Version July 2025
Patients treated with upadacitinib are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt upadacitinib until the infection is controlled. Reported infections include:
Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients should be tested for latent tuberculosis before upadacitinib use and during therapy. Treatment for latent infection should be considered prior to upadacitinib use.
Invasive fungal infections, including cryptococcosis and pneumocystosis.
Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens.
The risks and benefits of treatment with upadacitinib should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with upadacitinib, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy
In a large, randomized, postmarketing safety study in rheumatoid arthritis (RA) patients ≥50 years of age with ≥1 cardiovascular risk factor comparing another Janus kinase (JAK) inhibitor to tumor necrosis factor (TNF) blockers, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor.
Lymphoma and other malignancies have been observed in patients treated with upadacitinib. In RA patients treated with another JAK inhibitor, a higher rate of malignancies (excluding nonmelanoma skin cancer) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk.
In RA patients ≥50 years of age with ≥1 cardiovascular risk factor treated with another JAK inhibitor, a higher rate of major adverse cardiovascular events (defined as cardiovascular death, myocardial infarction [MI], and stroke) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue upadacitinib in patients that have experienced an MI or stroke.
Thromboses, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis, have occurred in patients treated for inflammatory conditions with JAK inhibitors, including upadacitinib. Many of these adverse events were serious and some resulted in death. In RA patients ≥50 years of age with ≥1 cardiovascular risk factor treated with another JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid upadacitinib in patients at risk. Patients with symptoms of thrombosis should discontinue upadacitinib and be promptly evaluated.
Note: Do not use in combination with biologic disease-modifying antirheumatic drugs (DMARDs) or potent immunosuppressants (eg, azathioprine, cyclosporine); do not initiate in patients with an absolute lymphocyte count <500/mm3, ANC <1,000/mm3, or Hb <8 g/dL.
Ankylosing spondylitis: Oral: 15 mg once daily.
Atopic dermatitis, refractory, moderate to severe: Note: Reserve for patients who had an inadequate response or intolerance to other systemic drug products, including biologics, or when use of those therapies is inadvisable.
Oral: 15 mg once daily; may increase to 30 mg once daily if inadequate response. Discontinue if an adequate response is not achieved with the 30 mg dose; use the lowest effective dose needed to maintain response.
Crohn disease: Oral: Induction: 45 mg once daily for 12 weeks; maintenance: 15 mg once daily; may increase to 30 mg once daily in patients with refractory, severe, or extensive disease. Discontinue if an adequate response is not achieved with the 30 mg dose; use the lowest effective dose needed to maintain response.
Giant cell arteritis: Oral: Initial: 15 mg once daily in combination with a tapering course of corticosteroids. Maintenance: 15 mg once daily.
Nonradiographic axial spondyloarthritis: Oral: 15 mg once daily.
Psoriatic arthritis: Oral: 15 mg once daily.
Rheumatoid arthritis:
Note: For use as adjunctive therapy in patients who have not met treatment goals despite maximally tolerated methotrexate therapy; may also be used off-label as an alternative to methotrexate in DMARD–naive patients with moderate to high disease activity (Ref).
Oral: 15 mg once daily.
Ulcerative colitis: Oral: Induction: 45 mg once daily for 8 weeks; maintenance: 15 mg once daily; may increase to 30 mg once daily in patients with refractory, severe, or extensive disease. Discontinue if an adequate response is not achieved with the 30 mg dose; use the lowest effective dose needed to maintain response.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Ankylosing spondylitis, giant cell arteritis, nonradiographic axial spondyloarthritis, psoriatic arthritis, rheumatoid arthritis:
Altered kidney function:
eGFR ≥15 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <15 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Atopic dermatitis:
Altered kidney function:
eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR 15 to <30 mL/minute/1.73 m2: 15 mg once daily.
eGFR <15 mL/minute/1.73 m2: Use is not recommended.
Crohn disease:
Altered kidney function:
eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR 15 to <30 mL/minute/1.73 m2: Induction: 30 mg once daily for 12 weeks; maintenance: 15 mg once daily.
eGFR <15 mL/minute/1.73 m2: Use is not recommended.
Ulcerative colitis:
Altered kidney function:
eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR 15 to <30 mL/minute/1.73 m2: Induction: 30 mg once daily for 8 weeks; maintenance: 15 mg once daily.
eGFR <15 mL/minute/1.73 m2: Use is not recommended.
Hepatic impairment prior to treatment initiation:
Ankylosing spondylitis, atopic dermatitis, giant cell arteritis, nonradiographic axial spondyloarthritis, psoriatic arthritis, rheumatoid arthritis :
Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment is necessary.
Severe impairment (Child-Pugh class C): Use is not recommended.
Crohn disease:
Mild to moderate impairment (Child-Pugh class A or B): Induction: 30 mg once daily for 12 weeks; maintenance: 15 mg once daily.
Severe impairment (Child-Pugh class C): Use is not recommended.
Ulcerative colitis :
Mild to moderate impairment (Child-Pugh class A or B): Induction: 30 mg once daily for 8 weeks; maintenance: 15 mg once daily.
Severe impairment (Child-Pugh class C): Use is not recommended.
Hepatotoxicity during treatment: Treatment should be interrupted if drug-induced liver injury is suspected.
Hematologic:
Absolute lymphocyte count (ALC) <500/mm3: Interrupt therapy until ALC ≥500/mm3.
ANC <1,000/mm3: Interrupt therapy until ANC ≥1,000/mm3.
Hemoglobin <8 g/dL: Interrupt therapy until hemoglobin ≥8 g/dL.
Hypersensitivity reaction (severe): Discontinue therapy.
Infection (serious), including herpes zoster: Interrupt treatment until the infection is controlled.
Ankylosing spondylitis, Crohn disease, giant cell arteritis, nonradiographic axial spondyloarthritis, psoriatic arthritis, rheumatoid arthritis, ulcerative colitis : Refer to adult dosing.
Atopic dermatitis: ≥65 years of age: Oral: 15 mg once daily.
(For additional information see "Upadacitinib: Pediatric drug information")
Dosage guidance:
Safety: Do not initiate therapy in patients with an absolute lymphocyte count (ALC) <500/mm3, ANC <1,000/mm3, or hemoglobin <8 g/dL.
Dosage form information: Upadacitinib extended-release tablets (Rinvoq) and oral solution (Rinvoq LQ) are NOT substitutable on a mg:mg basis.
Atopic dermatitis, refractory, moderate to severe:
Children ≥12 years and Adolescents, weighing ≥40 kg: Extended-release tablet: Oral: 15 mg once daily; may increase to 30 mg once daily if inadequate response; in clinical trials, used as either monotherapy or in combination with topical corticosteroids (Ref).
Juvenile idiopathic arthritis, polyarticular:
Children ≥2 years and Adolescents:
10 to <20 kg: Oral solution: Oral: 3 mg twice daily.
20 to <30 kg: Oral solution: Oral: 4 mg twice daily.
≥30 kg:
Oral solution: Oral: 6 mg twice daily.
Extended-release tablet: Oral: 15 mg once daily.
Psoriatic arthritis, active:
Children ≥2 years and Adolescents <18 years:
10 to <20 kg: Oral solution: Oral: 3 mg twice daily.
20 to <30 kg: Oral solution: Oral: 4 mg twice daily.
≥30 kg:
Oral solution: Oral: 6 mg twice daily.
Extended-release tablet: Oral: 15 mg once daily.
Adolescents ≥18 years: Extended-release tablet: Oral: 15 mg once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: Children ≥2 years and Adolescents: Extended-release tablets, oral solution:
Hematologic:
ALC <500/mm3: Interrupt therapy until ALC ≥500/mm3.
ANC <1,000/mm3: Interrupt therapy until ANC ≥1,000/mm3.
Hemoglobin <8 g/dL: Interrupt therapy until hemoglobin ≥8 g/dL.
Hypersensitivity reaction (severe): Discontinue therapy.
Infection (serious), including herpes zoster: Interrupt treatment until the infection is controlled.
Atopic dermatitis:
Altered kidney function:
Children ≥12 years and Adolescents, weighing ≥40 kg: Extended-release tablets: Oral:
eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR 15 to <30 mL/minute/1.73 m2: 15 mg once daily.
eGFR <15 mL/minute/1.73 m2: Use not recommended.
Juvenile idiopathic or psoriatic arthritis:
Altered kidney function:
Children ≥2 years and Adolescents: Extended-release tablets, oral solution: Oral:
eGFR ≥15 mL/minute/1.73 m2: No dosage adjustment is necessary.
eGFR <15 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Atopic dermatitis, juvenile idiopathic arthritis, or psoriatic arthritis:
Children ≥2 years and Adolescents: Extended-release tablets, oral solution: Oral:
Baseline hepatic impairment:
Mild to moderate impairment: No dosage adjustment is necessary.
Severe impairment: Use is not recommended.
Hepatotoxicity during treatment: Treatment should be interrupted if drug-induced liver injury is suspected.
Gastrointestinal (GI) perforation is a rare but serious adverse event that may occur with upadacitinib and other Janus kinase (JAK) inhibitors (Ref). A meta-analysis of multiple clinical trials found no significant difference in the risk of GI perforation with upadacitinib compared to conventional synthetic disease-modifying antirheumatic drugs (Ref). A cohort study found no significant difference between groups in the rate of GI perforation between JAK inhibitors as a class and adalimumab, a tumor necrosis factor blocker (Ref).
Mechanism: Inhibits JAK signal transducers and activators of transcription pathway involved in IL-6 signaling and may be associated with decreased intestinal repair and increased risk of GI perforation (Ref).
Onset: Delayed; median ~8 months (IQR ~4 to 21 months) (Ref).
Risk factors:
• Age ≥65 years (Ref)
• Concurrent systemic glucocorticoids (>7.5 mg/day) (Ref)
• History of GI perforation (Ref)
• History of GI disease (eg, diverticulitis, peptic ulcer disease) (Ref)
• History of hypertension (Ref)
Studies pooling data from clinical trials have shown increased liver enzymes and hepatic events with upadacitinib compared to placebo or active comparators (Ref). However, a meta-analysis of multiple clinical trials found no significant difference in the risk of serious hepatic events with upadacitinib compared to conventional synthetic disease-modifying antirheumatic drugs (Ref). Most increased serum alanine aminotransferase, increased serum aspartate aminotransferase, or increased creatinine phosphokinase in blood specimen were modest, asymptomatic, and transient (Ref).
Mechanism: Dose-related; not clearly established. In vitro data suggest Janus kinase inhibitor-associated increases in creatinine phosphokinase may represent restoration of myoblast differentiation (Ref).
Onset: Varied; may occur at any time but usually transient (Ref).
Risk factors:
• Higher dose (Ref)
Patients treated with upadacitinib are at increased risk for developing serious infections that may lead to hospitalization or death, including bacterial infection, viral infection (including reactivation of HBV and herpes zoster infection), fungal infection (including cryptococcosis and infection due to an organism in genus Pneumocystis), and other opportunistic infections. The most common serious infections reported included pneumonia and cellulitis. Other infections reported include urinary tract infections and nasopharyngitis (Ref).
Mechanism: Dose-related; related to pharmacologic action; immunosuppressive effects predispose to infection; Janus kinase signal transducers and activators of transcription pathway have several key functions in inflammatory cytokines and immune response (Ref).
Onset: Varied (Ref).
Risk factors:
• Higher dose (Ref)
• Concurrent non-methotrexate conventional synthetic disease-modifying antirheumatic drugs (Ref)
• Smoking (Ref)
• Age ≥65 years (Ref)
• Asian patients (herpes zoster) (Ref)
Studies pooling data from clinical trials have shown no major increase in cardiovascular events with upadacitinib compared to placebo or active comparators (Ref). More data are needed to determine if Janus kinase (JAK) inhibitors or the proatherogenic nature of inflammatory diseases increase the risk of major adverse cardiovascular events (Ref).
Mechanism: Unknown; although, JAK inhibitors increase lipid levels by reducing cholesterol ester metabolism (Ref).
Onset: Varied; no clear time-to-event pattern. In rheumatoid arthritis patients, more events occurred in the first 12 months vs >12 months (Ref).
Risk factors:
• Age ≥65 years (Ref)
• Males (Ref)
• Previous cardiovascular event (Ref)
• History of hypertension (Ref)
• History of diabetes mellitus (Ref)
• History of tobacco/nicotine use (Ref)
• Concurrent glucocorticoid, antithrombotic, statin, and aspirin use (Ref)
Malignant lymphoma and other malignant neoplasms have been observed in patients treated with upadacitinib, including skin carcinoma and lung carcinoma (Ref).
Mechanism: Dose-related; related to pharmacologic action; immunosuppressive effects predispose to malignancies; Janus kinase signal transducers and activators of transcription pathway have several key functions in inflammatory cytokines and immune response (Ref).
Onset: Varied; most malignancies were diagnosed within 3 months after the first dose (Ref).
Risk factors:
• Higher dose (Ref)
• Age ≥65 years (Ref)
Thrombosis, including deep vein thrombosis, pulmonary embolism, and arterial thrombosis, has occurred in patients treated with Janus kinase (JAK) inhibitors in general when used to treat inflammatory conditions. Studies pooling data from clinical trials have shown no major increase in thrombotic events with upadacitinib compared to placebo or active comparators (Ref).
Mechanism: Unknown; may be related to JAK inhibition specificity, resulting in an imbalance between pro- and anti-thrombotic pathway activity (Ref).
Onset: Varied; no clear time-to-event pattern. Event rates in the first 12 months were similar to rates >12 months (Ref).
Risk factors:
• Age ≥65 years (Ref)
• Males (Ref)
• Obesity (Ref)
• History of hypertension or cardiovascular disease (Ref)
• History of venous thromboembolism (Ref)
• History of tobacco/nicotine use (Ref)
• Concurrent antithrombotic, statin, and aspirin use (Ref)
Tuberculosis (TB), pulmonary or extrapulmonary, has been reported (Ref). In a meta-analysis of multiple trials with various Janus kinase (JAK) inhibitors and tumor necrosis factor blockers, no sign of increased risk for TB vs placebo was found, but power was limited (Ref).
Mechanism: Dose-related; related to pharmacologic action; immunosuppressive effects predispose to infection; JAK signal transducers and activators of transcription pathway have several key functions in inflammatory cytokines and immune response (Ref).
Risk factors:
• Residence in an area with high TB prevalence
• Known TB exposure or ongoing risk factors for TB exposure (eg, travel to areas with high TB prevalence)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults and adolescents.
>10%:
Dermatologic: Acne vulgaris (1% to 16%)
Respiratory: Upper respiratory tract infection (9% to 25%)
1% to 10%:
Dermatologic: Folliculitis (2% to 4%), skin carcinoma (0% to 1%; including non-melanoma) (table 1), skin rash (4% to 5%)
|
Drug (Upadacitinib) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Upadacitinib) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
<1% |
N/A |
15 mg and/or 30 mg once daily |
Extended-release tablets |
Atopic dermatitis |
1,805 |
902 |
Non-melanoma skin cancer |
|
1% |
0% |
30 mg once daily |
Extended-release tablets |
Ulcerative colitis |
251 |
245 |
Non-melanoma skin cancer |
|
0% |
0% |
15 mg once daily |
Extended-release tablets |
Ulcerative colitis |
250 |
245 |
Non-melanoma skin cancer |
Endocrine & metabolic: Hypercholesterolemia (2% to 4%), hyperlipidemia (2%), weight gain (2%)
Gastrointestinal: Abdominal pain (2% to 3%), gastroenteritis (3%), nausea (3% to 4%), oral candidiasis (<2%)
Hematologic & oncologic: Anemia (<1% to 7%) (table 2), leukopenia (1% to 2%), lymphocytopenia (2% to 3%) (table 3), neutropenia (1% to 6%) (table 4)
|
Drug (Upadacitinib) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Upadacitinib) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
<1% |
N/A |
15 mg and/or 30 mg once daily |
Extended-release tablets |
Atopic dermatitis |
1,805 |
902 |
|
7% |
6% |
45 mg once daily |
Extended-release tablets |
Crohn disease |
674 |
347 |
|
Drug (Upadacitinib) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Upadacitinib) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
3% |
2% |
15 mg once daily |
Extended-release tablets |
Ulcerative colitis |
250 |
245 |
|
3% |
1% |
45 mg once daily |
Extended-release tablets |
Ulcerative colitis |
719 |
378 |
|
2% |
2% |
30 mg once daily |
Extended-release tablets |
Ulcerative colitis |
251 |
245 |
|
Drug (Upadacitinib) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Upadacitinib) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
2% |
<1% |
30 mg once daily |
Extended-release tablets |
Atopic dermatitis |
906 |
902 |
|
1% |
<1% |
15 mg once daily |
Extended-release tablets |
Atopic dermatitis |
899 |
902 |
|
2% |
<1% |
45 mg once daily |
Extended-release tablets |
Crohn disease |
674 |
347 |
|
2% |
<1% |
30 mg once daily |
Extended-release tablets |
Crohn disease |
229 |
223 |
|
1% |
<1% |
15 mg once daily |
Extended-release tablets |
Crohn disease |
221 |
223 |
|
6% |
2% |
30 mg once daily |
Extended-release tablets |
Ulcerative colitis |
251 |
245 |
|
5% |
<1% |
45 mg once daily |
Extended-release tablets |
Ulcerative colitis |
719 |
378 |
|
3% |
2% |
15 mg once daily |
Extended-release tablets |
Ulcerative colitis |
250 |
245 |
Hepatic: Increased liver enzymes (2% to 6%; including cholestasis, drug-induced liver injury, increased gamma-glutamyl transferase, increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase, increased serum bilirubin) (table 5)
|
Drug (Upadacitinib) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Upadacitinib) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
3% |
<1% |
30 mg once daily |
Extended-release tablets |
Crohn disease |
229 |
223 |
|
2% |
<1% |
15 mg once daily |
Extended-release tablets |
Crohn disease |
221 |
223 |
|
6% |
1% |
15 mg once daily |
Extended-release tablets |
Ulcerative colitis |
250 |
245 |
|
4% |
1% |
30 mg once daily |
Extended-release tablets |
Ulcerative colitis |
251 |
245 |
|
3% |
2% |
45 mg once daily |
Extended-release tablets |
Ulcerative colitis |
719 |
378 |
Hypersensitivity: Hypersensitivity reaction (3%)
Infection: Herpes simplex infection (≤8%), herpes zoster infection (<1% to 6%) (table 6), influenza (2% to 3%)
|
Drug (Upadacitinib) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Upadacitinib) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
2% |
1% |
30 mg once daily |
Extended-release tablets |
Atopic dermatitis |
906 |
902 |
|
2% |
1% |
15 mg once daily |
Extended-release tablets |
Atopic dermatitis |
899 |
902 |
|
5% |
2% |
30 mg once daily |
Extended-release tablets |
Crohn disease |
229 |
223 |
|
3% |
2% |
15 mg once daily |
Extended-release tablets |
Crohn disease |
221 |
223 |
|
2% |
0% |
45 mg once daily |
Extended-release tablets |
Crohn disease |
674 |
347 |
|
1% |
0.8% |
15 mg once daily |
Extended-release tablets |
Psoriatic arthritis |
640 |
635 |
|
<1% |
N/A |
15 mg once daily |
Extended-release tablets |
Rheumatoid arthritis |
1,035 |
1,042 |
|
6% |
0% |
30 mg once daily |
Extended-release tablets |
Ulcerative colitis |
251 |
245 |
|
5% |
0% |
15 mg once daily |
Extended-release tablets |
Ulcerative colitis |
250 |
245 |
Nervous system: Fatigue (2% to 3%), headache (3% to 6%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (1% to 8%) (table 7), myalgia (2%)
|
Drug (Upadacitinib) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Upadacitinib) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
6% |
2% |
30 mg once daily |
Extended-release tablets |
Atopic dermatitis |
906 |
902 |
|
5% |
2% |
15 mg once daily |
Extended-release tablets |
Atopic dermatitis |
899 |
902 |
|
3% |
1% |
45 mg once daily |
Extended-release tablets |
Crohn disease |
674 |
347 |
|
3% |
1% |
30 mg once daily |
Extended-release tablets |
Crohn disease |
229 |
223 |
|
2% |
1% |
15 mg once daily |
Extended-release tablets |
Crohn disease |
221 |
223 |
|
1% |
0.3% |
15 mg once daily |
Extended-release tablets |
Rheumatoid arthritis |
1,035 |
1,042 |
|
8% |
2% |
30 mg once daily |
Extended-release tablets |
Ulcerative colitis |
251 |
245 |
|
6% |
2% |
15 mg once daily |
Extended-release tablets |
Ulcerative colitis |
250 |
245 |
|
5% |
1% |
45 mg once daily |
Extended-release tablets |
Ulcerative colitis |
719 |
378 |
Respiratory: Bronchitis (1% to 4%), cough (2% to 3%), flu-like symptoms (2%), pneumonia (<1% to 4%) (table 8)
|
Drug (Upadacitinib) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Upadacitinib) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
<1% |
N/A |
15 mg and/or 30 mg once daily |
Extended-release tablets |
Atopic dermatitis |
1,805 |
902 |
|
4% |
1% |
15 mg once daily |
Extended-release tablets |
Crohn disease |
221 |
223 |
|
<2% |
N/A |
45 mg once daily |
Extended-release tablets |
Crohn disease |
674 |
347 |
|
1% |
1% |
30 mg once daily |
Extended-release tablets |
Crohn disease |
229 |
223 |
|
<2% |
N/A |
45 mg once daily |
Extended-release tablets |
Ulcerative colitis |
719 |
378 |
Miscellaneous: Fever (1% to 7%)
<1%:
Gastrointestinal: Gastrointestinal perforation (table 9), oral herpes simplex infection
|
Drug (Upadacitinib) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Upadacitinib) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
0.1% |
0% |
45 mg once daily |
Extended-release tablets |
Crohn disease |
674 |
347 |
|
0% |
0% |
15 mg once daily |
Extended-release tablets |
Rheumatoid arthritis |
1,035 |
1,042 |
Ophthalmic: Retinal detachment
Frequency not defined:
Cardiovascular: Arterial thrombosis, thrombosis
Dermatologic: Cellulitis
Hypersensitivity: Anaphylaxis, angioedema
Infection: Reactivation of HBV
Postmarketing:
Cardiovascular: Acute myocardial infarction (Ref), deep vein thrombosis (Ref), pulmonary embolism (Ref), venous thrombosis (Ref)
Dermatologic: Eczema (herpeticum) (Ref), varicella-like rash (Kaposi varicelliform eruption) (Ref)
Endocrine & metabolic: Amenorrhea (Ref)
Gastrointestinal: Appendicitis (Ref), esophageal candidiasis (Ref), paralytic ileus (Ref)
Genitourinary: Urinary tract infection (Ref)
Hematologic & oncologic: Malignant lymphoma (Ref), malignant neoplasm (Ref)
Infection: Infection (including bacterial infection, cryptococcosis, fungal infection, opportunistic infection, serious infection, viral infection) (Ref)
Nervous system: Cerebrovascular accident (Ref)
Respiratory: Infection due to an organism in genus Pneumocystis (Ref), lung carcinoma (Ref), nasopharyngitis (Ref), tuberculosis (Ref)
Hypersensitivity to upadacitinib or any component of the formulation.
Concerns related to adverse effects:
• GI perforation: Use with caution in patients at increased risk for GI perforation (eg, history of diverticulitis, concomitant nonsteroidal anti-inflammatory drugs, corticosteroids); perforations have been reported in clinical trials. Promptly evaluate new-onset abdominal symptoms in patients taking upadacitinib.
• Hematologic toxicity: Hematologic toxicity, including lymphopenia, anemia, and neutropenia, may occur and is generally reversible and managed by treatment interruption. Do not initiate therapy in patients with an absolute lymphocyte count <500/mm3, ANC <1,000/mm3, or hemoglobin <8 g/dL. Monitor CBC at baseline and periodically thereafter.
• Hepatic effects: Liver enzyme elevation has been observed. Monitor LFTs at baseline and periodically thereafter; interrupt therapy if LFTs increased and drug-induced liver injury is suspected.
• Hypersensitivity reactions: Severe hypersensitivity, including anaphylaxis and angioedema, has been reported.
• Infections: Patients receiving upadacitinib are at increased risk for serious infections, which may result in hospitalization and/or fatality; rate of serious infections was increased in patients on higher doses. The most common serious infections reported included pneumonia and cellulitis. Reactivation of viral infections (eg, herpes zoster, hepatitis B) have been observed; the incidence of chronic viral hepatitis reactivation is unknown. If herpes zoster is reported, consider interrupting therapy until herpes zoster has resolved. Consultation with a hepatologist may be necessary if hepatitis B virus DNA is detected.
• Lipid abnormalities: Increased lipid parameters (eg, total, low-density lipoprotein [LDL], and high-density lipoprotein [HDL] cholesterol) have been observed. Mean LDL and HDL increased by ~15 mg/dL and ~8 mg/dL, respectively, 2 months after starting upadacitinib. Assess lipids 12 weeks after upadacitinib initiation and manage lipid abnormalities according to current clinical guidelines.
• Malignancy: Lymphoma and other malignancies have been reported in patients receiving upadacitinib. Consider risks versus benefits prior to use in patients with a known malignancy (other than successfully treated nonmelanoma skin cancers [NMSCs]) or when continuing upadacitinib in patients who develop a new malignancy. NMSCs have been reported.
• Medication residue in stool: Medication residue in stool or ostomy output has been reported in patients with anatomical conditions (eg, ileostomy, colostomy, intestinal resection) or functional conditions that slow GI transit times. Instruct patients to report medication residue in stool to a health care provider. Monitor patients for clinical response and consider alternative therapy if there is a lack of therapeutic response.
• Tuberculosis: Tuberculosis (TB) (pulmonary or extrapulmonary) has been reported in patients receiving upadacitinib. Use with caution in patients who have resided or traveled in regions where TB is endemic. Consider anti-TB therapy if an adequate course of treatment cannot be confirmed in patients with a history of TB infection or disease (latent or active TB) or for patients with risk factors despite negative skin test.
Special populations:
• Patients with rheumatic musculoskeletal disease undergoing hip or knee replacement surgery: Hold upadacitinib for at least 3 days prior to surgery to reduce infection risk; therapy can be restarted once surgical wound shows evidence of healing (eg, no swelling, erythema, or drainage), sutures/staples are removed, and no ongoing nonsurgical site infections (typically ~14 days to reduce infection risk) (ACR/AAHKS [Goodman 2022]).
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol and/or sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggest that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol and/or benzyl alcohol derivatives with caution in neonates. See manufacturer's labeling.
• Product interchangeability: Oral solution should not be substituted for the ER tablets; products are not bioequivalent and not interchangeable on a milligram-per-milligram basis. Oral solution is intended for pediatric use only.
Other warnings/precautions:
• Immunizations: Immunization status should be current before initiating therapy. Live vaccines should not be given concomitantly, or immediately prior to, upadacitinib; recommended interval between receipt of live vaccines and initiation of immunosuppressive agents such as upadacitinib should follow current vaccination clinical guidelines.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Oral:
Rinvoq LQ: 1 mg/mL (180 mL) [contains sodium benzoate]
Tablet Extended Release 24 Hour, Oral:
Rinvoq: 15 mg, 30 mg, 45 mg
No
Solution (Rinvoq LQ Oral)
1 mg/mL (per mL): $21.61
Tablet, 24-hour (Rinvoq Oral)
15 mg (per each): $270.11
30 mg (per each): $270.11
45 mg (per each): $540.22
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Extended Release 24 Hour, Oral:
Rinvoq: 15 mg, 30 mg, 45 mg
Oral: Administer with or without food. Swallow tablet whole; do not crush, split, or chew.
Oral: Administer with or without food.
Oral solution: Administer using provided press-in bottle adaptor and oral dosing syringe; must be administered within 1 hour after drawing up solution in syringe.
Extended-release tablet: Swallow tablet whole; do not crush, split, or chew.
This medication is not on the NIOSH (2024) list; however, it may meet the criteria for a hazardous drug. Upadacitinib may cause carcinogenicity and teratogenicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Rinvoq: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/211675s019lbl.pdf
Ankylosing spondylitis: Treatment of active ankylosing spondylitis in adults who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers.
Limitation of use: Use of upadacitinib in combination with other Janus-associated kinase inhibitors, biologic disease-modifying antirheumatic drugs, or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.
Atopic dermatitis: Treatment of refractory, moderate to severe atopic dermatitis in pediatric patients ≥12 years of age and adults who had an inadequate response or intolerance to other systemic drug products, including biologics, or when use of those therapies is inadvisable.
Limitation of use: Use of upadacitinib in combination with other Janus-associated kinase inhibitors, biologic immunomodulators, or with other immunosuppressants is not recommended.
Crohn disease: Treatment of moderate to severe Crohn disease in adults who have had an inadequate response or intolerance to one or more TNF blockers.
Limitation of use: Use of upadacitinib in combination with other Janus-associated kinase inhibitors, biologic therapies for Crohn disease, or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.
Giant cell arteritis: Treatment of giant cell arteritis in adults.
Limitation of use: Use of upadacitinib in combination with other Janus-associated kinase inhibitors, biologic disease-modifying antirheumatic drugs, or with potent immunosuppressants, such as azathioprine and cyclosporine, is not recommended.
Juvenile idiopathic arthritis: Treatment of active polyarticular juvenile idiopathic arthritis in patients ≥2 years of age who have had an inadequate response or intolerance to one or more TNF blockers.
Limitation of use: Use of upadacitinib in combination with other Janus-associated kinase inhibitors, biologic disease-modifying antirheumatic drugs, or with potent immunosuppressants, such as azathioprine and cyclosporine, is not recommended.
Nonradiographic axial spondyloarthritis: Treatment of active nonradiographic axial spondyloarthritis in adults with objective signs of inflammation who had an inadequate response or intolerance to TNF blockers.
Limitation of use: Use of upadacitinib in combination with other Janus-associated kinase inhibitors, biologic disease-modifying antirheumatic drugs, or with potent immunosuppressants, such as azathioprine and cyclosporine, is not recommended.
Psoriatic arthritis: Treatment of active psoriatic arthritis in adults and pediatric patients ≥2 years of age who have had an inadequate response or intolerance to one or more TNF blockers.
Limitation of use: Use of upadacitinib in combination with other Janus-associated kinase inhibitors, biologic disease-modifying antirheumatic drugs, or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.
Rheumatoid arthritis: Treatment of moderately to severely active rheumatoid arthritis in adults who have had an inadequate response or intolerance to one or more TNF blockers.
Limitation of use: Use of upadacitinib in combination with other Janus-associated kinase inhibitors, biologic disease-modifying antirheumatic drugs, or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.
Ulcerative colitis: Treatment of moderately to severely active ulcerative colitis in adults who have had an inadequate response or intolerance to 1 or more TNF blockers.
Limitation of use: Use of upadacitinib in combination with other Janus-associated kinase inhibitors, biological therapies for ulcerative colitis, or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.
Substrate of CYP2D6 (Minor), CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces BCRP, CYP3A4 (Weak), OATP1B1/1B3;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Anifrolumab: Biologic Disease-Modifying Antirheumatic Drugs may increase immunosuppressive effects of Anifrolumab. Risk X: Avoid
Atogepant: CYP3A4 Inducers (Weak) may decrease serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with CYP3A4 inducers. When used for treatment of chronic migraine, use of atogepant with CYP3A4 inducers should be avoided. Risk D: Consider Therapy Modification
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CloZAPine: CYP3A4 Inducers (Weak) may decrease serum concentration of CloZAPine. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Therapeutic Immunosuppressant Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
Corticosteroids (Systemic): May increase immunosuppressive effects of Upadacitinib. Management: Coadministration of upadacitinib with systemic corticosteroids at doses equivalent to greater than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks is not recommended. Risk D: Consider Therapy Modification
COVID-19 Vaccines: Upadacitinib may decrease therapeutic effects of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding baricitinib, tofactinib, or upadacitinib for 1 to 2 weeks after vaccine administration as permitted by the underlying disease. Risk D: Consider Therapy Modification
CYP2D6 Substrates (Narrow Therapeutic Index/Sensitive): Upadacitinib may increase serum concentration of CYP2D6 Substrates (Narrow Therapeutic Index/Sensitive). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Upadacitinib. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Upadacitinib. Risk X: Avoid
CYP3A4 Inhibitors (Strong): May increase serum concentration of Upadacitinib. Management: Upadacitinib dose adjustments are often needed when combined with strong CYP3A4 inhibitors. Specific adjustments vary based on upadacitinib indication. See full interact monograph for details. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Grapefruit Juice: May increase serum concentration of Upadacitinib. Risk X: Avoid
Immunosuppressants (Cytotoxic Chemotherapy): May increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Immunosuppressants (Miscellaneous Oncologic Agents): May increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Immunosuppressants (Therapeutic Immunosuppressant Agents): May increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate 2 to 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Methotrexate: May increase immunosuppressive effects of Upadacitinib. Management: Concomitant use of upadacitinib with high-dose or IV methotrexate is not recommended. Use with antirheumatic doses of methotrexate is permitted, and if combined, patients should be monitored for infection. Risk D: Consider Therapy Modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
NiMODipine: CYP3A4 Inducers (Weak) may decrease serum concentration of NiMODipine. Risk C: Monitor
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Pimecrolimus. Risk X: Avoid
Pneumococcal Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Rabies Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Selpercatinib: CYP3A4 Inducers (Weak) may decrease serum concentration of Selpercatinib. Risk C: Monitor
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ubrogepant: CYP3A4 Inducers (Weak) may decrease serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a weak CYP3A4 inducer. Risk D: Consider Therapy Modification
Vaccines (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zavegepant: OATP1B1/1B3 (SLCO1B1/1B3) Inducers may decrease serum concentration of Zavegepant. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Grapefruit increases exposure to upadacitinib. Management: Avoid grapefruit during therapy.
Verify pregnancy status prior to use in patients who could become pregnant. Patients who could become pregnant should use effective contraception during treatment and for 4 weeks following the last dose of upadacitinib.
Agents other than upadacitinib are preferred to treat inflammatory bowel disease in patients planning to become pregnant. Disease management should be optimized prior to pregnancy (Ref).
Based on data from animal reproduction studies, in utero exposure to upadacitinib may cause fetal harm.
Outcome data following maternal use of upadacitinib during pregnancy are available (Ref).
Agents other than upadacitinib are preferred to treat inflammatory bowel disease in pregnant patients (Ref). Janus kinase inhibitors, such as upadactinib, are not recommended for the treatment of atopic dermatitis during pregnancy (Ref).
Data collection to monitor pregnancy and infant outcomes following exposure to upadacitinib is ongoing. Health care providers should report patients exposed to upadacitinib during pregnancy by calling 1-800-633-9110.
It is not known if upadacitinib is present in breast milk.
Janus kinase inhibitors, such as upadacitinib, are not recommended for the treatment of atopic dermatitis in breastfeeding patients (Ref). Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 6 days following the last dose of upadacitinib.
Avoid grapefruit juice.
Lymphocyte count, neutrophil count, hemoglobin, and LFTs (baseline and periodically thereafter); lipids (12 weeks after therapy initiation and periodically thereafter); viral hepatitis (prior to initiating therapy and periodically thereafter); tuberculosis (TB) infection and disease (latent and active TB) screen at baseline; verify pregnancy status (prior to initiating therapy); signs/symptoms of infection (including TB) during and after therapy; skin examinations (periodically, in patients at increased risk for skin cancer); symptoms of thrombosis.
Upadacitinib inhibits Janus kinase (JAK) enzymes, which are intracellular enzymes involved in stimulating hematopoiesis and immune cell function through a signaling pathway. JAKs activate signal transducers and activators of transcription (STATs), which regulate gene expression and intracellular activity. The inhibition of JAKs prevents the activation of STATs.
Protein binding: 52% (plasma proteins)
Metabolism: Hepatic, primarily via CYP3A4
Half-life elimination: Terminal: 8 to 14 hours
Time to peak: ER tablets: 2 to 4 hours; oral solution: 1 hour.
Excretion: Urine (24% as unchanged drug); feces (38% as unchanged drug)
Altered kidney function: AUCinf 18%, 33%, and 44% higher in mild, moderate, and severe renal impairment, respectively, compared to subjects with normal renal function. Cmax similar in subjects with normal and impaired renal function.
Hepatic function impairment: AUCinf 28% and 24% higher in mild and moderate hepatic impairment, respectively, compared to subjects with normal hepatic function. Cmax unchanged in mild hepatic impairment and 43% higher in moderate hepatic impairment compared to subjects with normal hepatic function. Not studied in patients with severe hepatic impairment (Child-Pugh C).
