Get your patient on Rinvoq (Upadacitinib)

RINVOQ/RINVOQ LQ is a Janus kinase (JAK) inhibitor.

• 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. (
  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.
  )
  
  
  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. (
  1.1 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.
  )
  
  
• 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. (
  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.
  )
  
  
  Limitation
  s
  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. (
  1.2 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.
  )
  
  
• 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. (
  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.

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

  • Limitations of Use: RINVOQ is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or with other immunosuppressants.
  )
  
  
• RINVOQ is indicated for the treatment of adults 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.  (
  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.
  )
  
  
  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. (
  1.4 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.
  )
  
  
• RINVOQ is indicated for the treatment of adults 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. (
  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.
  )
  
  
  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. (
  1.5 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.
  )
  
  
• 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. (
  1.000000000000000e+00

  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.
  )
  
  
  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. (
  1.000000000000000e+00

  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.
  )
  
  
• 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. (
  1.000000000000000e+00

  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.
  )
  
  
  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. (
  1.000000000000000e+00

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

  • 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.
  )
  
  
  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. (
  1.8 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.

  • 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.
  )
  
  
• RINVOQ is indicated for the treatment of adults with giant cell arteritis (
  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.
  )
  
  
  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. (
  1.9 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.
  )

• RINVOQ
  LQ
   
  oral solution
  is not substitutable with
  RINVOQ extended-release tablets
   (
  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
    )].
    
    
    
  • 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
    )].
  ,
  2.000000000000000e+00

  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

  Patient Weight	RINVOQ LQ	RINVOQ
  10 kg to less than 20 kg	3 mg (3 mL oral solution) twice daily	Not recommended
  20 kg to less than 30 kg	4 mg (4 mL oral solution) twice daily	Not recommended
  30 kg and greater	6 mg (6 mL oral solution) twice daily	15 mg (one 15 mg tablet) once daily

  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.
  ).
  
  
• Changes between RINVOQ LQ oral solution and RINVOQ extended-release tablets should be made by the healthcare provider.
  
  
• Prior to treatment update immunizations and consider evaluating for active and latent tuberculosis, viral hepatitis, hepatic function, and pregnancy status (
  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 (
    5.8
    )]
    .
    
    
    
  • 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 (
    5.9
    ) and Use in Specific Populations (
    8.1
    ,
    8.3
    )].

  Update immunizations according to current immunization guidelines

  [see Warnings and Precautions (

  5.10

  )].
  )
  
  
• Avoid initiation or interrupt RINVOQ/RINVOQ LQ if absolute lymphocyte count is less than 500 cells/mm³, absolute neutrophil count is less than 1000 cells/mm³, or hemoglobin level is less than 8 g/dL. (
  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 (
    5.8
    )]
    .
    
    
    
  • 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 (
    5.9
    ) and Use in Specific Populations (
    8.1
    ,
    8.3
    )].

  Update immunizations according to current immunization guidelines

  [see Warnings and Precautions (

  5.10

  )].
  , 
  2.000000000000000e+00

  1

  4

  Dosage Interruption

  Infections

  If a patient develops a serious infection, including serious opportunistic infection, interrupt RINVOQ/RINVOQ LQ treatment until the infection is controlled

  [see Warnings and Precautions (

  5.1

  )]

  .

  Laboratory Abnormalities

  Interruption of dosing may be needed for management of laboratory abnormalities as described in Table 3

  [see Warnings and Precautions (

  5.8

  )]

  .

  Table 3: Recommended Dosage Interruptions for Laboratory Abnormalities

  Laboratory Measure	Action
  Absolute Neutrophil Count (ANC)	Interrupt treatment if ANC is less than 1000 cells/mm3; treatment may be restarted once ANC returns above this value
  Absolute Lymphocyte Count (ALC)	Interrupt treatment if ALC is less than 500 cells/mm3; treatment may be restarted once ALC returns above this value
  Hemoglobin (Hb)	Interrupt treatment if Hb is less than 8 g/dL; treatment may be restarted once Hb returns above this value
  Hepatic transaminases	Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded.
  )

• Adults:
  The recommended dosage of RINVOQ is 15 mg once daily. (
  2.3

  Recommended Dosage in Rheumatoid Arthritis

  The recommended dosage of RINVOQ is 15 mg once daily.
  ,
  2.000000000000000e+00

  8

  Recommended Dosage in

  Ankylosing Spondylitis

  The recommended dosage of RINVOQ is 15 mg once daily.
  , 
  2.000000000000000e+00

  9

  Recommend

  ed

  Dosage in Non-radiographic Axial Spondyloarthritis

  The recommended dosage of RINVOQ is 15 mg once daily.
  )

• Pediatric Patients 2 to less than 18 Years of Age Weighing at Least 10 kg:
   The recommended dosage is based on body weight (
  2.000000000000000e+00

  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

  Patient Weight	RINVOQ LQ	RINVOQ
  10 kg to less than 20 kg	3 mg (3 mL oral solution) twice daily	Not recommended
  20 kg to less than 30 kg	4 mg (4 mL oral solution) twice daily	Not recommended
  30 kg and greater	6 mg (6 mL oral solution) twice daily	15 mg (one 15 mg tablet) once daily

  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.
  )
  
  
• Adults:
  The recommended dosage of RINVOQ is 15 mg once daily. (
  2.000000000000000e+00

  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

  Patient Weight	RINVOQ LQ	RINVOQ
  10 kg to less than 20 kg	3 mg (3 mL oral solution) twice daily	Not recommended
  20 kg to less than 30 kg	4 mg (4 mL oral solution) twice daily	Not recommended
  30 kg and greater	6 mg (6 mL oral solution) twice daily	15 mg (one 15 mg tablet) once daily

  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.
  ) 

• 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 orally once daily. If an adequate response is not achieved, consider increasing the dosage to 30 mg orally 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.
  )
    
  
  
  
• Adults
  65 Years of Age
  and Older
  : 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.
  )
  
  
• Severe
  Renal Impairment
  : Recommended dosage of RINVOQ is 15 mg once daily. (
  2.1

  2

  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).
    
    
  • 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

  , Non-radiographic Axial Spondyloarthritis

  , pJIA

  , and Giant Cell Arteritis

  :

  No dosage adjustment is needed for patients with mild or moderate hepatic impairment (Child-Pugh A or B).

  Ulcerative Colitis:

  For patients with mild to moderate hepatic impairment (Child-Pugh A or B) the recommended dosage of RINVOQ is:

  • Induction:
    30 mg once daily for 8 weeks
    
    
  • Maintenance:
    15 mg once daily

  Crohn’s Disease:

  For patients with mild to moderate hepatic impairment (Child-Pugh A or B) the recommended dosage of RINVOQ is:

  • Induction:
    30 mg once daily for 12 weeks
    
    
  • Maintenance:
    15 mg once daily
  )

• Adults:
  The recommended induction dosage of RINVOQ is 45 mg once daily for 8 weeks. The recommended maintenance dosage of RINVOQ is 15 mg once daily. A maintenance dosage of 30 mg once daily may be considered for patients with refractory, severe, or extensive disease. Discontinue RINVOQ if adequate therapeutic response is not achieved with the 30 mg dosage. Use the lowest effective dosage needed to maintain response. (
  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.
  )
  
  
• See the Full Prescribing Information for the recommended dosage in patients with renal or hepatic impairment and for dosage modification due to drug interactions. (
  2.1

  2

  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).
    
    
  • 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

  , Non-radiographic Axial Spondyloarthritis

  , pJIA

  , and Giant Cell Arteritis

  :

  No dosage adjustment is needed for patients with mild or moderate hepatic impairment (Child-Pugh A or B).

  Ulcerative Colitis:

  For patients with mild to moderate hepatic impairment (Child-Pugh A or B) the recommended dosage of RINVOQ is:

  • Induction:
    30 mg once daily for 8 weeks
    
    
  • Maintenance:
    15 mg once daily

  Crohn’s Disease:

  For patients with mild to moderate hepatic impairment (Child-Pugh A or B) the recommended dosage of RINVOQ is:

  • Induction:
    30 mg once daily for 12 weeks
    
    
  • Maintenance:
    15 mg once daily
  ,
  2.000000000000000e+00

  1

  3

  Dosage Modifications Due to Drug Interactions

  Rheumatoid Arthritis, Psoriatic Arthritis,

  Ankylos

  ing

  Spondylitis

  , Non-radiographic Axial Spondyloarthritis

  , pJIA

  , and Giant Cell Arteritis

  No dosage adjustment is needed in patients receiving strong CYP3A4 inhibitors

  [see Drug Interactions (

  7.1

  )]

  .

  Atopic Dermatitis

  The recommended dosage of RINVOQ in patients receiving strong CYP3A4 inhibitors is 15 mg once daily

  [see Drug Interactions (

  7.1

  )]

  .

  Ulcerative Colitis

  The recommended dosage of RINVOQ in patients with ulcerative colitis receiving strong CYP3A4 inhibitors

  [see Drug Interactions

  (

  7.1

  )]:

  • Induction:
    30 mg once daily for 8 weeks
    
    
  • Maintenance:
    15 mg once daily

  Crohn’s Disease

  The recommended dosage of RINVOQ in patients with Crohn’s disease receiving strong CYP3A4 inhibitors

  [see Drug Interactions (

  7.1

  )]

  :

  • Induction:
    30 mg once daily for 12 weeks
    
    
  • Maintenance:
    15 mg once daily
  )

• Adults:
  The recommended induction dosage of RINVOQ is 45 mg once daily for 12 weeks. The recommended maintenance dosage of RINVOQ is 15 mg once daily. A maintenance 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.
  )
  
  
• See the Full Prescribing Information for the recommended dosage in patients with renal or hepatic impairment and for dosage modification due to drug interactions. (
  2.1

  2

  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).
    
    
  • 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

  , Non-radiographic Axial Spondyloarthritis

  , pJIA

  , and Giant Cell Arteritis

  :

  No dosage adjustment is needed for patients with mild or moderate hepatic impairment (Child-Pugh A or B).

  Ulcerative Colitis:

  For patients with mild to moderate hepatic impairment (Child-Pugh A or B) the recommended dosage of RINVOQ is:

  • Induction:
    30 mg once daily for 8 weeks
    
    
  • Maintenance:
    15 mg once daily

  Crohn’s Disease:

  For patients with mild to moderate hepatic impairment (Child-Pugh A or B) the recommended dosage of RINVOQ is:

  • Induction:
    30 mg once daily for 12 weeks
    
    
  • Maintenance:
    15 mg once daily
  ,
  2.000000000000000e+00

  1

  3

  Dosage Modifications Due to Drug Interactions

  Rheumatoid Arthritis, Psoriatic Arthritis,

  Ankylos

  ing

  Spondylitis

  , Non-radiographic Axial Spondyloarthritis

  , pJIA

  , and Giant Cell Arteritis

  No dosage adjustment is needed in patients receiving strong CYP3A4 inhibitors

  [see Drug Interactions (

  7.1

  )]

  .

  Atopic Dermatitis

  The recommended dosage of RINVOQ in patients receiving strong CYP3A4 inhibitors is 15 mg once daily

  [see Drug Interactions (

  7.1

  )]

  .

  Ulcerative Colitis

  The recommended dosage of RINVOQ in patients with ulcerative colitis receiving strong CYP3A4 inhibitors

  [see Drug Interactions

  (

  7.1

  )]:

  • Induction:
    30 mg once daily for 8 weeks
    
    
  • Maintenance:
    15 mg once daily

  Crohn’s Disease

  The recommended dosage of RINVOQ in patients with Crohn’s disease receiving strong CYP3A4 inhibitors

  [see Drug Interactions (

  7.1

  )]

  :

  • Induction:
    30 mg once daily for 12 weeks
    
    
  • Maintenance:
    15 mg once daily
  )

• The recommended dosage is based on body weight (
  2.000000000000000e+00

  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

  Patient Weight	RINVOQ LQ	RINVOQ
  10 kg to less than 20 kg	3 mg (3 mL oral solution) twice daily	Not recommended
  20 kg to less than 30 kg	4 mg (4 mL oral solution) twice daily	Not recommended
  30 kg and greater	6 mg (6 mL oral solution) twice daily	15 mg (one 15 mg tablet) once daily

  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.
  ) 

• 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 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.
  )

RINVOQ extended-release tablets:

• 15 mg upadacitinib: purple, biconvex oblong, with dimensions of 14 x 8 mm, and debossed with ‘a15’ on one side.
  
  
• 30 mg upadacitinib: red, biconvex oblong, with dimensions of 14 x 8 mm, and debossed with ‘a30’ on one side. 
  
  
• 45 mg upadacitinib: yellow to mottled yellow, biconvex oblong, with dimensions of 14 x 8 mm, and debossed with ‘a45’ on one side.

RINVOQ LQ oral solution:

• 1 mg/mL upadacitinib; clear, colorless to light yellow solution in bottle of 180 mL.

• Lactation
  : Advise not to breastfeed. (
  8.2 Lactation

  Risk Summary

  There are no data on the presence of upadacitinib in human milk, the effects on the breastfed infant, or the effects on milk production. Available pharmacodynamic/toxicological data in animals have shown excretion of upadacitinib in milk

  (see

  Data

  ).

  When a drug is present in animal milk, it is likely that 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 RINVOQ/RINVOQ LQ, and for 6 days (approximately 10 half-lives) after the last dose.

  Data

  A single oral dose of 10 mg/kg radiolabeled upadacitinib was administered to lactating female Sprague-Dawley rats on post-partum days 7-8. Drug exposure was approximately 30-fold greater in milk than in maternal plasma based on AUC_0-tvalues. Approximately 97% of drug-related material in milk was parent drug.
  )
  
  
• Hepatic Impairment
  : RINVOQ/RINVOQ LQ is not recommended in patients with severe hepatic impairment. (
  8.7 Hepatic Impairment

  The use of RINVOQ/RINVOQ LQ has not been studied in patients with severe hepatic impairment (Child Pugh C), and is therefore not recommended

  [see Dosage and Administration (

  2.12

  ) and Clinical Pharmacology (

  12.3

  )]

  .

  For patients with rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, pJIA, or giant cell arteritis, no dosage adjustment is needed in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment.

  For patients with ulcerative colitis or Crohn’s disease, the recommended dosage of RINVOQ for mild to moderate hepatic impairment is 30 mg once daily for induction and 15 mg once daily for maintenance

  [see Dosage and Administration (

  2.12

  )].
  )

RINVOQ/RINVOQ LQ is contraindicated in patients with known hypersensitivity to upadacitinib or any of its excipients

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

  Serious and sometimes fatal infections have been reported in patients receiving RINVOQ. The most frequent serious infections reported with RINVOQ included pneumonia and cellulitis

  [see Adverse Reactions (

  6.1

  )]

  . Among opportunistic infections, tuberculosis, multidermatomal herpes zoster, oral/esophageal candidiasis, and cryptococcosis, were reported with RINVOQ. A higher rate of serious infections was observed with RINVOQ 30 mg compared to RINVOQ 15 mg.

  Avoid use of RINVOQ/RINVOQ LQ in patients with an active, serious infection, including localized infections. Consider the risks and benefits of treatment prior to initiating RINVOQ/RINVOQ LQ in patients:

  • with chronic or recurrent infection
    
    
  • who have been exposed to tuberculosis
    
    
  • with a history of a serious or an opportunistic infection
    
    
  • who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or
    
    
  • with underlying conditions that may predispose them to infection.

  Closely monitor patients for the development of signs and symptoms of infection during and after treatment with RINVOQ/RINVOQ LQ. Interrupt RINVOQ/RINVOQ LQ if a patient develops a serious or opportunistic infection.

  A patient who develops a new infection during treatment with RINVOQ/RINVOQ LQ should undergo prompt and complete diagnostic testing appropriate for an immunocompromised patient; appropriate antimicrobial therapy should be initiated, the patient should be closely monitored, and RINVOQ/RINVOQ LQ should be interrupted if the patient is not responding to antimicrobial therapy. RINVOQ/RINVOQ LQ may be resumed once the infection is controlled.

  Tuberculosis

  Evaluate and test patients for latent and active tuberculosis (TB) infection prior to administration of RINVOQ/RINVOQ LQ. Patients with latent TB should be treated with standard antimycobacterial therapy before initiating RINVOQ/RINVOQ LQ. RINVOQ/RINVOQ LQ should not be given to patients with active TB. Consider anti-TB therapy prior to initiation of RINVOQ/RINVOQ LQ in patients with previously untreated latent TB or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but who have risk factors for TB infection.

  Consultation with a physician with expertise in the treatment of TB is recommended to aid in the decision about whether initiating anti-TB therapy is appropriate for an individual patient.

  During RINVOQ/RINVOQ LQ use, monitor patients for the development of signs and symptoms of TB, including patients who tested negative for latent TB infection prior to initiating therapy.

  Viral

  R

  eactivation

  Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster) and hepatitis B virus reactivation, were reported in clinical trials with RINVOQ

  [see Adverse Reactions (

  6.1

  )]

  . The risk of herpes zoster appears to be higher in patients treated with RINVOQ in Japan. If a patient develops herpes zoster, consider temporarily interrupting RINVOQ/RINVOQ LQ until the episode resolves.

  Screening for viral hepatitis and monitoring for reactivation should be performed in accordance with clinical guidelines before starting and during therapy with RINVOQ/RINVOQ LQ. Patients who were positive for hepatitis C antibody and hepatitis C virus RNA, were excluded from clinical trials. Patients who were positive for hepatitis B surface antigen or hepatitis B virus DNA were excluded from clinical trials. However, cases of hepatitis B reactivation were still reported in patients enrolled in the Phase 3 trials of RINVOQ. If hepatitis B virus DNA is detected while receiving RINVOQ/RINVOQ LQ, a liver specialist should be consulted.
  )
  
  
• Hypersensitivity
  : Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. Discontinue if a serious hypersensitivity reaction occurs. (
  5.000000000000000e+00

  6

  Hypersensitivity Reactions

  Serious hypersensitivity reactions such as anaphylaxis and angioedema were reported in patients receiving RINVOQ in clinical trials. If a clinically significant hypersensitivity reaction occurs, discontinue RINVOQ/RINVOQ LQ and institute appropriate therapy

  [see Adverse Reactions (

  6.1

  )]

  .
  ) 
  
  
• Gastrointestinal
  (GI)
  Perforations
  : Monitor patients at risk for GI perforations and promptly evaluate patients with symptoms. (
  5.000000000000000e+00

  7

  Gastrointestinal Perforations

  Gastrointestinal perforations have been reported in clinical trials with RINVOQ

  [see Adverse Reactions (

  6.1

  )

  ]

  .

  Monitor RINVOQ/RINVOQ LQ-treated patients who may be at risk for gastrointestinal perforation (e.g., patients with a 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.
  )
  
  
• Laboratory
  Abnormalities
  : Monitoring recommended due to potential changes in lymphocytes, neutrophils, hemoglobin, liver enzymes and lipids. (
  5.8 Laboratory Abnormalities

  Neutropenia

  Treatment with RINVOQ was associated with an increased incidence of neutropenia (ANC less than 1000 cells/mm³).

  Evaluate neutrophil counts at baseline and thereafter according to routine patient management. Avoid RINVOQ/RINVOQ LQ initiation and interrupt RINVOQ/RINVOQ LQ treatment in patients with a low neutrophil count (i.e., ANC less than 1000 cells/mm³)

  [see Dosage and Administration (

  2.1

  ,

  2.14

  )]

  .

  Lymphopenia

  ALC less than 500 cells/mm³were reported in RINVOQ-treated patients in clinical trials.

  Evaluate lymphocyte counts at baseline and thereafter according to routine patient management. Avoid RINVOQ/RINVOQ LQ initiation or interrupt RINVOQ/RINVOQ LQ treatment in patients with a low lymphocyte count (i.e., less than 500 cells/mm³)

  [see Dosage and Administration (

  2.1

  ,

  2.14

  )]

  .

  Anemia

  Decreases in hemoglobin levels to less than 8 g/dL were reported in RINVOQ-treated patients in clinical trials.

  Evaluate hemoglobin at baseline and thereafter according to routine patient management. Avoid RINVOQ/RINVOQ LQ initiation or interrupt RINVOQ/RINVOQ LQ treatment in patients with a low hemoglobin level (i.e., less than 8 g/dL)

  [see Dosage and Administration (

  2.1

  ,

  2.14

  )]

  .

  Lipids

  Treatment with RINVOQ was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol

  [see Adverse Reactions (

  6.1

  )]

  . Elevations in LDL cholesterol decreased to pre-treatment levels in response to statin therapy. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined.

  Assess lipid parameters approximately 12 weeks after initiation of treatment, and thereafter according to the clinical guidelines for hyperlipidemia. Manage patients according to clinical guidelines for the management of hyperlipidemia.

  Liver Enzyme Elevations

  Treatment with RINVOQ was associated with increased incidence of liver enzyme elevations compared to treatment with placebo.

  Evaluate liver enzymes at baseline and thereafter according to routine patient management. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury.

  If increases in ALT or AST are observed during routine patient management and drug-induced liver injury is suspected, RINVOQ/RINVOQ LQ should be interrupted until this diagnosis is excluded.
  )
  
  
• 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. (
  5.000000000000000e+00

  9

  Embryo-Fetal Toxicity

  Based on findings in animal studies, RINVOQ/RINVOQ LQ may cause fetal harm when administered to a pregnant woman. Administration of upadacitinib to rats and rabbits during organogenesis caused increases in fetal malformations. Verify the pregnancy status of patients of reproductive potential prior to starting treatment. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception during treatment with RINVOQ/RINVOQ LQ and for 4 weeks following completion of therapy

  [see Use in Specific Populations (

  8.1

  ,

  8.3

  )]

  .
  ,
  8.1 Pregnancy

  Pregnancy Surveillance Program

  There is a pregnancy surveillance program for RINVOQ/RINVOQ LQ that monitors pregnancy outcomes in women exposed to RINVOQ/RINVOQ LQ. If RINVOQ/RINVOQ LQ exposure occurs during pregnancy, healthcare providers or patients should report the pregnancy by calling 1-800-633-9110.

  Risk Summary

  Available data from the pharmacovigilance safety database and postmarketing case reports on use of RINVOQ in pregnant women are not sufficient to evaluate a drug-associated risk for major birth defects or miscarriage. Based on animal studies, RINVOQ/RINVOQ LQ has the potential to adversely affect a developing fetus. Advise patients of reproductive potential and pregnant patients of the potential risk to the fetus.

  In animal embryo-fetal development studies, oral upadacitinib administration to pregnant rats and rabbits at exposures equal to or greater than approximately 1.6 and 15 times the 15 mg tablet dose, 0.8 and 7.6 times the 30 mg tablet dose, and 0.6 and 5.6 times the maximum recommended human dose (MRHD) of 45 mg (on an AUC basis) resulted in dose-related increases in skeletal malformations (rats only), an increased incidence of cardiovascular malformations (rabbits only), increased post-implantation loss (rabbits only), and decreased fetal body weights in both rats and rabbits. No developmental toxicity was observed in pregnant rats and rabbits treated with oral upadacitinib during organogenesis at exposures approximately 0.29 and 2.2 times the 15 mg dose, 0.15 times and 1.1 times the 30 mg dose, and at 0.11 and 0.82 times the MRHD (on an AUC basis). In a pre- and post-natal development study in pregnant female rats, oral upadacitinib administration at exposures approximately 3 times the 15 mg dose, 1.4 times the 30 mg dose, and the same as the MRHD (on an AUC basis) resulted in no maternal or developmental toxicity (

  see

  Data

  )

  .

  The background risks of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages are 2-4% and 15-20%, respectively.

  Clinical Considerations

  Disease-Associated Maternal and/or Embryo/Fetal Risk

  Published data suggest that increased disease activity is associated with the risk of developing adverse pregnancy outcomes in women with rheumatoid arthritis or inflammatory bowel disease. 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.

  Data

  Animal Data

  In an oral embryo-fetal development study, pregnant rats received upadacitinib at doses of 5, 25, and 75 mg/kg/day during the period of organogenesis from gestation day 6 to 17. Upadacitinib was teratogenic (skeletal malformations that consisted of misshapen humerus and bent scapula) at exposures equal to or greater than approximately 1.7 times the 15 mg tablet dose, 0.9 times the 30 mg tablet dose, and 0.6 times the MRHD (on an AUC basis at maternal oral doses of 5 mg/kg/day and higher). Additional skeletal malformations (bent forelimbs/hindlimbs and rib/vertebral defects) and decreased fetal body weights were observed in the absence of maternal toxicity at an exposure approximately 84 times the 15 mg dose, 43 times the 30 mg dose, and 31 times the MRHD (on an AUC basis at a maternal oral dose of 75 mg/kg/day).

  In a second oral embryo-fetal development study, pregnant rats received upadacitinib at doses of 1.5 and 4 mg/kg/day during the period of organogenesis from gestation day 6 to 17. Upadacitinib was teratogenic (skeletal malformations that included bent humerus and scapula) at exposures approximately 1.6 times the 15 mg dose, 0.8 times the 30 mg dose, and 0.6 times the MRHD (on an AUC basis at maternal oral doses of 4 mg/kg/day). No developmental toxicity was observed in rats at an exposure approximately 0.29 times the 15 mg tablet dose, 0.15 times the 30 mg tablet dose, and 0.11 times the MRHD (on an AUC basis at a maternal oral dose of 1.5 mg/kg/day).

  In an oral embryo-fetal developmental study, pregnant rabbits received upadacitinib at doses of 2.5, 10, and 25 mg/kg/day during the period of organogenesis from gestation day 7 to 19. Embryolethality, decreased fetal body weights, and cardiovascular malformations were observed in the presence of maternal toxicity at an exposure approximately 15 times the 15 mg tablet dose, 7.6 times the 30 mg tablet dose, and 5.6 times the MRHD (on an AUC basis at a maternal oral dose of 25 mg/kg/day). Embryolethality consisted of increased post-implantation loss that was due to elevated incidences of both total and early resorptions. No developmental toxicity was observed in rabbits at an exposure approximately 2.2 times the 15 mg tablet dose, 1.1 times the 30 mg tablet dose, and 0.82 times the MRHD (on an AUC basis at a maternal oral dose of 10 mg/kg/day).

  In an oral pre- and post-natal development study, pregnant female rats received upadacitinib at doses of 2.5, 5, and 10 mg/kg/day from gestation day 6 through lactation day 20. No maternal or developmental toxicity was observed in either mothers or offspring, respectively, at an exposure approximately 3 times the 15 mg tablet dose, 1.4 times the 30 mg tablet dose, and at approximately the same exposure as the MRHD (on an AUC basis at a maternal oral dose of 10 mg/kg/day).
  ,
  8.3 Females and Males of Reproductive Potential

  Pregnancy Testing

  Verify the pregnancy status of females of reproductive potential prior to starting treatment with RINVOQ/RINVOQ LQ

  [see Use in Specific Populations (

  8.1

  )]

  .

  Contraception

  Females

  Based on animal studies, upadacitinib may cause embryo-fetal harm when administered to pregnant women

  [see Use in Specific Populations (

  8.1

  )]

  . Advise female patients of reproductive potential to use effective contraception during treatment with RINVOQ/RINVOQ LQ and for 4 weeks after the final dose.
  )
  
  
• Vaccinations
  : Avoid use with live vaccines. (
  5.000000000000000e+00

  10

  Vaccination

  s

  Avoid use of live vaccines during or immediately prior to RINVOQ/RINVOQ LQ therapy initiation. Prior to initiating RINVOQ/RINVOQ LQ treatment, it is recommended that patients be brought up to date with all immunizations, including prophylactic varicella zoster or herpes zoster vaccinations, in agreement with current immunization guidelines.
  )
  
  
• 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. (
  5.11 Medication Residue in Stool

  Reports of medication residue in stool or ostomy output have occurred in patients taking RINVOQ. Most reports described anatomic (e.g., ileostomy, colostomy, intestinal resection) or functional gastrointestinal conditions with shortened gastrointestinal transit times. Instruct patients to contact their healthcare provider if medication residue is observed repeatedly. Monitor patients clinically and consider alternative treatment if there is an inadequate therapeutic response.
  )

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Serious Infections
  [see Warnings and Precautions (
  5.1 Serious Infections

  Serious and sometimes fatal infections have been reported in patients receiving RINVOQ. The most frequent serious infections reported with RINVOQ included pneumonia and cellulitis

  [see Adverse Reactions (

  6.1

  )]

  . Among opportunistic infections, tuberculosis, multidermatomal herpes zoster, oral/esophageal candidiasis, and cryptococcosis, were reported with RINVOQ. A higher rate of serious infections was observed with RINVOQ 30 mg compared to RINVOQ 15 mg.

  Avoid use of RINVOQ/RINVOQ LQ in patients with an active, serious infection, including localized infections. Consider the risks and benefits of treatment prior to initiating RINVOQ/RINVOQ LQ in patients:

  • with chronic or recurrent infection
    
    
  • who have been exposed to tuberculosis
    
    
  • with a history of a serious or an opportunistic infection
    
    
  • who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or
    
    
  • with underlying conditions that may predispose them to infection.

  Closely monitor patients for the development of signs and symptoms of infection during and after treatment with RINVOQ/RINVOQ LQ. Interrupt RINVOQ/RINVOQ LQ if a patient develops a serious or opportunistic infection.

  A patient who develops a new infection during treatment with RINVOQ/RINVOQ LQ should undergo prompt and complete diagnostic testing appropriate for an immunocompromised patient; appropriate antimicrobial therapy should be initiated, the patient should be closely monitored, and RINVOQ/RINVOQ LQ should be interrupted if the patient is not responding to antimicrobial therapy. RINVOQ/RINVOQ LQ may be resumed once the infection is controlled.

  Tuberculosis

  Evaluate and test patients for latent and active tuberculosis (TB) infection prior to administration of RINVOQ/RINVOQ LQ. Patients with latent TB should be treated with standard antimycobacterial therapy before initiating RINVOQ/RINVOQ LQ. RINVOQ/RINVOQ LQ should not be given to patients with active TB. Consider anti-TB therapy prior to initiation of RINVOQ/RINVOQ LQ in patients with previously untreated latent TB or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but who have risk factors for TB infection.

  Consultation with a physician with expertise in the treatment of TB is recommended to aid in the decision about whether initiating anti-TB therapy is appropriate for an individual patient.

  During RINVOQ/RINVOQ LQ use, monitor patients for the development of signs and symptoms of TB, including patients who tested negative for latent TB infection prior to initiating therapy.

  Viral

  R

  eactivation

  Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster) and hepatitis B virus reactivation, were reported in clinical trials with RINVOQ

  [see Adverse Reactions (

  6.1

  )]

  . The risk of herpes zoster appears to be higher in patients treated with RINVOQ in Japan. If a patient develops herpes zoster, consider temporarily interrupting RINVOQ/RINVOQ LQ until the episode resolves.

  Screening for viral hepatitis and monitoring for reactivation should be performed in accordance with clinical guidelines before starting and during therapy with RINVOQ/RINVOQ LQ. Patients who were positive for hepatitis C antibody and hepatitis C virus RNA, were excluded from clinical trials. Patients who were positive for hepatitis B surface antigen or hepatitis B virus DNA were excluded from clinical trials. However, cases of hepatitis B reactivation were still reported in patients enrolled in the Phase 3 trials of RINVOQ. If hepatitis B virus DNA is detected while receiving RINVOQ/RINVOQ LQ, a liver specialist should be consulted.
  )]
  
  
  
• Mortality
  [see Warnings and Precautions (
  5.2 Mortality

  In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, 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 the benefits and risks for the individual patient prior to initiating or continuing therapy with RINVOQ/RINVOQ LQ.
  )]
  
  
  
• Malignancy and Lymphoproliferative Disorders 
  [see Warnings and Precautions (
  5.000000000000000e+00

  3

  Malignancy

  and Lymphoproliferative Disorders

  Malignancies, including lymphomas, were observed in clinical trials of RINVOQ

  [see Adverse Reactions (

  6.1

  )]

  .

  In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients, a higher rate of malignancies (excluding NMSC) was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lymphomas was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lung cancers was observed in current or past smokers treated with the JAK inhibitor compared to those treated with TNF blockers. In this study, current or past smokers had an additional increased risk of overall malignancies.

  Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with RINVOQ/RINVOQ LQ, particularly in patients with a known malignancy (other than a successfully treated NMSC), patients who develop a malignancy when on treatment, and patients who are current or past smokers.

  Non-Melanoma Skin Cancer

  NMSCs have been reported in patients treated with RINVOQ. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

  Exposure to sunlight and UV light should be limited by wearing protective clothing and using a broad-spectrum sunscreen.
  )]
  
  
  
• Major Adverse Cardiovascular Events
  [see Warnings and Precautions (
  5.4 Major Adverse Cardiovascular Events

  In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of major adverse cardiovascular events (MACE) defined as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke was observed with the JAK inhibitor compared to those treated with TNF blockers. Patients who are current or past smokers are at additional increased risk.

  Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with RINVOQ/RINVOQ LQ, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. Discontinue RINVOQ/RINVOQ LQ in patients that have experienced a myocardial infarction or stroke.
  )]
  
  
  
• Thrombosis
  [see Warnings and Precautions (
  5.000000000000000e+00

  5

  Thrombosis

  Thromboses, including deep venous thrombosis (DVT), pulmonary embolism (PE), 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

  [see Adverse Reactions (

  6.1

  )]

  .

  In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, higher rates of overall thrombosis, DVT, and PE were observed compared to those treated with TNF blockers.

  If symptoms of thrombosis occur, patients should discontinue RINVOQ/RINVOQ LQ and be evaluated promptly and treated appropriately. Avoid RINVOQ/RINVOQ LQ in patients that may be at increased risk of thrombosis.
  )]
  
  
  
• Hypersensitivity Reactions 
  [see Warnings and Precautions
  (
  5.000000000000000e+00

  6

  Hypersensitivity Reactions

  Serious hypersensitivity reactions such as anaphylaxis and angioedema were reported in patients receiving RINVOQ in clinical trials. If a clinically significant hypersensitivity reaction occurs, discontinue RINVOQ/RINVOQ LQ and institute appropriate therapy

  [see Adverse Reactions (

  6.1

  )]

  .
  )]
  
  
  
• Gastrointestinal Perforations
  [see Warnings and Precautions (
  5.000000000000000e+00

  7

  Gastrointestinal Perforations

  Gastrointestinal perforations have been reported in clinical trials with RINVOQ

  [see Adverse Reactions (

  6.1

  )

  ]

  .

  Monitor RINVOQ/RINVOQ LQ-treated patients who may be at risk for gastrointestinal perforation (e.g., patients with a 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.
  )]
  
  
  
• Laboratory Abnormalities 
  [see Warnings and Precautions (
  5.8 Laboratory Abnormalities

  Neutropenia

  Treatment with RINVOQ was associated with an increased incidence of neutropenia (ANC less than 1000 cells/mm³).

  Evaluate neutrophil counts at baseline and thereafter according to routine patient management. Avoid RINVOQ/RINVOQ LQ initiation and interrupt RINVOQ/RINVOQ LQ treatment in patients with a low neutrophil count (i.e., ANC less than 1000 cells/mm³)

  [see Dosage and Administration (

  2.1

  ,

  2.14

  )]

  .

  Lymphopenia

  ALC less than 500 cells/mm³were reported in RINVOQ-treated patients in clinical trials.

  Evaluate lymphocyte counts at baseline and thereafter according to routine patient management. Avoid RINVOQ/RINVOQ LQ initiation or interrupt RINVOQ/RINVOQ LQ treatment in patients with a low lymphocyte count (i.e., less than 500 cells/mm³)

  [see Dosage and Administration (

  2.1

  ,

  2.14

  )]

  .

  Anemia

  Decreases in hemoglobin levels to less than 8 g/dL were reported in RINVOQ-treated patients in clinical trials.

  Evaluate hemoglobin at baseline and thereafter according to routine patient management. Avoid RINVOQ/RINVOQ LQ initiation or interrupt RINVOQ/RINVOQ LQ treatment in patients with a low hemoglobin level (i.e., less than 8 g/dL)

  [see Dosage and Administration (

  2.1

  ,

  2.14

  )]

  .

  Lipids

  Treatment with RINVOQ was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol

  [see Adverse Reactions (

  6.1

  )]

  . Elevations in LDL cholesterol decreased to pre-treatment levels in response to statin therapy. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined.

  Assess lipid parameters approximately 12 weeks after initiation of treatment, and thereafter according to the clinical guidelines for hyperlipidemia. Manage patients according to clinical guidelines for the management of hyperlipidemia.

  Liver Enzyme Elevations

  Treatment with RINVOQ was associated with increased incidence of liver enzyme elevations compared to treatment with placebo.

  Evaluate liver enzymes at baseline and thereafter according to routine patient management. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury.

  If increases in ALT or AST are observed during routine patient management and drug-induced liver injury is suspected, RINVOQ/RINVOQ LQ should be interrupted until this diagnosis is excluded.
  )]

• Strong CYP3A4 Inhibitors
  : See the Full Prescribing Information for dosage modification for patients with atopic dermatitis, ulcerative colitis, and Crohn’s disease. (
  2.000000000000000e+00

  1

  3

  Dosage Modifications Due to Drug Interactions

  Rheumatoid Arthritis, Psoriatic Arthritis,

  Ankylos

  ing

  Spondylitis

  , Non-radiographic Axial Spondyloarthritis

  , pJIA

  , and Giant Cell Arteritis

  No dosage adjustment is needed in patients receiving strong CYP3A4 inhibitors

  [see Drug Interactions (

  7.1

  )]

  .

  Atopic Dermatitis

  The recommended dosage of RINVOQ in patients receiving strong CYP3A4 inhibitors is 15 mg once daily

  [see Drug Interactions (

  7.1

  )]

  .

  Ulcerative Colitis

  The recommended dosage of RINVOQ in patients with ulcerative colitis receiving strong CYP3A4 inhibitors

  [see Drug Interactions

  (

  7.1

  )]:

  • Induction:
    30 mg once daily for 8 weeks
    
    
  • Maintenance:
    15 mg once daily

  Crohn’s Disease

  The recommended dosage of RINVOQ in patients with Crohn’s disease receiving strong CYP3A4 inhibitors

  [see Drug Interactions (

  7.1

  )]

  :

  • Induction:
    30 mg once daily for 12 weeks
    
    
  • Maintenance:
    15 mg once daily
  , 
  7.1 Strong CYP3A4 Inhibitors

  Upadacitinib exposure is increased when it is co-administered with a strong CYP3A4 inhibitor (such as ketoconazole, clarithromycin, and grapefruit), which may increase the risk of adverse reactions

  [see Clinical Pharmacology (

  12.3

  )]

  . Monitor patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondylarthritis, pJIA, or giant cell arteritis closely for adverse reactions when co-administering RINVOQ/RINVOQ LQ with strong CYP3A4 inhibitors. Food or drink containing grapefruit should be avoided during treatment with RINVOQ/RINVOQ LQ.

  For patients with atopic dermatitis, coadministration of RINVOQ 30 mg once daily with strong CYP3A4 inhibitors is not recommended.

  For patients with ulcerative colitis or Crohn’s disease taking strong CYP3A4 inhibitors, reduce the RINVOQ induction dosage to 30 mg once daily. The recommended maintenance dosage is 15 mg once daily

  [see Dosage and Administration (

  2.13

  )]

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

  Upadacitinib exposure is decreased when it is co-administered with strong CYP3A4 inducers (such as rifampin), which may lead to reduced therapeutic effect

  [see Clinical Pharmacology (

  12.3

  )]

  . Coadministration of RINVOQ/RINVOQ LQ with strong CYP3A4 inducers is not recommended.
  )

RINVOQ and RINVOQ LQ are formulated with upadacitinib, a JAK inhibitor.

Upadacitinib has the following chemical name: (3

The strength of upadacitinib is based on anhydrous upadacitinib. The solubility of upadacitinib in water is 38 to less than 0.2 mg/mL across a pH range of 2 to 9 at 37 ^oC.

Upadacitinib has a molecular weight of 389.38 g/mol and a molecular formula of C₁₇H₁₉F₃N₆O • ½ H₂O. The chemical structure of upadacitinib is:

RINVOQ 15 mg extended-release tablets for oral administration are purple, biconvex oblong, with dimensions of 14 x 8 mm, and debossed with ‘a15’ on one side. Each tablet contains the following 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.

RINVOQ 30 mg extended-release tablets for oral administration are red, biconvex oblong, with dimensions of 14 x 8 mm, and debossed with ‘a30’ on one side. Each tablet contains the following inactive ingredients: colloidal silicon dioxide, hypromellose, iron oxide red, magnesium stearate, mannitol, microcrystalline cellulose, polyvinyl alcohol, polyethylene glycol, talc, tartaric acid and titanium dioxide. 

RINVOQ 45 mg extended-release tablets for oral administration are yellow to mottled yellow, biconvex oblong, with dimensions of 14 x 8 mm, and debossed with ‘a45’ on one side. Each tablet contains the following inactive ingredients: colloidal silicon dioxide, hypromellose, iron oxide yellow, iron oxide red, magnesium stearate, mannitol, microcrystalline cellulose, polyvinyl alcohol, polyethylene glycol, talc, tartaric acid and titanium dioxide.

RINVOQ LQ oral solution for oral administration is a 1 mg/mL clear, colorless to light yellow solution. Each 1 mL RINVOQ LQ contains 1 mg of upadacitinib as free base (equivalent to 1.02 mg upadacitinib hemihydrate) and the following inactive ingredients: citric acid anhydrous, purified water, sodium benzoate, sodium citrate dihydrate, and sucralose. 

Upadacitinib is a Janus kinase (JAK) inhibitor. JAKs are intracellular enzymes which transmit signals arising from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoiesis and immune cell function. Within the signaling pathway, JAKs phosphorylate and activate signal transducers and activators of transcription (STATs) which modulate intracellular activity including gene expression. Upadacitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs.

JAK enzymes transmit cytokine signaling through their pairing (e.g., JAK1/JAK2, JAK1/JAK3, JAK1/TYK2, JAK2/JAK2, JAK2/TYK2). In a cell-free isolated enzyme assay, upadacitinib had greater inhibitory potency at JAK1 and JAK2 relative to JAK3 and TYK2. In human leukocyte cellular assays, upadacitinib inhibited cytokine-induced STAT phosphorylation mediated by JAK1 and JAK1/JAK3 more potently than JAK2/JAK2 mediated STAT phosphorylation. The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.

The carcinogenic potential of upadacitinib was evaluated in Sprague-Dawley rats and Tg.rasH2 mice. No evidence of tumorigenicity was observed in male or female rats that received upadacitinib for up to 101 weeks at oral doses up to 15 or 20 mg/kg/day, respectively (approximately 4 and 10 times the 15 mg tablet dose, 2 and 5 times the 30 mg tablet dose, and 1.6 and 4 times the maximum recommended human dose (MRHD) of 45 mg on an AUC basis, respectively). No evidence of tumorigenicity was observed in male or female Tg.rasH2 mice that received upadacitinib for 26 weeks at oral doses up to 20 mg/kg/day.

Upadacitinib tested negative in the following genotoxicity assays: the

Upadacitinib had no effect on fertility in male or female rats at oral doses up to 50 mg/kg/day in males and 75 mg/kg/day in females (approximately 42 and 84 times the 15 mg dose, 22 and 43 times the 30 mg dose, and 16 and 31 times the MRHD, respectively, on an AUC basis). However, maintenance of pregnancy was adversely affected at oral doses of 25 mg/kg/day and 75 mg/kg/day based upon dose-related findings of increased post-implantation losses (increased resorptions) and decreased numbers of mean viable embryos per litter (approximately 22 and 84 times the 15 mg tablet dose, 11 and 43 times the 30 mg tablet dose, and 8 and 31 times the MRHD on an AUC basis, respectively). The number of viable embryos was unaffected in female rats that received upadacitinib at an oral dose of 5 mg/kg/day and were mated to males that received the same dose (approximately 2 times the 15 mg dose, 0.9 times the 30 mg dose, and at 0.6 times the MRHD on an AUC basis).

RINVOQ extended-release tablets are supplied as:

• 15 mg: purple, biconvex oblong, with dimensions of 14 x 8 mm, and debossed with ‘a15’ on one side.
  
  30 tablets in a bottle; NDC: 0074-2306-30
  
  
• 30 mg: red, biconvex oblong, with dimensions of 14 x 8 mm, and debossed with ‘a30’ on one side.
  
  30 tablets in a bottle; NDC: 0074-2310-30
  
  
• 45 mg: yellow to mottled yellow, biconvex oblong, with dimensions of 14 x 8 mm, and debossed with ‘a45’ on one side.
  
  28 tablets in a bottle; NDC: 0074-1043-28 

RINVOQ LQ oral solution is supplied as:

• A 1 mg/mL oral solution in HDPE bottles with a child-resistant cap. Each bottle contains a labeled volume of 180 mL of clear, colorless to light yellow solution. The bottle is packaged in a carton with one press-in bottle adapter and one 10 mL oral dosing syringe; NDC: 0074-2320-01

RINVOQ extended-release tablets

• Store at 2˚C to 25˚C (36˚F to 77˚F).
  
  
• Store in the original bottle in order to protect from moisture. 

RINVOQ LQ oral solution

• Store between 2°C to 30°C (36°F to 86°F).
  
  
• Discard remaining oral solution 60 days after opening the bottle.

oral solution

Read this Instructions for Use before you give RINVOQ LQ to your child, and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your child’s medical condition or treatment.

     
Keep the bottle and supplies out of sight and reach of children.

     
Only use the syringe provided.

     
Call your healthcare provider or 1-800-2-RINVOQ or 1-800-274-6867 if you need help or have any questions about how to give RINVOQ LQ the right way.

     
Contact your healthcare provider if your child takes too much oral solution or does not receive the full dose.

• Use RINVOQ LQ within 60 days of opening the bottle. To help you remember, write the date you opened the bottle on the carton.
  
  
• Do not
  open a new bottle of RINVOQ LQ until you have finished the previous bottle. Use a new syringe when you open a new bottle.
  
  
• RINVOQ LQ oral solution is clear and colorless to light yellow in color.
  
  
• Keep these instructions and the carton your RINVOQ LQ oral solution and supplies came in for future use.

     
Dispose of (throw away) the syringe and the bottle when you have finished the bottle or 60 days after opening.

• Ask your pharmacist how to properly dispose of (throw away) any unused medicine.
  
  
• Rinse syringe then place in household trash.

a. Check your child’s prescribed dose in milliliters (mL) and find this mL marking on the syringe.

b. Only use the syringe provided to give the prescribed dose.

a. Check the bottle and make sure the expiration date has not passed (see

a. Check the supplies and make sure they are not damaged (see

b.

c. Make sure that the plunger is all the way in the syringe.

a. Press down and twist the cap to remove it from the bottle (see

a. While holding the bottle firmly, use your thumb to push the adapter all the way down to the rim of the bottle (see

Note: You may need to apply pressure to the adapter.

a. Insert the tip of the syringe into the adapter.

b. With the syringe attached to the bottle, turn the bottle upside down (see

a. Slowly pull the plunger down (see

b. Check the syringe for air bubbles.

Note: You may feel pressure when pulling the plunger.

a. While holding the bottle, flick the sides of the syringe to send large air bubbles to the tip.

b. With the syringe attached to the bottle, move the plunger up and down to return air bubbles back into the bottle.

c. Repeat

Note: Small air bubbles are normal.

a. After any large air bubbles are removed, move the plunger until it is even with the marking of the dose (see

a. With the syringe attached to the bottle, turn the bottle upright.

b. Hold the middle of the syringe and carefully remove it from the bottle (see

a. Check that the syringe has the correct dose of oral solution (see

b. Check the syringe for large air bubbles.

c. If the dose is not correct or you see large air bubbles, return to

a. Place the syringe against the inside of the child’s cheek.

b. Push the plunger to give the entire dose into the child’s mouth (see

c. Give the child a drink of water.

Note: Oral solution must be given within 1 hour of filling the syringe.

a. With the adapter still inserted in the bottle, screw the cap back on to the bottle to seal it (see

b. Store the bottle upright in the carton between uses.

c. Store the bottle in the carton between 36°F to 86°F (2°C to 30°C) in a cool, dark place.

d. Keep the bottle, supplies, and all medicines out of the sight and reach of children.

a. Remove the plunger from the syringe then rinse both parts with water (see

b. Allow separated parts to air dry on a clean surface.

c. Store the syringe in a clean, dry place.

Manufactured by: AbbVie Inc., North Chicago, IL 60064, USA

RINVOQ^® is a registered trademark of AbbVie Biotechnology Ltd.

©2019-2024 AbbVie Inc.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Issued: April 2024

20081174 R1

Upadacitinib is a Janus kinase (JAK) inhibitor. JAKs are intracellular enzymes which transmit signals arising from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoiesis and immune cell function. Within the signaling pathway, JAKs phosphorylate and activate signal transducers and activators of transcription (STATs) which modulate intracellular activity including gene expression. Upadacitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs.

JAK enzymes transmit cytokine signaling through their pairing (e.g., JAK1/JAK2, JAK1/JAK3, JAK1/TYK2, JAK2/JAK2, JAK2/TYK2). In a cell-free isolated enzyme assay, upadacitinib had greater inhibitory potency at JAK1 and JAK2 relative to JAK3 and TYK2. In human leukocyte cellular assays, upadacitinib inhibited cytokine-induced STAT phosphorylation mediated by JAK1 and JAK1/JAK3 more potently than JAK2/JAK2 mediated STAT phosphorylation. The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.