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Aug.09.2022

Baricitinib

Indications/Dosage

Labeled

  • alopecia
  • coronavirus disease 2019 (COVID-19)
  • rheumatoid arthritis
  • severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection

Off-Label

    † Off-label indication

    For the treatment of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, in hospitalized patients requiring supplemental oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)

    NOTE: Prior to initiating treatment, obtain a baseline complete blood count (CBC), hepatic function, and renal function. Monitor patients for laboratory changes and modify dosage based on laboratory abnormalities.[63229] [66126]

    Oral dosage

    Adults

    4 mg PO once daily for 14 days or until hospital discharge, whichever comes first. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.[63229] The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend use of baricitinib with dexamethasone in patients on supplemental oxygen, including noninvasive ventilation, high-flow oxygen, mechanical ventilation, or ECMO.[65314]

    Children and Adolescents 9 to 17 years†

    4 mg PO once daily for a recommended duration of 14 days or until hospital discharge, whichever comes first. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.[66126] The NIH COVID-19 treatment guidelines recommend consideration of the addition of baricitinib for patients requiring high-flow oxygen, noninvasive ventilation, mechanical ventilation, or ECMO who do not have rapid (e.g., within 24 hours) improvement in oxygenation after initiation of dexamethasone. Remdesivir may be added for patients requiring high-flow oxygen or noninvasive ventilation.[65314]

    Children 2 to 8 years†

    2 mg PO once daily for a recommended duration of 14 days or until hospital discharge, whichever comes first. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.[66126] The NIH COVID-19 treatment guidelines recommend consideration of the addition of baricitinib for patients requiring high-flow oxygen, noninvasive ventilation, mechanical ventilation, or ECMO who do not have rapid (e.g., within 24 hours) improvement in oxygenation after initiation of dexamethasone. Remdesivir may be added for patients requiring high-flow oxygen or noninvasive ventilation.[65314]

    For the treatment of moderately to severely active rheumatoid arthritis in patients who have had an inadequate response to 1 or more tumor necrosis factor (TNF) inhibitors

    NOTE: Reserve baricitinib for patients who have an inadequate response or intolerance to 1 or more TNF inhibitors. Consider the benefits and risks for the individual patient before initiation or continuation of therapy, particularly in those who smoke, have cardiovascular risk factors, develop malignancy, or have a known malignancy other than successfully treated non-melanoma skin cancer (NMSC). A large randomized safety clinical trial with another JAK inhibitor, tofacitinib, showed an increased risk of malignancy, all-cause mortality (including sudden cardiac death), major adverse cardiovascular events (MACE; defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke), and thrombosis (including deep venous thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis), compared to tumor necrosis factor (TNF) inhibitors in patients with RA. Baricitinib has not been studied in similar trials; however, the risks may be similar for all JAK inhibitors used for inflammatory conditions.[63229] [66958]

    Oral dosage

    Adults

    2 mg PO once daily. May give with or without methotrexate or other non-biologic (conventional) disease-modifying antirheumatic drugs (DMARDs). Do not use in combination with other Janus kinase (JAK) inhibitors, biologic or targeted DMARDs, or potent immunosuppressants such as azathioprine and cyclosporine. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.[63229]

    For the treatment of severe alopecia areata

    Oral dosage

    Adults

    2 mg PO once daily. May increase to 4 mg PO once daily if the response to treatment is inadequate. For patients with nearly complete or complete scalp hair loss, with or without substantial eyelash or eyebrow hair loss, consider initiating treatment at 4 mg PO once daily. Once an adequate response is achieved, decrease to 2 mg PO once daily. Do not use in combination with other Janus kinase (JAK) inhibitors, biologic immunomodulators, cyclosporine, or other potent immunosuppressants. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.[63229]

    Therapeutic Drug Monitoring

    Anemia

    Rheumatoid arthritis and Alopecia areata:

    Determine hemoglobin concentration before baricitinib initiation, and do not start the drug in patients with a hemoglobin less than 8 grams/dL. Monitor the hemoglobin concentration according to routine patient management. For a hemoglobin concentration less than 8 grams/dL, delay or interrupt baricitinib therapy until hemoglobin concentration is 8 grams/dL or more.[63229]

     

    COVID-19:

    There are limited data regarding use of baricitinib in COVID-19 patients with hemoglobin less than 8 grams/dL.[63229]

     

    Lymphopenia

    Rheumatoid arthritis and Alopecia areata:

    Determine absolute lymphocyte count (ALC) before baricitinib initiation, and do not start the drug in patients with an ALC less than 500 cells/mm3. Monitor the ALC according to routine patient management. For an ALC less than 500 cells/mm3, delay or interrupt baricitinib therapy until ALC is 500 cells/mm3 or more.[63229]

     

    COVID-19:

    Determine ALC before baricitinib initiation, and do not start the drug in patients with an ALC less than 200 cells/mm3. Monitor the ALC according to routine patient management. For an ALC less than 200 cells/mm3, delay or interrupt baricitinib therapy until ALC is 200 cells/mm3 or more.[63229][66126]

     

    Neutropenia

    Rheumatoid arthritis and Alopecia areata:

    Determine absolute neutrophil count (ANC) before baricitinib initiation, and do not start the drug in patients with an ANC less than 1,000 cells/mm3. Monitor the ANC according to routine patient management. For an ANC less than 1,000 cells/mm3, delay or interrupt baricitinib therapy until ANC is 1,000 cells/mm3 or more.[63229]

     

    COVID-19:

    Determine ANC before baricitinib initiation, and do not start the drug in patients with an ANC less than 500 cells/mm3. Monitor the ANC according to routine patient management. For an ANC less than 500 cells/mm3, delay or interrupt baricitinib therapy until ANC is 500 cells/mm3 or more.[63229][66126]

     

    Serious Infection

    Rheumatoid arthritis and Alopecia areata:

    Avoid use in patients with active, serious or opportunistic infection, including localized infections. If a serious infection occurs during treatment, hold baricitinib until the infection is controlled.[63229]

     

    COVID-19:

    Monitor patients for signs and symptoms of new infection during treatment. The risks and benefits of treatment with baricitinib in COVID-19 patients with other concurrent infections should be considered.[63229]

     

    Lipid Elevations

    Rheumatoid arthritis and Alopecia areata:

    Assess lipid profile approximately 12 weeks after initiation of baricitinib therapy. If elevations occur, manage patients according to clinical guidelines.[63229]

    Maximum Dosage Limits

    • Adults

      2 mg/day PO for rheumatoid arthritis; 4 mg/day PO for alopecia areata; 4 mg/day PO for COVID-19.

    • Geriatric

      2 mg/day PO for rheumatoid arthritis; 4 mg/day PO for alopecia areata; 4 mg/day PO for COVID-19.

    • Adolescents

      Safety and efficacy have not been established; however, investigational doses of 4 mg/day PO have been used for COVID-19.

    • Children

      Children 9 to 12 years: Safety and efficacy have not been established; investigational doses of 4 mg/day PO have been used for COVID-19.

      Children 2 to less than 9 years: Safety and efficacy have not been established; however, investigational doses of 2 mg/day PO have been used for COVID-19.

      Children less than 2 years: Safety and efficacy have not been established.

    • Infants

      Safety and efficacy have not been established.

    • Neonates

      Safety and efficacy have not been established.

    Patients with Hepatic Impairment Dosing

    Dosage Adjustments for Rheumatoid Arthritis and Alopecia areata:

    Mild or moderate impairment: No dosage adjustments needed; however, if increases in alanine transaminase (ALT) or aspartate transaminase (AST) are observed and drug-induced liver injury is suspected, interrupt baricitinib until the diagnosis of drug-induced liver injury has been excluded.

    Severe impairment: Not recommended.[63229]

     

    Dosage Adjustments for COVID-19:

    Mild or moderate impairment: No dosage adjustments needed; however, if increases in ALT or AST are observed and drug-induced liver injury is suspected, interrupt baricitinib until the diagnosis of drug-induced liver injury has been excluded.

    Severe impairment: Administer only if the potential benefits outweigh the potential risks.[63229][66126]

    Patients with Renal Impairment Dosing

    Dosage Adjustments for Rheumatoid Arthritis:[63229]

    eGFR 60 mL/minute/1.73 m2 or more: No dosage adjustment is needed.

    eGFR 30 to 59 mL/minute/1.73 m2: Reduce to 1 mg PO once daily.

    eGFR less than 30 mL/minute/1.73 m2: Use not recommended.

     

    Dosage Adjustments for Alopecia areata:[63229]

    eGFR 60 mL/minute/1.73 m2 or more: No dosage adjustment is needed.

    eGFR 30 to 59 mL/minute/1.73 m2: Reduce recommended dose by 50%.

    eGFR less than 30 mL/minute/1.73 m2: Use not recommended.

     

    Dosage Adjustments for COVID-19:[63229][66126]

    Adults, Adolescents, and Children 9 years and older

    eGFR 60 mL/minute/1.73 m2 or more: No dosage adjustment is needed.

    eGFR 30 to 59 mL/minute/1.73 m2: Reduce to 2 mg PO once daily.

    eGFR 15 to 29 mL/minute/1.73 m2: Reduce to 1 mg PO once daily.

    eGFR less than 15 mL/minute/1.73 m2: Use not recommended.

     

    Children 2 to less than 9 years

    eGFR 60 mL/minute/1.73 m2 or more: No dosage adjustment is needed.

    eGFR 30 to 59 mL/minute/1.73 m2: Reduce to 1 mg PO once daily.

    eGFR less than 30 mL/minute/1.73 m2: Use not recommended.

     

    Baricitinib is not recommended for use in patients who are on dialysis, have end-stage renal disease (ESRD) defined as eGFR less than 15 mL/minute/1.73 m2, or have acute kidney injury.

    † Off-label indication
    Revision Date: 08/09/2022, 01:37:33 PM

    References

    63229 - Olumiant (baricitinib) tablets package insert. Indianapolis, IN: Lilly USA, LLC; 2022 Jun.65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed August 18, 2022. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.66126 - Food and Drug Administration (FDA). Fact sheet for health care providers emergency use authorization (EUA) of baricitinib. Retrieved May 11, 2022. Available on the World Wide Web at http://pi.lilly.com/eua/baricitinib-eua-factsheet-hcp.pdf.66958 - U.S. Food and Drug Administration (FDA). FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. Retrieved Sept 1, 2021. Available at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death?utm_medium=email&utm_source=govdelivery

    How Supplied

    Baricitinib Oral tablet

    Olumiant 1mg Tablet (00002-4732) (Eli Lilly and Co) null

    Baricitinib Oral tablet

    Olumiant 2mg Tablet (00002-4182) (Eli Lilly and Co) null

    Baricitinib Oral tablet

    Olumiant 4mg Tablet (00002-4479) (Eli Lilly and Co) null

    Description/Classification

    Description

    Baricitinib is an oral Janus kinase (JAK) inhibitor and is considered a targeted synthetic disease-modifying antirheumatic drug (tsDMARD). Janus kinases are intracellular enzymes that transmit signals arising from cytokine interactions on the cellular membrane to influence cellular processes of immune cell function. JAK inhibitors have been shown useful for a variety of inflammatory conditions. Baricitinib is indicated for use in adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to 1 or more tumor necrosis factor (TNF) inhibitors. The drug is also indicated for the treatment of adults with severe alopecia areata. Finally, it is FDA approved for the treatment of coronavirus disease 2019 (COVID-19) in hospitalized adults requiring supplemental oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).[63229] Although not FDA approved for use in pediatric patients, the FDA has issued an Emergency Use Authorization which allows for baricitinib to be used to treat COVID-19 in hospitalized pediatric patients (ages, 2 to 17 years) who require supplemental oxygen, noninvasive or invasive mechanical ventilation, or ECMO.[66126]

     

    For COVID-19, the National Institutes of Health (NIH) has issued the following recommendations for the use of baricitinib based on disease severity:[65314]

    Adult patients

    • The NIH recommends baricitinib for use in combination with dexamethasone (with or without remdesivir) for hospitalized patients requiring supplemental oxygen, IF the patient is exhibiting signs of systemic inflammation and rapidly increasing oxygen needs while on dexamethasone.
    • The NIH recommends baricitinib for use in combination with dexamethasone (with or without remdesivir) for hospitalized patients requiring noninvasive ventilation or high-flow oxygen.
    • The NIH recommends baricitinib for use in combination with dexamethasone for hospitalized patients requiring mechanical ventilation or ECMO.
    • The NIH recommends against the use of baricitinib in patients discharged from inpatient hospital settings in stable condition who do not require supplemental oxygen.
    • The NIH recommends against the use of baricitinib in combination with tocilizumab due to the increased risk for immunosuppression and infection.

    Pediatric patients

    • The NIH recommends consideration of the addition of baricitinib for pediatric patients requiring high-flow oxygen, noninvasive ventilation, mechanical ventilation, or ECMO who do not have rapid (e.g., within 24 hours) improvement in oxygenation after initiation of dexamethasone. Remdesivir may be added for patients requiring high-flow oxygen or noninvasive ventilation.

     

    For patients with rheumatoid arthritis (RA), baricitinib is used as monotherapy or in combination with methotrexate or other non-biologic disease-modifying antirheumatic drugs (DMARDs). Baricitinib improves RA symptoms and inhibits the radiographic progression of structural joint damage.[63229] Guidelines for RA were published before the availability of baricitinib, but the drug, like other tsDMARDs, is usually reserved for patients with contraindications, intolerance, or inadequate response to biologic agents such as the TNF inhibitors. The ideal combination of therapy for individual patients with inflammatory arthritis conditions such as RA is determined by treat to target strategies and severity of the disease.[56233] The use of baricitinib does present some safety concerns. Serious infections, blood clots, and malignancy may be precipitated by JAK inhibitors; the drug is not to be used in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants such as azathioprine and cyclosporine.[63229]

     

    A large, postmarketing, randomized, safety clinical trial showed an increased risk of all-cause mortality (including sudden cardiovascular death), major adverse cardiovascular events (MACE; defined as cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke), thrombosis (including deep venous thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis), and cancer with use of tofacitinib, another JAK inhibitor, compared to tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis. Baricitinib has not been studied in similar trials; however, the risks may be similar for all JAK inhibitors used for inflammatory conditions. A higher rate of cancer (e.g., lymphomas, lung cancer) was also observed. Current or past tobacco smokers were at increased risk of lung cancer, overall cancers, and major adverse cardiovascular events. Consider the benefits and risks for the individual patient before initiation or continuation of therapy, particular in those with risk factors such as smoking, cardiovascular risk factors, those who develop malignancy, and those with a known malignancy other than successfully treated non-melanoma skin cancer. Reserve baricitinib for patients who have an inadequate response or intolerance to 1 or more TNF inhibitors. Advise patients to seek emergency medical attention if they experience signs and symptoms of a heart attack, stroke, or blood clot.[63229][66958]

    Classifications

    • Antineoplastic and Immunomodulating Agents
      • Agents that Suppress the Immune System
        • Janus Associated Kinase (JAK) Inhibitors
    • Musculo-Skeletal System
      • Antiinflammatory Agents and Antirheumatic Agents
        • Specific Anti-Rheumatic Agents
          • Other Specific Antirheumatics
    Revision Date: 08/15/2022, 04:49:25 PM

    References

    56233 - Singh JA, Furst DE, Bharat A, et al. 2012 Update of the 2008 American College of Rheumatology Recommendations for the Use of Disease-Modifying Antirheumatic Drugs and Biologic Agents in the Treatment of Rheumatoid Arthritis. Arthritis Care & Research 2012;64(5):625-639.63229 - Olumiant (baricitinib) tablets package insert. Indianapolis, IN: Lilly USA, LLC; 2022 Jun.65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed August 18, 2022. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.66126 - Food and Drug Administration (FDA). Fact sheet for health care providers emergency use authorization (EUA) of baricitinib. Retrieved May 11, 2022. Available on the World Wide Web at http://pi.lilly.com/eua/baricitinib-eua-factsheet-hcp.pdf.66958 - U.S. Food and Drug Administration (FDA). FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. Retrieved Sept 1, 2021. Available at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death?utm_medium=email&utm_source=govdelivery

    Administration Information

    General Administration Information

    For storage information, see the specific product information within the How Supplied section.

     

    COVID-19 per the Emergency Use Authorization (EUA):

    NOTE: Baricitinib is not FDA-approved to treat coronavirus disease 2019 (COVID-19) in pediatric patients; however, the FDA has issued an Emergency Use Authorization which allows for baricitinib to be used to treat COVID-19 in hospitalized pediatric patients (ages, 2 to 17 years) requiring supplemental oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Under the EUA, health care providers are required to communicate to the patient, parent, or caregiver information consistent with the "Fact Sheet for Patients, Parents and Caregivers" prior to the patient receiving treatment; such information includes the following:

    • The option to accept or refuse baricitinib
    • The significant known and potential risks and benefits of baricitinib, and the extent to which such potential risks and benefits are unknown
    • Available alternative treatments and the risks and benefits of those alternatives

     

    NOTE: If provision of this information delays treatment to the degree that would endanger the lives of patients, then the information must be provided as soon as practical following baricitinib administration.

     

    NOTE: Under the EUA, health care providers are required to report all medication errors and serious adverse events potentially related to baricitinib therapy within 7 calendar days from the health care provider's awareness of the event.[66126]

    Route-Specific Administration

    Oral Administration

    Oral Solid Formulations

    • Administer tablets with or without food.[63229]
    • For a 1 mg dose when the 1 mg tablet is not available: A 2 mg tablet can be split using a tablet splitter that has a razor blade to administer half a 2 mg tablet once daily. The tablet should be split along the longest diameter. If the portions of the tablet are determined to be visually unequal, they should be discarded. Take care in storing the second tablet half to avoid breakage prior to the next dose.[66126]

    Extemporaneous Compounding-Oral

    • For patients unable to swallow whole tablets, one of the following alternative administration methods may be used.
    • Intact tablets are not hazardous; however, it is not known if powder from crushed tablets may constitute a reproductive hazard to the preparer. If tablets are crushed, use proper control measures (e.g., ventilated enclosure) or personal protective equipment (i.e., N95 respirator).
    • Tablets dispersed in water are stable for up to 4 hours.[63229]

     

    Oral administration of dispersed tablets in water:

    • Place the needed number of tablets to achieve a single dose (maximum 4 mg) into a container with approximately 10 mL (minimum 5 mL) of room temperature water. Either 1 mg, 2 mg, 4 mg, or a combination of tablets may be utilized to achieve the desired dose.
    • Gently swirl the water to disperse the tablets and immediately drink. Tablets may be crushed to facilitate dispersion.
    • Rinse the container with an additional 10 mL (minimum 5 mL) of room temperature water and swallow the entire contents.[63229]

     

    Administration via gastrostomy tube (G tube):

    • Place the needed number of tablets to achieve a single dose (maximum 4 mg) into a container with approximately 15 mL (minimum 10 mL) of room temperature water. Either 1 mg, 2 mg, 4 mg, or a combination of tablets may be utilized to achieve the desired dose.
    • Gently swirl the water to disperse the tablets and ensure that the tablets are sufficiently dispersed to allow free passage through the tip of the syringe. Tablets may be crushed to facilitate dispersion.
    • Withdraw the entire contents from the container into an appropriate syringe and immediately administer into the gastric tube.
    • Rinse container with 15 mL (minimum 10 mL) of room temperature water, withdraw entire contents into the syringe, and administer through the gastric tube.[63229]

     

    Administration via nasogastric tube (NG tube) or orogastric tube (OG tube):

    • Place the needed number of tablets to achieve a single dose (maximum 4 mg) into a container with approximately 30 mL of room temperature water. Either 1 mg, 2 mg, 4 mg, or a combination of tablets may be utilized to achieve the desired dose.
    • Gently swirl the water to disperse the tablets and ensure that the tablets are sufficiently dispersed to allow free passage through the tip of the syringe. Tablets may be crushed to facilitate dispersion.
    • Withdraw the entire contents from the container into an appropriate syringe and immediately administer into the NG or OG tube.
    • To avoid clogging of small diameter tubes (smaller than French size 12), the syringe may be held horizontally and shaken during administration.
    • Rinse container with a sufficient amount of room temperature water (minimum 15 mL), withdraw entire contents into the syringe, and administer through the NG or OG tube.[63229]

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
      Revision Date: 05/12/2022, 09:39:38 AM

      References

      63229 - Olumiant (baricitinib) tablets package insert. Indianapolis, IN: Lilly USA, LLC; 2022 Jun.66126 - Food and Drug Administration (FDA). Fact sheet for health care providers emergency use authorization (EUA) of baricitinib. Retrieved May 11, 2022. Available on the World Wide Web at http://pi.lilly.com/eua/baricitinib-eua-factsheet-hcp.pdf.

      Adverse Reactions

      Moderate

      • anemia
      • candidiasis
      • cystitis
      • elevated hepatic enzymes
      • hypercholesterolemia
      • hypertriglyceridemia
      • lymphopenia
      • neutropenia
      • thrombocytosis
      • tracheitis

      Mild

      • abdominal pain
      • acne vulgaris
      • acneiform rash
      • fatigue
      • folliculitis
      • headache
      • infection
      • influenza
      • laryngitis
      • nausea
      • pharyngitis
      • rash
      • rhinitis
      • sinusitis
      • urticaria
      • weight gain

      Severe

      • angioedema
      • GI perforation
      • hepatotoxicity
      • lymphoma
      • myocardial infarction
      • new primary malignancy
      • pulmonary embolism
      • skin cancer
      • stroke
      • thromboembolism
      • thrombosis

      Serious and sometimes fatal bacterial infection, mycobacterial infection, invasive fungal infection, viral infection, or infections due to other opportunistic pathogens have been reported in patients receiving baricitinib. Pooled safety data from 2 COVID-19 clinical trials identified infections in 14.8% of baricitinib treated patients (n = 194/1,307) and 16.7% of patients who received placebo (n = 219/1,310). Serious infections were reported in 7.5% of baricitinib treated patients (n = 98/1,307) and 9.2% of patients who received placebo (n = 120/1,310). The most commonly reported serious infections were pneumonia (2.1%) and septic shock (2.1%). Opportunistic infections were identified in 0.9% of baricitinib patients (n = 12/1,307) and 1.1% of placebo patients (n = 14/1,310), with tuberculosis being reported in 1 patient treated with baricitinib and no patients treated with placebo. The most commonly reported adverse reactions during baricitinib clinical trials for alopecia areata and rheumatoid arthritis (RA) were upper respiratory tract infections (16.3% to 21.3% vs. 11.7% to 19.9% placebo). Included in upper respiratory tract infections were acute sinusitis, sinusitis, acute tonsillitis, tonsillitis, adenoiditis, epiglottitis, influenza, laryngitis, nasopharyngitis, oropharyngeal pain, pharyngitis, pharyngotonsillitis, rhinitis, rhinovirus infection, sinobronchitis, and tracheitis. Other infections reported by alopecia areata patients during clinical trials included urinary tract infections (3%, cystitis and pyelonephritis), lower respiratory tract infections (2%, bronchitis, bronchiolitis, pneumonia), vulvovaginal candidiasis (2%), herpes zoster (1%), and fungal skin infections (less than 1%). In the RA clinical trials, overall infections during the 16-week treatment period were reported in 139 patients (99.1 events per 100 patient-years) treated with baricitinib 2 mg compared to 253 patients (82.1 events per 100 patient-years) receiving placebo. During 0 to 52-week exposure, infections were reported in 200 patients (59.6 events per 100 patient-years) receiving baricitinib 2 mg. During the 0 to 52 week exposure, the most commonly reported infections included viral upper respiratory infection, upper respiratory tract infection, urinary tract infection, and bronchitis. During the 16-week treatment period, serious infections were reported in 5 patients (3.6 events per 100 patient-years) receiving baricitinib 2 mg and in 13 patients (4.2 events per 100 patient-years) receiving placebo. During the 0 to 52 week exposure, serious infection was reported in 14 patients (4.2 events per 100 patient-years) receiving baricitinib 2 mg. The most common serious infections reported with baricitinib included pneumonia, herpes zoster, and urinary tract infections. Among opportunistic infections, tuberculosis, cryptococcosis, acute histoplasmosis, esophageal candidiasis, pneumocystosis, multidermatomal herpes zoster, cytomegalovirus infections, and BK virus were reported with baricitinib. During the 0 to 16 week treatment period for RA, an opportunistic infection was reported in 2 placebo patients (0.6 events per 100 patient-years), no patients taking baricitinib 2 mg, and two patients taking baricitinib 4 mg (0.7 events per 100 patient-years). In the 0 to 52 week treatment period, opportunistic infections were reported in 1 patient (0.1 events per 100 patient-years) and 5 patients (0.6 per 100 patient-years) with baricitinib 2 mg and baricitinib 4 mg, respectively. Viral reactivation, including cases of herpes infection reactivation (e.g., herpes zoster), were observed in RA clinical studies. Herpes simplex and herpes zoster were reported in 0.8% and 1% of patients treated with baricitinib 2 mg, respectively compared to 0.7% and 0.4% of those receiving placebo, respectively. Included in herpes simplex were eczema herpeticum, genital herpes, ophthalmic herpes simplex, and oral herpes. If a patient develops herpes zoster, interrupt baricitinib therapy until the episode resolves. Baricitinib should not be administered to patients with active tuberculosis. Patients should be evaluated and tested for latent or active TB infection prior to and per applicable guidelines during baricitinib administration. There were no reported cases of tuberculosis during the 0 to 16 week treatment period. In the 0 to 52 week treatment period, tuberculosis was reported in 1 patient taking baricitinib 4 mg and 0 patients on baricitinib 2 mg. Cases of disseminated tuberculosis also were reported. Some patients have presented with disseminated rather than localized infection and were often taking concomitant immunosuppression agents such as methotrexate or corticosteroid therapy. Patients should be closely monitored for the development of signs and symptoms of infection during and after baricitinib treatment. Interrupt therapy with baricitinib if a patient develops a serious infection, an opportunistic infection, or sepsis. A patient who develops a new infection during treatment with baricitinib should undergo prompt and complete diagnostic testing appropriate for an immunocompromised patient; appropriate antimicrobial therapy should be initiated, and the patient should be closely monitored.[63229]

      Hematologic laboratory abnormalities have been reported during baricitinib clinical trials. In rheumatoid arthritis (RA) and alopecia areata patients, neutropenia, defined as an absolute neutrophil count (ANC) below 1,000 cells/mm3, was reported in up to 1.3% of patients receiving baricitinib. Avoid or interrupt baricitinib treatment in RA and alopecia areata patients with an ANC less than 1,000 cells/mm3. Anemia, defined as hemoglobin less than 8 grams/dL, was also reported in up to 1.3% of baricitinib recipients during clinical trials. Avoid or interrupt treatment in RA and alopecia areata patients with a hemoglobin less than 8 grams/dL. Lymphopenia, defined as absolute lymphocyte count (ALC) less than 500 cells/mm3 was reported during baricitinib clinical trials in less than 1% of patients. Lymphocyte counts less than the lower limit of normal were associated with infection in patients treated with baricitinib but not in those receiving placebo. Avoid or interrupt baricitinib treatment in RA and alopecia areata patients with an ALC less than 500 cells/mm3. Increases in platelet counts (thrombocytosis) above 600,000 cells/mm3 were reported in 1.1% of RA patients receiving 2 mg/day baricitinib and 1.1% in those receiving placebo. After 16 weeks of treatment, the mean platelet count increased by 3,000 cells/mm3 in patients receiving placebo and by 15,000 cells/mm3 in patients treated with baricitinib 2 mg. Hematologic laboratory abnormalities have also been reported in patients who received baricitinib for COVID-19. Pooled safety data from 2 COVID-19 clinical trials identified neutropenia and thrombocytosis in 2.2% and 7.9% of baricitinib treated patients, respectively. For COVID-19 patients with an ANC less than 500 cells/mm3, delay or interruption in baricitinib therapy until ANC is 500 cells/mm3 or more. For COVID-19 patients with an ALC less than 200 cells/mm3, delay or interruption in baricitinib therapy until ALC is 200 cells/mm3 or more.[63229]

      Serious and even fatal venous thromboembolism, including deep venous thrombosis (DVT) and pulmonary embolism (PE), have been reported during baricitinib clinical trials. Pooled safety data from 2 COVID-19 clinical trials identified venous thrombotic events in 3% of baricitinib treated patients (n = 40/1,307) and 2.2% of patients who received placebo (n = 29/1,310). More specifically, among baricitinib recipients, 20 patients (1.5%) developed a PE and 20 patients (1.5%) experienced a DVT. In clinical trials of patients with alopecia areata, venous thromboembolic events (including DVT and PE) were observed after Week 52. Additionally, less than 1% of baricitinib recipients developed an arterial thrombosis. In a rheumatoid arthritis (RA) trial, during the 16-week treatment period, DVT or PE was reported in 5 patients (1.7 events per 100 patient-years) receiving 4 mg daily; DVT or PE was not reported in those receiving placebo or 2 mg daily. Arterial thrombosis during the 16-week treatment period was reported in 1 patient receiving placebo (0.3 events per 100 patient-years), 2 patients receiving baricitinib 2 mg (1.4 events per 100 patient-years) and 2 patients (0.7 events per 100 patient-years) receiving baricitinib 4 mg per day. During the 0 to 52 week treatment period, venous thromboses were reported in 2 patients (0.6 events per 100 patient-years) receiving 2 mg per day and 7 patients (0.8 events per 100 patient-years) receiving 4 mg per day. Arterial thromboses were reported in 3 patients (0.9 events per 100 patient-years) receiving baricitinib 2 mg/day and 3 patients (0.3 events per 100 patient-years) receiving 4 mg/day. Baricitinib may cause increases in platelet counts (thrombocytosis). There is no clear relationship between platelet count elevations and thrombotic events. Higher rates of all cause mortality, including sudden cardiac death, and major cardiovascular adverse events (MACE), defined as cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke were reported with tofacitinib, another Janus kinase (JAK) inhibitor, compared to tumor necrosis factor (TNF) inhibitors in a large, postmarketing, randomized, safety study involving rheumatoid arthritis patients aged 50 years an older with one or more cardiovascular risk factors. Risks may be similar with all JAK inhibitors used for inflammatory conditions. Current and past tobacco smokers have an additional risk for these adverse events. Advise patients to seek emergency medical attention if they experience signs and symptoms of a heart attack, stroke, DVT, PE, or arterial thrombosis. Discontinue therapy if a patient develops a thromboembolic event.[63229]

      During clinical trials, abdominal pain and nausea were reported in up to 3.8% and up to 2.7% of patients receiving baricitinib, respectively. Gastrointestinal (GI) serious reactions, such as GI perforation, have been noted among baricitinib recipients. Promptly evaluate patients presenting with new-onset abdominal symptoms, such as abdominal pain, for early identification of GI perforation. Cautious use of baricitinib is advised for patients who may be at increased risk for GI perforation.[63229]

      Elevated hepatic enzymes have been reported in clinical trials with the use of baricitinib. During clinical trials of patients with alopecia areata, elevated hepatic enzymes were observed in 1.1% of patients receiving baricitinib 2 mg and 3% of patients receiving the 4 mg dose (vs. 2.4% placebo). Among rheumatoid arthritis (RA) patients receiving baricitinib 2 mg during a 16-week treatment period, alanine aminotransferase (ALT) elevations 3-times the upper limit of normal (ULN) or greater occurred in 1.7% of patients (vs. 1% placebo) and aspartate aminotransferase (AST) elevations 3-times the ULN or greater were reported in 1.3% of patients (vs. 0.8% placebo). Increases 5-times the ULN or more and 10-times the ULN or more were observed for both ALT and AST in patients in clinical trials. Elevated hepatic enzymes have also been reported in patients who received baricitinib for COVID-19. Pooled safety data from 2 COVID-19 clinical trials identified increases in the ALT and AST of at least 3-times the ULN in 18.1% and 11.8% of baricitinib treated patients, respectively. Prompt investigation of the cause of hepatic enzyme elevation is recommended to identify potential cases of drug-induced liver injury. If increases are observed and drug-induced hepatotoxicity is suspected, interrupt baricitinib treatment until this diagnosis is excluded.[63229]

      During baricitinib clinical trials, dose-related increases in lipid parameters were reported. In the alopecia areata clinical trials, 3.6% of patients receiving baricitinib 2 mg and 5.9% receiving the 4 mg dose developed hyperlipidemia, defined as hypercholesterolemia, hypertriglyceridemia, or dyslipidemia. During the rheumatoid arthritis (RA) trials, lipid elevations were observed at 12 weeks and remained stable thereafter. In RA patients treated with baricitinib 2 mg for 12 weeks, mean LDL cholesterol, mean HDL cholesterol, and mean triglycerides increased by 8 mg/dL, 7 mg/dL, and 7 mg/dL, respectively. The mean LDL/HDL ratio remained stable. Manage alopecia areata and RA patients according to clinical guidelines for the management of hyperlipidemia, hypercholesterolemia, or hypertriglyceridemia as per standards of care. Other laboratory alterations have also been reported. Baricitinib treatment was associated with increases in creatine phosphokinase (CPK) within 1 week of starting the drug in RA patients, but the CPK elevation leveled off after 8 to 12 weeks. At 16 weeks, the mean change in CPK for baricitinib 2 mg/day was 37 International Units/L. Elevated CPK concentrations have also been reported in patients who received baricitinib for alopecia areata and COVID-19. In alopecia areata patients, increased CPK was observed in 0.8% of patients receiving baricitinib 2 mg and 4.3% of patients receiving the 4 mg dose. Safety data from a COVID-19 clinical trial identified increased CPK concentrations greater than 5-times the ULN in 4.5% of baricitinib treated patients. In controlled clinical trials, dose-related increases in serum creatinine (SCr) were also observed; at 52 weeks, the mean increase in SCr was less than 0.1 mg/dL with baricitinib 4 mg. The clinical significance of the observed SCr increases is unknown.[63229]

      Baricitinib may cause a new primary malignancy; malignancies were reported during clinical trials. During clinical trials of patients with alopecia areata, B cell lymphoma was noted in less than 1% of drug recipients, and malignancy, including non-melanoma skin cancer (NMSC), was observed after Week 52. Among rheumatoid arthritis (RA) patients, 1 patient (0.7 events per 100 patient-years) receiving baricitinib 2 mg per day during the 16-week treatment period developed a malignancy other than NMSC; no events were reported in the placebo group. During the 0 to 52 week treatment period, malignancies other than NMSC were reported in 2 patients (0.6 events per 100 patient-years) receiving baricitinib 2 mg per day. NMSC has also been reported in patients treated with baricitinib. Periodic skin evaluations are recommended for patients at an increased risk of skin cancer. Consider the risks and benefits of baricitinib when considering the continuation of the drug in patients with a known malignancy (other than successfully treated NMSC), who develop a malignancy and patients who are current or past smokers.[63229]

      Acne (i.e., acneiform rash or dermatitis and acne vulgaris) was reported in up to 5.9% of patients receiving baricitinib during clinical trials. Additionally, 1.4% to 2.2% of patients receiving baricitinib for treatment of alopecia areata developed folliculitis during the clinical trials. Folliculitis was most commonly localized in the scalp region associated with hair regrowth.[63229]

      Angioedema, rash, and urticaria have been reported with postmarketing use of baricitinib and may reflect a serious hypersensitivity reaction. Promptly discontinue baricitinib therapy if a hypersensitivity reaction is suspected.[63229]

      Patients receiving treatment with baricitinib for alopecia areata during clinical trials reported headache (5.5% to 6.6%), fatigue (0.8% to 2.2%), and weight gain (0.9% to 1.6%).[63229]

      Revision Date: 06/15/2022, 08:35:18 AM

      References

      63229 - Olumiant (baricitinib) tablets package insert. Indianapolis, IN: Lilly USA, LLC; 2022 Jun.66126 - Food and Drug Administration (FDA). Fact sheet for health care providers emergency use authorization (EUA) of baricitinib. Retrieved May 11, 2022. Available on the World Wide Web at http://pi.lilly.com/eua/baricitinib-eua-factsheet-hcp.pdf.

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • anemia
      • angioedema
      • breast-feeding
      • cardiac disease
      • children
      • corticosteroid therapy
      • diabetes mellitus
      • dialysis
      • diverticulitis
      • fungal infection
      • geriatric
      • GI perforation
      • hepatic disease
      • hepatitis
      • hepatitis C infection
      • herpes infection
      • human immunodeficiency virus (HIV) infection
      • hypercholesterolemia
      • hyperlipidemia
      • hypertension
      • immunosuppression
      • infants
      • infection
      • lymphoma
      • mortality
      • myocardial infarction
      • neutropenia
      • new primary malignancy
      • pregnancy
      • pulmonary disease
      • renal disease
      • renal failure
      • renal impairment
      • serious hypersensitivity reactions or anaphylaxis
      • skin cancer
      • stroke
      • thrombocytosis
      • thromboembolic disease
      • thromboembolism
      • thrombosis
      • tobacco smoking
      • tuberculosis
      • vaccination
      • viral infection

      Avoid the use of baricitinib in rheumatoid arthritis and alopecia areata patients with an active, serious or opportunistic infection, including localized infections. In patients with COVID-19 and concomitant active serious infections, data are limited; therefore, the risks and benefits of baricitinib treatment in COVID-19 patients with other concurrent infections should be considered. Serious and sometimes fatal bacterial infection, mycobacterial infection, invasive fungal infection, viral infection, or infections due to other opportunistic pathogens have been reported in rheumatoid arthritis patients receiving baricitinib. The risks and benefits of treatment should be considered prior to initiating baricitinib in patients: 1) with chronic or recurrent infection; 2) who have been exposed to tuberculosis; 3) with a history of a serious or an opportunistic infection; 4) who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or 5) with underlying conditions that may predispose them to infection (e.g., diabetes mellitus, human immunodeficiency virus (HIV) infection, chronic pulmonary disease, low lymphocyte counts, and pre-existing immunosuppression). The most common serious infections reported with baricitinib included pneumonia, herpes zoster, and urinary tract infections. Among opportunistic infections, tuberculosis, cryptococcosis, acute histoplasmosis, esophageal candidiasis, pneumocystosis, multidermatomal herpes zoster, cytomegalovirus infections, and BK virus were reported with baricitinib. Some patients have presented with disseminated rather than localized disease, and were often taking concomitant immunosuppression agents such as methotrexate or corticosteroid therapy. Ask patients if they have lived or have traveled to the Ohio and Mississippi River valleys or the Southwest because of an increased chance of acquiring certain kinds of fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis. Viral reactivation, including cases of herpes infection reactivation (e.g., herpes zoster), were observed in clinical studies. If a patient develops herpes zoster, interrupt baricitinib therapy until the episode resolves. Carefully consider the risks and benefits of baricitinib before starting the drug in patients who have been exposed to tuberculosis (TB). Baricitinib should not be administered to patients with active tuberculosis. Patients, except those with COVID-19, should be evaluated and tested for latent TB infection prior to and per applicable guidelines during baricitinib administration. Consider anti-tuberculosis therapy before baricitinib administration in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed and for patients with a negative test for latent tuberculosis but who have risk factors for tuberculosis infection. Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision about whether initiating anti-tuberculosis therapy is appropriate for an individual patient. Monitor patients for the development of signs and symptoms of tuberculosis in all patients during treatment. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with baricitinib. Therapy with baricitinib should be interrupted if a patient develops a serious infection, an opportunistic infection, or sepsis. A patient who develops a new infection during treatment with baricitinib should undergo prompt and complete diagnostic testing appropriate for an immunocompromised patient; appropriate antimicrobial therapy should be initiated, and the patient should be closely monitored.[63229]

      Perform screening for viral hepatitis in accordance with clinical guidelines before starting therapy with baricitinib. The impact of baricitinib on chronic viral hepatitis reactivation is unknown. Patients with evidence of active hepatitis B or hepatitis C infection were excluded from clinical trials. In clinical trials in patients with rheumatoid arthritis or alopecia areata, patients who were positive for hepatitis C antibody but negative for hepatitis C virus RNA were permitted to enroll. Patients with positive hepatitis B surface antibody and hepatitis B core antibody, without hepatitis B surface antigen, were permitted to enroll; such patients should be monitored for expression of hepatitis B virus (HBV) DNA. Should HBV DNA be detected, consult with a hepatologist. Use baricitinib with caution in any other patient with hepatic disease or impairment. Increases in liver enzymes of 5-times and up to 10-times the upper limit of normal (ULN) were reported for both ALT and AST in clinical trials. Liver function tests (LFTs) should be evaluated at baseline and thereafter according to routine patient management. If increases in ALT or AST are seen and drug-induced liver toxicity is suspected, interrupt baricitinib treatment until drug-induced toxicity is excluded. Baricitinib is not recommended for rheumatoid arthritis or alopecia areata patients with severe hepatic impairment. For patients with COVID-19, baricitinib has not been studied in patients with severe hepatic impairment and should only be used if the potential benefit outweighs the potential risk.[63229]

      Determine neutrophil and lymphocyte counts before baricitinib initiation. Do not start the drug in rheumatoid arthritis or alopecia areata patients with an absolute lymphocyte count (ALC) less than 500 cells/mm3 or in patients with absolute neutrophil count (ANC) less than 1,000 cells/mm3. For COVID-19 patients, do not start the drug if the ALC is less than 200 cells/mm3 or the ANC is less than 500 cells/mm3. Baricitinib may cause lymphopenia and neutropenia. Monitor the ANC and ALC periodically during baricitinib treatment according to routine patient management. Interrupt treatment in rheumatoid arthritis and alopecia areata patients with an ANC less than 1,000 cells/mm3 or an ALC less than 500 cells/mm3 until the counts have recovered to amounts equal to or above these thresholds. Interrupt treatment in COVID-19 patients with an ANC less than 500 cells/mm3 or an ALC less than 200 cells/mm3 until the counts have recovered to amounts equal to or above these thresholds.[63229]

      Determine the hemoglobin concentration before baricitinib initiation, and do not start the drug in rheumatoid arthritis or alopecia areata patients with anemia defined as hemoglobin less than 8 grams/dL. Baricitinib may cause anemia. For patients who have hemoglobin 8 grams/dL or greater, monitor the hemoglobin concentration according to routine patient management. Treatment with baricitinib should be interrupted in patients who develop hemoglobin levels less than 8 grams/dL until the hemoglobin has recovered to 8 grams/dL or higher. There are limited data regarding the use of baricitinib in patients with COVID-19 and a hemoglobin less than 8 grams/dL.[63229]

      Baricitinib may increase the risk for a new primary malignancy.[63229] In a large, postmarketing, randomized safety clinical trial in rheumatoid arthritis patients 50 years of age and older with one or more CV risk factors, higher rates of cancer [excluding non-melanoma skin cancer (NMSC)] and lymphoma were observed with use of tofacitinib, another JAK inhibitor, compared to tumor necrosis factor (TNF) inhibitors. Baricitinib has not been studied in similar trials; however, the risks may be similar for all JAK inhibitors used for inflammatory conditions. A higher rate of lung cancer was also observed in patients with a history of current or past tobacco smoking treated with the JAK inhibitor compared to those treated with a TNF inhibitor. Patients with a history of current or past tobacco smoking were at also at an increased risk of overall cancers. Consider the benefits and risks for the individual patient before initiation or continuation of therapy, particular in those with risk factors such as smoking, those who develop malignancy, and those with a known malignancy other than successfully treated non-melanoma skin cancer (NMCS). Reserve baricitinib for patients who have an inadequate response or intolerance to one or more TNF inhibitors.[63229] [66958] NMSCs have also been reported in patients treated with baricitinib. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.[63229]

      Avoid use of baricitinib in patients who are at an increased risk of thrombosis and thromboembolism, including those with thromboembolic disease. Thrombosis, including deep venous thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis, have been reported with baricitinib therapy. Many of these events were serious and some resulted in death. In COVID-19 patients, baricitinib has been associated with increases in platelet counts (thrombocytosis) and serious venous thrombosis, including PE. COVID-19 patients receiving baricitinib during clinical trials, were recommended or required to receive venous thromboembolism (VTE) prophylaxis unless a major contraindication was noted. In a large, postmarketing, randomized safety clinical trial in rheumatoid arthritis patients 50 years of age and older with one or more CV risk factors, higher rates of all-cause mortality (including sudden CV death), major adverse CV events (MACE; defined as CV death, non-fatal myocardial infarction (MI), and non-fatal stroke), and thrombosis (including DVT and PE) were observed in patients taking tofacitinib, another Janus kinase (JAK) inhibitor, compared to patients taking tumor necrosis factor (TNF) inhibitors. Many of the observed thrombotic events were serious and some resulted in death. Baricitinib has not been studied in similar trials; however, the risks may be similar for all JAK inhibitors used for inflammatory conditions. Current or past tobacco smokers have an additional increased risk of major CV adverse events. Consider the benefits and risks for the individual patient before initiation or continuation of therapy, particular in those with cardiovascular risk factors (e.g., cardiac disease, hypertension, previous myocardial infarction) or those who are current or past smokers. Reserve baricitinib for patients who have an inadequate response or intolerance to one or more TNF inhibitors. Advise patients of the potential increased risk for major adverse CV events and to seek emergency medical attention if they experience signs and symptoms of a heart attack, stroke, or blood clot. If a patient develops a thromboembolic event, discontinue the drug.[63229] [66958]

      Use baricitinib with caution in patients with renal impairment. Dosage reductions are recommended in patients with an estimated glomerular filtration rate (eGFR) less than 60 mL/minute/1.73 m2. For rheumatoid arthritis and alopecia areata patients, treatment with baricitinib is not recommended in patients with severe renal impairment or renal failure (i.e., eGFR less than 30 mL/minute/1.73 m2). For adult COVID-19 patients, baricitinib is not recommended in patients who have end-stage renal disease (ESRD, eGFR less than 15 mL/minute/1.73 m2), are on dialysis, or who have acute kidney injury.[63229] COVID-19 per the Emergency Use Authorization (EUA): The eGFR must be obtained prior to administration of the first baricitinib dose. Baricitinib is not recommended in pediatric COVID-19 patients on dialysis, who have end-stage renal disease (ESRD, eGFR less than 15 mL/minute/1.73 m2), or who have acute kidney injury. Dosage reductions are recommended in pediatric patients 2 years and older with an eGFR of 30 to 59 mL/minute/1.73 m2. In pediatric patients 9 years and older with an eGFR of 15 to 29 mL/minute/1.73 m2, reduced dose baricitinib should only be used if the potential benefit outweighs the potential risk. Baricitinib therapy is not recommended in pediatric patients 2 years to less than 9 years with an eGFR less than 30 mL/minute/1.73 m2.[66126]

      Update immunizations in agreement with current immunization guidelines prior to initiating baricitinib therapy in patients with rheumatoid arthritis or alopecia areata. Patients who are taking baricitinib should not receive vaccination with live vaccines. These patients may receive non-live vaccines during baricitinib therapy. The interval between live vaccinations and the initiation of baricitinib therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents.[63229]

      Cautious use of baricitinib is advised for patients who may be at increased risk for gastrointestinal (GI) perforation (e.g., patients with a history of diverticulitis). GI perforation has been noted among baricitinib recipients. Patients presenting with new onset abdominal symptoms should be evaluated promptly for early identification of GI perforation.[63229]

      Use baricitinib with caution in patients with hyperlipidemia or hypercholesterolemia. Treatment with baricitinib 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 initiation of baricitinib therapy in patients with rheumatoid arthritis or alopecia areata. Manage patients according to clinical guidelines for the management of hyperlipidemia.[63229]

      During clinical trials, no overall differences in safety or effectiveness were noted between geriatric and younger adult patients receiving baricitinib for rheumatoid arthritis. However, greater sensitivity of some older individuals cannot be ruled out. Baricitinib is extensively excreted by the kidney, and the risk of adverse reactions may be greater for patients with impaired renal function. Geriatric patients are more likely to have decreased renal function; therefore, cautious dose selection and monitoring of renal function may be warranted in geriatric patients.[63229]

      Available data from clinical trials and postmarketing case reports regarding use of baricitinib during human pregnancy are insufficient to inform a drug-associated risk for major birth defects, miscarriages, or other adverse maternal or fetal outcomes. There are no human data on chronic baricitinib exposure throughout pregnancy; therefore, the risks and benefits with chronic use of the drug should be considered. When deciding whether to use the drug in pregnant patients with rheumatoid arthritis, consider that published data suggest increased disease activity is associated with risk of developing adverse pregnancy outcomes, including preterm delivery (before 37 weeks gestation), low birth weight (less than 2,500 grams) infants, and small for gestational age at birth. Based on finding from animal studies, exposure to baricitinib during pregnancy may cause fetal harm. In embryofetal development studies, oral administration to rats and rabbits at exposures at least 11- and 46-times the maximum recommended human dose (MRHD) of 4 mg per day, respectively, resulted in reduced fetal body weights, increased embryolethality (rabbits only), and dose-related increases in skeletal malformations. Developmental toxicity was not observed in pregnant rats and rabbits treated with baricitinib at approximately 2- and 7-times the MRHD, respectively. In a pre- and post-development study in pregnant rats, oral baricitinib administration at exposures approximately 24-times the MRHD resulted in a reduction in pup viability, decreased fetal birth weight, reduced fetal body weight gain, decreased cytotoxic T cells on post-natal day 35 with no evidence of recovery by day 65, and developmental delays that might be attributable to decreased body weight gain. No developmental toxicity was observed at exposures approximately 5-times the MRHD.[63229] The National Institutes of Health (NIH) states that there are limited data available on the use of Janus kinase (JAK) inhibitors, such as baricitinib, during pregnancy in patients with COVID-19. Among 33 reported cases of JAK inhibitor use during pregnancy in patients with non-COVID-19 indications (e.g., ulcerative colitis, rheumatoid arthritis, psoriasis), the outcomes were similar to those of the general population. However, because of the small molecular size, JAK inhibitors are likely to pass through the placenta; thus, fetal risk cannot be ruled out. The decision to administer baricitinib to a pregnant patient with COVID-19 must be shared between the patient and their healthcare providers, and potential maternal benefit and fetal risks must be considered.[65314] Consider pregnancy planning and contraception requirements for patients of childbearing potential. Report drug exposures during pregnancy to the manufacturer at 1-800-545-5979.[63229]

      Due to the potential for serious adverse reactions in a nursing infant, breast-feeding is not recommended during baricitinib therapy and for 4 days after the last dose (approximately 5 to 6 elimination half-lives). No data are available on the presence of baricitinib in human milk, the effects of the drug on the breast-fed infant, or the effects on milk production. Baricitinib is present in the milk of lactating rats; the clinical relevance of this to human lactation is not known.[63229] Etanercept and infliximab may be potential alternatives to consider during breast-feeding. However, assessment of indication and patient-specific factors should be performed before considering an alternative agent.[61808] [62180]

      The safety and efficacy of baricitinib in infants, children, and adolescents under the age of 18 years have not been established.[63229]

      Angioedema, urticaria, and rash have been reported with baricitinib therapy and may be a result of serious hypersensitivity reactions or anaphylaxis. Promptly discontinue baricitinib therapy if a serious hypersensitivity reaction is suspected.[63229]

      Revision Date: 08/09/2022, 03:20:36 PM

      References

      61808 - Mahadevan U, McConnell RA, Chambers C. Drug safety and risk of adverse outcomes for pregnant patients with inflammatory bowel diseases. Gastroenterology 2017;152:451-462.e2.62180 - Gotestam Skorpen C, Hoeltzenbein M, Tincani A, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis 2016;75(5):795-810.63229 - Olumiant (baricitinib) tablets package insert. Indianapolis, IN: Lilly USA, LLC; 2022 Jun.65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed August 18, 2022. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.66126 - Food and Drug Administration (FDA). Fact sheet for health care providers emergency use authorization (EUA) of baricitinib. Retrieved May 11, 2022. Available on the World Wide Web at http://pi.lilly.com/eua/baricitinib-eua-factsheet-hcp.pdf.66958 - U.S. Food and Drug Administration (FDA). FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. Retrieved Sept 1, 2021. Available at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death?utm_medium=email&utm_source=govdelivery

      Mechanism of Action

      Baricitinib is an oral Janus kinase (JAK) inhibitor. Janus kinases are intracellular enzymes that transmit signals arising from cytokine or growth factor receptor interactions on the cellular membrane to influence cellular processes of immune cell function and hematopoiesis. JAK-mediated signaling is pivotal in immune activation, as cytokine receptors are expressed on most immune cells. Within the signaling pathway, JAKs phosphorylate and activate signal transducers and activators of transcription proteins (STATs), which modulate intracellular activity including gene expression. Baricitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs. Cytokine signaling is transmitted through pairing of JAKs such as JAK1/JAK2, JAK1/JAK3, JAK1/TYK2, JAK2/JAK2, and JAK2/TYK2. Baricitinib has greater affinity for JAK1, JAK2, and TYK2, relative to JAK3. In human leukocytes, baricitinib inhibits cytokine-induced STAT phosphorylation mediated by JAK1/JAK2, JAK1/JAK3, JAK1/TYK2, or JAK2/TYK2 with comparable potencies. However, the relevance of specific JAK combinations to therapeutic effectiveness is not known.[63229]

      Revision Date: 04/10/2020, 01:05:23 PM

      References

      63229 - Olumiant (baricitinib) tablets package insert. Indianapolis, IN: Lilly USA, LLC; 2022 Jun.

      Pharmacokinetics

      Baricitinib is administered orally. After intravenous administration, the volume of distribution is 76 L, indicating the distribution of baricitinib into tissues. Plasma and serum protein bindings are approximately 50% and 45%, respectively. Approximately 6% of the orally administered baricitinib dose is identified as metabolites (3 from urine and 1 from feces), with CYP3A4 identified as the main metabolizing enzyme. No metabolites of baricitinib were quantifiable in plasma. In a clinical pharmacology study, approximately 75% of the administered dose was eliminated in the urine, while about 20% of the dose was eliminated in the feces. Baricitinib is predominately excreted as unchanged drug in the urine (69%) and feces (15%). The elimination half-life is approximately 12 to 16 hours in patients with rheumatoid arthritis (RA) and alopecia areata. In COVID-19 patients who are intubated and have baricitinib administered via nasogastric (NG) or orogastric (OG) tube, the total body clearance and half-life of baricitinib is 14.2 L/hour and 10.8 hours, respectively.[63229]

       

      Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4, OAT3, P-glycoprotein (P-gp), BCRP, and MATE2-K

      In vitro studies indicate that baricitinib is a substrate of CYP3A4, OAT3, P-gp, BCRP, and MATE2-K. In clinical pharmacology studies, coadministration with ketoconazole (a strong CYP3A4) did not have an effect on the pharmacokinetics of baricitinib. In addition, no clinically meaningful effects on baricitinib pharmacokinetics when it was coadministered with fluconazole (CYP3A/CYP2C19/CYP2C9 inhibitor) or rifampin (a strong CYP3A4 inducer). Coadministration with probenecid (a strong OAT3 inhibitor) resulted in an approximately 2-fold increase in baricitinib exposure. Coadministration with OAT3 inhibitors with less inhibition potential (i.e., ibuprofen and diclofenac) had minimal effect on baricitinib exposure. No clinically meaningful effect on the pharmacokinetics of baricitinib was noted with the coadministration of cyclosporine (a P-gp and BCRP inhibitor). In vitro data indicate baricitinib inhibits OAT1, OAT2, OAT3, OCT1, OCT2, OAT1B3, BCRP, and MATE1 and MATE2-K, but clinically meaningful changes in the pharmacokinetics of drugs that are substrates for these transporters are unlikely.[63229]

      Route-Specific Pharmacokinetics

      Oral Route

      The absolute oral bioavailability of baricitinib is approximately 80%. In clinical trials, baricitinib was administered without regard to meals. Administration with meals is not associated with a clinically relevant effect on exposure. Peak plasma concentrations of baricitinib after oral administration were reached within 1 hour, and a dose-proportional increase in systemic exposure was observed in the therapeutic dose range. Steady-state concentrations are achieved in 2 to 3 days with negligible accumulation.[63229]

      Special Populations

      Hepatic Impairment

      The systemic exposure and maximum concentration of baricitinib is increased by 1.19- and 1.08-fold for patients with moderate hepatic impairment compared to those with normal hepatic function. Baricitinib is not recommended in patients with severe hepatic impairment due to a lack of data.[63229]

      Renal Impairment

      The systemic exposure (AUC) of baricitinib was increased by 1.41-, 2.22-, 4.05-, and 2.41-fold for mild, moderate, severe, and end-stage renal disease (ESRD with hemodialysis) renal impairment groups compared to subjects with normal renal function. The maximum concentration (Cmax) increased by 1.16-, 1.46-, 1.40- and 0.88-fold for mild, moderate, severe, and ESRD patients, respectively, compared to patients with normal renal function.[63229]

      Pediatrics

      There are no pediatric data regarding the pharmacokinetics of baricitinib.[63229] Based on an analysis of interim pharmacokinetic data from ongoing clinical trials of baricitinib in other pediatric chronic autoimmune disorders, the authorized COVID-19 dosing regimen is expected to result in comparable steady-state plasma exposures of baricitinib in pediatric patients 2 to 17 years as observed in health adults.[66126]

      Geriatric

      Age did not have a clinically relevant effect on the pharmacokinetic profile of baricitinib.[63229]

      Gender Differences

      Gender did not have a clinically relevant effect on the pharmacokinetic profile of baricitinib.[63229]

      Ethnic Differences

      Ethnic differences did not have a clinically relevant effect on the pharmacokinetic profile of baricitinib.[63229]

      Obesity

      Body weight did not have a clinically relevant effect on the pharmacokinetic profile of baricitinib.[63229]

      Revision Date: 06/16/2022, 12:59:31 AM

      References

      63229 - Olumiant (baricitinib) tablets package insert. Indianapolis, IN: Lilly USA, LLC; 2022 Jun.66126 - Food and Drug Administration (FDA). Fact sheet for health care providers emergency use authorization (EUA) of baricitinib. Retrieved May 11, 2022. Available on the World Wide Web at http://pi.lilly.com/eua/baricitinib-eua-factsheet-hcp.pdf.

      Pregnancy/Breast-feeding

      pregnancy

      Available data from clinical trials and postmarketing case reports regarding use of baricitinib during human pregnancy are insufficient to inform a drug-associated risk for major birth defects, miscarriages, or other adverse maternal or fetal outcomes. There are no human data on chronic baricitinib exposure throughout pregnancy; therefore, the risks and benefits with chronic use of the drug should be considered. When deciding whether to use the drug in pregnant patients with rheumatoid arthritis, consider that published data suggest increased disease activity is associated with risk of developing adverse pregnancy outcomes, including preterm delivery (before 37 weeks gestation), low birth weight (less than 2,500 grams) infants, and small for gestational age at birth. Based on finding from animal studies, exposure to baricitinib during pregnancy may cause fetal harm. In embryofetal development studies, oral administration to rats and rabbits at exposures at least 11- and 46-times the maximum recommended human dose (MRHD) of 4 mg per day, respectively, resulted in reduced fetal body weights, increased embryolethality (rabbits only), and dose-related increases in skeletal malformations. Developmental toxicity was not observed in pregnant rats and rabbits treated with baricitinib at approximately 2- and 7-times the MRHD, respectively. In a pre- and post-development study in pregnant rats, oral baricitinib administration at exposures approximately 24-times the MRHD resulted in a reduction in pup viability, decreased fetal birth weight, reduced fetal body weight gain, decreased cytotoxic T cells on post-natal day 35 with no evidence of recovery by day 65, and developmental delays that might be attributable to decreased body weight gain. No developmental toxicity was observed at exposures approximately 5-times the MRHD.[63229] The National Institutes of Health (NIH) states that there are limited data available on the use of Janus kinase (JAK) inhibitors, such as baricitinib, during pregnancy in patients with COVID-19. Among 33 reported cases of JAK inhibitor use during pregnancy in patients with non-COVID-19 indications (e.g., ulcerative colitis, rheumatoid arthritis, psoriasis), the outcomes were similar to those of the general population. However, because of the small molecular size, JAK inhibitors are likely to pass through the placenta; thus, fetal risk cannot be ruled out. The decision to administer baricitinib to a pregnant patient with COVID-19 must be shared between the patient and their healthcare providers, and potential maternal benefit and fetal risks must be considered.[65314] Consider pregnancy planning and contraception requirements for patients of childbearing potential. Report drug exposures during pregnancy to the manufacturer at 1-800-545-5979.[63229]

      breast-feeding

      Due to the potential for serious adverse reactions in a nursing infant, breast-feeding is not recommended during baricitinib therapy and for 4 days after the last dose (approximately 5 to 6 elimination half-lives). No data are available on the presence of baricitinib in human milk, the effects of the drug on the breast-fed infant, or the effects on milk production. Baricitinib is present in the milk of lactating rats; the clinical relevance of this to human lactation is not known.[63229] Etanercept and infliximab may be potential alternatives to consider during breast-feeding. However, assessment of indication and patient-specific factors should be performed before considering an alternative agent.[61808] [62180]

      Revision Date: 08/09/2022, 03:20:36 PM

      References

      61808 - Mahadevan U, McConnell RA, Chambers C. Drug safety and risk of adverse outcomes for pregnant patients with inflammatory bowel diseases. Gastroenterology 2017;152:451-462.e2.62180 - Gotestam Skorpen C, Hoeltzenbein M, Tincani A, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis 2016;75(5):795-810.63229 - Olumiant (baricitinib) tablets package insert. Indianapolis, IN: Lilly USA, LLC; 2022 Jun.65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed August 18, 2022. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.

      Interactions

      Level 2 (Major)

      • Abatacept
      • Adalimumab
      • Anakinra
      • Azathioprine
      • Bacillus Calmette-Guerin Vaccine, BCG
      • Canakinumab
      • Certolizumab pegol
      • Cyclosporine
      • Etanercept
      • Golimumab
      • Infliximab
      • Intranasal Influenza Vaccine
      • Live Vaccines
      • Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live
      • Measles/Mumps/Rubella Vaccines, MMR
      • Probenecid
      • Probenecid; Colchicine
      • Rituximab
      • Rituximab; Hyaluronidase
      • Rotavirus Vaccine
      • Rubella Virus Vaccine Live
      • Sarilumab
      • Secukinumab
      • Smallpox and Monkeypox Vaccine, Live, Nonreplicating
      • Smallpox Vaccine, Vaccinia Vaccine
      • Tocilizumab
      • Tofacitinib
      • Tumor Necrosis Factor modifiers
      • Typhoid Vaccine
      • Upadacitinib
      • Ustekinumab
      • Varicella-Zoster Virus Vaccine, Live
      • Yellow Fever Vaccine, Live

      Level 3 (Moderate)

      • Leflunomide
      • Teriflunomide
      Abatacept: (Major) Concomitant use of baricitinib with biologic DMARDs, such as abatacept, is not recommended because of the possibility of additive immunosuppression and increased infection risk. There is insufficient experience to assess the safety and efficacy of this combination. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs. [31761] [63229] Adalimumab: (Major) Concomitant use of baricitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs. [63229] Anakinra: (Major) Concomitant use of baricitinib with biologic DMARDs, such as anakinra, is not recommended because of the possibility of increased immunosuppression and increased infection risk. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs. [63229] Azathioprine: (Major) Concomitant use of baricitinib with azathioprine is not recommended because of the possibility of additive immunosuppression and increased infection risk. There is insufficient experience to assess the safety and efficacy of this combination. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs. [63229] Bacillus Calmette-Guerin Vaccine, BCG: (Major) Do not administer live virus vaccines to patients taking baricitinib, as no data are available on the secondary transmission of infection by live vaccines. Also, no data are available on the response to vaccination with any vaccine during baricitinib receipt. Before baricitinib initiation, review the vaccination status of patients, and update immunizations in agreement with current immunization guidelines. [63229] Canakinumab: (Major) Concomitant use of baricitinib with biologic DMARDs, such as canakinumab, is not recommended because of the possibility of additive immunosuppression and increased infection risk. [63229] Certolizumab pegol: (Major) Concomitant use of baricitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs. [63229] Cyclosporine: (Major) Concomitant use of baricitinib with cyclosporine is not recommended because of the possibility of additive immunosuppression and increased infection risk. There is insufficient experience to assess the safety and efficacy of this combination. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs. [63229] Etanercept: (Major) Concomitant use of baricitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs. [63229] Golimumab: (Major) Concomitant use of baricitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs. [63229] Infliximab: (Major) Concomitant use of baricitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs. [63229] Intranasal Influenza Vaccine: (Major) Do not administer live virus vaccines to patients taking baricitinib, as no data are available on the secondary transmission of infection by live vaccines. Also, no data are available on the response to vaccination with any vaccine during baricitinib receipt. Before baricitinib initiation, review the vaccination status of patients, and update immunizations in agreement with current immunization guidelines. [63229] Leflunomide: (Moderate) Monitor for increased baricitinib effects if administered with leflunomide as baricitinib exposure may increase; a baricitinib dose reduction may be necessary. Baricitinib is an OAT3 substrate; leflunomide is an OAT3 inhibitor. [49634] [63229] Live Vaccines: (Major) Do not administer live virus vaccines to patients taking baricitinib, as no data are available on the secondary transmission of infection by live vaccines. Also, no data are available on the response to vaccination with any vaccine during baricitinib receipt. Before baricitinib initiation, review the vaccination status of patients, and update immunizations in agreement with current immunization guidelines. [63229] Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Do not administer live virus vaccines to patients taking baricitinib, as no data are available on the secondary transmission of infection by live vaccines. Also, no data are available on the response to vaccination with any vaccine during baricitinib receipt. Before baricitinib initiation, review the vaccination status of patients, and update immunizations in agreement with current immunization guidelines. [63229] Measles/Mumps/Rubella Vaccines, MMR: (Major) Do not administer live virus vaccines to patients taking baricitinib, as no data are available on the secondary transmission of infection by live vaccines. Also, no data are available on the response to vaccination with any vaccine during baricitinib receipt. Before baricitinib initiation, review the vaccination status of patients, and update immunizations in agreement with current immunization guidelines. [63229] Probenecid: (Major) Reduce the recommended baricitinib dose by half in patients receiving concomitant therapy with probenecid. If the recommended dose is 4 mg daily, reduce to 2 mg daily. If the recommended dose is 2 mg daily, reduce to 1 mg daily. If the recommended dose is 1 mg daily, consider discontinuing probenecid. Coadministration of baricitinib and probenecid results in increased baricitinib exposure. In a drug interaction study, administration of probenecid increased baricitinib exposure by 2-fold. Baricitinib is an OAT3 substrate and probenecid is a strong OAT3 inhibitor. [63229] [66126] Probenecid; Colchicine: (Major) Reduce the recommended baricitinib dose by half in patients receiving concomitant therapy with probenecid. If the recommended dose is 4 mg daily, reduce to 2 mg daily. If the recommended dose is 2 mg daily, reduce to 1 mg daily. If the recommended dose is 1 mg daily, consider discontinuing probenecid. Coadministration of baricitinib and probenecid results in increased baricitinib exposure. In a drug interaction study, administration of probenecid increased baricitinib exposure by 2-fold. Baricitinib is an OAT3 substrate and probenecid is a strong OAT3 inhibitor. [63229] [66126] Rituximab: (Major) Concomitant use of baricitinib with biologic DMARDs, such as rituximab, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs. [63229] Rituximab; Hyaluronidase: (Major) Concomitant use of baricitinib with biologic DMARDs, such as rituximab, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs. [63229] Rotavirus Vaccine: (Major) Do not administer live virus vaccines to patients taking baricitinib, as no data are available on the secondary transmission of infection by live vaccines. Also, no data are available on the response to vaccination with any vaccine during baricitinib receipt. Before baricitinib initiation, review the vaccination status of patients, and update immunizations in agreement with current immunization guidelines. [63229] Rubella Virus Vaccine Live: (Major) Do not administer live virus vaccines to patients taking baricitinib, as no data are available on the secondary transmission of infection by live vaccines. Also, no data are available on the response to vaccination with any vaccine during baricitinib receipt. Before baricitinib initiation, review the vaccination status of patients, and update immunizations in agreement with current immunization guidelines. [63229] Sarilumab: (Major) Avoid the concomitant use of sarilumab with other biological DMARDs such as baricitinib; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. [61976] [63229] Secukinumab: (Major) Concomitant use of baricitinib with biologic DMARDs, such as secukinumab, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs. [63229] Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Major) Do not administer live virus vaccines to patients taking baricitinib, as no data are available on the secondary transmission of infection by live vaccines. Also, no data are available on the response to vaccination with any vaccine during baricitinib receipt. Before baricitinib initiation, review the vaccination status of patients, and update immunizations in agreement with current immunization guidelines. [63229] Smallpox Vaccine, Vaccinia Vaccine: (Major) Do not administer live virus vaccines to patients taking baricitinib, as no data are available on the secondary transmission of infection by live vaccines. Also, no data are available on the response to vaccination with any vaccine during baricitinib receipt. Before baricitinib initiation, review the vaccination status of patients, and update immunizations in agreement with current immunization guidelines. [63229] Teriflunomide: (Moderate) Monitor for increased baricitinib effects if administered with teriflunomide as baricitinib exposure may increase; a baricitinib dose reduction may be necessary. Baricitinib is an OAT3 substrate; teriflunomide is an OAT3 inhibitor. [51794] [63229] Tocilizumab: (Major) Avoid the concomitant use of tocilizumab with other biological DMARDs such as baricitinib; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. [38283] [63229] Tofacitinib: (Major) Concomitant use of baricitinib with tofacitinib is not recommended because of the duplication of the mechanism of action (both are Janus kinase inhibitors, also known as JAK inhibitors) and the possibility of increased immunosuppression and increased infection risk. Both drugs are known to cause elevations in hepatic enzymes and gastrointestinal perforation, and a possibility for increased thrombotic risk. [63229] Tumor Necrosis Factor modifiers: (Major) Concomitant use of baricitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs. [63229] Typhoid Vaccine: (Major) Do not administer live virus vaccines to patients taking baricitinib, as no data are available on the secondary transmission of infection by live vaccines. Also, no data are available on the response to vaccination with any vaccine during baricitinib receipt. Before baricitinib initiation, review the vaccination status of patients, and update immunizations in agreement with current immunization guidelines. [63229] Upadacitinib: (Major) Concomitant use of baricitinib with upadacitinib is not recommended because of the duplication of the mechanism of action (both are Janus kinase inhibitors, also known as JAK inhibitors) and the possibility of increased immunosuppression and increased infection risk. Both drugs are known to cause elevations in hepatic enzymes and gastrointestinal perforation, and a possibility for increased thrombotic risk. [64572] Ustekinumab: (Major) Concomitant use of baricitinib with biologic DMARDs, such as ustekinumab, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs. [63229] Varicella-Zoster Virus Vaccine, Live: (Major) Do not administer live virus vaccines to patients taking baricitinib, as no data are available on the secondary transmission of infection by live vaccines. Also, no data are available on the response to vaccination with any vaccine during baricitinib receipt. Before baricitinib initiation, review the vaccination status of patients, and update immunizations in agreement with current immunization guidelines. [63229] Yellow Fever Vaccine, Live: (Major) Do not administer live virus vaccines to patients taking baricitinib, as no data are available on the secondary transmission of infection by live vaccines. Also, no data are available on the response to vaccination with any vaccine during baricitinib receipt. Before baricitinib initiation, review the vaccination status of patients, and update immunizations in agreement with current immunization guidelines. [63229]
      Revision Date: 09/25/2022, 02:52:00 AM

      References

      31761 - Orencia (abatacept) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2021 Dec.38283 - Actemra (tocilizumab) injection package insert. South San Francisco, CA: Genentech, Inc.; 2022 Feb.49634 - Arava (leflunomide) package insert. Bridgewater, NJ:. Sanofi-Aventis U.S. LLC; 2016 Feb.51794 - Aubagio (teriflunomide) tablets package insert. Genzyme Corporation: Cambridge, MA; 2021 Apr.61976 - Kevzara (sarilumab) package insert. Bridgewater, NJ: Sanofi-Aventis US. LLC; 2018 Apr.63229 - Olumiant (baricitinib) tablets package insert. Indianapolis, IN: Lilly USA, LLC; 2022 Jun.64572 - Rinvoq (upadacitinib) package insert. North Chicago, IL: Abbvie Inc.; 2022 Apr.66126 - Food and Drug Administration (FDA). Fact sheet for health care providers emergency use authorization (EUA) of baricitinib. Retrieved May 11, 2022. Available on the World Wide Web at http://pi.lilly.com/eua/baricitinib-eua-factsheet-hcp.pdf.

      Monitoring Parameters

      • CBC with differential
      • hemoglobin/hematocrit
      • LFTs
      • serum cholesterol profile
      • serum creatinine/BUN
      • skin cancer screening exam
      • tuberculin skin test

      US Drug Names

      • OLUMIANT
      ;