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.

Introduction

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

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; can be used alone or in combination with methotrexate or other nonbiologic DMARDs (e.g., hydroxychloroquine, leflunomide, sulfasalazine). 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]}. 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.

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.

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

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). Baricitinib was previously used in this setting following FDA issuance of an Emergency Use Authorization (EUA). Baricitinib received approval for this use in 2022. 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. 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.

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]}. 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.

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

Alopecia Areata

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

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.

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

Related/similar drugs

triamcinolone, hydroxychloroquine, Paxlovid, Humira, minoxidil topical, Enbrel, Remicade

Baricitinib Dosage and Administration

General

Pretreatment Screening

• Evaluate for active or latent tuberculosis infection prior to initiation of therapy; initiate antimycobacterial therapy if indicated prior to use in patients with rheumatoid arthritis or alopecia areata.

• Evaluate for risk of thrombosis and GI perforation prior to initiation of therapy.

• Evaluate for risk of major cardiovascular events prior to initiation of therapy, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors.

• Measure absolute lymphocyte count, absolute neutrophil count (ANC), and hemoglobin prior to initiation of therapy. Do not initiate therapy for rheumatoid arthritis or alopecia areata in patients with an absolute lymphocyte count (ALC) of less than 500/mm³, an ANC of less than 1000/mm³, or hemoglobin concentration of less than 8 g/dL. Do not initiate therapy for COVID-19 in patients with an ALC less than 200/mm³ or if the ANC is less than 500/mm³.

• Screen for viral hepatitis infection before initiating therapy.

• Evaluate renal and liver function tests at baseline.

• Weigh benefits of therapy against risks of all-cause mortality prior to initiating therapy.

• In patients with rheumatoid arthritis or alopecia areata, update immunizations according to current guidelines.

• Weigh benefits of therapy against risks of developing malignancies prior to initiating therapy with baricitinib, particularly in patients with a known malignancy (other than successfully treated nonmelanoma skin cancer), patients who develop a malignancy, and patients who are current or past smokers.

Patient Monitoring

• Monitor patients with positive hepatitis B surface antibody and hepatitis B core antibody, without hepatitis B surface antigen for expression of hepatitis B virus (HBV) DNA. Consult a hepatologist if HBV DNA is detected.

• Monitor closely for signs or symptoms of infection, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis prior to initiating therapy, during, and after treatment with the drug.

• Evaluate for risk of major cardiovascular events during therapy.

• Routinely monitor ANC, lymphocyte count, and hemoglobin concentrations during therapy.

• Perform dermatologic examinations periodically during therapy in patients at increased risk for skin cancer.

• Measure lipids approximately 12 weeks after initiation of therapy in patients with rheumatoid arthritis or alopecia areata.

• Monitor for onset of new abdominal symptoms.

• Monitor for changes in renal and liver function.

• Monitor for thrombosis.

• Weigh benefits of therapy against risk of all-cause mortality prior to continuing therapy with the drug.

• Weigh benefits of therapy against risks of developing malignancies prior to continuing therapy with baricitinib, particularly in patients with a known malignancy (other than successfully treated nonmelanoma skin cancer), patients who develop a malignancy, and patients who are current or past smokers.

Premedication and Prophylaxis

• In studies supporting approval for use in treatment of hospitalized adults with COVID-19, prophylaxis for venous thromboembolic events was recommended or required for all patients unless a major contraindication was present.

Dispensing and Administration Precautions

Handling and Disposal

• The package insert and Emergency Use Authorization (EUA) for baricitinib that permits use of the drug for the treatment of COVID-19 in adults and pediatric patients^{† [off-label]} state that proper control measures (e.g., ventilated enclosure) or personal protective equipment (i.e., N95 respirator) should be used when crushing baricitinib tablets, since it is not known if powder from crushed tablets is hazardous.

Other General Considerations

• Do not use concomitantly with other Janus kinase (JAK) inhibitors, biologic disease-modifying antirheumatic drugs (DMARDs), or potent immunosuppressive agents.

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

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. The resulting solution should be immediately consumed by the patient. Rinse container with an additional 10 mL (minimum of 5 mL) of room temperature water; the patient should then consume the remaining contents. Tablets dispersed in water are stable for up to 4 hours.

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. Ensure the tablet(s) are sufficiently dispersed to allow free passage through the tip of the syringe. Withdraw entire contents from the container into an appropriate syringe and immediately administer through the gastric feeding tube. 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. Tablets dispersed in water are stable for up to 4 hours.

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. Ensure the tablet(s) are sufficiently dispersed to allow free passage through the tip of the syringe. Withdraw the entire contents from the container into an appropriate syringe and immediately administer through the enteral feeding tube. Hold syringe horizontally and shake during administration to avoid clogging small diameter tubes (smaller than 12 Fr). 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. Tablets dispersed in water are stable for up to 4 hours.

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^†.

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.

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.

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.

Treatment Interruption for Toxicity

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

Adults

Rheumatoid Arthritis

Oral

2 mg once daily.

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

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. In studies of hospitalized patients with COVID-19, prophylaxis for venous thromboembolism was recommended unless contraindicated.

Alopecia Areata

Oral

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

Treatment Interruption for Toxicity

Treatment Interruption for Infection

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

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.

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

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. If the recommended baricitinib dose is 1 mg once daily, consider discontinuing probenecid.

Special Populations

Hepatic Impairment

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

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

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

Renal Impairment

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

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

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

Geriatric Patients

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

Other Special Populations

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

Cautions for Baricitinib

Contraindications

• None.

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). Infections may be disseminated.

Do not initiate baricitinib in patients with serious active infections, including localized infections. 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.

Closely monitor patients during and after treatment with baricitinib for the development of signs or symptoms of infection. If new infection occurs during therapy, perform thorough diagnostic evaluation (appropriate for immunocompromised patient), initiate appropriate anti-infective therapy, and closely monitor patient. 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.

Evaluate all patients for active or latent tuberculosis prior to and periodically during therapy. Do not use in patients with active tuberculosis. When indicated, initiate appropriate antimycobacterial regimen for treatment of latent tuberculosis infection prior to baricitinib therapy. 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. Consultation with a tuberculosis specialist is recommended when deciding whether to initiate antimycobacterial therapy.

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

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

Effect on risk of reactivation of chronic viral hepatitis not known; patients with evidence of HBV or HCV infection were excluded from clinical trials. Screen all patients for viral hepatitis in accordance with current standards of care prior to baricitinib therapy. Patients testing positive for hepatitis C antibody but negative for HCV RNA may receive baricitinib. 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.

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. All study patients were ≥50 years of age and had ≥1 cardiovascular risk factor.

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

Malignancies and Lymphoproliferative Disorders

Lymphoma and other malignancies observed.

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. Patients who are current or past smokers are at additional risk.

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.

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

Major Adverse Cardiovascular Events (MACE)

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

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.

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

Thromboembolic Events

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

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.

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

Other Warnings and Precautions

Hypersensitivity Reactions

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

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

GI Perforation

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

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

Hematologic Effects

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

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

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

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.

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.

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

Hepatic Effects

Elevated hepatic enzyme concentrations reported.

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

Metabolic Effects

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

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

Immunization

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

Specific Populations

Pregnancy

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

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

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

Lactation

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

Females and Males of Reproductive Potential

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

Pediatric Use

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

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. Limited data in pediatric patients with conditions other than COVID-19.

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. Select dosage with caution because of age-related decreases in renal function; consider monitoring renal function.

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

Hepatic Impairment

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

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

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.

Renal Impairment

Dosage adjustment not necessary in patients with mild renal impairment.

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. Not recommended for these uses in severe impairment (eGFR less than 30 mL/minute per 1.73 m²).

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. 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.

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. 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.

Common Adverse Effects

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

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.

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.

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.

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

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

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.

Drugs Affecting Organic Anion Transport

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

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

Immunosuppressive Agents

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

Vaccines

Avoid live vaccines.

Specific Drugs

Baricitinib Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations attained approximately 1 hour following oral administration.

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

Absolute oral bioavailability is approximately 80%.

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.

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.

Moderate hepatic impairment does not substantially increase AUC.

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

Distribution

Extent

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

Plasma Protein Binding

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

Elimination

Metabolism

Minimal metabolism; mediated by CYP3A4.

Elimination Route

Eliminated principally by renal filtration and active secretion.

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

Half-life

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

Stability

Storage

Oral

Tablets

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

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

Actions

• Inhibits JAK1 and JAK2 and, to a lesser extent, tyrosine kinase 2 (TYK2) relative to JAK3. JAKs mediate signaling of cytokines and growth factors important for hematopoiesis and immune function.

• Binding of cytokines to receptors on the cell surface activates pairing of JAKs (e.g., JAK1/JAK2, JAK1/JAK3, JAK1/TYK2, JAK2/JAK2, JAK2/TYK2), which leads to phosphorylation and subsequent localization of signal transducer and activator of transcription (STAT) proteins to the nucleus and modulation of gene expression. Baricitinib prevents phosphorylation and activation of STATs.

• Inhibits cytokine-induced STAT phosphorylation mediated by JAK1/JAK2, JAK1/JAK3, JAK1/TYK2, or JAK2/TYK2 combinations with comparable potencies; relevance of inhibition of specific JAKs to therapeutic efficacy not known.

• Causes dose-dependent inhibition of IL-6-induced STAT3 phosphorylation in whole blood of healthy individuals. Maximal inhibition observed approximately 1 hour after dosing; activity returns to near baseline by 24 hours.

• Mean serum IgG, IgM, and IgA concentrations decrease within 12 weeks of initiation of baricitinib (but generally remain within normal reference ranges) and remain stable throughout treatment. Decreases in C-reactive protein (CRP) concentrations observed as early as 1 week in patients with rheumatoid arthritis and are maintained throughout treatment.

Advice to Patients

• Importance of advising patients about potential benefits and risks of baricitinib. Importance of patients reading the medication guide prior to initiation of therapy and each time the prescription is refilled.

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses or any history of cancer, thromboembolism, diverticulitis, gastric or intestinal ulcers, tuberculosis, hepatitis B virus or hepatitis C virus infection, or other chronic or recurring infections.

• Increased susceptibility to infection. Risk of herpes zoster, which may be serious. Importance of promptly informing clinicians if any signs or symptoms of infection (e.g., fever, sweating, chills, myalgia, cough, dyspnea, fatigue, diarrhea, dysuria, erythema) develop.

• Risk of lymphoma and other malignancies. Importance of periodic skin examinations.

• Risk of major adverse cardiovascular events, including MI, stroke, and cardiovascular death. Instruct all patients, especially current or past smokers and those with other cardiovascular risk factors, to monitor for the development of signs and symptoms of cardiovascular events.

• Risk of thromboembolic events. Importance of contacting clinicians if symptoms of thromboembolism (e.g., shortness of breath; chest pain; swelling, pain, or tenderness in the leg) develop.

• Risk of GI perforation. Importance of seeking immediate medical care if abdominal pain, fever, chills, nausea, or vomiting occur.

• Risk of hypersensitivity reactions. Importance of seeking immediate medical attention if signs and symptoms of serious allergic reactions occur.

• Importance of periodic laboratory monitoring.

• Importance of informing clinicians of receipt of baricitinib prior to any potential vaccinations.

• Importance of females informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

• Prior to administration of baricitinib for treatment of COVID-19 in hospitalized pediatric patients 2 years of age and older, the patient or their caregiver must be provided with information consistent with the Fact Sheet for Patients, Parents and Caregivers Emergency Use Authorization (EUA) of baricitinib and given a copy of the fact sheet or directed to the manufacturer's website to obtain the fact sheet.

• Inform recipients or their caregivers that FDA authorized the emergency use of the baricitinib for treatment of COVID-19 in hospitalized pediatric patients 2 years of age and older, which is an investigational treatment that has not received FDA approval. In addition, inform the parent/caregiver (and patient if age-appropriate) that they have the option to accept or refuse baricitinib, inform them about important known and potential risks and benefits of baricitinib and the extent to which risks and benefits are unknown, and provide information on available alternative treatments and the risks and benefits of those alternatives.

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. Consult manufacturer's website for specific information regarding distribution of the drug.

For use of baricitinib under the FDA Emergency Use Authorization (EUA), inpatient pharmacies may obtain baricitinib directly from an Authorized Distributor of Record. 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.

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Frequently asked questions

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