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Baricitinib (Monograph)

Brand name: Olumiant
Drug class: Disease-modifying Antirheumatic Drugs
- JAK Inhibitor
- Janus Kinase Inhibitor
Chemical name: 2-[1-ethylsulfonyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]azetidin-3-yl]acetonitrile
Molecular formula: C16H17N7O2S
CAS number: 1187594-09-7

Medically reviewed by Drugs.com on Dec 27, 2022. Written by ASHP.

Warning

    Serious Infections
  • Serious, sometimes fatal infections including tuberculosis (pulmonary or extrapulmonary disease), bacterial and viral infections, invasive fungal infections (may be disseminated), and other opportunistic infections reported.1

  • Carefully consider risks and benefits prior to initiating baricitinib therapy in patients with chronic or recurring infections.1

  • Evaluate patients for latent tuberculosis infection prior to and periodically during treatment; if indicated, initiate appropriate antimycobacterial regimen prior to initiating baricitinib therapy.1

  • Closely monitor patients for infection, including active tuberculosis in those with a negative test for latent tuberculosis, during and after treatment.1 If serious infection develops, interrupt baricitinib therapy until infection is controlled.1

    Mortality
  • Higher overall mortality rate, including sudden cardiovascular death, reported with another JAK inhibitor compared with tumor necrosis factor (TNF) blocking agents in a postmarketing safety study in rheumatoid arthritis patients ≥50 years of age with ≥1 cardiovascular risk factor.1 27

    Malignancies
  • Lymphoma and other malignancies reported.1

  • Risk of lymphomas and lung cancers also increased with another JAK inhibitor compared with TNF blocking agents; patients who are current or past smokers are at additional risk.1

    Major Adverse Cardiovascular Events
  • Higher rate of major adverse cardiovascular events reported with another JAK inhibitor compared with TNF blocking agents in a postmarketing safety study in patients with rheumatoid arthritis ≥50 years of age with ≥1 cardiovascular risk factor.1 Patients who are current or past smokers are at additional risk.1

  • Discontinue baricitinib in patients that experience a MI or stroke.1

    Thrombosis
  • Serious, sometimes fatal thromboembolic events, including DVT, PE, and arterial thrombosis, reported.1 Promptly evaluate patients with symptoms of thrombosis.1

Introduction

Immunomodulating agent and disease-modifying antirheumatic drug (DMARD); Janus kinase (JAK) inhibitor.1 5 7

Uses for Baricitinib

Rheumatoid Arthritis in Adults

Management of moderately to severely active rheumatoid arthritis in adults who have had an inadequate response to ≥1 tumor necrosis factor (TNF) blocking agents;1 3 4 14 15 can be used alone or in combination with methotrexate or other nonbiologic DMARDs (e.g., hydroxychloroquine, leflunomide, sulfasalazine).1 Safety and efficacy of baricitinib in rheumatoid arthritis were based principally on the results of 2 randomized controlled trials (RA-BUILD and RA-BEACON) in adults with active disease; baricitinib has also been studied in confirmatory clinical trials at a higher dosage of 4 mg once daily [off-label].1 2 3 14 15 Guidelines generally support use of JAK inhibitors, including baricitinib, as add on therapy to methotrexate in patients who do not meet treatment goals with methotrexate alone.2003

Concomitant use with other JAK inhibitors (e.g., tofacitinib) or biologic DMARDs, such as TNF blocking agents (e.g., adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), interleukin-1 (IL-1) receptor antagonists (e.g., anakinra), anti-CD20 monoclonal antibodies (e.g., rituximab), selective costimulation modulators (e.g., abatacept), and anti-interleukin-6-receptor monoclonal antibodies (e.g., sarilumab, tocilizumab), not recommended.1

Concomitant use with potent immunosuppressive agents (e.g., azathioprine, cyclosporine) also not recommended.1

Treatment of Coronavirus Disease 2019 (COVID-19)

Baricitinib is used for the treatment of COVID-19 caused by SARS-CoV-2 in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).16 17 18 19 20 Baricitinib was previously used in this setting following FDA issuance of an Emergency Use Authorization (EUA).19 Baricitinib received approval for this use in 2022.1 Safety and efficacy of baricitinib for this use were based principally on results of 2 randomized placebo-controlled trials that evaluated baricitinib in hospitalized adults with COVID-19.1 16 17 33 Guidelines generally recommend the addition of baricitinib to other therapies (e.g., remdesivir, corticosteroids) in adult patients hospitalized with severe COVID-19; clinicians should consult the most recent COVID-19 guidelines for additional information.6000 6001

Baricitinib is being investigated and used for the treatment of COVID-19 caused by SARS-CoV-2 in hospitalized pediatric patients ≥2 years of age requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or ECMO [off-label].16 17 18 19 20 Although efficacy and safety of baricitinib have not been definitively established for the treatment of COVID-19 in this population, it is available under an FDA EUA.18 19 20

For additional information, the baricitinib EUA letter of authorization ([Web]),19 EUA fact sheet for healthcare providers ([Web]),20 and EUA fact sheet for patients, parents, and caregivers ([Web])18 should be consulted.

Alopecia Areata

Baricitinib is used in the treatment of adults with severe alopecia areata.1 Specific place in therapy not been addressed in guidelines; typical treatments include intralesional, topical, and systemic corticosteroids; minoxidil; and other immunomodulators.200

Concomitant use of baricitinib with other JAK inhibitors (e.g., tofacitinib) or biologic DMARDs, such as TNF blocking agents (e.g., adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), IL-1 receptor antagonists (e.g., anakinra), anti-CD20 monoclonal antibodies (e.g., rituximab), selective costimulation modulators (e.g., abatacept), and anti-interleukin-6-receptor monoclonal antibodies (e.g., sarilumab, tocilizumab) not recommended.1

Concomitant use with potent immunosuppressive agents (e.g., azathioprine, cyclosporine) also not recommended.1

Baricitinib Dosage and Administration

General

Pretreatment Screening

Patient Monitoring

Premedication and Prophylaxis

Dispensing and Administration Precautions

Other General Considerations

Administration

Oral Administration

Alternative Administration in Patients Unable to Swallow Tablets

The package insert and the EUA that permits use of baricitinib for the treatment of COVID-19 in hospitalized pediatric patients 2 years and older requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) [off-label] provide information on alternative administration of the drug via oral dispersion, gastrostomy tube, or nasogastric or orogastric tube for patients who are unable to swallow whole tablets.1 20 Tablets dispersed in water are stable for up to 4 hours.1 20

Oral administration of dispersed tablets: Place tablets (1-mg, 2-mg, or 4-mg tablets, or any combination needed to achieve the desired dose up to 4 mg) in a container containing approximately 10 mL (minimum of 5 mL) of room temperature water; disperse the tablets by gently swirling the container.1 20 The resulting solution should be immediately consumed by the patient.1 20 Rinse container with an additional 10 mL (minimum of 5 mL) of room temperature water; the patient should then consume the remaining contents.1 20 Tablets dispersed in water are stable for up to 4 hours.1 20

Administration via gastrostomy feeding tube: Place tablets (1-mg, 2-mg, or 4-mg tablets, or any combination needed to achieve the desired dose up to 4 mg) in a container containing approximately 15 mL (minimum of 10 mL) of room temperature water; disperse tablets by gently swirling the container.1 20 Ensure the tablet(s) are sufficiently dispersed to allow free passage through the tip of the syringe.1 20 Withdraw entire contents from the container into an appropriate syringe and immediately administer through the gastric feeding tube.1 20 Rinse container with approximately 15 mL (minimum of 10 mL) of room temperature water, then withdraw solution into the syringe and administer through the gastric feeding tube.1 20 Tablets dispersed in water are stable for up to 4 hours.1 20

Administration via nasogastric or orogastric feeding tube: Place tablets (1-mg, 2-mg, or 4-mg tablets, or any combination needed to achieve the desired dose up to 4 mg) in a container containing approximately 30 mL of room temperature water; disperse tablets by gently swirling the container.1 20 Ensure the tablet(s) are sufficiently dispersed to allow free passage through the tip of the syringe.1 20 Withdraw the entire contents from the container into an appropriate syringe and immediately administer through the enteral feeding tube.1 20 Hold syringe horizontally and shake during administration to avoid clogging small diameter tubes (smaller than 12 Fr).1 20 Rinse container with a sufficient amount (minimum of 15 mL) of room temperature water, withdraw solution into the syringe, and administer through the enteral feeding tube.1 20 Tablets dispersed in water are stable for up to 4 hours.1 20

Dosage

Pediatric Patients

Treatment of COVID-19† [off-label]
Oral

Limited data available regarding baricitinib dosing in pediatric patients for the treatment of COVID-19.20

For patients ≥9 years of age requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or ECMO, EUA permits use of 4 mg once daily for a total duration of 14 days or until hospital discharge, whichever occurs first.20

For patients 2 to <9 years of age requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or ECMO, EUA permits use of 2 mg once daily for a total duration of 14 days or until hospital discharge, whichever occurs first.20

In patients receiving concomitant therapy with potent inhibitors of organic anion transporter (OAT)3 (e.g., probenecid), reduce dosage of baricitinib from 4 mg once daily to 2 mg once daily or from 2 mg once daily to 1 mg once daily.20

Treatment Interruption for Toxicity

In hospitalized pediatric patients with COVID-19 who develop laboratory abnormalities, dosage modification may be necessary (see Table 1).20

Table 1. Recommended Dosage Modification for Laboratory Abnormalities in Pediatric Patients with COVID-19†20

Laboratory Abnormality

Dosage Modification

ALC <200 cells/mm3

Consider interrupting baricitinib therapy until ALC ≥200 cells/mm3

ANC <500 cells/mm3

Consider interrupting baricitinib therapy until ANC ≥500 cells/mm3

Increased serum ALT or AST concentrations and drug-induced hepatic injury is suspected

Interrupt baricitinib until diagnosis of drug-induced liver injury is excluded

Adults

Rheumatoid Arthritis
Oral

2 mg once daily.1

4 mg once daily dosage has been evaluated in clinical trials.15

Treatment of COVID-19
Oral

For treatment of COVID-19 in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or ECMO, the recommended dosage of baricitinib is 4 mg once daily for a total duration of 14 days or until hospital discharge, whichever occurs first.1 In studies of hospitalized patients with COVID-19, prophylaxis for venous thromboembolism was recommended unless contraindicated.20

Alopecia Areata
Oral

2 mg once daily.1 Increase the dosage to 4 mg once daily if the response is not adequate.1 For patients with nearly complete or complete scalp hair loss, with or without substantial eyelash or eyebrow hair loss, consider treating with 4 mg once daily.1 Once patients achieve an adequate response to treatment with 4 mg, decrease the dosage to 2 mg once daily.1

Treatment Interruption for Toxicity
Treatment Interruption for Infection

If a serious infection develops, interrupt treatment until the infection is controlled.1

Treatment Interruption for Hematologic Toxicity

In patients with rheumatoid arthritis or alopecia areata who experience abnormalities in ALC, ANC, or hemoglobin, modify the dosage of baricitinib according to Table 2.1

Table 2. Dosage modifications for cytopenias and anemia in patients with rheumatoid arthritis or alopecia areata.1

Laboratory analyte

Value

Recommendation

ALC

≥500 cells/mm3

Maintain dosage

<500 cells/mm3

Interrupt therapy until ALC ≥500 cells/mm3

ANC

≥1000 cells/mm3

Maintain dosage

<1000 cells/mm3

Interrupt therapy until ANC ≥1000 cells/mm3

Hemoglobin

≥8 g/dL

Maintain dosage

<8 g/dL

Interrupt therapy until hemoglobin ≥8 g/dL

In hospitalized adult patients with COVID-19 who develop laboratory abnormalities, dosage modification may be necessary (see Table 3).1

Table 3. Dosage modifications for cytopenias in hospitalized adults with COVID-19.1

Laboratory analyte

Value

Recommendation

ALC

≥200 cells/mm3

Maintain dosage

<200 cells/mm3

Interrupt therapy until ALC ≥200 cells/mm3

ANC

≥500 cells/mm3

Maintain dosage

<500 cells/mm3

Interrupt therapy until ANC ≥500 cells/mm3

Dosage Modifications for Drug Interactions

In patients receiving concomitant therapy with potent inhibitors of organic anion transporter (OAT) 3 (e.g., probenecid), reduce dosage of baricitinib from 4 mg once daily to 2 mg once daily or from 2 mg once daily to 1 mg once daily.1 20 If the recommended baricitinib dose is 1 mg once daily, consider discontinuing probenecid.1 20

Special Populations

Hepatic Impairment

Rheumatoid Arthritis: Dosage adjustment not necessary in mild or moderate hepatic impairment.1 Use in patients with severe hepatic impairment not evaluated and not recommended.1 Interrupt treatment if increases in ALT or AST are observed and drug-induced liver injury (DILI) is suspected, until DILI is excluded.1

COVID-19: Not studied in patients with severe hepatic impairment; use only if the potential benefit outweighs the potential risk.1 20 Interrupt treatment if increases in ALT or AST are observed and DILI is suspected, until DILI is excluded.1

Alopecia Areata: Dosage adjustment not necessary in mild or moderate hepatic impairment.1 Use in patients with severe hepatic impairment not evaluated and not recommended.1 Interrupt treatment if increases in ALT or AST are observed and DILI is suspected, until DILI is excluded.1

Renal Impairment

Rheumatoid Arthritis: Dosage adjustment not necessary in mild or moderate hepatic impairment.1 In patients with mild renal impairment (eGFR 60–<90 mL/min per 1.73 m2), maintain recommended dosage of 2 mg once daily.1 Recommended dosage in patients with moderate renal impairment (eGFR 30–<60 mL/min per 1.73 m2) is 1 mg once daily.1 Not recommended in patients with severe renal impairment (eGFR <30 mL/minute per 1.73 m2).1 9

COVID-19: Dosage adjustments based on eGFR may be necessary (see Table 4).1 20

Table 4. Recommended Dosage Modification for Renal Impairment in Patients with COVID-19120

eGFR Value

Adults

Pediatric Patients ≥9 years of age

Pediatric Patients 2 to <9 years of age

60 to <90 mL/min per 1.73 m2

4 mg once daily

4 mg once daily

2 mg once daily

30 to <60 mL/min per 1.73 m2

Reduce initial dosage to 2 mg once daily

Reduce initial dosage to 2 mg once daily

Reduce initial dosage to 1 mg once daily

15 to <30 mL/min per 1.73 m2

Reduce initial dosage to 1 mg once daily

Reduce initial dosage to 1 mg once daily

Use not recommended

<15 mL/min per 1.73 m2

Use not recommended

Use not recommended

Use not recommended

Alopecia Areata: Dosage adjustments based on eGFR may be necessary (see Table 5).1

Table 5. Recommended Dosage Modification for Renal Impairment in Patients with Alopecia Areata1

eGFR Value

Recommendation

If the recommended dosage is 2 mg once daily

If the recommended dosage is 4 mg once daily

60 to <90 mL/min per 1.73 m2

Maintain dosage

Maintain dosage

30 to <60 mL/min per 1.73 m2

Reduce to 1 mg once daily

Reduce to 2 mg once daily

<30 mL/min per 1.73 m2

Use not recommended

Use not recommended

Geriatric Patients

No dosage adjustment needed based on age.1 Select dosage with caution because of possible age-related decrease in renal function.1

Other Special Populations

Dosage adjustment based on body weight, ethnicity, or sex not required.1

Cautions for Baricitinib

Contraindications

Warnings/Precautions

Warnings

Infectious Complications

Serious, sometimes fatal infections (including pneumonia, urinary tract infection, tuberculosis, multidermatomal herpes zoster, esophageal candidiasis, pneumocystosis, acute histoplasmosis, cryptococcosis, cytomegalovirus infection, and BK virus infection) reported, particularly in patients receiving concomitant therapy with immunosuppressive agents (e.g., methotrexate, corticosteroids).1 Infections may be disseminated.1

Do not initiate baricitinib in patients with serious active infections, including localized infections.1 Consider potential risks and benefits of the drug prior to initiating therapy in patients with a history of chronic, recurring, serious, or opportunistic infections; patients with underlying conditions that may predispose them to infections; and patients who have been exposed to tuberculosis or who have resided or traveled in regions where tuberculosis or mycoses are endemic.1

Closely monitor patients during and after treatment with baricitinib for the development of signs or symptoms of infection.1 If new infection occurs during therapy, perform thorough diagnostic evaluation (appropriate for immunocompromised patient), initiate appropriate anti-infective therapy, and closely monitor patient.1 If infection fails to respond to anti-infective therapy or if serious infection, opportunistic infection, or sepsis develops, interrupt baricitinib treatment until the infection is controlled.1

Evaluate all patients for active or latent tuberculosis prior to and periodically during therapy.1 Do not use in patients with active tuberculosis.1 When indicated, initiate appropriate antimycobacterial regimen for treatment of latent tuberculosis infection prior to baricitinib therapy.1 Consider initiation of antimycobacterial therapy prior to initiation of baricitinib in individuals with a history of latent or active tuberculosis in whom an adequate course of antimycobacterial treatment cannot be confirmed and in individuals with a negative test for latent tuberculosis who have risk factors for tuberculosis.1 Consultation with a tuberculosis specialist is recommended when deciding whether to initiate antimycobacterial therapy.1

Monitor all patients, including those with a negative test for latent tuberculosis, for active tuberculosis.1

Viral reactivation, including herpes zoster reactivation, reported.1 If herpes zoster reactivation occurs, interrupt baricitinib treatment until the episode is resolved.1

Effect on risk of reactivation of chronic viral hepatitis not known; patients with evidence of HBV or HCV infection were excluded from clinical trials.1 Screen all patients for viral hepatitis in accordance with current standards of care prior to baricitinib therapy.1 Patients testing positive for hepatitis C antibody but negative for HCV RNA may receive baricitinib.1 Patients testing positive for hepatitis B surface antibody (anti-HBs) and hepatitis B core antibody (anti-HBc) but negative for hepatitis B surface antigen (HBsAg) also may receive baricitinib but should be monitored for expression of HBV DNA; consultation with liver disease experts is recommended if HBV DNA is detected.1

Mortality

Higher rate of all-cause mortality, including sudden cardiovascular death, reported in a postmarketing safety study in patients with rheumatoid arthritis receiving another JAK inhibitor compared with those who received a TNF blocking agent.1 27 All study patients were ≥50 years of age and had ≥1 cardiovascular risk factor.25 26 27

Consider the risks and benefits of baricitinib prior to initiating or continuing therapy.1

Malignancies and Lymphoproliferative Disorders

Lymphoma and other malignancies observed.1

In a large, randomized, postmarketing safety study of another JAK inhibitor in patients with rheumatoid arthritis, a higher rate of malignancies (excluding nonmelanoma skin cancer) was observed in patients treated with another JAK inhibitor compared to those treated with a TNF blocking agent.1 Patients who are current or past smokers are at additional risk.1

Consider risks and benefits of baricitinib prior to initiating therapy or when considering whether to continue baricitinib, particularly in patients with a known malignancy (other than successfully treated nonmelanoma skin cancer), in those who develop a malignancy, and those who are current or past smokers.1

Periodic dermatologic examinations recommended for patients at increased risk for skin cancer.1

Major Adverse Cardiovascular Events (MACE)

Major adverse cardiovascular events (i.e., cardiovascular death, nonfatal MI, nonfatal stroke) reported in patients receiving baricitinib.1 Patients who are current or past smokers are at additional risk.1

Consider risks and benefits of baricitinib prior to initiating therapy or when considering whether to continue baricitinib, particularly in patients who are current or past smokers and in those with other cardiovascular risk factors.1

Inform patients of symptoms of serious cardiovascular events.1 Discontinue baricitinib if a patient experiences a MI or stroke.1

Thromboembolic Events

Serious, sometimes fatal thromboembolic events (e.g., DVT, PE, arterial thrombosis in the extremities) reported.1 Relationship between platelet count elevation and thromboembolic events not established.1

Increased risk thromboembolic events (e.g., DVT, PE) in patients ≥50 years of age with rheumatoid arthritis and at least one cardiovascular risk factor receiving another JAK inhibitor compared with those receiving a TNF blocking agent.1 32

Avoid in patients at increased risk of thrombosis.1 Promptly discontinue baricitinib and evaluate all patients with signs or symptoms suggestive of DVT, PE, or arterial thrombosis and initiate treatment as appropriate.1

Other Warnings and Precautions

Hypersensitivity Reactions

Hypersensitivity reactions (i.e., angioedema, urticaria, rash), sometimes serious, reported in patients receiving baricitinib in clinical trials.1

If a serious hypersensitivity reaction occurs, discontinue baricitinib while evaluating for other potential causes.1

GI Perforation

GI perforation reported;1 role of JAK inhibition by baricitinib not known.1

Use with caution in patients at increased risk for GI perforation (e.g., patients with history of diverticulitis).1 Promptly evaluate patients with new onset abdominal symptoms for early identification of GI perforation.1

Hematologic Effects

Possible lymphopenia, neutropenia, and anemia.1 May require interruption of baricitinib therapy.1

Lymphocyte counts below the lower limit of normal associated with increased incidence of infections.1

Dose-related increases in platelet count observed;1 4 relationship between platelet count elevation and thromboembolic events not established.1

Do not initiate baricitinib in patients with rheumatoid arthritis or alopecia areata with lymphocyte count <500/mm3, ANC <1000/mm3, or hemoglobin concentration <8 g/dL.1

In patients with COVID-19, there is limited information on use with absolute lymphocyte counts <200/mm3, ANC <1000/mm3, or hemoglobin <8 g/dL; avoid initiation or interrupt treatment in these patients if absolute lymphocyte count is <200/mm3, or ANC is <500/mm3.1

Monitor lymphocyte count, ANC, and hemoglobin concentrations at baseline and periodically during treatment.1

Hepatic Effects

Elevated hepatic enzyme concentrations reported.1

Monitor liver function tests at baseline and periodically during treatment.1 In case of elevations, promptly evaluate patient for drug-induced hepatotoxicity.1 If drug-induced hepatic injury is suspected, interrupt baricitinib therapy until such diagnosis excluded.1

Metabolic Effects

Dose-related increases in total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride concentrations reported.1 11 Ratio of LDL-cholesterol to HDL-cholesterol not substantially affected.1 Increases observed at 12 weeks of therapy and remained stable thereafter.1

Measure lipid concentrations approximately 12 weeks after initiation of therapy in patients with rheumatoid arthritis or alopecia areata.1 Manage dyslipidemia according to current standards of care.1

Immunization

Avoid live vaccines.1 Update immunizations according to current administration guidelines prior to initiation of baricitinib in patients with rheumatoid arthritis or alopecia areata.1

Specific Populations

Pregnancy

Based on findings from animal reproduction studies, may cause fetal harm during pregnancy.1

Skeletal malformations, reduced fetal body weight, and embryolethality observed in animal studies at exposures ≥11 times the exposure at the maximum recommended human dosage.1 No evidence of developmental toxicity at exposures 2–7 times the exposure at the maximum recommended human dosage.1

Consider the association between increased disease activity and risk for adverse pregnancy outcomes in women with rheumatoid arthritis.1 Report pregnancies to the manufacturer according to instructions in the prescribing information.1

Lactation

Distributed into milk in rats; not known whether baricitinib distributes into human milk, affects nursing infants, or affects milk production.1 Discontinue nursing or the drug.1 Do not breast-feed during treatment with baricitinib and for 4 days after the last dose.1

Females and Males of Reproductive Potential

May cause fetal harm when administered during pregnancy.1 Consider pregnancy planning and prevention for females of reproductive potential.1

Pediatric Use

Safety and efficacy not established with rheumatoid arthritis or alopecia areata.1

Emergency use authorization (EUA) for use of baricitinib for the treatment of COVID-19 in hospitalized pediatric patients includes authorization for pediatric patients ≥2 years of age.18 19 20 Limited data in pediatric patients with conditions other than COVID-19.20

Geriatric Use

No overall differences in safety and efficacy relative to younger adults in trials of rheumatoid arthritis, but increased sensitivity cannot be ruled out.1 Select dosage with caution because of age-related decreases in renal function; consider monitoring renal function.1

In trials of patients with alopecia areata, insufficient number of patients age ≥65 years to determine whether these patients respond differently from younger patients.1 Select dosage with caution because of age-related decreases in renal function; consider monitoring renal function.1

Hepatic Impairment

Systemic exposure not substantially affected by moderate hepatic impairment.1 9 Dosage adjustment not necessary for mild or moderate hepatic impairment.1

Not studied in patients with severe hepatic impairment; use not recommended in patients with rheumatoid arthritis or alopecia areata.1

When used for the treatment of COVID-19 in hospitalized adults and treatment of COVID-19 in hospitalized pediatric patients, use in patients with severe hepatic impairment only if the potential benefit outweighs the potential risk.1 20

Renal Impairment

Dosage adjustment not necessary in patients with mild renal impairment.1

In patients with rheumatoid arthritis or alopecia areata and moderate renal impairment (eGFR 30 to less than 60 mL/minute per 1.73 m2), reduced recommended dosage by half.1 Not recommended for these uses in severe impairment (eGFR less than 30 mL/minute per 1.73 m2).1

In hospitalized adult patients and pediatric patients ≥9 years old with COVID-19 and moderate renal impairment (eGFR 30 to less than 60 mL/minute per 1.73 m2) or severe renal impairment (eGFR 15 to less than 30 mL/minute per 1.73 m2), recommended dosage is 2 mg once daily and 1 mg once daily, respectively.1 Not recommended for this use in patients who are on dialysis, have end-stage renal disease, or who have an eGFR less than 15 mL/minute per 1.73 m2.1

In hospitalized pediatric patients age 2 to <9 years with COVID-19 and moderate renal impairment (eGFR 30 to less than 60 mL/minute per 1.73 m2), recommended dosage is 1 mg once daily.20 Not recommended for this use in pediatric patients age 2 to <9 years who have an eGFR less than 30 mL/min per 1.73 m2.20

Common Adverse Effects

Adverse effects occurring in ≥1% of patients with rheumatoid arthritis: Upper respiratory tract infection,1 nausea,1 herpes simplex,1 herpes zoster.1 2 3

Adverse effects occurring in ≥1% of hospitalized adults and hospitalized pediatric patients with COVID-19: increases of liver enzymes, thrombocytosis, creatine phosphokinase increases, neutropenia, deep vein thrombosis, pulmonary embolism, and urinary tract infection.1 20

Adverse effects occurring in ≥1% of patients with alopecia areata: upper respiratory tract infection, headache, acne, hyperlipidemia, blood creatine phosphokinase increase, urinary tract infection, liver enzyme elevations, folliculitis, fatigue, lower respiratory tract infections, nausea, genital Candida infections, anemia, neutropenia, abdominal pain, herpes zoster, and weight increase.1

Drug Interactions

Substrate for organic anion transporter (OAT) 3, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug and toxin extrusion transporter (MATE) 2K in vitro.1

Substrate for CYP3A4 in vitro; however, no clinically important pharmacokinetic interactions observed with index CYP3A inducers or inhibitors.1 9

Does not inhibit or induce CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A in vitro.1 Also does not inhibit P-gp or organic anion transporting polypeptide (OATP) 1B1 in vitro.1

Inhibits OAT1, OAT2, OAT3, organic cation transporter (OCT) 1, OCT2, OATP1B3, BCRP, MATE1, and MATE2K in vitro; however, clinically important changes in the pharmacokinetics of substrates of these transporters are unlikely.1

Drugs Affecting Organic Anion Transport

Potent OAT3 inhibitors: Substantial increase in baricitinib exposure.1 In patients receiving concomitant therapy with potent inhibitors of OAT3 (e.g., probenecid), reduce dosage of baricitinib.1 In patients receiving concomitant therapy with potent inhibitors of OAT3 (e.g., probenecid), dosage of baricitinib should be reduced from 4 mg once daily to 2 mg once daily or from 2 mg once daily to 1 mg once daily.1 20 If the recommended baricitinib dose is 1 mg once daily, consider discontinuing probenecid.1 20

Less-potent OAT3 inhibitors (i.e., less potent than probenecid): Clinically important pharmacokinetic interactions not expected.1 9 Dosage adjustment not required.1

Immunosuppressive Agents

Possible increased risk of serious infection.14 Concomitant use with potent immunosuppressive agents not recommended.1

Vaccines

Avoid live vaccines.1

Specific Drugs

Drug

Interaction

Comments

Antifungals, azoles (e.g., fluconazole, ketoconazole)

No clinically important effect on pharmacokinetics of baricitinib1

Dosage adjustment of baricitinib not necessary1

Azathioprine

Possible increased risk of serious infection14

Concomitant use not recommended1

Contraceptives, oral

No clinically important effects on pharmacokinetics of ethinyl estradiol or levonorgestrel 1 9

Cyclosporine

Possible increased risk of serious infection14

No clinically important effect on pharmacokinetics of baricitinib1

Concomitant use not recommended1

Diclofenac

Clinically important pharmacokinetic interactions not expected1 9

No dosage adjustment required1

Digoxin

No clinically important effect on pharmacokinetics of digoxin1

Dosage adjustment of digoxin not necessary1

DMARDs, biologic (e.g., TNF blocking agents)

Concomitant use not recommended1

Ibuprofen

Clinically important pharmacokinetic interactions not expected1 9

No dosage adjustment required1

Methotrexate

No clinically important effect on pharmacokinetics of either drug1

Dosage adjustments not necessary1

Omeprazole

No clinically important effect on pharmacokinetics of baricitinib1

Dosage adjustment of baricitinib not necessary1

Probenecid

Approximately twofold increase in AUC of baricitinib1

Concomitant use not recommended; if concomitant use is necessary, consider reducing baricitinib dosage1

Reduce recommended dose from 4 mg once daily to 2 mg once daily or from 2 mg once daily to 1 mg once daily.1 20 If recommended dose is 1 mg once daily, consider discontinuing probenecid.1 20

Rifampin

No clinically important effect on pharmacokinetics of baricitinib1

Dosage adjustment of baricitinib not necessary1

Simvastatin

No clinically important effect on pharmacokinetics of simvastatin1

Dosage adjustment of simvastatin not necessary1

Baricitinib Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations attained approximately 1 hour following oral administration.1

Steady-state concentrations attained in 2–3 days following once-daily dosing, with minimal accumulation.1

Absolute oral bioavailability is approximately 80%.1

Food

High-fat meal delays time to peak plasma concentration by 0.5 hours and reduces AUC and peak plasma concentrations by 11 and 18%, respectively; not considered clinically important.1

Special Populations

Mild, moderate, or severe renal impairment increased AUC by 1.41-, 2.22-, or 4.05-fold, respectively; in individuals with end-stage renal disease receiving hemodialysis, AUC increased by 2.41-fold.1 9

Moderate hepatic impairment does not substantially increase AUC.1 9

Age, sex, body weight, and race do not affect pharmacokinetics.1

Distribution

Extent

Distributed into milk in rats; not known whether distributed into human milk.1

Plasma Protein Binding

Approximately 50% bound to plasma proteins and 45% bound to serum proteins.1

Elimination

Metabolism

Minimal metabolism; mediated by CYP3A4.1

Elimination Route

Eliminated principally by renal filtration and active secretion.1

Excreted as unchanged drug in urine (69%) and feces (15%).1 Approximately 6% of a dose eliminated as metabolites.1

Half-life

Approximately 12–16 hours in patients with rheumatoid arthritis and alopecia areata.1 Approximately 10.8 hours in hospitalized adults with COVID-19 who are intubated and have baricitinib administered via nasogastric or orogastric tube.1

Stability

Storage

Oral

Tablets

20–25°C (excursions permitted between 15–30°C).1

Tablets dispersed in water are stable for up to 4 hours.20

Actions

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Distribution of baricitinib is restricted.12 Consult manufacturer's website for specific information regarding distribution of the drug.12

For use of baricitinib under the FDA Emergency Use Authorization (EUA), inpatient pharmacies may obtain baricitinib directly from an Authorized Distributor of Record.20 Consult the manufacturer's website for a list of Authorized Distributors of Record ([Web]) or the EUA for additional information regarding access to the drug.20

Baricitinib

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

1 mg

Olumiant

Lilly

2 mg

Olumiant

Lilly

4 mg

Olumiant

Lilly

AHFS DI Essentials™. © Copyright 2024, Selected Revisions December 27, 2022. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Eli Lilly and Company. Olumiant (baricitinib) tablets prescribing information. Indianapolis, IN; 2022 Jun. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=866e9f35-9035-4581-a4b1-75a621ab55cf

2. Dougados M, van der Heijde D, Chen YC et al. Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study. Ann Rheum Dis. 2017; 76:88-95. http://www.ncbi.nlm.nih.gov/pubmed/27689735?dopt=AbstractPlus

3. Genovese MC, Kremer J, Zamani O et al. Baricitinib in Patients with Refractory Rheumatoid Arthritis. N Engl J Med. 2016; 374:1243-52. http://www.ncbi.nlm.nih.gov/pubmed/27028914?dopt=AbstractPlus

4. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 207924Orig1s000: Summary review. From FDA website. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/207924Orig1s000SumR.pdf

5. Kotyla PJ. Are Janus Kinase Inhibitors Superior over Classic Biologic Agents in RA Patients?. Biomed Res Int. 2018; 2018:7492904. http://www.ncbi.nlm.nih.gov/pubmed/29862290?dopt=AbstractPlus

6. Kyttaris VC. Kinase inhibitors: a new class of antirheumatic drugs. Drug Des Devel Ther. 2012; 6:245-50. http://www.ncbi.nlm.nih.gov/pubmed/23055694?dopt=AbstractPlus

7. Nakayamada S, Kubo S, Iwata S et al. Chemical JAK inhibitors for the treatment of rheumatoid arthritis. Expert Opin Pharmacother. 2016; :. http://www.ncbi.nlm.nih.gov/pubmed/27690665?dopt=AbstractPlus

8. Rivellese F, Lobasso A, Barbieri L et al. Novel therapeutic approaches in Rheumatoid Arthritis: Role of Janus Kinases Inhibitors. Curr Med Chem. 2018; http://www.ncbi.nlm.nih.gov/pubmed/29424301?dopt=AbstractPlus

9. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 207924Orig1s000: Clinical pharmacology and biopharmaceutics review(s). From FDA website. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/207924Orig1s000ClinPharmR.pdf

10. Gadina M, Johnson C, Schwartz D et al. Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs. J Leukoc Biol. 2018; 104:499-514. http://www.ncbi.nlm.nih.gov/pubmed/29999544?dopt=AbstractPlus

11. Taylor PC, Kremer JM, Emery P et al. Lipid profile and effect of statin treatment in pooled phase II and phase III baricitinib studies. Ann Rheum Dis. 2018; 77:988-995. http://www.ncbi.nlm.nih.gov/pubmed/29463520?dopt=AbstractPlus

12. Eli Lilly and Company. The role of a specialty pharmacy. Available from Olumiant website. Accessed 2022 Aug 19. https://www.olumiant.com

13. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 207924Orig1s000: Medical review(s). From FDA website. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/207924Orig1s000MedR.pdf

14. Fleischmann R, Schiff M, van der Heijde D et al. Baricitinib, Methotrexate, or Combination in Patients With Rheumatoid Arthritis and No or Limited Prior Disease-Modifying Antirheumatic Drug Treatment. Arthritis Rheumatol. 2017; 69:506-517. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=PMC5347954&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/27723271?dopt=AbstractPlus

15. Taylor PC, Keystone EC, van der Heijde D et al. Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2017; 376:652-662. http://www.ncbi.nlm.nih.gov/pubmed/28199814?dopt=AbstractPlus

16. Marconi VC, Ramanan AV, de Bono S et al. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Respir Med. 2021; 9:1407-1418. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=PMC8409066&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/34480861?dopt=AbstractPlus

17. Kalil AC, Patterson TF, Mehta AK et al. Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19. N Engl J Med. 2021; 384:795-807. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=PMC7745180&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/33306283?dopt=AbstractPlus

18. US Food and Drug Administration. Fact Sheet for Patients, Parents and Caregivers Emergency Use Authorization (EUA) of Baricitinib. US Food and Drug Administration. Updated May 2022. Accessed 2022 Aug 29. https://www.fda.gov/media/143824/download

19. US Food and Drug Administration. Letter of authorization: Emergency use authorization (EUA) for Olumiant (baricitinib) for treatment COVID-19. US Food and Drug Administration. Published May 10, 2022. Accessed 2022 Aug 29. https://www.fda.gov/media/143825/download

20. US Food and Drug Administration. Fact Sheet for Healthcare Providers: Emergency Use Authorization (EUA) of Baricitinib. US Food and Drug Administration. Updated May 2022. Accessed 2022 Aug 29. https://www.fda.gov/media/143823/download

25. US Food and Drug Administration. FDA Drug Safety Communication: Safety trial finds risk of blood clots in the lungs and death with higher dose of tofacitinib (Xeljanz, Xeljanz XR) in rheumatoid arthritis patients; FDA to investigate. 2019 Feb 25. From FDA website. Accessed 2022 Aug 29. https://www.fda.gov/downloads/Drugs/DrugSafety/UCM631989.pdf

26. Pfizer Inc. Pfizer announces modification to ongoing tofacitinib FDA post-marketing requirement study in patients with rheumatoid arthritis. New York, NY; 2019 Feb 19. Press release. https://investors.pfizer.com/investor-news/press-release-details/2019/Pfizer-Announces-Modification-to-Ongoing-Tofacitnib-FDA-Post-Marketing-Requirement-Study-in-Patients-with-Rheumatoid-Arthritis/default.aspx

27. US Food and Drug Administration. FDA Drug Safety Communication: FDA approves boxed warning about increased risk of blood clots and death with higher dose of arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR). 2019 Jul 26. From FDA website. Accessed 2022 Aug 29. https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-boxed-warning-about-increased-risk-blood-clots-and-death-higher-dose-arthritis-and

32. US Food and Drug Administration. 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. US Food and Drug Administration. Published September 1, 2021. Updated December 7, 2021. Accessed 2022 Aug 29. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death

33. Ely EW, Ramanan AV, Kartman CE, et al. Efficacy and safety of baricitinib plus standard of care for the treatment of critically ill hospitalised adults with COVID-19 on invasive mechanical ventilation or extracorporeal membrane oxygenation: an exploratory, randomised, placebo-controlled trial. Lancet Respir Med. 2022;10(4):327-336.

34. RECOVERY Collaborative Group. Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis. Lancet. 2022;400(10349):359-368.

35. Wolfe CR, Tomashek KM, Patterson TF, et al. Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial. Lancet Respir Med. 2022.

36. King B, Ohyama M, Kwon O, et al. Two Phase 3 Trials of Baricitinib for Alopecia Areata. N Engl J Med. 2022;386(18):1687-1699.

200. Zhou C, Li X, Wang C, Zhang J. Alopecia Areata: an Update on Etiopathogenesis, Diagnosis, and Management. Clin Rev Allergy Immunol. 2021;61:403-423.

2003. Fraenkel L, Bathon JM, England BR et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2021; 73:924-939. http://www.ncbi.nlm.nih.gov/pubmed/34101387?dopt=AbstractPlus

2053. van Vollenhoven RF, Geborek P, Forslind K et al. Conventional combination treatment versus biological treatment in methotrexate-refractory early rheumatoid arthritis: 2 year follow-up of the randomised, non-blinded, parallel-group Swefot trial. Lancet. 2012; 379:1712-20. http://www.ncbi.nlm.nih.gov/pubmed/22464340?dopt=AbstractPlus

2054. Moreland LW, O'Dell JR, Paulus HE et al. A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment of Early Aggressive Rheumatoid Arthritis Trial. Arthritis Rheum. 2012; 64:2824-35. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=PMC4036119&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/22508468?dopt=AbstractPlus

2055. O'Dell JR, Mikuls TR, Taylor TH et al. Therapies for active rheumatoid arthritis after methotrexate failure. N Engl J Med. 2013; 369:307-18. http://www.ncbi.nlm.nih.gov/pubmed/23755969?dopt=AbstractPlus

6000. National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. National Institutes of Health. Updated August 18, 2022. Accessed August 26, 2022. https://files.covid19treatmentguidelines.nih.gov/guidelines/covid19treatmentguidelines.pdf

6001. Infectious Diseases Society of America. IDSA Guideline on the Treatment and Management of COVID-19. Infectious Diseases Society of America. Updated June 29, 2022. Accessed August 26, 2022. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management

Frequently asked questions