Dosing & Uses
Dosage Forms & Strengths
tablet, extended-release
- 15mg
Rheumatoid Arthritis
Indicated for moderately to severely active rheumatoid arthritis (RA) in adults who have had an inadequate response or intolerance to ≥1 tumor necrosis factor (TNF) blockers
15 mg PO qDay
Psoriatic Arthritis
Indicated for active psoriatic arthritis (PsA) in adults who have had an inadequate response or intolerance to ≥1 TNF blockers
15 mg PO qDay
Atopic Dermatitis
Indicated for refractory moderate-to-severe atopic dermatitis (AD) in adults whose disease is not adequately with other systemic therapies or if those therapies are inadvisable
<65 years
- 15 mg PO qDay initially; consider increasing to 30 mg qDay if an adequate response is not achieved
- Discontinue if 30-mg dose if adequate response not achieved
- Use lowest effective dose needed to maintain response
Dosage Modifications
Coadministration of strong CYP3A4 inhibitors: 15 mg PO qDay
Infection
- If serious infection (eg, serious opportunistic infections) develops, interrupt treatment until infection is controlled
Dose interruption for laboratory abnormalities
- Absolute neutrophil count (ANC) <1000 cells/mm3: Interrupt; may restart once ANC >1000 cells/mm3
- Absolute lymphocyte count (ALC) <500 cells/mm3: Interrupt; may restart once ALC >500 cells/mm3
- Hemoglobin (Hb) <8 g/dL: Interrupt; may restart once Hb >8 g/dL
- Hepatic transaminases: Interrupt if drug-induced liver injury suspected
Renal impairment
-
RA and PsA
- Mild, moderate, or severe: No dose adjustment necessary
- ESRD: Not studied
-
AD
- Mild or moderate (CrCl >30 mL/min): No dose adjustment necessary
- Severe (CrCl <30 mL/min): 15 mg PO qDay
- ESRD: Not studied
Hepatic impairment
-
RA, PsA, AD
- Mild or moderate (Child-Pugh A or B): No dose adjustment required
- Severe (Child-Pugh C): Not recommended
Dosing Considerations
ALC <500 cells/mm3, ANC <1000 cell/mm3, or Hb <8 g/dL: Do not initiate
-
Before initiating
- Test for tuberculosis (TB) before initiating; initiate antitubercular treatment for previously untreated latent TB or active TB before initiating treatment
- Verify pregnancy status in females of reproductive potential before initiating
- Screen viral hepatitis in accordance with clinical guidelines
- Update immunizations according to current immunization guidelines
-
Limitations of use
- RA or PsA: Use in combination with other JAK inhibitors, biologic disease-modifying antirheumatic drugs (DMARDs), or with potent immunosuppressants (eg, azathioprine, cyclosporine), is not recommended
- AD: Not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or with other immunosuppressants
Dosage Forms & Strengths
tablet, extended-release
- 15mg
Atopic Dermatitis
Indicated for refractory moderate-to-severe atopic dermatitis (AD) in adults and pediatric patients aged ≥12 years whose disease is not adequately with other systemic therapies or if those therapies are inadvisable
≥12 years and >40 kg
- 15 mg PO qDay initially; consider increasing to 30 mg qDay if an adequate response is not achieved
- Discontinue if 30-mg dose if adequate response not achieved
- Use lowest effective dose needed to maintain response
Dosage Modifications
Coadministration of strong CYP3A4 inhibitors: 15 mg PO qDay
Infection
- If serious infection (eg, serious opportunistic infections) develops, interrupt treatment until infection is controlled
Renal impairment
-
RA and PsA
- Mild, moderate, or severe: No dose adjustment necessary
- ESRD: Not studied
-
AD
- Mild or moderate (CrCl >30 mL/min): No dose adjustment necessary
- Severe (CrCl <30 mL/min): 15 mg PO qDay
- ESRD: Not studied
Hepatic impairment
-
RA, PsA, AD
- Mild or moderate (Child-Pugh A or B): No dose adjustment required
- Severe (Child-Pugh C): Not recommended
Ulcerative Colitis (Orphan)
Orphan designation for treatment of pediatric ulcerative colitis
Sponsor
- AbbVie; 1 North Waukegan Road; North Chicago, Illinois 60044
Dosing Considerations
-
Before initiating
- Test for tuberculosis (TB) before initiating; initiate antitubercular treatment for previously untreated latent TB or active TB before initiating treatment
- Verify pregnancy status in females of reproductive potential before initiating
- Screen viral hepatitis in accordance with clinical guidelines
- Update immunizations according to current immunization guidelines
-
Limitations of use
- RA or PsA: Use in combination with other JAK inhibitors, biologic disease-modifying antirheumatic drugs (DMARDs), or with potent immunosuppressants (eg, azathioprine, cyclosporine), is not recommended
- AD: Not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or with other immunosuppressants
Atopic Dermatitis
Indicated for refractory moderate-to-severe atopic dermatitis (AD) in adults whose disease is not adequately with other systemic therapies or if those therapies are inadvisable
≥65 years: 15 mg PO qDay
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (46)
- abametapir
abametapir will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.
- adenovirus types 4 and 7 live, oral
upadacitinib decreases effects of adenovirus types 4 and 7 live, oral by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- amobarbital
amobarbital will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- apalutamide
apalutamide will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- BCG vaccine live
upadacitinib decreases effects of BCG vaccine live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- bosentan
bosentan will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- butabarbital
butabarbital will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- butalbital
butalbital will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- carbamazepine
carbamazepine will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- cholera vaccine
upadacitinib decreases effects of cholera vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- dabrafenib
dabrafenib will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- dengue vaccine
upadacitinib decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- efavirenz
efavirenz will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- enzalutamide
enzalutamide will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- etravirine
etravirine will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- fexinidazole
fexinidazole will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.
- fosphenytoin
fosphenytoin will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- influenza virus vaccine quadrivalent, intranasal
upadacitinib decreases effects of influenza virus vaccine quadrivalent, intranasal by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- ivosidenib
ivosidenib will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- lonafarnib
lonafarnib will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.
- lorlatinib
lorlatinib will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- lumacaftor/ivacaftor
lumacaftor/ivacaftor will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- measles (rubeola) vaccine
upadacitinib decreases effects of measles (rubeola) vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- measles mumps and rubella vaccine, live
upadacitinib decreases effects of measles mumps and rubella vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- measles, mumps, rubella and varicella vaccine, live
upadacitinib decreases effects of measles, mumps, rubella and varicella vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- mitotane
mitotane will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- nafcillin
nafcillin will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- pentobarbital
pentobarbital will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- phenobarbital
phenobarbital will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- phenytoin
phenytoin will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- primidone
primidone will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- rifabutin
rifabutin will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- rifampin
rifampin will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- rifapentine
rifapentine will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- rotavirus oral vaccine, live
upadacitinib decreases effects of rotavirus oral vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- rubella vaccine
upadacitinib decreases effects of rubella vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- secobarbital
secobarbital will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- smallpox (vaccinia) vaccine, live
upadacitinib decreases effects of smallpox (vaccinia) vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- St John's Wort
St John's Wort will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.
- tucatinib
tucatinib will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.
- typhoid polysaccharide vaccine
upadacitinib decreases effects of typhoid polysaccharide vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- typhoid vaccine live
upadacitinib decreases effects of typhoid vaccine live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- varicella virus vaccine live
upadacitinib decreases effects of varicella virus vaccine live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- voxelotor
voxelotor will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.
- yellow fever vaccine
upadacitinib decreases effects of yellow fever vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- zoster vaccine live
upadacitinib decreases effects of zoster vaccine live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
Monitor Closely (26)
- atazanavir
atazanavir will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.
- chloramphenicol
chloramphenicol will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.
- clarithromycin
clarithromycin will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.
- cobicistat
cobicistat will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.
- conivaptan
conivaptan will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.
- darunavir
darunavir will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.
- elagolix
elagolix decreases levels of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.
- idelalisib
idelalisib will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.
- indinavir
indinavir will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.
- isoniazid
isoniazid will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.
- istradefylline
istradefylline will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
- itraconazole
itraconazole will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.
- ketoconazole
ketoconazole will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.
- lopinavir
lopinavir will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.
- mifepristone
mifepristone will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.
- nefazodone
nefazodone will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.
- nelfinavir
nelfinavir will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.
- posaconazole
posaconazole will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.
- ribociclib
ribociclib will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ritonavir
ritonavir will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.
- rucaparib
rucaparib will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
- saquinavir
saquinavir will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.
- stiripentol
stiripentol will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.
- tazemetostat
tazemetostat will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tipranavir
tipranavir will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.
- voriconazole
voriconazole will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
Minor (0)
Adverse Effects
>10%
RA
- Upper respiratory tract infection (13.5%)
AD
- Upper respiratory tract infection (23-25%)
- Acne (10-16%)
1-10%
RA
- Nausea (3.5%)
- Neutropenia (1.1-2.4%)
- Lymphopenia (0.3-2.4%)
- Cough (2.2%)
- Elevated ALT (0.8-2.1%)
- Increased creatine phosphokinase (0.3-1.6%)
- Elevated AST (1-1.5%)
- Pyrexia (1.2%)
PsA
- Bronchitis (3.9%)
- Herpes simplex (1.4%)
- Acne (1.3%)
- Herpes zoster (1.1%)
AD
- Herpes simplex virus (4-8%)
- Headache (6%)
- Increased blood creatine phosphokinase (5-6%)
- Cough (3%)
- Hypersensitivity (2-3%)
- Folliculitis (2-3%)
- Nausea (3%)
- Abdominal pain (2-3%)
- Pyrexia (2%)
- Increased weight (2%)
- Herpes zoster (2%)
- Influenza (2%)
- Fatigue (1-2%)
- Neutropenia (1-2%)
- Myalgia (1-2%)
- Influenza like illness (1-2%)
<1%
RA
- Pneumonia
- Herpes zoster
- Herpes simplex (includes oral herpes)
- Oral candidiasis
- Anemia (<0.1%)
Frequency Not Defined
RA
- Tuberculosis
- Malignancies, excluding nonmelanoma skin cancer
- Venous thrombosis
- Elevated LDL
- Elevated HDL
Warnings
Black Box Warnings
Serious infection
- Increases risk for developing serious infections that may lead to hospitalization or death
- Most patients with severe infections were also taking concomitant immunosuppressants (eg, methotrexate, corticosteroids)
- If a serious infection develops, interrupt therapy until infection is controlled
- Carefully consider risks and benefits before initiating upadacitinib in patients with chronic or recurrent infection
- Closely monitor for signs and symptoms of infection during and after treatment, including possible development of TB in patients who tested negative for latent TB infection before initiating therapy
-
Reported infections include
- Active tuberculosis (TB), which may present with pulmonary or extrapulmonary disease; test for latent TB before use and during therapy; consider treating latent infection before upadacitinib use
- Invasive fungal infections, including cryptococcosis and pneumocystosis
- Bacterial, viral ( including herpes zoster), and other infections due to opportunistic pathogens
Mortality
- Patients with RA aged ≥50 years with at least 1 cardiovascular risk factor comparing another Janus kinase (JAK) inhibitor to TNF blockers, showed a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor
Malignancies
- Lymphoma and other malignancies reported
- Higher rate of malignancies (excluding non-melanoma skin cancer) observed
- Current or past smokers are at additional increased risk
Thrombosis
- Thrombosis, including deep venous thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis have occurred in patients treated with JAK inhibitors used to treat inflammatory conditions
- Many of these adverse events were serious and some resulted in death
- Consider risks and benefits prior to treating patients who may be at increased risk
- Avoid therapy in patients at risk
- Promptly evaluate and treat patients with symptoms of thrombosis
Major adverse cardiovascular events (MACE)
- In patients with RA ≥50 years with at least 1 cardiovascular risk factor treated with another JAK inhibitor, a higher rate of MACE (defined as cardiovascular death, myocardial infarction, and stroke), was observed
- Patients who are current or past smokers are at additional increased risk
- Discontinue therapy in patients that have experienced a myocardial infarction or stroke
Contraindications
Hypersensitivity to upadacitinib or any of its excipients
Cautions
Malignancies reported; consider risks and benefits of treatment before initiating in patients with known malignancy, other than previously treated nonmelanoma skin cancer; screen for malignancies during treatment according to guidelines
Thrombosis reported, including DVT, PE, and arterial thrombosis; avoid therapy in patients that may be at increased risk of thrombosis
Gastrointestinal perforation reported; unknown if JAK inhibition is implicated in these events; many patients were also receiving NSAIDs
Higher rate of major adverse cardiovascular events (MACE; defined as cardiovascular death, myocardial infarction, and stroke) reported with another JAK inhibitor Vs TNF blockers in RA patients
Patients with RA aged ≥50 years with at least 1 cardiovascular risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed
May cause neutropenia, lymphopenia, anemia, elevated lipids, or elevated liver enzymes; monitor for abnormal laboratory values and assess the need to interrupt dosing
Based on findings in animal studies, may cause fetal harm when administered to pregnant females
Serious and fatal infections
- Serious and fatal infections reported
- Most frequent infections reported included pneumonia and cellulitis
- Opportunistic infections reported included TB, multidermatomal herpes zoster, oral/esophageal candidiasis, and cryptococcosis
- Closely monitor for developing signs and symptoms of infection during and after treatment
- Interrupt therapy if a serious or opportunistic infection develops
- Initiate prompt and complete diagnostic testing appropriate for an immunocompromised patient if new infection develops; initiate appropriate antimicrobial therapy, closely monitor, and interrupt therapy if not responding to antimicrobial therapy; resume once infection controlled
- Screen patients for opportunistic infections (eg, TB) and treated according to guidelines
- Avoid use with an active, serious infection, including localized infections
-
Consider risks and benefits of treatment before initiating in the following patients
- With chronic or recurrent infection
- Who have been exposed to TB
- With history of serious or opportunistic infection
- Who have resided or traveled in areas of endemic tuberculosis or endemic mycoses
- With underlying conditions that may predispose them to infection
-
Viral reactivation
- Viral reactivation, including cases of herpes virus reactivation (eg, herpes zoster) and hepatitis B virus reactivation, were reported
- If herpes zoster develops, consider temporarily interrupting therapy until episode resolves
- Screen for viral hepatitis and monitor for reactivation in accordance with clinical guidelines before starting and during therapy
Increased risk of serious heart-related problems and cancer
- On September 1st, 2021, FDA is requiring revisions to warnings for upadacitinib to include information about the risks of serious heart-related events, cancer, blood clots, and death
- Revisions are based on results from completed trial show a higher occurrence of serious heart-related events and cancer in tofacitinib-treated group (both doses) compared to TNF inhibitor-treated group; results also showed an increased risk of blood clots and death with lower doses of tofacitinib
- Not studied in trials, so risks have not been adequately evaluated; however, owing to similar mechanisms of action, FDA considers upadacitinib may have similar risks
- A higher rate of all-cause mortality, including sudden cardiovascular death, was observed in patients treated with the JAK inhibitor compared with TNF blockers; consider benefits and risks for individual patient before initiating or continuing treatment, especially the following patients:
- Who are current or past smokers
- Who have other cardiovascular risk factors
- Who have developed a malignancy
- Who have a known malignancy other than a successfully treated nonmelanoma skin cancer
- Reserve JAK inhibitors (eg, tofacitinib) if patients have an inadequate response or intolerance to ≥1 TNF blockers
- Counsel patients about the benefits and risks of these medicines and advise them to seek emergency medical attention if they experience signs and symptoms of a heart attack, stroke, or blood clot
Drug interaction overview
- Substrate of CYP3A4 (major) and CYP2D6 (minor)
-
Strong CYP3A4 inhibitors
- Use caution; maintain upadacitinib dose to 15 mg qDay
- Coadministration of upadacitinib 30 mg qDay with strong CYP3A4 inhibitors is not recommended
- Upadacitinib systemic exposure is increased when coadministered with strong CYP3A4 inhibitors
-
Strong CYP3A4 inducers
- Coadministration not recommended
- Upadacitinib systemic exposure is decreased when coadministered with strong CYP3A4 inducers
-
Vaccines
- Use of live, attenuated vaccines during or immediately before initiating upadacitinib is not recommended
- Before initiating, assess vaccination history, including prophylactic zoster vaccinations
- Ensure vaccinations are current before initiating upadacitinib
Pregnancy & Lactation
Pregnancy
Limited human data on use in pregnant women are not sufficient to evaluate a drug-associated risk for major birth defects or miscarriage
Verify pregnancy status of females of reproductive potential before starting treatment
Animal data
- Based on animal studies, upadacitinib has the potential to adversely affect a developing fetus
- In animal embryofetal development studies, oral upadacitinib administration to pregnant rats and rabbits at exposures greater or equal than ~1.6 and 15 times the maximum recommended human dose (MRHD), respectively, resulted in dose-related increases in skeletal malformations (rats only), an increased incidence of cardiovascular malformations (rabbits only), increased postimplantation loss (rabbits only), and decreased fetal body weights in both rats and rabbits
Contraception
- Females of reproductive potential: Use effective contraception during treatment and for 4 weeks after final dose
Clinical considerations
- Published data suggest that increased disease activity is associated with risk of developing adverse pregnancy outcomes in women with rheumatoid arthritis
- Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth
Lactation
No data available on the presence of upadacitinib in human milk, the effects on the breastfed infant, or the effects on milk production
Available data in animals have shown upadacitinib excreted in milk
If a drug is present in animal milk, it is likely the drug will be present in human milk
Because of the potential for serious adverse reactions in the breastfed infant, advise patients that breastfeeding is not recommended during treatment with upadacitinib, and for 6 days (~10 half-lives) after the last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Janus kinase-1 (JAK1)-selective inhibitor; JAK1 is essential for certain cytokines to elicit signals from various interleukins, cardiotrophin, neurotrophin, and interferons
These signals are crutial in maintaining the inflammatory condition in rheumatoid arthritis (RA); inhibition of JAK reduces production of and modulates proinflammatory cytokines central to RA
Absorption
Peak plasma time: 2-4 hr
Steady-state reached within 4 days
Distribution
Protein bound: 52%
Metabolism
Metabolized by mainly CYP3A4 and potentially minor contribution from CYP2D6
Elimination
Half-life: 8-14 hr
Excretion
- Urine (24%); feces (38%)
- ~34% of upadacitinib dose was metabolites
Administration
Oral Administration
Take orally with or without food
Swallow tablet whole; do not split, crush, or chew
Storage
Store at 2-25ºC (36-77ºF)
Store in original bottle to protect from moisture
Images
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
