Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.phenytoinSerious - Use Alternative (1)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.ponesimodSerious - Use Alternative (1)ponesimod, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.posaconazoleMonitor Closely (1)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.primidoneSerious - Use Alternative (1)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.ravulizumabSerious - Use Alternative (1)ravulizumab, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.ribociclibMonitor Closely (1)ribociclib will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.rifabutinSerious - Use Alternative (1)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.rifampinSerious - Use Alternative (1)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.rifapentineSerious - Use Alternative (1)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.rilonaceptSerious - Use Alternative (1)rilonacept, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.risankizumabSerious - Use Alternative (1)risankizumab, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.ritonavirMonitor Closely (1)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.rotavirus oral vaccine, liveSerious - Use Alternative (1)upadacitinib decreases effects of rotavirus oral vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.rozanolixizumabContraindicated (1)rozanolixizumab, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.rubella vaccineSerious - Use Alternative (1)upadacitinib decreases effects of rubella vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.rucaparibMonitor Closely (1)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.saquinavirMonitor Closely (1)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.sarilumabSerious - Use Alternative (1)sarilumab, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.satralizumabSerious - Use Alternative (1)satralizumab, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.secobarbitalSerious - Use Alternative (1)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.secukinumabSerious - Use Alternative (1)secukinumab, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.siponimodSerious - Use Alternative (1)siponimod, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.sirolimusSerious - Use Alternative (1)sirolimus, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.smallpox (vaccinia) vaccine, liveSerious - Use Alternative (1)upadacitinib decreases effects of smallpox (vaccinia) vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.St John's WortSerious - Use Alternative (1)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.stiripentolMonitor Closely (1)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.sutimlimabSerious - Use Alternative (1)sutimlimab, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.tacrolimusSerious - Use Alternative (1)tacrolimus, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.tazemetostatMonitor Closely (1)tazemetostat will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tipranavirMonitor Closely (1)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.tisagenlecleucelSerious - Use Alternative (1)upadacitinib, tisagenlecleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.tocilizumabSerious - Use Alternative (1)tocilizumab, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.tofacitinibSerious - Use Alternative (1)tofacitinib, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.tucatinibSerious - Use Alternative (1)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 vaccineSerious - Use Alternative (1)upadacitinib decreases effects of typhoid polysaccharide vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.typhoid vaccine liveSerious - Use Alternative (1)upadacitinib decreases effects of typhoid vaccine live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.ublituximabMonitor Closely (1)ublituximab and upadacitinib both increase immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Owing to potential additive immunosuppressive effects, consider duration of effect and mechanism of action of these therapies if coadministeredustekinumabSerious - Use Alternative (1)ustekinumab, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.varicella virus vaccine liveSerious - Use Alternative (1)upadacitinib decreases effects of varicella virus vaccine live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.vedolizumabSerious - Use Alternative (1)vedolizumab, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.voclosporinSerious - Use Alternative (1)voclosporin, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.voriconazoleMonitor Closely (1)voriconazole will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.voxelotorSerious - Use Alternative (1)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 vaccineSerious - Use Alternative (1)upadacitinib decreases effects of yellow fever vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.zoster vaccine liveSerious - Use Alternative (1)upadacitinib decreases effects of zoster vaccine live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. >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 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 varicella-zoster or prophylactic 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; periodic skin examination recommended for patients who are at increased risk for skin cancer Thrombosis reported, including DVT, PE, and arterial thrombosis; avoid therapy in patients that may be at increased risk of thrombosis Gastrointestinal perforation reported; monitor treated patients who may be at risk for gastrointestinal perforation (eg, patients with history of diverticulitis and those taking concomitant medications including NSAIDs or corticosteroids); evaluate promptly patients presenting with new onset abdominal pain for early identification of gastrointestinal perforation 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 Exposure to sunlight and UV light should be limited by wearing protective clothing and using a broad-spectrum sunscreen Serious hypersensitivity reactions such as anaphylaxis and angioedema were reported; if a clinically significant hypersensitivity reaction occurs, discontinue therapy and institute appropriate therapy 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 Evaluate and test patients for latent and active tuberculosis (TB) infection prior to treating; patients with latent TB should be treated with standard antimycobacterial therapy before initiating treatment 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,