HIGHLIGHTS OF PRESCRIBING INFORMATION RINVOQ ... - …

1 HIGHLIGHTS OF PRESCRIBING INFORMATION Adults and pediatric patients 12 years of age and older with refractory, These HIGHLIGHTS do not include all the INFORMATION needed to use moderate to severe atopic dermatitis whose disease is not adequately RINVOQ safely and effectively. See full PRESCRIBING INFORMATION for controlled with other systemic drug products, including biologics, or when RINVOQ . use of those therapies are inadvisable. ( ). Limitations of Use RINVOQ (upadacitinib) extended-release tablets, for oral use RINVOQ is not recommended for use in combination with other JAK. Initial Approval: 2019 inhibitors, biologic immunomodulators, or with other immunosuppressants. ( ). WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR DOSAGE AND ADMINISTRATION. EVENTS (MACE), AND THROMBOSIS Prior to treatment update immunizations and consider evaluating for active See full PRESCRIBING INFORMATION for complete boxed warning. and latent tuberculosis, viral hepatitis, hepatic function, and pregnancy Increased risk of serious bacterial, fungal, viral, and status ( ).

2 Opportunistic infections leading to hospitalization or death, Avoid initiation or interrupt RINVOQ if absolute lymphocyte count is less including tuberculosis (TB). Interrupt treatment with RINVOQ than 500 cells/mm3, absolute neutrophil count is less than 1000 cells/mm3, if serious infection occurs until the infection is controlled. Test or hemoglobin level is less than 8 g/dL. ( , ). for latent TB before and during therapy; treat latent TB prior to use. Monitor all patients for active TB during treatment, even Rheumatoid Arthritis patients with initial negative, latent TB test. ( ) The recommended dosage of RINVOQ is 15 mg once daily. ( ). Higher rate of all-cause mortality, including sudden Psoriatic Arthritis cardiovascular death with another Janus kinase (JAK) inhibitor The recommended dosage of RINVOQ is 15 mg once daily. ( ). vs. tumor necrosis factor (TNF) blockers in rheumatoid arthritis Atopic Dermatitis (RA) patients. ( ). Pediatric Patients 12 Years of Age and Older Weighing at Least 40 kg and Malignancies have occurred in patients treated with RINVOQ .

3 Adults Less Than 65 Years of Age: Initiate treatment with 15 mg orally Higher rate of lymphomas and lung cancers with another JAK once daily. If an adequate response is not achieved, consider increasing the inhibitor vs. TNF blockers in RA patients. ( ) dosage to 30 mg orally once daily. ( ). Higher rate of MACE (defined as cardiovascular death, Adults 65 Years of Age and Older: Recommended dosage is 15 mg once myocardial infarction, and stroke) with another JAK inhibitor daily. ( ). vs. TNF blockers in RA patients. ( ). Severe Renal Impairment: Recommended dosage is 15 mg once daily. ( ). Thrombosis has occurred in patients treated with RINVOQ . Increased incidence of pulmonary embolism, venous and arterial thrombosis with another JAK inhibitor vs. TNF blockers. ( ) DOSAGE FORMS AND STRENGTHS. Extended-release tablets: 15 mg and 30 mg (3). RECENT MAJOR CHANGES CONTRAINDICATIONS. Boxed Warning 12/2021 Known hypersensitivity to upadacitinib or any of the excipients in RINVOQ .

4 Indications and Usage, Rheumatoid Arthritis ( ) 12/2021 (4). Indications and Usage, Psoriatic Arthritis ( ) 12/2021 . WARNINGS AND PRECAUTIONS. Indications and Usage, Atopic Dermatitis ( ) 1/2022 Serious Infections: Avoid use of RINVOQ in patients with active, serious Dosage and Administration infection, including localized infections. ( ). Recommended Evaluations and Immunizations Prior to Hypersensitivity: Serious hypersensitivity reactions ( , anaphylaxis) have Treatment Initiation ( ) 1/2022 been reported. Discontinue RINVOQ if a serious hypersensitivity reaction Recommended Dosage in Psoriatic Arthritis ( ) 12/2021 occurs. ( ). Recommended Dosage in Atopic Dermatitis ( ) 1/2022 Gastrointestinal (GI) Perforations: Monitor patients at risk for GI. Recommended Dosage in Patients with Renal perforations and promptly evaluate patients with symptoms. ( ). Impairment or Severe Hepatic Impairment ( ) 1/2022 Laboratory Abnormalities: Monitoring recommended due to potential Dosage Modifications Due to drug Interactions ( ) 1/2022 changes in lymphocytes, neutrophils, hemoglobin, liver enzymes and lipids.

5 ( ). Contraindications (4) 1/2022. Embryo-Fetal Toxicity: RINVOQ may cause fetal harm based on animal Warnings and Precautions studies. Advise female patients of reproductive potential of the potential Serious Infections ( ) 12/2021 risk to a fetus and to use effective contraception. ( , , ). Mortality ( ) 12/2021 Vaccinations: Avoid use of RINVOQ with live vaccines. ( ). Malignancy and Lymphoproliferative Disorders ( ) 12/2021. Major Adverse Cardiovascular Events ( ) 12/2021 ADVERSE REACTIONS. Thrombosis ( ) 12/2021 Rheumatoid arthritis and psoriatic arthritis: Adverse reactions ( 1%) were: upper respiratory tract infections, herpes zoster, herpes simplex, bronchitis, Hypersensitivity Reactions ( ) 1/2022. nausea, cough, pyrexia and acne. ( ). Gastrointestinal Perforations ( ) 12/2021 Atopic Dermatitis: Adverse reactions ( 1%) are: upper respiratory tract Embryo-Fetal Toxicity ( ) 1/2022 infections, acne, herpes simplex, headache, blood creatine phosphokinase increased, cough, hypersensitivity, folliculitis, nausea, abdominal pain, INDICATIONS AND USAGE pyrexia, increased weight, herpes zoster, influenza, fatigue, neutropenia, RINVOQ is a Janus kinase (JAK) inhibitor indicated for the treatment of myalgia, and influenza like illness.

6 ( ). Adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more TNF blockers. To report SUSPECTED ADVERSE REACTIONS, contact AbbVie Inc. ( ) at 1-800-633-9110 or FDA at 1-800-FDA-1088 or Limitations of Use Use of RINVOQ in combination with other JAK inhibitors, biologic drug INTERACTIONS. DMARDs, or with potent immunosuppressants such as azathioprine and Strong CYP3A4 Inhibitors: Recommended dosage of RINVOQ in patients cyclosporine is not recommended. ( ) taking strong CYP3A4 inhibitors is 15 mg once daily. ( ). Adults with active psoriatic arthritis who have had an inadequate response Strong CYP3A4 Inducers: Coadministration of RINVOQ with strong or intolerance to one or more TNF blockers. ( ) CYP3A4 inducers is not recommended. ( ). Limitations of Use Use of RINVOQ in combination with other JAK inhibitors, biologic USE IN SPECIFIC POPULATIONS. DMARDs, or with potent immunosuppressants such as azathioprine and Lactation: Advise not to breastfeed.

7 ( ). cyclosporine is not recommended. ( ) Hepatic Impairment: RINVOQ is not recommended in patients with severe hepatic impairment. ( ). See 17 for PATIENT COUNSELING INFORMATION and Medication Revised: 1/2022. Guide. FULL PRESCRIBING INFORMATION : CONTENTS*. Vaccination WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, 6 ADVERSE REACTIONS. MAJOR ADVERSE CARDIOVASCULAR EVENTS, AND Clinical Trials Experience THROMBOSIS 7 drug INTERACTIONS. 1 INDICATIONS AND USAGE Strong CYP3A4 Inhibitors Rheumatoid Arthritis Strong CYP3A4 Inducers Psoriatic Arthritis 8 USE IN SPECIFIC POPULATIONS. Atopic Dermatitis Pregnancy 2 DOSAGE AND ADMINISTRATION Lactation Recommended Evaluations and Immunizations Prior to Treatment Females and Males of Reproductive Potential Initiation Pediatric Use Important Administration Instructions Geriatric Use Recommended Dosage in Rheumatoid Arthritis Renal Impairment Recommended Dosage in Psoriatic Arthritis Hepatic Impairment Recommended Dosage in Atopic Dermatitis 11 DESCRIPTION.

8 Recommended Dosage in Patients with Renal Impairment or Severe 12 CLINICAL PHARMACOLOGY. Hepatic Impairment Mechanism of Action Dosage Modifications Due to drug Interactions Pharmacodynamics Dosage Interruption Pharmacokinetics 3 DOSAGE FORMS AND STRENGTHS 13 NONCLINICAL TOXICOLOGY. 4 CONTRAINDICATIONS Carcinogenesis, Mutagenesis, Impairment of Fertility 5 WARNINGS AND PRECAUTIONS 14 CLINICAL STUDIES. Serious Infections Rheumatoid Arthritis Mortality Psoriatic Arthritis Malignancy and Lymphoproliferative Disorders Atopic Dermatitis Major Adverse Cardiovascular Events 16 HOW SUPPLIED/STORAGE AND HANDLING. Thrombosis 17 PATIENT COUNSELING INFORMATION . Hypersensitivity Reactions Gastrointestinal Perforations *Sections or subsections omitted from the full PRESCRIBING INFORMATION are not Laboratory Abnormalities listed. Embryo-Fetal Toxicity FULL PRESCRIBING INFORMATION . WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR. ADVERSE CARDIOVASCULAR EVENTS, AND THROMBOSIS.

9 SERIOUS INFECTIONS. Patients treated with RINVOQ are at increased risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions ( ), Adverse Reactions ( )]. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt RINVOQ 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 RINVOQ use and during therapy. Treatment for latent infection should be considered prior to RINVOQ 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 RINVOQ should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection.

10 Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with RINVOQ , including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy [see Warnings and Precautions ( )]. MORTALITY. In a large, randomized, postmarketing safety study in rheumatoid arthritis (RA). patients 50 years of age and older with at least one 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 [see Warnings and Precautions ( )]. MALIGNANCIES. Lymphoma and other malignancies have been observed in patients treated with RINVOQ . In RA patients treated with another JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed when compared with TNF blockers.