Olumiant (Baricitinib)

OLUMIANT^® is a Janus kinase (JAK) inhibitor indicated for:

• the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF blockers. (
  1.1 Rheumatoid Arthritis

  OLUMIANT^®(baricitinib) is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor (TNF) blockers.

  Limitations of Use

  : 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.
  )

• the treatment of COVID-19 in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or ECMO. (
  1.2 Coronavirus Disease 2019 (COVID-19)

  OLUMIANT is indicated for the treatment of coronavirus disease 2019 (COVID-19) in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).
  )
• the treatment of adult patients with severe alopecia areata. (
  1.3 Alopecia Areata

  OLUMIANT is indicated for the treatment of adult patients with severe alopecia areata.

  Limitations of Use

  : Not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants.
  )

Administration Instructions:

• See the full prescribing information for recommended evaluations and immunizations prior to treatment. (
  2.1 Recommended Evaluations and Immunization Prior to Treatment Initiation

  Prior to OLUMIANT treatment initiation, consider performing the following evaluations:

  • Active and latent tuberculosis (TB) infection evaluation – OLUMIANT should not be given to patients with active tuberculosis (TB). If latent infection is positive in patients with rheumatoid arthritis or alopecia areata, consider treatment for TB prior to OLUMIANT use
    [see Warnings and Precautions ]
    .
  • Viral hepatitis screening in accordance with clinical guidelines
    [see Warnings and Precautions ]
    .
  • Complete blood count – Assess baseline values and verify whether treatment can be initiated:
    • -
      In patients with rheumatoid arthritis or alopecia areata, OLUMIANT initiation is not recommended in patients with an absolute lymphocyte count (ALC) <500 cells/μl, absolute neutrophil count (ANC) <1000 cells/μl, or hemoglobin level <8 g/dL.
    • -
      In patients with COVID-19, OLUMIANT initiation is not recommended if the ALC is <200 cells/μl or if the ANC is <500 cells/μl.

    Monitor complete blood counts during treatment and modify dosage as recommended

    [see Dosage and Administration and Warnings and Precautions ]
    .

  • Baseline hepatic and renal function – Assess baseline values and monitor patients for laboratory changes. Modify dosage based on hepatic and renal impairment, and laboratory abnormalities
    [see Dosage and Administration and Warnings and Precautions ]
    .

  In patients with rheumatoid arthritis or alopecia areata, update immunizations in agreement with current immunization guidelines

  [see Warnings and Precautions ]

  .
  )
• Rheumatoid Arthritis and Alopecia Areata:
  Avoid initiation or interrupt OLUMIANT in patients with anemia (hemoglobin <8 g/dL), lymphopenia (ALC <500 cells/mm³) or neutropenia (ANC <1000 cells/mm³). (
  2.1 Recommended Evaluations and Immunization Prior to Treatment Initiation

  Prior to OLUMIANT treatment initiation, consider performing the following evaluations:

  • Active and latent tuberculosis (TB) infection evaluation – OLUMIANT should not be given to patients with active tuberculosis (TB). If latent infection is positive in patients with rheumatoid arthritis or alopecia areata, consider treatment for TB prior to OLUMIANT use
    [see Warnings and Precautions ]
    .
  • Viral hepatitis screening in accordance with clinical guidelines
    [see Warnings and Precautions ]
    .
  • Complete blood count – Assess baseline values and verify whether treatment can be initiated:
    • -
      In patients with rheumatoid arthritis or alopecia areata, OLUMIANT initiation is not recommended in patients with an absolute lymphocyte count (ALC) <500 cells/μl, absolute neutrophil count (ANC) <1000 cells/μl, or hemoglobin level <8 g/dL.
    • -
      In patients with COVID-19, OLUMIANT initiation is not recommended if the ALC is <200 cells/μl or if the ANC is <500 cells/μl.

    Monitor complete blood counts during treatment and modify dosage as recommended

    [see Dosage and Administration and Warnings and Precautions ]
    .

  • Baseline hepatic and renal function – Assess baseline values and monitor patients for laboratory changes. Modify dosage based on hepatic and renal impairment, and laboratory abnormalities
    [see Dosage and Administration and Warnings and Precautions ]
    .

  In patients with rheumatoid arthritis or alopecia areata, update immunizations in agreement with current immunization guidelines

  [see Warnings and Precautions ]

  .
  ,
  2.5 Dosage Modifications Due to Infections, Cytopenias and Anemia

  Rheumatoid Arthritis and Alopecia Areata

  • Avoid use of OLUMIANT in patients with active, serious or opportunistic infection, including localized infections. If a patient develops a serious infection hold treatment with OLUMIANT until the infection is controlled
    [see Warnings and Precautions ]
    .
  • Dosage modifications for patients with rheumatoid arthritis or alopecia areata and cytopenias or anemia are described in Table 1.

  Table 1: Dosage Modifications for Cytopenias and Anemia in Patients with Rheumatoid Arthritis or Alopecia Areata

  Laboratory Analyte	Laboratory Analyte Value	Recommendation
  Absolute Lymphocyte Count (ALC)	≥500 cells/μL	Maintain dosage
  	<500 cells/μL	Interrupt OLUMIANT until ALC ≥500 cells/μL
  Absolute Neutrophil Count (ANC)	≥1000 cells/μL	Maintain dosage
  	<1000 cells/μL	Interrupt OLUMIANT until ANC ≥1000 cells/μL
  Hemoglobin	≥8 g/dL	Maintain dosage
  	<8 g/dL	Interrupt OLUMIANT until hemoglobin ≥8 g/dL

  COVID-19

  • Monitor patients for signs and symptoms of new infections during treatment with OLUMIANT. The risks and benefits of treatment with OLUMIANT in COVID-19 patients with other concurrent infections should be considered
    [see Warnings and Precautions ]
    .
  • Dosage modifications for patients with COVID-19 and cytopenias are described in Table 2.

  Table 2: Dosage Modifications for Cytopenias in Patients with COVID-19

  Laboratory Analyte	Laboratory Analyte Value	Recommendation
  Absolute Lymphocyte Count (ALC)	≥200 cells/μL	Maintain dosage
  	<200 cells/μL	Interrupt OLUMIANT until ALC ≥200 cells/μL
  Absolute Neutrophil Count (ANC)	≥500 cells/μL	Maintain dosage
  	<500 cells/μL	Interrupt OLUMIANT until ANC ≥500 cells/μL
  ,
  5.8 Laboratory Abnormalities

  Neutropenia

  – Treatment with OLUMIANT was associated with an increased incidence of neutropenia (ANC less than 1000 cells/mm³) compared to placebo.

  In patients with rheumatoid arthritis or alopecia areata, avoid initiation or interrupt OLUMIANT treatment in patients with an ANC less than 1000 cells/mm³.

  In patients with COVID-19, there is limited information regarding use of OLUMIANT in patients with ANC less than 1000 cells/mm³. Avoid initiation or interrupt OLUMIANT treatment in patients with COVID-19 and an ANC less than 500 cells/mm³.

  Evaluate at baseline and thereafter according to routine patient management. Adjust dosing based on ANC

  [see Dosage and Administration and Adverse Reactions ]

  .

  Lymphopenia

  – ALC less than 500 cells/mm³were reported in OLUMIANT clinical trials. Lymphocyte counts less than the lower limit of normal were associated with infection in patients treated with OLUMIANT, but not placebo.

  In patients with rheumatoid arthritis or alopecia areata, avoid initiation or interrupt OLUMIANT treatment in patients with an ALC less than 500 cells/mm³.

  In patients with COVID-19, there is limited information regarding use of OLUMIANT in patients with ALC less than 200 cells/mm³. Avoid initiation or interrupt OLUMIANT treatment in patients with COVID-19 and an ALC less than 200 cells/mm³.

  Evaluate at baseline and thereafter according to routine patient management. Adjust dosing based on ALC

  [see Dosage and Administration ]

  .

  Anemia

  – Decreases in hemoglobin levels to less than 8 g/dL were reported in OLUMIANT clinical trials. In patients with rheumatoid arthritis or alopecia areata, avoid initiation or interrupt OLUMIANT treatment in patients with hemoglobin less than 8 g/dL. Evaluate at baseline and thereafter according to routine patient management. Adjust dosing based on hemoglobin levels

  [see Dosage and Administration ]

  .

  In patients with COVID-19, there is limited information regarding use of OLUMIANT in patients with hemoglobin less than 8 g/dL.

  Liver Enzyme Elevations

  – Treatment with OLUMIANT was associated with increased incidence of liver enzyme elevation compared to placebo. Increases of ALT ≥5 times the upper limit of normal (ULN) and increases of AST ≥10 times the ULN were observed in patients in OLUMIANT clinical trials. Evaluate 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 and drug-induced liver injury is suspected, interrupt OLUMIANT until this diagnosis is excluded

  [see Adverse Reactions ]

  .

  Lipid Elevations

  – Treatment with OLUMIANT was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. Assessment of lipid parameters should be performed approximately 12 weeks following OLUMIANT initiation in patients with rheumatoid arthritis or alopecia areata

  [see Adverse Reactions ]

  . Manage patients according to clinical guidelines for the management of hyperlipidemia.
  )
• COVID-19:
  Avoid initiation or interrupt OLUMIANT in patients with lymphopenia (ALC <200 cells/mm³) or neutropenia (ANC <500 cells/mm³). (
  2.1 Recommended Evaluations and Immunization Prior to Treatment Initiation

  Prior to OLUMIANT treatment initiation, consider performing the following evaluations:

  • Active and latent tuberculosis (TB) infection evaluation – OLUMIANT should not be given to patients with active tuberculosis (TB). If latent infection is positive in patients with rheumatoid arthritis or alopecia areata, consider treatment for TB prior to OLUMIANT use
    [see Warnings and Precautions ]
    .
  • Viral hepatitis screening in accordance with clinical guidelines
    [see Warnings and Precautions ]
    .
  • Complete blood count – Assess baseline values and verify whether treatment can be initiated:
    • -
      In patients with rheumatoid arthritis or alopecia areata, OLUMIANT initiation is not recommended in patients with an absolute lymphocyte count (ALC) <500 cells/μl, absolute neutrophil count (ANC) <1000 cells/μl, or hemoglobin level <8 g/dL.
    • -
      In patients with COVID-19, OLUMIANT initiation is not recommended if the ALC is <200 cells/μl or if the ANC is <500 cells/μl.

    Monitor complete blood counts during treatment and modify dosage as recommended

    [see Dosage and Administration and Warnings and Precautions ]
    .

  • Baseline hepatic and renal function – Assess baseline values and monitor patients for laboratory changes. Modify dosage based on hepatic and renal impairment, and laboratory abnormalities
    [see Dosage and Administration and Warnings and Precautions ]
    .

  In patients with rheumatoid arthritis or alopecia areata, update immunizations in agreement with current immunization guidelines

  [see Warnings and Precautions ]

  .
  ,
  2.5 Dosage Modifications Due to Infections, Cytopenias and Anemia

  Rheumatoid Arthritis and Alopecia Areata

  • Avoid use of OLUMIANT in patients with active, serious or opportunistic infection, including localized infections. If a patient develops a serious infection hold treatment with OLUMIANT until the infection is controlled
    [see Warnings and Precautions ]
    .
  • Dosage modifications for patients with rheumatoid arthritis or alopecia areata and cytopenias or anemia are described in Table 1.

  Table 1: Dosage Modifications for Cytopenias and Anemia in Patients with Rheumatoid Arthritis or Alopecia Areata

  Laboratory Analyte	Laboratory Analyte Value	Recommendation
  Absolute Lymphocyte Count (ALC)	≥500 cells/μL	Maintain dosage
  	<500 cells/μL	Interrupt OLUMIANT until ALC ≥500 cells/μL
  Absolute Neutrophil Count (ANC)	≥1000 cells/μL	Maintain dosage
  	<1000 cells/μL	Interrupt OLUMIANT until ANC ≥1000 cells/μL
  Hemoglobin	≥8 g/dL	Maintain dosage
  	<8 g/dL	Interrupt OLUMIANT until hemoglobin ≥8 g/dL

  COVID-19

  • Monitor patients for signs and symptoms of new infections during treatment with OLUMIANT. The risks and benefits of treatment with OLUMIANT in COVID-19 patients with other concurrent infections should be considered
    [see Warnings and Precautions ]
    .
  • Dosage modifications for patients with COVID-19 and cytopenias are described in Table 2.

  Table 2: Dosage Modifications for Cytopenias in Patients with COVID-19

  Laboratory Analyte	Laboratory Analyte Value	Recommendation
  Absolute Lymphocyte Count (ALC)	≥200 cells/μL	Maintain dosage
  	<200 cells/μL	Interrupt OLUMIANT until ALC ≥200 cells/μL
  Absolute Neutrophil Count (ANC)	≥500 cells/μL	Maintain dosage
  	<500 cells/μL	Interrupt OLUMIANT until ANC ≥500 cells/μL
  ,
  5.8 Laboratory Abnormalities

  Neutropenia

  – Treatment with OLUMIANT was associated with an increased incidence of neutropenia (ANC less than 1000 cells/mm³) compared to placebo.

  In patients with rheumatoid arthritis or alopecia areata, avoid initiation or interrupt OLUMIANT treatment in patients with an ANC less than 1000 cells/mm³.

  In patients with COVID-19, there is limited information regarding use of OLUMIANT in patients with ANC less than 1000 cells/mm³. Avoid initiation or interrupt OLUMIANT treatment in patients with COVID-19 and an ANC less than 500 cells/mm³.

  Evaluate at baseline and thereafter according to routine patient management. Adjust dosing based on ANC

  [see Dosage and Administration and Adverse Reactions ]

  .

  Lymphopenia

  – ALC less than 500 cells/mm³were reported in OLUMIANT clinical trials. Lymphocyte counts less than the lower limit of normal were associated with infection in patients treated with OLUMIANT, but not placebo.

  In patients with rheumatoid arthritis or alopecia areata, avoid initiation or interrupt OLUMIANT treatment in patients with an ALC less than 500 cells/mm³.

  In patients with COVID-19, there is limited information regarding use of OLUMIANT in patients with ALC less than 200 cells/mm³. Avoid initiation or interrupt OLUMIANT treatment in patients with COVID-19 and an ALC less than 200 cells/mm³.

  Evaluate at baseline and thereafter according to routine patient management. Adjust dosing based on ALC

  [see Dosage and Administration ]

  .

  Anemia

  – Decreases in hemoglobin levels to less than 8 g/dL were reported in OLUMIANT clinical trials. In patients with rheumatoid arthritis or alopecia areata, avoid initiation or interrupt OLUMIANT treatment in patients with hemoglobin less than 8 g/dL. Evaluate at baseline and thereafter according to routine patient management. Adjust dosing based on hemoglobin levels

  [see Dosage and Administration ]

  .

  In patients with COVID-19, there is limited information regarding use of OLUMIANT in patients with hemoglobin less than 8 g/dL.

  Liver Enzyme Elevations

  – Treatment with OLUMIANT was associated with increased incidence of liver enzyme elevation compared to placebo. Increases of ALT ≥5 times the upper limit of normal (ULN) and increases of AST ≥10 times the ULN were observed in patients in OLUMIANT clinical trials. Evaluate 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 and drug-induced liver injury is suspected, interrupt OLUMIANT until this diagnosis is excluded

  [see Adverse Reactions ]

  .

  Lipid Elevations

  – Treatment with OLUMIANT was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. Assessment of lipid parameters should be performed approximately 12 weeks following OLUMIANT initiation in patients with rheumatoid arthritis or alopecia areata

  [see Adverse Reactions ]

  . Manage patients according to clinical guidelines for the management of hyperlipidemia.
  )

• 2 mg once daily. (
  2.2 Dosage Recommendations in Rheumatoid Arthritis

  The recommended dosage of OLUMIANT is 2 mg once daily orally, with or without food

  [see Clinical Pharmacology ]

  . An alternative administration for patients unable to swallow tablets may be used

  [see Dosage and Administration ]

  . OLUMIANT may be used as monotherapy or in combination with methotrexate or other non-biologic DMARDs.
  )
• OLUMIANT may be used as monotherapy or in combination with methotrexate or other non-biologic DMARDs. (
  2.2 Dosage Recommendations in Rheumatoid Arthritis

  The recommended dosage of OLUMIANT is 2 mg once daily orally, with or without food

  [see Clinical Pharmacology ]

  . An alternative administration for patients unable to swallow tablets may be used

  [see Dosage and Administration ]

  . OLUMIANT may be used as monotherapy or in combination with methotrexate or other non-biologic DMARDs.
  )

• 4 mg once daily for up to 14 days. (
  2.3 Dosage Recommendations in COVID-19

  The recommended dosage of OLUMIANT for adults is 4 mg once daily orally, with or without food, for 14 days or until hospital discharge, whichever occurs first. An alternative administration for patients unable to swallow tablets may be used

  [see Dosage and Administration ]

  .
  )

• 2 mg once daily. Increase to 4 mg once daily, if the response to treatment is not adequate. (
  2.4 Dosage Recommendations in Alopecia Areata

  The recommended dosage of OLUMIANT is 2 mg once daily orally, with or without food. Increase to 4 mg once daily if the response to treatment is not adequate.

  For patients with nearly complete or complete scalp hair loss, with or without substantial eyelash or eyebrow hair loss, consider treating with 4 mg once daily, with or without food.

  Once patients achieve an adequate response to treatment with 4 mg, decrease the dosage to 2 mg once daily.
  )
• For patients with nearly complete or complete scalp hair loss, with or without substantial eyelash or eyebrow hair loss, consider treating with 4 mg once daily. (
  2.4 Dosage Recommendations in Alopecia Areata

  The recommended dosage of OLUMIANT is 2 mg once daily orally, with or without food. Increase to 4 mg once daily if the response to treatment is not adequate.

  For patients with nearly complete or complete scalp hair loss, with or without substantial eyelash or eyebrow hair loss, consider treating with 4 mg once daily, with or without food.

  Once patients achieve an adequate response to treatment with 4 mg, decrease the dosage to 2 mg once daily.
  )
• Reduce the dose to 2 mg once daily when an adequate response has been achieved. (
  2.4 Dosage Recommendations in Alopecia Areata

  The recommended dosage of OLUMIANT is 2 mg once daily orally, with or without food. Increase to 4 mg once daily if the response to treatment is not adequate.

  For patients with nearly complete or complete scalp hair loss, with or without substantial eyelash or eyebrow hair loss, consider treating with 4 mg once daily, with or without food.

  Once patients achieve an adequate response to treatment with 4 mg, decrease the dosage to 2 mg once daily.
  )

• See the full prescribing information for dosage modifications by indication. (
  2.5 Dosage Modifications Due to Infections, Cytopenias and Anemia

  Rheumatoid Arthritis and Alopecia Areata

  • Avoid use of OLUMIANT in patients with active, serious or opportunistic infection, including localized infections. If a patient develops a serious infection hold treatment with OLUMIANT until the infection is controlled
    [see Warnings and Precautions ]
    .
  • Dosage modifications for patients with rheumatoid arthritis or alopecia areata and cytopenias or anemia are described in Table 1.

  Table 1: Dosage Modifications for Cytopenias and Anemia in Patients with Rheumatoid Arthritis or Alopecia Areata

  Laboratory Analyte	Laboratory Analyte Value	Recommendation
  Absolute Lymphocyte Count (ALC)	≥500 cells/μL	Maintain dosage
  	<500 cells/μL	Interrupt OLUMIANT until ALC ≥500 cells/μL
  Absolute Neutrophil Count (ANC)	≥1000 cells/μL	Maintain dosage
  	<1000 cells/μL	Interrupt OLUMIANT until ANC ≥1000 cells/μL
  Hemoglobin	≥8 g/dL	Maintain dosage
  	<8 g/dL	Interrupt OLUMIANT until hemoglobin ≥8 g/dL

  COVID-19

  • Monitor patients for signs and symptoms of new infections during treatment with OLUMIANT. The risks and benefits of treatment with OLUMIANT in COVID-19 patients with other concurrent infections should be considered
    [see Warnings and Precautions ]
    .
  • Dosage modifications for patients with COVID-19 and cytopenias are described in Table 2.

  Table 2: Dosage Modifications for Cytopenias in Patients with COVID-19

  Laboratory Analyte	Laboratory Analyte Value	Recommendation
  Absolute Lymphocyte Count (ALC)	≥200 cells/μL	Maintain dosage
  	<200 cells/μL	Interrupt OLUMIANT until ALC ≥200 cells/μL
  Absolute Neutrophil Count (ANC)	≥500 cells/μL	Maintain dosage
  	<500 cells/μL	Interrupt OLUMIANT until ANC ≥500 cells/μL
  ,
  2.6 Dosage Modifications for Patients with Renal Impairment or Hepatic Impairment

  Rheumatoid Arthritis

  Renal Impairment

  Dosage modifications for patients with rheumatoid arthritis and renal impairment are described in Table 3.

  Table 3: Dosage Modifications for Patients with Rheumatoid Arthritis and Renal Impairment

  Renal Impairment Stage	Estimated Glomerular Filtration Rate (eGFR)	Recommendation
  Mild	60 – <90 mL/minute/1.73 m2	2 mg once daily
  Moderate	30 - <60 mL/min/1.73 m2	1 mg once daily
  Severe	<30 mL/minute/1.73 m2	Not recommended

  Hepatic Impairment

  • OLUMIANT is not recommended for use in patients with severe hepatic impairment.
  • Interrupt OLUMIANT, if increases in ALT or AST are observed and drug-induced liver injury (DILI) is suspected, until the diagnosis of DILI is excluded
    [see Warnings and Precautions ].

  COVID-19

  Renal Impairment

  • Dosage modifications for patients with COVID-19 and renal impairment are described in Table 4.

  Table 4: Dosage Modifications for Patients with COVID-19 and Renal Impairment

  Renal Impairment Stage	Estimated Glomerular Filtration Rate (eGFR)	Recommendation
  Mild	60 - <90 mL/min/1.73m2	4 mg once daily
  Moderate	30 - <60 mL/min/1.73m2	2 mg once daily
  Severe	15 - <30 mL/min/1.73m2	1 mg once daily
  End Stage Renal Disease, Patients on Dialysis, or Acute Kidney Injury	<15 mL/min/1.73m2	Not recommended

  Hepatic Impairment

  • It is not known if dosage adjustment is needed in patients with COVID-19 and severe hepatic impairment. OLUMIANT should only be used in patients with COVID-19 and severe hepatic impairment if the potential benefit outweighs the potential risk.
  • Interrupt OLUMIANT, if increases in ALT or AST are observed and DILI is suspected, until the diagnosis of DILI is excluded
    [see Warnings and Precautions ]
    .

  Alopecia Areata

  Renal Impairment

  Dosage modifications for patients with alopecia areata and renal impairment are described in Table 5.

  Table 5: Dosage Modifications for Patients with Alopecia Areata and Renal Impairment

  Renal Impairment Stage	Estimated Glomerular Filtration Rate (eGFR)	Recommendation
  		If the recommended dosage is 2 mg once daily	If the recommended dosage is 4 mg once daily
  Mild	60 – <90 mL/minute/1.73 m2	Maintain dosage
  Moderate	30 – <60 mL/min/1.73 m2	Reduce to 1 mg once daily	Reduce to 2 mg once daily
  Severe	<30 mL/minute/1.73 m2	Not recommended

  Hepatic Impairment

  • OLUMIANT is not recommended for use in patients with severe hepatic impairment.
  • Interrupt OLUMIANT, if increases in ALT or AST are observed and DILI is suspected, until the diagnosis of DILI is excluded
    [see Warnings and Precautions ].
  ,
  5.8 Laboratory Abnormalities

  Neutropenia

  – Treatment with OLUMIANT was associated with an increased incidence of neutropenia (ANC less than 1000 cells/mm³) compared to placebo.

  In patients with rheumatoid arthritis or alopecia areata, avoid initiation or interrupt OLUMIANT treatment in patients with an ANC less than 1000 cells/mm³.

  In patients with COVID-19, there is limited information regarding use of OLUMIANT in patients with ANC less than 1000 cells/mm³. Avoid initiation or interrupt OLUMIANT treatment in patients with COVID-19 and an ANC less than 500 cells/mm³.

  Evaluate at baseline and thereafter according to routine patient management. Adjust dosing based on ANC

  [see Dosage and Administration and Adverse Reactions ]

  .

  Lymphopenia

  – ALC less than 500 cells/mm³were reported in OLUMIANT clinical trials. Lymphocyte counts less than the lower limit of normal were associated with infection in patients treated with OLUMIANT, but not placebo.

  In patients with rheumatoid arthritis or alopecia areata, avoid initiation or interrupt OLUMIANT treatment in patients with an ALC less than 500 cells/mm³.

  In patients with COVID-19, there is limited information regarding use of OLUMIANT in patients with ALC less than 200 cells/mm³. Avoid initiation or interrupt OLUMIANT treatment in patients with COVID-19 and an ALC less than 200 cells/mm³.

  Evaluate at baseline and thereafter according to routine patient management. Adjust dosing based on ALC

  [see Dosage and Administration ]

  .

  Anemia

  – Decreases in hemoglobin levels to less than 8 g/dL were reported in OLUMIANT clinical trials. In patients with rheumatoid arthritis or alopecia areata, avoid initiation or interrupt OLUMIANT treatment in patients with hemoglobin less than 8 g/dL. Evaluate at baseline and thereafter according to routine patient management. Adjust dosing based on hemoglobin levels

  [see Dosage and Administration ]

  .

  In patients with COVID-19, there is limited information regarding use of OLUMIANT in patients with hemoglobin less than 8 g/dL.

  Liver Enzyme Elevations

  – Treatment with OLUMIANT was associated with increased incidence of liver enzyme elevation compared to placebo. Increases of ALT ≥5 times the upper limit of normal (ULN) and increases of AST ≥10 times the ULN were observed in patients in OLUMIANT clinical trials. Evaluate 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 and drug-induced liver injury is suspected, interrupt OLUMIANT until this diagnosis is excluded

  [see Adverse Reactions ]

  .

  Lipid Elevations

  – Treatment with OLUMIANT was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. Assessment of lipid parameters should be performed approximately 12 weeks following OLUMIANT initiation in patients with rheumatoid arthritis or alopecia areata

  [see Adverse Reactions ]

  . Manage patients according to clinical guidelines for the management of hyperlipidemia.
  )

OLUMIANT is available as debossed, film-coated tablets:

• 1 mg tablet contains a recessed area on each face of the tablet surface, is very light pink, round, debossed with “Lilly” on one side and “1” on the other.
• 2 mg tablet contains a recessed area on each face of the tablet surface, is light pink, oblong, debossed with “Lilly” on one side and “2” on the other.
• 4 mg tablet contains a recessed area on each face of the tablet surface, is medium pink, round, debossed with “Lilly” on one side and “4” on the other.

• Hepatic Impairment
  : Not recommended in patients with RA or AA and severe hepatic impairment. OLUMIANT has not been studied in patients with COVID-19 and severe hepatic impairment. (
  2.5 Dosage Modifications Due to Infections, Cytopenias and Anemia

  Rheumatoid Arthritis and Alopecia Areata

  • Avoid use of OLUMIANT in patients with active, serious or opportunistic infection, including localized infections. If a patient develops a serious infection hold treatment with OLUMIANT until the infection is controlled
    [see Warnings and Precautions ]
    .
  • Dosage modifications for patients with rheumatoid arthritis or alopecia areata and cytopenias or anemia are described in Table 1.

  Table 1: Dosage Modifications for Cytopenias and Anemia in Patients with Rheumatoid Arthritis or Alopecia Areata

  Laboratory Analyte	Laboratory Analyte Value	Recommendation
  Absolute Lymphocyte Count (ALC)	≥500 cells/μL	Maintain dosage
  	<500 cells/μL	Interrupt OLUMIANT until ALC ≥500 cells/μL
  Absolute Neutrophil Count (ANC)	≥1000 cells/μL	Maintain dosage
  	<1000 cells/μL	Interrupt OLUMIANT until ANC ≥1000 cells/μL
  Hemoglobin	≥8 g/dL	Maintain dosage
  	<8 g/dL	Interrupt OLUMIANT until hemoglobin ≥8 g/dL

  COVID-19

  • Monitor patients for signs and symptoms of new infections during treatment with OLUMIANT. The risks and benefits of treatment with OLUMIANT in COVID-19 patients with other concurrent infections should be considered
    [see Warnings and Precautions ]
    .
  • Dosage modifications for patients with COVID-19 and cytopenias are described in Table 2.

  Table 2: Dosage Modifications for Cytopenias in Patients with COVID-19

  Laboratory Analyte	Laboratory Analyte Value	Recommendation
  Absolute Lymphocyte Count (ALC)	≥200 cells/μL	Maintain dosage
  	<200 cells/μL	Interrupt OLUMIANT until ALC ≥200 cells/μL
  Absolute Neutrophil Count (ANC)	≥500 cells/μL	Maintain dosage
  	<500 cells/μL	Interrupt OLUMIANT until ANC ≥500 cells/μL
  ,
  8.6 Hepatic Impairment

  No dose adjustment is necessary in patients with mild or moderate hepatic impairment.

  The use of OLUMIANT has not been studied in patients with rheumatoid arthritis or alopecia areata and severe hepatic impairment and is therefore not recommended. OLUMIANT has not been studied in patients with COVID-19 and severe hepatic impairment. OLUMIANT should only be used in patients with COVID-19 and severe hepatic impairment if the potential benefit outweighs the potential risk

  [see Dosage and Administration and Clinical Pharmacology ]

  .
  )
• Renal Impairment
  : Not recommended in COVID-19 patients with eGFR <15 mL/min/1.73m², who are on dialysis, have ESRD, or acute kidney injury. OLUMIANT is not recommend in patients with RA or AA with eGFR <30 mL/min/1.73m². (
  2.6 Dosage Modifications for Patients with Renal Impairment or Hepatic Impairment

  Rheumatoid Arthritis

  Renal Impairment

  Dosage modifications for patients with rheumatoid arthritis and renal impairment are described in Table 3.

  Table 3: Dosage Modifications for Patients with Rheumatoid Arthritis and Renal Impairment

  Renal Impairment Stage	Estimated Glomerular Filtration Rate (eGFR)	Recommendation
  Mild	60 – <90 mL/minute/1.73 m2	2 mg once daily
  Moderate	30 - <60 mL/min/1.73 m2	1 mg once daily
  Severe	<30 mL/minute/1.73 m2	Not recommended

  Hepatic Impairment

  • OLUMIANT is not recommended for use in patients with severe hepatic impairment.
  • Interrupt OLUMIANT, if increases in ALT or AST are observed and drug-induced liver injury (DILI) is suspected, until the diagnosis of DILI is excluded
    [see Warnings and Precautions ].

  COVID-19

  Renal Impairment

  • Dosage modifications for patients with COVID-19 and renal impairment are described in Table 4.

  Table 4: Dosage Modifications for Patients with COVID-19 and Renal Impairment

  Renal Impairment Stage	Estimated Glomerular Filtration Rate (eGFR)	Recommendation
  Mild	60 - <90 mL/min/1.73m2	4 mg once daily
  Moderate	30 - <60 mL/min/1.73m2	2 mg once daily
  Severe	15 - <30 mL/min/1.73m2	1 mg once daily
  End Stage Renal Disease, Patients on Dialysis, or Acute Kidney Injury	<15 mL/min/1.73m2	Not recommended

  Hepatic Impairment

  • It is not known if dosage adjustment is needed in patients with COVID-19 and severe hepatic impairment. OLUMIANT should only be used in patients with COVID-19 and severe hepatic impairment if the potential benefit outweighs the potential risk.
  • Interrupt OLUMIANT, if increases in ALT or AST are observed and DILI is suspected, until the diagnosis of DILI is excluded
    [see Warnings and Precautions ]
    .

  Alopecia Areata

  Renal Impairment

  Dosage modifications for patients with alopecia areata and renal impairment are described in Table 5.

  Table 5: Dosage Modifications for Patients with Alopecia Areata and Renal Impairment

  Renal Impairment Stage	Estimated Glomerular Filtration Rate (eGFR)	Recommendation
  		If the recommended dosage is 2 mg once daily	If the recommended dosage is 4 mg once daily
  Mild	60 – <90 mL/minute/1.73 m2	Maintain dosage
  Moderate	30 – <60 mL/min/1.73 m2	Reduce to 1 mg once daily	Reduce to 2 mg once daily
  Severe	<30 mL/minute/1.73 m2	Not recommended

  Hepatic Impairment

  • OLUMIANT is not recommended for use in patients with severe hepatic impairment.
  • Interrupt OLUMIANT, if increases in ALT or AST are observed and DILI is suspected, until the diagnosis of DILI is excluded
    [see Warnings and Precautions ].
  ,
  8.7 Renal Impairment

  Renal function was found to significantly affect baricitinib exposure.

  Rheumatoid Arthritis and Alopecia Areata

  -

  The recommended dosage of OLUMIANT in patients with moderate renal impairment (estimated glomerular filtration rate (GFR) between 30 and <60 mL/min/1.73 m²) should be reduced by half the recommended dose. OLUMIANT is not recommended for use in patients with rheumatoid arthritis or alopecia areata and severe renal impairment (estimated GFR of less than 30 mL/min/1.73 m²)

  [see Dosage and Administration and Clinical Pharmacology ]

  .

  COVID-19

  -

  The recommended dosage of OLUMIANT in patients with moderate renal impairment (estimated GFR between 30 and <60 mL/min/1.73²) or severe renal impairment (estimated GFR between 15 and <30 mL/min/1.73 m²) is 2 mg once daily and 1 mg once daily, respectively. OLUMIANT is not recommended for use in patients who are on dialysis, have end-stage renal disease (ESRD), or with estimated GFR of <15 mL/min/1.73 m²

  [see Dosage and Administration and Clinical Pharmacology ].
  )
• Pregnancy
  : Based on animal data, may cause fetal harm. (
  8.1 Pregnancy

  Risk Summary

  Based on the findings from animal reproduction studies, OLUMIANT may cause fetal harm during pregnancy. Available data from clinical trials and postmarketing case reports with OLUMIANT exposure in pregnancy are insufficient to inform a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are no human data on chronic baricitinib exposure throughout pregnancy. There are risks to the mother and the fetus associated with rheumatoid arthritis in pregnancy

  (see Clinical Considerations)

  . Consider the risks and benefits with chronic use of OLUMIANT during pregnancy.

  In animal embryo-fetal development studies, oral baricitinib administration to pregnant rats and rabbits at exposures equal to and greater than approximately 11 and 46 times the maximum recommended human dose (MRHD) of 4 mg/day, respectively, resulted in reduced fetal body weights, increased embryolethality (rabbits only), and dose-related increases in skeletal malformations. No developmental toxicity was observed in pregnant rats and rabbits treated with oral baricitinib during organogenesis at approximately 2 and 7 times the exposure at the MRHD, respectively. In a pre- and post-natal development study in pregnant female rats, oral baricitinib administration at exposures approximately 24 times the MRHD resulted in reduction in pup viability (increased incidence of stillborn pups and early neonatal deaths), decreased fetal birth weight, reduced fetal body weight gain, decreased cytotoxic T cells on post-natal day (PND) 35 with evidence of recovery by PND 65, and developmental delays that might be attributable to decreased body weight gain. No developmental toxicity was observed at an exposure approximately 5 times the exposure at the MRHD

  (see Data)

  .

  The background risks of major birth defects and miscarriage for the indicated population(s) 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 miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

  Report pregnancies to Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979).

  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. 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 embryofetal development study in pregnant rats, dosed orally during the period of organogenesis from gestation days 6 to 17, baricitinib was teratogenic (skeletal malformations that consisted of bent limb bones and rib anomalies) at exposures equal to or greater than approximately 11 times the MRHD (on an AUC basis at maternal oral doses of 10 mg/kg/day and higher). No developmental toxicity was observed in rats at an exposure approximately 2 times the MRHD (on an AUC basis at a maternal oral dose of 2 mg/kg/day).

  In an embryofetal development study in pregnant rabbits, dosed orally during the period of organogenesis from gestation days 7 to 20, embryolethality, decreased fetal body weights, and skeletal malformations (rib anomalies) were observed in the presence of maternal toxicity at an exposure approximately 46 times the MRHD (on an AUC basis at a maternal oral dose of 30 mg/kg/day). Embryolethality consisted of increased post-implantation loss that was due to elevated incidences of both early and late resorptions. No developmental toxicity was observed in rabbits at an exposure approximately 7 times the MRHD (on an AUC basis at a maternal oral dose of 10 mg/kg/day).

  In a pre- and post-natal development study in pregnant female rats dosed orally from gestation day 6 through lactation day 20, adverse findings observed in pups included decreased survival from birth to post-natal day 4 (due to increased stillbirths and early neonatal deaths), decreased birth weight, decreased body weight gain during the pre-weaning phase, increased incidence of malrotated forelimbs during the pre-weaning phase, and decreased cytotoxic T cells on PND 35 with recovery by PND 65 at exposures approximately 24 times the MRHD (on an AUC basis at a maternal oral dose of 25 mg/kg/day). Developmental delays (that may be secondary to decreased body weight gain) were observed in males and females at exposures approximately 24 times the MRHD (on an AUC basis at a maternal oral dose of 25 mg/kg/day). These findings included decreased forelimb and hindlimb grip strengths, and delayed mean age of sexual maturity. No developmental toxicity was observed in rats at an exposure approximately 5 times the MRHD (on an AUC basis at a maternal oral dose of 5 mg/kg/day).
  ,
  8.3 Females and Males of Reproductive Potential

  Contraception

  Based on animal studies, OLUMIANT may cause fetal harm when administered during pregnancy

  [see Use in Specific Populations ]

  . Consider pregnancy planning and prevention for females of reproductive potential.
  )
• Lactation
  : Advise not to breastfeed. (
  8.2 Lactation

  Risk Summary

  No information is available on the presence of OLUMIANT in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Baricitinib is present in the milk of lactating rats

  (see Data)

  . Because of the potential for serious adverse reactions in nursing infants advise women not to breastfeed during treatment with OLUMIANT and for 4 days after the last dose (approximately 5 to 6 elimination half-lives).

  Data

  A single oral dose of 25 mg/kg radiolabeled baricitinib was administered to lactating female Sprague-Dawley rats on post-partum day 13. Drug exposure was approximately 45-fold greater in milk than in plasma based on AUC_0-tvalues.
  )