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Baricitinib

Indications/Dosage

Labeled

  • rheumatoid arthritis

Off-Label

  • coronavirus disease 2019 (COVID-19)
  • severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
† Off-label indication

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) antagonists

Oral dosage

Adults

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

INVESTIGATIONAL USE: For use in combination with remdesivir for the treatment of suspected or laboratory confirmed coronavirus disease 2019 (COVID-19)†, due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection†, in hospitalized patients requiring supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)

NOTE: Patients must have eGFR, aminotransferases (liver function tests), and complete blood count (CBC) with differential evaluated prior to first dose of baricitinib.[66126]

Oral dosage

Adults

4 mg PO once daily for a recommended treatment duration of 14 days or until hospital discharge, whichever comes first; optimal treatment duration unknown. Baricitinib is to be taken in combination with remdesivir. Limited data available on concomitant baricitinib and systemic corticosteroids; however, this does not preclude coadministration.[66126] Due to broad immunosuppressive effects, the National Institutes of Health (NIH) COVID-19 treatment guidelines recommend against the use of JAK inhibitors outside of clinical trials.[65314]

Children and Adolescents 9 years of age and older

4 mg PO once daily for a recommended treatment duration of 14 days or until hospital discharge, whichever comes first; optimal treatment duration unknown. Baricitinib is to be taken in combination with remdesivir. Limited data available on concomitant baricitinib and systemic corticosteroids; however, this does not preclude coadministration.[66126] Due to broad immunosuppressive effects, the National Institutes of Health (NIH) COVID-19 treatment guidelines recommend against the use of JAK inhibitors outside of clinical trials.[65314]

Children 2 to less than 9 years

2 mg PO once daily for a recommended treatment duration of 14 days or until hospital discharge, whichever comes first; optimal treatment duration unknown. Baricitinib is to be taken in combination with remdesivir. Limited data available on concomitant baricitinib and systemic corticosteroids; however, this does not preclude coadministration.[66126] Due to broad immunosuppressive effects, the National Institutes of Health (NIH) COVID-19 treatment guidelines recommend against the use of JAK inhibitors outside of clinical trials.[65314]

Therapeutic Drug Monitoring

Anemia

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]

 

Lymphopenia

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 per the Emergency Use Authorization (EUA):

Determine ALC before baricitinib initiation and monitor during therapy according to routine patient management. No dosage adjustments needed for an ALC of 200 cells/mm3 or more. For an ALC less than 200 cells/mm3, consider a delay or interruption in baricitinib therapy until ALC is 200 cells/mm3 or more.[66126]

 

Neutropenia

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 per the Emergency Use Authorization (EUA):

Determine ANC before baricitinib initiation and monitor during therapy according to routine patient management. No dosage adjustments needed for an ANC of 500 cells/mm3 or more. For an ANC less than 500 cells/mm3, consider a delay or interruption in baricitinib therapy until ANC is 500 cells/mm3 or more.[66126]

 

Serious Infection

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

 

Lipid Elevations

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 <p>2 mg/day PO; investigational doses of 4 mg/day PO have been used for COVID-19.</p>
  • Geriatric <p>2 mg/day PO; investigational doses of 4 mg/day PO have been used for COVID-19.</p>
  • Adolescents <p>Safety and efficacy have not been established; however, investigational doses of 4 mg/day PO have been used for COVID-19.</p>
  • Children <p><em>Children 9 to 12 years:</em> Safety and efficacy have not been established; investigational doses of 4 mg/day PO have been used for COVID-19.</p> <p><em>Children 2 to less than 9 years:</em> Safety and efficacy have not been established; however, investigational doses of 2 mg/day PO have been used for COVID-19.</p> <p><em>Children less than 2 years:</em> Safety and efficacy have not been established.</p>
  • Infants <p>Safety and efficacy have not been established.</p>
  • Neonates <p>Safety and efficacy have not been established.</p>

Patients with Hepatic Impairment Dosing

Mild or moderate impairment: No dosage adjustments needed.

Severe impairment: Not recommended.[63229]

 

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

If increases in alanine transaminase (ALT) or aspartate transaminase (AST) occur and drug-induced liver injury is suspected, interrupt baricitinib until the diagnosis of drug-induced liver disease has been excluded.[66126]

Patients with Renal Impairment Dosing

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

eGFR 30 to 60 mL/minute/1.73 m2: Reduce to 1 mg PO once daily.

eGFR less than 30 mL/minute/1.73 m2: Use not recommended.[63229]

 

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

Baricitinib is not recommended 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.

 

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 less than 60 mL/minute/1.73 m2: Reduce to 2 mg PO once daily.

eGFR 15 to less than 30 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 less than 60 mL/minute/1.73 m2: Reduce to 1 mg PO once daily.

eGFR less than 30 mL/minute/1.73 m2: Use not recommended.[66126]

† Off-label indication
Revision Date: 11/23/2020, 02:57:38 PM

References

63229 - Olumiant (baricitinib) tablets package insert. Indianapolis, IN: Lilly USA, LLC; 2020 Jul.65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed November 18, 2020. 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 November 20, 2020. Available on the World Wide Web at http://pi.lilly.com/eua/baricitinib-eua-factsheet-hcp.pdf.

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

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 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. 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 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. Also, JAK inhibitors have been associated with an increased risk of thrombosis.[63229]

 

Updates for coronavirus disease 2019 (COVID-19):

Baricitinib is not FDA-approved to treat coronavirus disease 2019 (COVID-19); however, the FDA has issued an Emergency Use Authorization for the use of baricitinib, in combination with remdesivir, to treat suspected or laboratory-confirmed COVID-19 in hospitalized adult and pediatric patients 2 years and older requiring supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).[66126] However, due to the broad immunosuppressive effect, the National Institutes of Health (NIH) COVID-19 treatment guidelines recommend against the use of JAK inhibitors outside of clinical trials.[65314]

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: 11/23/2020, 01:01:34 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; 2020 Jul.65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed November 18, 2020. 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 November 20, 2020. Available on the World Wide Web at http://pi.lilly.com/eua/baricitinib-eua-factsheet-hcp.pdf.

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); however, the FDA has issued an Emergency Use Authorization for the use of baricitinib, in combination with remdesivir, to treat suspected or laboratory-confirmed COVID-19 in hospitalized adult and pediatric patients 2 years and older requiring supplemental oxygen, 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 onset of the event.[66126]

Route-Specific Administration

Oral Administration

Oral Solid Formulations

  • Administer tablets with or without food.[63229]

Extemporaneous Compounding-Oral

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

  • Proper control measure, such as a ventilated enclosure, or personal protective equipment (i.e., N95 respirator) should be used in the preparation of extemporaneous oral formulations; it is unknown whether the powder from crushed tablets constitute a reproductive hazard.[66126]

 

Oral administration of dispersed tablets in water:

  • For patients unable to swallow whole tablets.
  • 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, 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 container with 10 mL (minimum 5 mL) of room temperature water and swallow the entire contents.
  • Tablets dispersed in water are stable for 4 hours.[66126]

 

Administration via gastrostomy feeding 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, 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.
  • Tablets dispersed in water are stable for 4 hours.[66126]

 

Administration via nasogastric feeding tube (NG 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, 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 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 tube.
  • Tablets dispersed in water are stable for 4 hours.[66126]

Clinical Pharmaceutics Information

From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
    Revision Date: 11/23/2020, 03:29:34 PM

    References

    63229 - Olumiant (baricitinib) tablets package insert. Indianapolis, IN: Lilly USA, LLC; 2020 Jul.66126 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of baricitinib. Retrieved November 20, 2020. Available on the World Wide Web at http://pi.lilly.com/eua/baricitinib-eua-factsheet-hcp.pdf.

    Adverse Reactions

    Mild

    • abdominal pain
    • acne vulgaris
    • infection
    • laryngitis
    • nausea
    • pharyngitis
    • rash
    • rhinitis
    • sinusitis
    • urticaria

    Moderate

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

    Severe

    • angioedema
    • GI perforation
    • hepatotoxicity
    • lymphoma
    • new primary malignancy
    • pulmonary embolism
    • skin cancer
    • 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. The most commonly reported adverse reactions during baricitinib clinical trials for rheumatoid arthritis were upper respiratory tract infections (16.3% vs. 11.7% placebo). Included in upper respiratory tract infections were acute sinusitis, sinusitis, acute tonsillitis, tonsillitis, epiglottitis, laryngitis, nasopharyngitis, oropharyngeal pain, pharyngitis, pharyngotonsillitis, rhinitis, sinobronchitis, and tracheitis. During the 16-week treatment period, overall infections 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, 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); baricitinib 4 mg is not an FDA-approved dose. 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 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] Serious infections have been reported in COVID-19 patients who received baricitinib. Infection was reported in 6% of baricitinib plus remdesivir patients compared to 10% of placebo plus remdesivir patients.[66126]

    Hematologic laboratory abnormalities have been reported during baricitinib clinical trials. Neutropenia, defined as an absolute neutrophil count (ANC) below 1,000 cells/mm3, was reported in 0.6% of patients receiving baricitinib 2 mg daily (none reported with placebo). ANC counts below 500 cells/mm3 were not reported in any treatment group. Avoid or interrupt baricitinib treatment in patients with an ANC less than 1,000 cells/mm3. Anemia, defined as hemoglobin less than 8 grams/dL, was reported during baricitinib clinical trials. Avoid or interrupt treatment in 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. 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 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 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.[63229]

    Serious and even fatal venous thromboembolism, including deep venous thrombosis (DVT) and pulmonary embolism (PE), have been reported during baricitinib clinical trials. 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 (not an FDA approved dose); 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. If signs and symptoms of DVT, PE, or arterial thrombosis occur, promptly evaluate and treat patients.[63229] Serious venous thrombosis, including PE, have been reported in COVID-19 patients who received baricitinib. Venous thromboembolic events occurred in 4% of patients that received baricitinib plus remdesivir compared to 3% of patients that received placebo plus baricitinib. Pulmonary embolism occurred in 1% of baricitinib plus remdesivir patients compared to 0.4% of placebo plus baricitinib patients.[66126]

    During baricitinib clinical trials, nausea was reported in 2.7% of patients receiving baricitinib 2 mg and at rates greater than with placebo. Gastrointestinal (GI) serious reactions, such as GI perforation, have been noted among baricitinib recipients, although the role of the drug in these events is unknown. 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. Among 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. 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. Elevations were observed at 12 weeks and remained stable thereafter. In 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 patients according to clinical guidelines for the management of hyperlipidemia, hypercholesterolemia or hypertriglyceridemia as per standards of care. Other laboratory alterations have been reported. Baricitinib treatment was associated with increases in creatine phosphokinase (CPK) within one week of starting the drug, 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. 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 (non-FDA-approved dose). The clinical significance of the observed SCr increases is unknown.[63229]

    Acne vulgaris was reported in less than 1% of patients receiving baricitinib during clinical trials.[63229]

    Baricitinib may cause a new primary malignancy; malignancies were reported during clinical trials. During the 16-week treatment period, 1 patient (0.7 events per 100 patient-years) receiving baricitinib 2 mg per day developed a malignancy other than non-melanoma skin cancer (NMSC); no events were reported in the placebo group. Lymphoma and other cancers have been observed in patients taking baricitinib. 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 who develop a malignancy.[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]

    Revision Date: 11/23/2020, 03:19:06 PM

    References

    63229 - Olumiant (baricitinib) tablets package insert. Indianapolis, IN: Lilly USA, LLC; 2020 Jul.66126 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of baricitinib. Retrieved November 20, 2020. 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
    • 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
    • immunosuppression
    • infants
    • infection
    • lymphoma
    • neutropenia
    • new primary malignancy
    • pregnancy
    • pulmonary disease
    • renal failure
    • renal impairment
    • serious hypersensitivity reactions or anaphylaxis
    • skin cancer
    • thrombocytosis
    • thromboembolic disease
    • thromboembolism
    • thrombosis
    • tuberculosis
    • vaccination
    • viral infection

    Avoid use of baricitinib in patients with an active, serious infection, including localized infections. 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 should be evaluated and tested for latent or active 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] COVID-19 per Emergency Use Authorization (EUA): Avoid use of baricitinib in COVID-19 patients with known active TB infection. In patients with active serious infections other than COVID-19 or chronic/recurrent infections, consider whether the potential benefits of baricitinib therapy outweigh the potential risks.[66126]

    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. 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. Baricitinib is not recommended for patients with severe hepatic 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.[63229] COVID-19 per the Emergency Use Authorization (EUA): LFTs must be obtained prior to administration of the first baricitinib dose. Baricitinib has not been studied in patients with severe liver impairment and should only be administered to this patient population if the potential benefit outweighs the potential risk. It is not known whether dosage adjustments are needed in patients with severe liver impairment. If increases in ALT or AST occur and drug-induced liver injury is suspected, interrupt baricitinib treatment until the diagnosis of drug-induced liver injury is excluded.[66126]

    Determine neutrophil and lymphocyte counts before baricitinib initiation. Do not start the drug in 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. Baricitinib may cause lymphopenia and neutropenia. Monitor the ANC and ALC periodically during baricitinib treatment according to routine patient management. Interrupt treatment in 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.[63229] COVID-19 per the Emergency Use Authorization (EUA): Complete blood count (CBC) with differential must be obtained prior to administration of the first baricitinib dose. No dosage adjustments needed in COVID-19 patients for an ANC of 500 cells/mm3 or more. For an ANC less than 500 cells/mm3, consider a delay or interruption in baricitinib therapy until ANC is 500 cells/mm3 or more. No dosage adjustments needed in COVID-19 patients for an ALC of 200 cells/mm3 or more. For an ALC less than 200 cells/mm3, consider a delay or interruption in baricitinib therapy until ALC is 200 cells/mm3 or more.[66126]

    Determine the hemoglobin concentration before baricitinib initiation, and do not start the drug in 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.[63229]

    Baricitinib may increase the risk for a new primary malignancy. Consider the risks and benefits of baricitinib prior to initiating therapy in patients with a known cancer other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing the drug in patients who develop a malignancy. Lymphoma and other cancers have also been observed in patients taking baricitinib. 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]

    Use baricitinib with caution in patients with thromboembolic disease or who are at an increased risk of thromboembolism. Serious and even fatal venous thromboembolism, including deep venous thrombosis (DVT) and pulmonary embolism (PE), have been reported at an increased rate in patients treated with baricitinib compared to placebo. In addition, arterial thrombosis events in the extremities have been reported in clinical studies; many of these adverse events were serious and some resulted in death. Baricitinib may cause increases in platelet counts (thrombocytosis). There is no clear relationship between platelet count elevations and thrombotic events. If signs and symptoms of DVT, PE, or arterial thrombosis occur, promptly evaluate and treat patients.[63229] Serious venous thrombosis, including PE, have been reported in COVID-19 patients treated with baricitinib. Venous thromboembolism (VTE) prophylaxis is recommended for hospitalized COVID-19 patients unless contraindicated. Any patient that displays clinical features of DVT or PE should be promptly evaluated and treated.[66126]

    Use baricitinib with caution in patients with renal impairment. Dosage reductions are recommended in patients with an estimated glomerular filtration rate (eGFR) of 30 to 60 mL/minute/1.73 m2. Baricitinib is not recommended in patients with renal failure or an eGFR less than 30 mL/minute/1.73 m2.[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 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 adult and pediatric patients 2 years and older with an eGFR of 30 to less than 60 mL/minute/1.73 m2. In adult and pediatric patients 9 years and older with an eGFR of 15 to less than 30 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. 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, although the role of baricitinib in these events is not known. 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 in all patients should be performed approximately 12 weeks following initiation of baricitinib therapy. 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. 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]

    Sufficient data are not available to inform a drug-associated risk for major birth defects or miscarriage with the use of baricitinib during human pregnancy. In embryofetal animal studies, oral administration to rats and rabbits at exposures greater than 20 and 84 times the maximum recommended human dose (MRHD), 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 5 and 13 times the MRHD, respectively. In a pre- and post-development study in pregnant rats, oral baricitinib administration at exposures approximately 43 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 9 times the MRHD.[63229] COVID-19 per Emergency Use Authorization (EUA): Baricitinib should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and fetus.[66126] The NIH states that there is limited data available on the use of janus kinase (JAK) inhibitors, such as baricitinib, during pregnancy. Among 33 reported cases of JAK 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. Risks of use should be balanced against potential benefits.[65314]

    Because of the potential for serious adverse reactions in a nursing infant, breast-feeding during baricitinib therapy is not recommended. 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: 11/20/2020, 10:21:15 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;152:451-62.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;75:795-810.63229 - Olumiant (baricitinib) tablets package insert. Indianapolis, IN: Lilly USA, LLC; 2020 Jul.65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed November 18, 2020. 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 November 20, 2020. Available on the World Wide Web at http://pi.lilly.com/eua/baricitinib-eua-factsheet-hcp.pdf.

    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; 2020 Jul.

    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 hours in patients with rheumatoid arthritis (RA).[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; however, no dosage adjustment is recommended for mild or moderate hepatic impairment. 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. Dosage reduction is recommended for patients with moderate renal impairment (estimated GFR of 30 to 60 mL/minute/1.73 m2). Baricitinib is not recommended for use in patients with severe renal impairment (estimated GFR of less than 30 mL/minute/1.73 m2).[63229]

    Pediatrics

    There are no pediatric data regarding the pharmacokinetics of baricitinib.[63229]

    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: 04/10/2020, 02:01:48 PM

    References

    63229 - Olumiant (baricitinib) tablets package insert. Indianapolis, IN: Lilly USA, LLC; 2020 Jul.

    Pregnancy/Breast-feeding

    pregnancy

    Sufficient data are not available to inform a drug-associated risk for major birth defects or miscarriage with the use of baricitinib during human pregnancy. In embryofetal animal studies, oral administration to rats and rabbits at exposures greater than 20 and 84 times the maximum recommended human dose (MRHD), 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 5 and 13 times the MRHD, respectively. In a pre- and post-development study in pregnant rats, oral baricitinib administration at exposures approximately 43 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 9 times the MRHD.[63229] COVID-19 per Emergency Use Authorization (EUA): Baricitinib should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and fetus.[66126] The NIH states that there is limited data available on the use of janus kinase (JAK) inhibitors, such as baricitinib, during pregnancy. Among 33 reported cases of JAK 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. Risks of use should be balanced against potential benefits.[65314]

    breast-feeding

    Because of the potential for serious adverse reactions in a nursing infant, breast-feeding during baricitinib therapy is not recommended. 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: 11/20/2020, 09:27:26 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;152:451-62.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;75:795-810.63229 - Olumiant (baricitinib) tablets package insert. Indianapolis, IN: Lilly USA, LLC; 2020 Jul.65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed November 18, 2020. 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 November 20, 2020. Available on the World Wide Web at http://pi.lilly.com/eua/baricitinib-eua-factsheet-hcp.pdf.

    Interactions

    Level 2 (Major)

    • Abatacept
    • Adalimumab
    • Anakinra
    • Azathioprine
    • Bacillus Calmette-Guerin Vaccine, BCG
    • Canakinumab
    • Certolizumab pegol
    • Colchicine; Probenecid
    • 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
    • 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] Colchicine; Probenecid: (Major) Reduce the dose of baricitinib to 1 mg/day PO in patients receiving concomitant therapy with probenecid. For COVID-19 patients receiving baricitinib 4 mg/day PO, reduce dose to 2 mg/day PO. For COVID-19 patients receiving baricitinib 2 mg/day PO, reduce dose to 1 mg/day PO. For COVID-19 patients receiving baricitinib 1 mg/day PO, consider discontinuing probenecid. Coadministration of baricitinib and probenecid may result in increased baricitinib exposure. Baricitinib is an OAT3 substrate and probenecid is a strong OAT3 inhibitor. In a drug interaction study, administration of probenecid increased baricitinib exposure by 2-fold. [63229] [66126] 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 dose of baricitinib to 1 mg/day PO in patients receiving concomitant therapy with probenecid. For COVID-19 patients receiving baricitinib 4 mg/day PO, reduce dose to 2 mg/day PO. For COVID-19 patients receiving baricitinib 2 mg/day PO, reduce dose to 1 mg/day PO. For COVID-19 patients receiving baricitinib 1 mg/day PO, consider discontinuing probenecid. Coadministration of baricitinib and probenecid may result in increased baricitinib exposure. Baricitinib is an OAT3 substrate and probenecid is a strong OAT3 inhibitor. In a drug interaction study, administration of probenecid increased baricitinib exposure by 2-fold. [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: 11/24/2020, 02:37:00 AM

    References

    31761 - Orencia (abatacept) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2020 Jun.38283 - Actemra (tocilizumab) injection package insert. South San Francisco, CA: Genentech, Inc.; 2020 May.49634 - Arava (leflunomide) package insert. Bridgewater, NJ:. Sanofi-Aventis U.S. LLC; 2016 Feb.51794 - Aubagio (teriflunomide) tablets package insert. Genzyme Corporation: Cambridge, MA; 2020 Nov.61976 - Kevzara (sarilumab) package insert. Bridgewater, NJ: Sanofi-Aventis US. LLC; 2018 Apr.63229 - Olumiant (baricitinib) tablets package insert. Indianapolis, IN: Lilly USA, LLC; 2020 Jul.64572 - Rinvoq (upadacitinib) package insert. North Chicago, IL: Abbvie Inc.; 2020 Jul.66126 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of baricitinib. Retrieved November 20, 2020. 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

    Global Drug names

    Austria

    • Olumiant - (Lilly)

    Belgium

    • Olumiant - (Lilly)

    Canada

    • Olumiant - (Lilly)

    Denmark

    • Olumiant - (Lilly)

    Finland

    • Olumiant - (Lilly)

    France

    • Olumiant - (Lilly)

    Germany

    • Olumiant - (Lilly)

    Hungary

    • Olumiant - (Lilly)

    Ireland

    • Olumiant - (Lilly)

    Israel

    • Olumiant - (Lilly)

    Japan

    • Olumiant - (Lilly)

    Netherlands

    • Olumiant - (Lilly)

    Norway

    • Olumiant - (Lilly)

    Poland

    • Olumiant - (Lilly)

    Russian Federation

    • Olumiant - (Lilly)

    Spain

    • Olumiant - (Lilly)

    Sweden

    • Olumiant - (Lilly)

    Switzerland

    • Olumiant - (Lilly)

    United Kingdom

    • Olumiant - (Lilly)