arthritis: Analyses of Phase I-III Clinical Trials.
Clinical Pharmacokinetics
2019 Aug58(8):1045-1058. doi: 10.1007/s40262-019-00739-3
Parmentier J.M., Voss J., Graff C., Schwartz A., Argiriadi M., Friedman M., Camp H.S., Padley R.J., George J.S., Hyland D., Rosebraugh M., Wishart N., Olson L., Long A.J.
In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494).
BMC Rheumatol
2018 Aug 282:23. doi: 10.1186/s41927-018-0031-x. eCollection 2018
Mohamed M.F., Zeng J., Marroum P.J., Song I.H., Othman A.A.
Pharmacokinetics of Upadacitinib With the Clinical Regimens of the Extended-Release Formulation Utilized in Rheumatoid Arthritis Phase 3 Trials.
Clinical Pharmacology Drug Development
2019 Feb8(2):208-216. doi: 10.1002/cpdd.462. Epub 2018 Apr 24
Biggioggero M., Becciolini A., Crotti C., Agape E., Favalli E.G.
Upadacitinib and filgotinib: the role of JAK1 selective inhibition in the treatment of rheumatoid arthritis.
Drugs Context
2019 Oct 248:212595. doi: 10.7573/dic.212595. eCollection 2019
Schwartz D.M., Kanno Y., Villarino A., Ward M., Gadina M., O'Shea J.J.
JAK inhibition as a therapeutic strategy for immune and inflammatory diseases.
Nature Reviews Drug Discovery
2017 Dec 2817(1):78. doi: 10.1038/nrd.2017.267
Rivellese F., Lobasso A., Barbieri L., Liccardo B., de Paulis A., Rossi F.W.
Novel Therapeutic Approaches in Rheumatoid Arthritis: Role of Janus Kinases Inhibitors.
Curr Medicine Chemistry
201926(16):2823-2843. doi: 10.2174/0929867325666180209145243
Guschin D., Rogers N., Briscoe J., Witthuhn B., Watling D., Horn F., Pellegrini S., Yasukawa K., Heinrich P., Stark G.R., et al.
A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction pathway in response to interleukin-6..
The EMBO Journal
199514(7):1421-1429. doi: 10.1002/j.1460-2075.1995.tb07128.x
Choy E.H.
Clinical significance of Janus Kinase inhibitor selectivity.
Rheumatology (Oxford)
2019 Jun 158(6):953-962. doi: 10.1093/rheumatology/key339
ATC classification(1 code)
ATC L04AF03
Affected organisms(1)
Humans and other mammals
International brands(1)
Salt forms(2)
Upadacitinib hemihydrate(DBSALT002885)
Upadacitinib tartrate(DBSALT002886)
Experimental properties(2)
Commercial products(18)
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Show
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Linked compound data from DrugBank Open Data (CC BY-NC 4.0)
Upadacitinib
Additional database identifiers
Drugs Product Database (DPD)
23404
ChemSpider
44210449
BindingDB
50503287
HUGO Gene Nomenclature Committee (HGNC)
HGNC:6190
GeneCards
JAK1
Guide to Pharmacology
2047
UniProt Accession
JAK1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2637
GenAtlas
CYP3A4
GeneCards
CYP3A4
GenBank Gene Database
M18907
Guide to Pharmacology
1337
UniProt Accession
CP3A4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2625
GenAtlas
CYP2D6
GeneCards
CYP2D6
GenBank Gene Database
M20403
GenBank Protein Database
181350
Guide to Pharmacology
1329
UniProt Accession
CP2D6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:40
GenAtlas
ABCB1
GeneCards
ABCB1
GenBank Gene Database
M14758
GenBank Protein Database
307180
Guide to Pharmacology
768
UniProt Accession
MDR1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:74
GenAtlas
ABCG2
GeneCards
ABCG2
GenBank Gene Database
AF103796
GenBank Protein Database
4185796
Guide to Pharmacology
792
UniProt Accession
ABCG2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10959
GenAtlas
SLCO1B1
GeneCards
SLCO1B1
GenBank Gene Database
AF060500
GenBank Protein Database
5051630
Guide to Pharmacology
1220
UniProt Accession
SO1B1_HUMAN
Patent information
44 active patents
11607411
United States
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11564922
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9963459
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10519164
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Approved 31 Dec 2019 · Expires 17 Oct 2036
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Source: DrugBank · CC BY-NC 4.0. Patent data sourced from national patent offices. Expiry dates may not reflect extensions, regulatory exclusivity periods, or legal challenges.
DrugBank citations
If you use DrugBank data in your research, please cite the following publications:
Knox C., Wilson M., Klinger C.M., et al
DrugBank 6.
0: the DrugBank Knowledgebase for 2024
Nucleic Acids Res. 2024 Jan 552(D1):D1265-D1275
Wishart D.S., Feunang Y.D., Guo A.C., et al
DrugBank 5.
0: a major update to the DrugBank database for 2018
Nucleic Acids Res. 2017 Nov 846(D1):D1074-D1082
Show earlier publications
Law V., Knox C., Djoumbou Y., et al
DrugBank 4.
0: shedding new light on drug metabolism
Nucleic Acids Res. 2014 Jan 142(1):D1091-7
Knox C., Law V., Jewison T., et al
DrugBank 3.
0: a comprehensive resource for 'omics' research on drugs
Nucleic Acids Res. 2011 Jan39(Database issue):D1035-41
Wishart D.S., Knox C., Guo A.C., et al
DrugBank: a knowledgebase for drugs, drug actions and drug targets.
Nucleic Acids Research
2008 Jan36(Database issue):D901-6
Wishart D.S., Knox C., Guo A.C., et al
DrugBank: a comprehensive resource for in silico drug discovery and exploration.
Nucleic Acids Research
2006 Jan 134(Database issue):D668-72
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Updated 26 days ago(8 Mar 2026)