New SKYRIZI® (risankizumab-rzaa) and RINVOQ® (upadacitinib) Data Demonstrate Disease Control for Patients Living With Inflammatory Bowel Disease

• Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with SKYRIZI [see Warnings and Precautions (5.3)].

• Complete all age-appropriate vaccinations as recommended by current immunization guidelines [see Warnings and Precautions (5.5)].

2.2 General Considerations for Administration

• Visually inspect SKYRIZI for particulate matter and discoloration prior to administration. The solution may contain a few translucent to white particles.

o SKYRIZI 55 mg/0.37 mL prefilled syringe, 150 mg/mL prefilled pen or prefilled syringe, 180 mg/1.2 mL prefilled syringe or prefilled cartridge, and 360 mg/2.4 mL prefilled cartridge: a colorless to yellow, and clear to slightly opalescent solution.

o SKYRIZI 90 mg/mL prefilled syringe and 600 mg/10 mL vial: a colorless to slightly yellow, and clear to slightly opalescent solution.

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o Do not use if the solution contains large particles or is cloudy or discolored.

• Discard after use. Do not reuse.

2.3 Recommended Dosage for Moderate-to-Severe Plaque Psoriasis

Adults

The recommended dosage for adults is 150 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter.

Pediatric Patients 6 Years of Age and Older

The recommended dosage for pediatric patients 6 years of age and older is based on body weight (see Table 1) and administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter.

Table 1. Recommended Dose of SKYRIZI for Pediatric Patients 6 Years of Age and Older with Moderate-to-Severe Plaque Psoriasis Body Weight Recommended Dose

2.4 Recommended Dosage for Active Psoriatic Arthritis

Adults

The recommended dosage for adult patients is 150 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter.

SKYRIZI may be administered alone or in combination with non-biologic disease-modifying antirheumatic drugs (DMARDs).

Pediatric Patients 6 Years of Age and Older

The recommended dosage for pediatric patients 6 years of age and older is based on body weight (see Table 2) and administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter.

Table 2. Recommended Dose of SKYRIZI for Pediatric Patients 6 Years of Age and Older with Active Psoriatic Arthritis Body Weight Recommended Dose

SKYRIZI may be administered alone or in combination with non-biologic disease-modifying antirheumatic drugs (DMARDs).

2.5 Preparation and Administration Instructions (Moderate-to-Severe Plaque Psoriasis and Active Psoriatic Arthritis)

• Administer SKYRIZI 55 mg/0.37 mL prefilled syringe, 150 mg/mL prefilled pen or prefilled syringe subcutaneously.

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• Provide proper training to patients and/or caregivers on the subcutaneous injection technique of SKYRIZI. After proper training:

Adults

o Adults may self-inject SKYRIZI.

Pediatric Patients 6 Years of Age and Older

o For pediatric patients 10 years of age and older, it is recommended that SKYRIZI be administered by or under the supervision of an adult.

o For pediatric patients 6 to less than 10 years of age, SKYRIZI should be administered by an adult.

• Before injecting, remove the carton with SKYRIZI from the refrigerator and without removing the prefilled pen or prefilled syringe from the carton, allow SKYRIZI to reach room temperature out of direct sunlight (30 to 90 minutes for the prefilled pen and 15 to 30 minutes for the prefilled syringe).

• Do not inject into areas where the skin is tender, bruised, erythematous, indurated or affected by psoriasis. Administration of SKYRIZI in the upper, outer arm may only be performed by a healthcare professional or caregiver.

• If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.

The SKYRIZI “Instructions for Use” contains more detailed instructions on the preparation and administration of SKYRIZI [see Instructions for Use]. Instruct the patient to read the Instructions for Use before administration.

2.6 Recommended Dosage for Moderately to Severely Active Crohn’s Disease

Adult Patients: Induction

The recommended induction dosage of SKYRIZI is 600 mg administered by intravenous infusion over a period of at least one hour at Week 0, Week 4, and Week 8.

Adult Patients: Maintenance

The recommended maintenance dosage of SKYRIZI is 180 mg or 360 mg administered by subcutaneous injection at Week 12, and every 8 weeks thereafter. Use the lowest effective dosage needed to maintain therapeutic response.

2.7 Recommended Dosage for Moderately to Severely Active Ulcerative Colitis

Adult Patients: Induction

The recommended induction dosage of SKYRIZI is 1,200 mg administered by intravenous infusion over a period of at least two hours at Week 0, Week 4, and Week 8.

Adult Patients: Maintenance

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The recommended maintenance dosage of SKYRIZI is 180 mg or 360 mg administered by subcutaneous injection at Week 12, and every 8 weeks thereafter. Use the lowest effective dosage needed to maintain therapeutic response.

2.8 Preparation and Administration Instructions (Moderately to Severely Active Crohn’s Disease and Ulcerative Colitis)

Intravenous Induction Dosing Regimen:

1. SKYRIZI vial for intravenous administration is intended for administration by a healthcare provider using aseptic technique.

2. Prior to intravenous administration, determine the dose and number of SKYRIZI vials needed based on the patient’s indication (see table below). Withdraw 10 mL of SKYRIZI solution from a vial (600 mg/10 mL) and inject into an intravenous infusion bag or glass bottle containing 5% Dextrose Injection or 0.9% Sodium Chloride Injection (see Table 3 below) for a final concentration of approximately 1.2 mg/mL to 6 mg/mL. Discard any remaining solution in the vial.

Table 3. Total Volume of Diluent Required for Intravenous Induction Dose

3. Infuse the diluted solution intravenously over a period of at least one hour for the SKYRIZI 600 mg dose; at least two hours for the SKYRIZI 1,200 mg dose. If stored refrigerated, allow the diluted SKYRIZI solution in the infusion bag or glass bottle to warm to room temperature prior to the start of the intravenous infusion.

4. Do not administer SKYRIZI diluted solution concomitantly in the same intravenous line with other medicinal products.

Handling and Storage of the Vial and the Diluted Solution:

• Do not shake the vial or diluted solution in the infusion bag or glass bottle.

• Use the prepared infusion immediately. If not used immediately, store the diluted SKYRIZI solution refrigerated and protected from light for up to 20 hours between 36°F to 46°F (2°C to 8°C).

• Immediately after preparation or removal from refrigeration, the diluted SKYRIZI solution can be stored at room temperature at up to 77°F (25°C) (protected from sunlight) for up to 8 hours. Storage time at room temperature begins once the diluted solution has been prepared. The infusion should be completed within 8 hours after dilution in the infusion bag.

• Exposure to indoor light is acceptable during room temperature storage and administration.

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• Do not freeze.

Subcutaneous Maintenance Dosing Regimen:

Using the single-dose 180 mg or 360 mg prefilled cartridge with On-Body Injector:

• SKYRIZI is intended for use under the guidance and supervision of a healthcare professional.

• Patients may self-inject SKYRIZI using the on-body injector with prefilled cartridge after training in subcutaneous injection technique. Provide proper training to patients and/or caregivers on the subcutaneous injection technique of SKYRIZI.

• Before using the on-body injector with prefilled cartridge, remove the carton from the refrigerator and allow to reach room temperature out of direct sunlight (45 to 90 minutes) without removing the prefilled cartridge or on-body injector from the carton.

• Use the on-body injector to administer SKYRIZI 180 mg/1.2 mL or SKYRIZI 360 mg/2.4 mL prefilled cartridge subcutaneously on thigh or abdomen.

• Start the injection within 5 minutes after inserting the prefilled cartridge into the On-Body Injector.

• Do not inject into areas where the skin is tender, bruised, erythematous, indurated or affected by any lesions.

• If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.

The SKYRIZI “Instructions for Use” contains more detailed instructions on the preparation and administration of SKYRIZI [see Instructions for Use]. Instruct the patient to read the Instructions for Use before administration.

Using the 90 mg/mL or 180 mg/1.2 mL prefilled syringe:

• Administer each SKYRIZI 90 mg/mL or 180 mg/1.2 mL prefilled syringe subcutaneously.

• Patients may self-inject SKYRIZI after training in subcutaneous injection technique. Provide proper training to patients and/or caregivers on the subcutaneous injection technique of SKYRIZI.

• Before injecting, remove the carton from the refrigerator and without removing the prefilled syringes from the carton, allow SKYRIZI to reach room temperature out of direct sunlight (15 to 30 minutes).

• Use the 90 mg/mL or 180 mg/1.2 mL prefilled syringe(s) to administer SKYRIZI 180 mg or SKYRIZI 360 mg subcutaneously as follows:

o 180 mg maintenance dose:

▪ SKYRIZI 90 mg/mL prefilled syringes: Two 90 mg prefilled syringes are required. Inject one prefilled syringe after the other in different anatomic locations (such as thighs or abdomen).

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▪ SKYRIZI 180 mg/1.2 mL prefilled syringe: One 180 mg prefilled syringe is required.

o 360 mg maintenance dose:

▪ SKYRIZI 90 mg/mL prefilled syringes: Four 90 mg prefilled syringes are required. Inject one prefilled syringe after the other in different anatomic locations (such as thighs or abdomen).

▪ SKYRIZI 180 mg/1.2 mL prefilled syringes: Two 180 mg prefilled syringes are required. Inject one prefilled syringe after the other in different anatomic locations (such as thighs or abdomen).

• Do not inject into areas where the skin is tender, bruised, erythematous, indurated or affected by any lesions. Administration of SKYRIZI in the upper, outer arm may only be performed by a healthcare professional or caregiver.

• If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.

The SKYRIZI “Instructions for Use” contains more detailed instructions on the preparation and administration of SKYRIZI [see Instructions for Use]. Instruct the patient to read the Instructions for Use before administration.

3 DOSAGE FORMS AND STRENGTHS

Subcutaneous Injection

SKYRIZI Pen

• Injection: 150 mg/mL as a colorless to yellow and clear to slightly opalescent solution in each single-dose prefilled pen.

SKYRIZI Prefilled Syringe

• Injection: 55 mg/0.37 mL as a colorless to yellow and clear to slightly opalescent solution in each single-dose prefilled syringe.

• Injection: 90 mg/mL as a colorless to slightly yellow and clear to slightly opalescent solution in each single-dose prefilled syringe.

• Injection: 150 mg/mL as a colorless to yellow and clear to slightly opalescent solution in each single-dose prefilled syringe.

• Injection: 180 mg/1.2 mL (150 mg/mL) as a colorless to yellow and clear to slightly opalescent solution in each single-dose prefilled syringe.

SKYRIZI Prefilled Cartridge with Supplied On-Body Injector

• Injection: 180 mg/1.2 mL (150 mg/mL) as a colorless to yellow, and clear to slightly opalescent solution in each single-dose prefilled cartridge for use with the on-body injector.

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• Injection: 360 mg/2.4 mL (150 mg/mL) as a colorless to yellow, and clear to slightly opalescent solution in each single-dose prefilled cartridge for use with the on-body injector.

Intravenous Infusion

SKYRIZI Vial

• Injection: 600 mg/10 mL (60 mg/mL) as a colorless to slightly yellow, and clear to slightly opalescent solution in each single-dose vial.

4 CONTRAINDICATIONS

SKYRIZI is contraindicated in patients with a history of serious hypersensitivity reaction to risankizumab-rzaa or any of the excipients [see Warnings and Precautions (5.1)].

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylaxis, have been reported with use of SKYRIZI. If a serious hypersensitivity reaction occurs, discontinue SKYRIZI and initiate appropriate therapy immediately [see Adverse Reactions (6.1)].

5.2 Infections

SKYRIZI may increase the risk of infections [see Adverse Reactions (6.1)].

Treatment with SKYRIZI should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated.

In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior to prescribing SKYRIZI. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur. If a patient develops such an infection or is not responding to standard therapy, monitor the patient closely and do not administer SKYRIZI until the infection resolves.

5.3 Tuberculosis

Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with SKYRIZI. Across the Phase 3 psoriasis clinical studies, of the 72 subjects with latent TB who were concurrently treated with SKYRIZI and appropriate TB prophylaxis during the studies, none developed active TB during the mean follow-up of 61 weeks on SKYRIZI. Two subjects taking isoniazid for treatment of latent TB discontinued treatment due to liver injury. Of the 31 subjects from the PsO-3 study with latent TB who did not receive prophylaxis during the study, none developed active TB during the mean follow-up of 55 weeks on SKYRIZI. Consider anti-TB therapy prior to initiating SKYRIZI in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Monitor patients for signs and symptoms of active TB during and after SKYRIZI treatment. Do not administer SKYRIZI to patients with active TB.

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5.4 Hepatotoxicity

A serious adverse reaction of drug-induced liver injury in conjunction with a rash that required hospitalization was reported in a patient with Crohn’s disease (ALT 54x ULN, AST 30x ULN, and total bilirubin 2.2x ULN) following two 600 mg intravenous doses of SKYRIZI. The liver test abnormalities resolved following administration of steroids. SKYRIZI was subsequently discontinued.

For the treatment of Crohn’s disease and ulcerative colitis, evaluate liver enzymes and bilirubin at baseline, and during induction at least up to 12 weeks of treatment. Monitor thereafter according to routine patient management.

Consider other treatment options in patients with evidence of liver cirrhosis.

Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded. Instruct patients to seek immediate medical attention if they experience symptoms suggestive of hepatic dysfunction.

5.5 Immunizations

Avoid use of live vaccines in patients treated with SKYRIZI. Drugs that interact with the immune system may increase the risk of infection following administration of live vaccines. Prior to initiating therapy with SKYRIZI, complete all age-appropriate vaccinations according to current immunization guidelines. No data are available on the response to live or inactive vaccines.

6 ADVERSE REACTIONS

The following adverse reactions are discussed in other sections of labeling:

• Hypersensitivity Reactions [see Warnings and Precautions (5.1)]

• Infections [see Warnings and Precautions (5.2)]

• Tuberculosis [see Warnings and Precautions (5.3)]

• Hepatotoxicity [see Warnings and Precautions (5.4)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse drug reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse Reactions in Adults with Plaque Psoriasis

A total of 2234 subjects were treated with SKYRIZI in clinical development trials in plaque psoriasis. Of these, 1208 subjects with psoriasis were exposed to SKYRIZI for at least one year.

Data from placebo- and active-controlled trials were pooled to evaluate the safety of SKYRIZI for up to 16 weeks. In total, 1306 subjects were evaluated in the SKYRIZI 150 mg group.

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Table 4 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the SKYRIZI group than the placebo group during the 16-week controlled period of pooled clinical trials.

Table 4. Adverse Reactions Occurring in ≥ 1% of Adults with Plaque Psoriasis on SKYRIZI through Week 16 SKYRIZI Placebo

Adverse reactions that occurred in < 1% but > 0.1% of subjects in the SKYRIZI group and at a higher rate than in the placebo group through Week 16 were folliculitis and urticaria.

Specific Adverse Reactions

Infections: In the first 16 weeks, infections occurred in 22.1% of the SKYRIZI group (90.8 events per 100 patient-years) compared with 14.7% of the placebo group (56.5 events per 100 patient-years) and did not lead to discontinuation of SKYRIZI. The rates of serious infections for the SKYRIZI group and the placebo group were ≤0.4%. Serious infections in the SKYRIZI group included cellulitis, osteomyelitis, sepsis, and herpes zoster. In Trials PsO-1 and PsO-2, through Week 52, the rate of infections (73.9 events per 100 patient-years) was similar to the rate observed during the first 16 weeks of treatment.

Safety Through Week 52

Through Week 52, no new adverse reactions were identified, and the rates of the adverse reactions were similar to those observed during the first 16 weeks of treatment. During this period, serious infections that led to trial discontinuation included pneumonia.

Plaque Psoriasis of the Scalp or Genital Area

The overall safety profile observed in clinical trials of subjects with moderate-to-severe plaque psoriasis of the scalp or genital area treated with SKYRIZI is generally consistent with the safety profile observed in previous clinical trials of subjects with moderate-to-severe plaque psoriasis [see Clinical Studies (14.1)].

Adverse Reactions in Pediatric Subjects 6 Years of Age and Older with Plaque Psoriasis

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The safety of SKYRIZI was evaluated in a four-part trial that included 137 pediatric subjects 6 years of age and older with moderate-to-severe plaque psoriasis [see Clinical Studies (14.1)]. Overall, the safety profile observed in pediatric subjects 6 years of age and older treated with SKYRIZI for up to 52 weeks was consistent with the safety profile observed in adult subjects with moderate-to-severe plaque psoriasis.

Adverse Reactions in Adult Subjects with Psoriatic Arthritis

The overall safety profile observed in adult subjects with psoriatic arthritis treated with SKYRIZI is generally consistent with the safety profile in adult subjects with plaque psoriasis. Additionally, in the Phase 3 placebo-controlled trials the incidence of hepatic events was higher in the SKYRIZI group (5.4%, 16.7 events per 100 patient-years) compared to the placebo group (3.9%, 12.6 events per 100 patient-years). Of these, the most common events that were reported more frequently in both the placebo group and the SKYRIZI group were ALT increased (placebo: n=12 (1.7%); SKYRIZI: n=16 (2.3%)), AST increased (placebo: n=9 (1.3%); SKYRIZI: n=13 (1.8%)), and GGT increased (placebo: n=5 (0.7%); SKYRIZI: n=8 (1.1%)). There were no serious hepatic events reported. The incidence of hypersensitivity reactions was higher in the SKYRIZI group (n=16, 2.3%) compared to the placebo group (n=9, 1.3%). In the Phase 3 placebo-controlled trials, hypersensitivity reactions reported at a higher rate in the SKYRIZI group included rash (placebo: n=4 (0.6%); SKYRIZI: n=5 (0.7%)), allergic rhinitis (placebo: n=1 (0.1%); SKYRIZI: n=2 (0.3%)), and facial swelling (placebo: n=0 (0.0%); SKYRIZI n=1 (0.1%)). One case of anaphylaxis was reported in a subject who received SKYRIZI in the Phase 2 clinical trial.

Adverse Reactions in Adult Subjects with Crohn’s Disease

SKYRIZI was studied up to 12 weeks in subjects with moderately to severely active Crohn’s disease in two randomized, double-blind, placebo-controlled induction trials (CD-1, CD-2) and a randomized, double-blind, placebo-controlled, dose-finding trial (CD-4; NCT02031276). Longterm safety up to 52 weeks was evaluated in subjects who responded to induction therapy in a randomized, double-blind, placebo-controlled maintenance trial (CD-3) [see Clinical Studies (14.3)].

In the two induction trials (CD-1, CD-2) and the dose finding trial (CD-4), 620 subjects received the SKYRIZI intravenous induction regimen at Weeks 0, 4 and 8. In the maintenance trial (CD- 3), 297 subjects who achieved clinical response, defined as a reduction in CDAI of at least 100 points from baseline after 12 weeks of induction treatment with intravenous SKYRIZI in trials CD-1 and CD-2, received a maintenance regimen of SKYRIZI either 180 mg or 360 mg subcutaneously at Week 12 and every 8 weeks thereafter for up to an additional 52 weeks.

Adverse reactions reported in > 3% of subjects in induction trials and at a higher rate than placebo are shown in Table 5.

Table 5. Adverse Drug Reactions Reported in > 3% of Subjects with Crohn’s Disease Treated with SKYRIZI in Placebo-Controlled 12-Week Induction Trials (CD-1, CD-2, and CD-4)

• See the Full Prescribing Information for the recommended dosage in patients with renal or hepatic impairment and for dosage modification due to drug interactions. (2.12, 2.13)

Polyarticular Juvenile Idiopathic Arthritis

• The recommended dosage is based on body weight (2.10)

Giant Cell Arteritis

• The recommended dosage of RINVOQ is 15 mg once daily in combination with a tapering course of corticosteroids. RINVOQ 15 mg once daily can be used as monotherapy following discontinuation of corticosteroids (2.11)

DOSAGE FORMS AND STRENGTHS

• RINVOQ extended-release tablets: 15 mg, 30 mg, and 45 mg (3)

• RINVOQ LQ oral solution: 1 mg/mL (3)

CONTRAINDICATIONS

Known hypersensitivity to upadacitinib or any of the excipients in RINVOQ/RINVOQ LQ. (4, 5.6)

WARNINGS AND PRECAUTIONS

• Serious Infections: Avoid use in patients with active, serious infection, including localized infections. (5.1)

• Hypersensitivity: Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. Discontinue if a serious hypersensitivity reaction occurs. (5.6)

• Gastrointestinal (GI) Perforations: Monitor patients at risk for GI perforations and promptly evaluate patients with symptoms. (5.7)

• Hypoglycemia in Patients with Diabetes: Consider increased monitoring of blood glucose; advise patients with diabetes to notify their healthcare provider if they develop signs or symptoms of hypoglycemia. (5.8)

• Laboratory Abnormalities: Monitoring recommended due to potential changes in lymphocytes, neutrophils, hemoglobin, liver enzymes and lipids. (5.9)

• Embryo-Fetal Toxicity: May cause fetal harm based on animal studies. Advise female patients of reproductive potential of the potential risk to a fetus and to use effective contraception. (5.10, 8.1, 8.3)

• Vaccinations: Avoid use with live vaccines. (5.11)

• Medication Residue in Stool: Observed in stool or ostomy output in patients with shortened GI transit times. Monitor patients clinically and consider alternative treatment if inadequate therapeutic response. (5.12)

ADVERSE REACTIONS

• Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and non- radiographic axial spondyloarthritis: Adverse reactions (≥ 1%) were: upper respiratory tract infections, herpes zoster, herpes simplex, bronchitis, nausea, cough, pyrexia, acne, and headache. (6.1)

• Giant cell arteritis: Adverse reactions (≥ 5%) are upper respiratory tract infections, headache, fatigue, peripheral edema, cough, anemia, rash, herpes zoster, and nausea. (6.1)

• Atopic dermatitis: Adverse reactions (≥ 1%) are: upper respiratory tract infections, acne, herpes simplex, headache, blood creatine phosphokinase increased, cough, hypersensitivity, folliculitis, nausea, abdominal pain, pyrexia, increased weight, herpes zoster, influenza, fatigue, neutropenia, myalgia, and influenza like illness. (6.1)

• Ulcerative colitis: Adverse reactions (≥ 5%) reported during induction or maintenance are: upper respiratory tract infections, increased blood creatine phosphokinase, acne, neutropenia, elevated liver enzymes, pyrexia, and rash. (6.1)

• Crohn’s disease: Adverse reactions (≥ 5%) reported during induction or maintenance are: upper respiratory tract infections, anemia, pyrexia, acne, herpes zoster, and headache. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact AbbVie Inc. at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

• Strong CYP3A4 Inhibitors: See the Full Prescribing Information for dosage modification for patients with atopic dermatitis, ulcerative colitis, and Crohn’s disease. (2.13, 7.1)

• Strong CYP3A4 Inducers: Coadministration of RINVOQ/RINVOQ LQ with strong CYP3A4 inducers is not recommended. (7.2)

USE IN SPECIFIC POPULATIONS

• Lactation: Advise not to breastfeed. (8.2)

• Hepatic Impairment: RINVOQ/RINVOQ LQ is not recommended in patients with severe hepatic impairment. (8.7)

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 6/2026

FULL PRESCRIBING INFORMATION: CONTENTS*

WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, and THROMBOSIS

1 INDICATIONS AND USAGE

1.1 Rheumatoid Arthritis

1.2 Psoriatic Arthritis

1.3 Atopic Dermatitis

1.4 Ulcerative Colitis

1.5 Crohn’s Disease

1.6 Ankylosing Spondylitis

1.7 Non-radiographic Axial Spondyloarthritis

1.8 Polyarticular Juvenile Idiopathic Arthritis

1.9 Giant Cell Arteritis

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Evaluations and Immunizations Prior to Treatment Initiation

2.2 Important Administration Instructions

2.3 Recommended Dosage in Rheumatoid Arthritis

2.4 Recommended Dosage in Psoriatic Arthritis

2.5 Recommended Dosage in Atopic Dermatitis

2.6 Recommended Dosage in Ulcerative Colitis

2.7 Recommended Dosage in Crohn’s Disease

2.8 Recommended Dosage in Ankylosing Spondylitis

2.9 Recommended Dosage in Non-radiographic Axial Spondyloarthritis

2.10 Recommended Dosage in Polyarticular Juvenile Idiopathic Arthritis

2.11 Recommended Dosage in Giant Cell Arteritis

2.12 Recommended Dosage in Patients with Renal Impairment or Hepatic Impairment

2.13 Dosage Modifications Due to Drug Interactions

2.14 Dosage Interruption

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Serious Infections

5.2 Mortality

5.3 Malignancy and Lymphoproliferative Disorders

5.4 Major Adverse Cardiovascular Events

5.5 Thrombosis

5.6 Hypersensitivity Reactions

5.7 Gastrointestinal Perforations

5.8 Hypoglycemia in Patients with Diabetes

5.9 Laboratory Abnormalities

5.10 Embryo-Fetal Toxicity

5.11 Vaccinations

5.12 Medication Residue in Stool

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience 6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Strong CYP3A4 Inhibitors 7.2 Strong CYP3A4 Inducers

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8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.3 Females and Males of Reproductive Potential 8.4 Pediatric Use

8.5 Geriatric Use

8.6 Renal Impairment

8.7 Hepatic Impairment

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14.1 Rheumatoid Arthritis

14 CLINICAL STUDIES

14.2 Psoriatic Arthritis

14.3 Atopic Dermatitis

14.4 Ulcerative Colitis

14.5 Crohn’s Disease

14.6 Ankylosing Spondylitis

14.7 Non-radiographic Axial Spondyloarthritis

14.8 Polyarticular Juvenile Idiopathic Arthritis

14.9 Giant Cell Arteritis

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

*****Sections or subsections omitted from the full prescribing information are not listed.

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FULL PRESCRIBING INFORMATION

WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, and THROMBOSIS

SERIOUS INFECTIONS

Patients treated with RINVOQ/RINVOQ LQ are at increased risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions (5.1), Adverse Reactions (6.1)]. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

If a serious infection develops, interrupt RINVOQ/RINVOQ LQ 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/RINVOQ LQ use and during therapy. Treatment for latent infection should be considered prior to RINVOQ/RINVOQ LQ 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/RINVOQ LQ 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 RINVOQ/RINVOQ LQ, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy [see Warnings and Precautions (5.1)].

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 (5.2)].

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. Patients who are current or past smokers are at additional increased risk [see Warnings and Precautions (5.3)].

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MAJOR ADVERSE CARDIOVASCULAR EVENTS

In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke), was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue RINVOQ/RINVOQ LQ in patients that have experienced a myocardial infarction or stroke [see Warnings and Precautions (5.4)].

THROMBOSIS

Thromboses, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis, have occurred in patients treated for inflammatory conditions with JAK inhibitors, including RINVOQ. Many of these adverse events were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid RINVOQ/RINVOQ LQ in patients at risk. Patients with symptoms of thrombosis should discontinue RINVOQ/RINVOQ LQ and be promptly evaluated [see Warnings and Precautions (5.5)].

1 INDICATIONS AND USAGE

1.1 Rheumatoid Arthritis

RINVOQ^® is indicated for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more TNF blockers.

• Limitations of Use: RINVOQ is not recommended for use in combination with other JAK inhibitors, biologic disease-modifying antirheumatic drugs (DMARDs), or with potent immunosuppressants such as azathioprine and cyclosporine.

1.2 Psoriatic Arthritis

RINVOQ/RINVOQ LQ is indicated for the treatment of adults and pediatric patients 2 years of age and older with active psoriatic arthritis who have had an inadequate response or intolerance to one or more TNF blockers.

• Limitations of Use: RINVOQ/RINVOQ LQ is not recommended for use in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants such as azathioprine and cyclosporine.

1.3 Atopic Dermatitis

RINVOQ is indicated for the treatment of adults and pediatric patients 12 years of age and older with refractory, moderate to severe atopic dermatitis whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies are inadvisable.

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• Limitations of Use: RINVOQ is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or with other immunosuppressants.

1.4 Ulcerative Colitis

RINVOQ is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response or intolerance to one or more TNF blockers. If TNF blockers are clinically inadvisable, patients should have received at least one approved systemic therapy prior to use of RINVOQ.

• Limitations of Use: RINVOQ is not recommended for use in combination with other JAK inhibitors, biological therapies for UC, or with potent immunosuppressants such as azathioprine and cyclosporine.

1.5 Crohn’s Disease

RINVOQ is indicated for the treatment of adult patients with moderately to severely active Crohn’s disease (CD) who have had an inadequate response or intolerance to one or more TNF blockers. If TNF blockers are clinically inadvisable, patients should have received at least one approved systemic therapy prior to use of RINVOQ.

• Limitations of Use: RINVOQ is not recommended for use in combination with other JAK inhibitors, biological therapies for CD, or with potent immunosuppressants such as azathioprine and cyclosporine.

1.6 Ankylosing Spondylitis

RINVOQ is indicated for the treatment of adults with active ankylosing spondylitis who have had an inadequate response or intolerance to one or more TNF blockers.

• Limitations of Use: RINVOQ is not recommended for use in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants such as azathioprine and cyclosporine.

1.7 Non-radiographic Axial Spondyloarthritis

RINVOQ is indicated for the treatment of adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation who have had an inadequate response or intolerance to TNF blocker therapy.

• Limitations of Use: RINVOQ is not recommended for use in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants such as azathioprine and cyclosporine.

1.8 Polyarticular Juvenile Idiopathic Arthritis

RINVOQ/RINVOQ LQ is indicated for the treatment of patients 2 years of age and older with active polyarticular juvenile idiopathic arthritis (pJIA) who have had an inadequate response or intolerance to one or more TNF blockers.

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• Limitations of Use: RINVOQ/RINVOQ LQ is not recommended for use in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants such as azathioprine and cyclosporine.

1.9 Giant Cell Arteritis

RINVOQ is indicated for the treatment of adults with giant cell arteritis.

• Limitations of Use: RINVOQ is not recommended for use in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants such as azathioprine and cyclosporine.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Evaluations and Immunizations Prior to Treatment Initiation

Prior to RINVOQ/RINVOQ LQ treatment initiation, consider performing the following evaluations:

• Active and latent tuberculosis (TB) infection evaluation - If positive, treat for TB prior to RINVOQ/RINVOQ LQ use [see Warnings and Precautions (5.1)].

• Viral hepatitis screening in accordance with clinical guidelines - RINVOQ/RINVOQ LQ initiation is not recommended in patients with active hepatitis B or hepatitis C [see Warnings and Precautions (5.1)].

• A complete blood count - RINVOQ/RINVOQ LQ initiation is not recommended in patients with an absolute lymphocyte count less than 500 cells/mm³, absolute neutrophil count less than 1000 cells/mm³, or hemoglobin level less than 8 g/dL [see Dosage and Administration (2.14) and Warnings and Precautions (5.9)].

• Baseline hepatic function: RINVOQ/RINVOQ LQ initiation is not recommended for patients with severe hepatic impairment (Child-Pugh C) [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

• Pregnancy Status: Verify the pregnancy status of females of reproductive potential prior to starting treatment [see Warnings and Precautions (5.10) and Use in Specific Populations (8.1, 8.3)].

Update immunizations according to current immunization guidelines [see Warnings and Precautions (5.11)].

2.2 Important Administration Instructions

• RINVOQ LQ oral solution is not substitutable with RINVOQ extended-release tablets [see Dosage and Administration (2.4, 2.10)].

• Changes between RINVOQ LQ oral solution and RINVOQ extended-release tablets should be made by the health care provider.

• RINVOQ/RINVOQ LQ should be taken orally with or without food [see Clinical Pharmacology (12.3)].

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• RINVOQ tablets should be swallowed whole. RINVOQ tablets should not be split, crushed, or chewed.

• RINVOQ LQ should be administered using the provided press-in bottle adapter and oral dosing syringe [see Instructions for Use].

• RINVOQ LQ is dosed twice daily [see Dosage and Administration (2.4, 2.10)].

2.3 Recommended Dosage in Rheumatoid Arthritis

The recommended dosage of RINVOQ is 15 mg once daily.

2.4 Recommended Dosage in Psoriatic Arthritis

Pediatric Patients 2 to Less Than 18 Years of Age

The recommended dosage is based on body weight (Table 1).

Table 1: RINVOQ/RINVOQ LQ Dosage for Pediatric Patients 2 Years to Less Than 18 Years of Age with Psoriatic Arthritis

Years of Age with Psoriatic Arthritis

RINVOQ LQ oral solution is not substitutable with RINVOQ extended-release tablets. Changes between RINVOQ LQ oral solution and RINVOQ extended-release tablets should be made by the health care provider.

Adults 18 Years of Age and Older

The recommended dosage of RINVOQ is 15 mg once daily.

2.5 Recommended Dosage in Atopic Dermatitis

Pediatric Patients 12 Years of Age and Older Weighing at Least 40 kg and Adults Less Than 65 Years of Age

Initiate treatment with RINVOQ 15 mg once daily. If an adequate response is not achieved, consider increasing the dosage to 30 mg once daily. Discontinue RINVOQ if an adequate response is not achieved with the 30 mg dose. Use the lowest effective dose needed to maintain response.

Adults 65 Years of Age and Older

The recommended dosage of RINVOQ is 15 mg once daily.

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2.6 Recommended Dosage in Ulcerative Colitis

Adult Patients: Induction

The recommended induction dosage of RINVOQ is 45 mg once daily for 8 weeks.

Adult Patients: Maintenance

The recommended dosage of RINVOQ for maintenance treatment is 15 mg once daily. A dosage of 30 mg once daily may be considered for patients with refractory, severe or extensive disease. Discontinue RINVOQ if an adequate therapeutic response is not achieved with the 30 mg dosage. Use the lowest effective dosage needed to maintain response.

2.7 Recommended Dosage in Crohn’s Disease

Adult Patients: Induction

The recommended induction dosage of RINVOQ is 45 mg once daily for 12 weeks.

Adult Patients: Maintenance

The recommended dosage of RINVOQ for maintenance treatment is 15 mg once daily. A dosage of 30 mg once daily may be considered for patients with refractory, severe or extensive disease. Discontinue RINVOQ if an adequate therapeutic response is not achieved with the 30 mg dosage. Use the lowest effective dosage needed to maintain response.

2.8 Recommended Dosage in Ankylosing Spondylitis

The recommended dosage of RINVOQ is 15 mg once daily.

2.9 Recommended Dosage in Non-radiographic Axial Spondyloarthritis

The recommended dosage of RINVOQ is 15 mg once daily.

2.10 Recommended Dosage in Polyarticular Juvenile Idiopathic Arthritis

The recommended dosage is based on body weight (Table 2).

Table 2: RINVOQ/RINVOQ LQ Dosage for Patients 2 years and older with pJIA

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RINVOQ LQ oral solution is not substitutable with RINVOQ extended-release tablets. Changes between RINVOQ LQ oral solution and RINVOQ extended-release tablets should be made by the health care provider.

2.11 Recommended Dosage in Giant Cell Arteritis

The recommended dosage of RINVOQ is 15 mg once daily in combination with a tapering course of corticosteroids.

RINVOQ 15 mg once daily can be used as monotherapy following discontinuation of corticosteroids.

2.12 Recommended Dosage in Patients with Renal Impairment or Hepatic Impairment

Renal Impairment

Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Non-radiographic Axial Spondyloarthritis, pJIA, and Giant Cell Arteritis:

• No dosage adjustment is needed for patients with mild, moderate, or severe renal impairment.

Atopic Dermatitis:

• For patients with severe renal impairment [estimated glomerular filtration rate (eGFR) 15 to < 30 mL/min/1.73m²] the recommended dosage of RINVOQ is 15 mg once daily [see Use in Specific Populations (8.6)].

• No dosage adjustment is needed for patients with mild or moderate renal impairment (eGFR ≥ 30 mL/min/1.73m²).

• RINVOQ is not recommended for use in patients with end stage renal disease (eGFR < 15 mL/min/1.73m²) [see Use in Specific Populations (8.6)].

Ulcerative Colitis:

• For patients with severe renal impairment (eGFR 15 to < 30 mL/min/1.73m²), the recommended dosage of RINVOQ is:

• Induction: 30 mg once daily for 8 weeks

• Maintenance: 15 mg once daily

• No dosage adjustment is needed for patients with mild or moderate renal impairment (eGFR ≥ 30 mL/min/1.73m²).

• RINVOQ is not recommended for use in patients with end stage renal disease (eGFR < 15 mL/min/1.73m²) [see Use in Specific Populations (8.6)].

Crohn’s Disease:

• For patients with severe renal impairment (eGFR 15 to < 30 mL/min/1.73m²), the recommended dosage of RINVOQ is:

• Induction: 30 mg once daily for 12 weeks

• Maintenance: 15 mg once daily

• No dosage adjustment is needed for patients with mild or moderate renal impairment (eGFR ≥ 30 mL/min/1.73m²).

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• RINVOQ is not recommended for use in patients with end stage renal disease (eGFR < 15 mL/min/1.73m²) [see Use in Specific Populations (8.6)].

Hepatic Impairment

RINVOQ/RINVOQ LQ is not recommended for use in patients with severe hepatic impairment (Child-Pugh C) [see Use in Specific Populations (8.7)].

Rheumatoid Arthritis, Psoriatic Arthritis, Atopic Dermatitis, Ankylosing Spondylitis, Nonradiographic Axial Spondyloarthritis, pJIA, and Giant Cell Arteritis:

What is RINVOQ/RINVOQ LQ? RINVOQ/RINVOQ LQ is a prescription medicine that is a Janus kinase (JAK) inhibitor.

• RINVOQ is used to treat adults with moderate to severe rheumatoid arthritis when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.

• RINVOQ is used to treat adults with active psoriatic arthritis when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.

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• RINVOQ is used to treat adults and children 12 years of age and older with moderate to severe eczema (atopic dermatitis) that did not respond to previous treatment and their eczema is not well controlled with other pills or injections, including biologic medicines, or the use of other pills or injections is not recommended.

• RINVOQ is used to treat adults with moderate to severe ulcerative colitis when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used and did not work well or could not be tolerated, or after taking a different injection or pill (systemic therapy) when your healthcare provider does not recommend TNF blockers.

• RINVOQ is used to treat adults with moderate to severe Crohn’s disease when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used and did not work well or could not be tolerated, or after taking a different injection or pill (systemic therapy) when your healthcare provider does not recommend TNF blockers.

• RINVOQ is used to treat adults with active ankylosing spondylitis when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.

• RINVOQ is used to treat adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation when a tumor necrosis factor (TNF) blocker medicine has been used, and did not work well or could not be tolerated.

• RINVOQ/RINVOQ LQ is used to treat children 2 years of age and older with active polyarticular juvenile idiopathic arthritis (pJIA) when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.

• RINVOQ/RINVOQ LQ is used to treat children 2 to less than 18 years of age with active psoriatic arthritis when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.

• RINVOQ is used to treat adults with giant cell arteritis.

It is not known if RINVOQ/RINVOQ LQ is safe and effective in children with ankylosing spondylitis, non-radiographic axial spondyloarthritis, ulcerative colitis, or Crohn’s disease.

It is not known if RINVOQ is safe and effective in children under 12 years of age with atopic dermatitis.

It is not known if RINVOQ LQ is safe and effective in children with atopic dermatitis.

It is not known if RINVOQ/RINVOQ LQ is safe and effective in children under 2 years of age with pJIA or psoriatic arthritis. Do not take RINVOQ/RINVOQ LQ if you are allergic to upadacitinib or any of the ingredients in RINVOQ/RINVOQ LQ. See the end of this Medication Guide for a complete list of ingredients in RINVOQ/RINVOQ LQ.

Before taking RINVOQ/RINVOQ LQ, tell your healthcare provider about all of your medical conditions, including if you:

• See “What is the most important information I should know about RINVOQ/RINVOQ LQ?”

• have an infection.

• are a current or past smoker.

• have had a heart attack, other heart problems, or stroke.

• have liver problems.

• have kidney problems.

• have unexplained stomach (abdominal) pain, have a history of diverticulitis or ulcers in your stomach or intestines, or are taking NSAIDs.

• have diabetes.

• have low red or white blood cell counts.

• have recently received or are scheduled to receive an immunization (vaccine). People who take RINVOQ/RINVOQ LQ should not receive live vaccines.

• are pregnant or plan to become pregnant. Based on animal studies, RINVOQ/RINVOQ LQ may harm your unborn baby. Females who are able to become pregnant:

o Your healthcare provider will check whether or not you are pregnant before you start treatment with RINVOQ/RINVOQ LQ.

o You should use effective birth control (contraception) to avoid becoming pregnant during treatment with RINVOQ/RINVOQ LQ and for 4 weeks after your last dose of RINVOQ/RINVOQ LQ.

o Tell your healthcare provider if you think you are pregnant or become pregnant during treatment with RINVOQ/RINVOQ LQ.

o There is a pregnancy surveillance program for RINVOQ/RINVOQ LQ. The purpose of the program is to collect information about the health of you and your baby. If you become pregnant while taking RINVOQ/RINVOQ LQ, you are encouraged to report the pregnancy by calling 1-800-633-9110.

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• flu

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• increased blood levels of creatine phosphokinase
• cough

• tiredness
• low white blood cell count (neutropenia)

Active ingredient: upadacitinib Inactive ingredients: colloidal silicon dioxide, ferrosoferric oxide, hypromellose, iron oxide red, magnesium stearate, mannitol, microcrystalline cellulose, polyvinyl alcohol, polyethylene glycol, talc, tartaric acid and titanium dioxide.

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What are the ingredients in RINVOQ 30 mg tablets? Active ingredient: upadacitinib Inactive ingredients: colloidal silicon dioxide, hypromellose, iron oxide red, magnesium stearate, mannitol, microcrystalline cellulose, polyvinyl alcohol, polyethylene glycol, talc, tartaric acid and titanium dioxide. What are the ingredients in RINVOQ 45 mg tablets? Active ingredient: upadacitinib Inactive ingredients: colloidal silicon dioxide, hypromellose, iron oxide yellow and iron oxide red, magnesium stearate, mannitol, microcrystalline cellulose, polyvinyl alcohol, polyethylene glycol, talc, tartaric acid and titanium dioxide. What are the ingredients in RINVOQ LQ? Active ingredient: upadacitinib Inactive ingredients: citric acid anhydrous, purified water, sodium benzoate, sodium citrate dihydrate and sucralose. Manufactured by: AbbVie Inc., North Chicago, IL 60064, USA RINVOQ^\circledR is a registered trademark of AbbVie Biotechnology Ltd. ©2019-2026 AbbVie Inc. For more information, call 1-800 2-RINVOQ (1-800-274-6867) or go to www.RINVOQ.com. This Medication Guide has been approved by the U.S. Food and Drug Administration 20101619