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Baricitinib

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 Apr 28, 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.

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

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

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

    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.

    Malignancies
  • Lymphoma and other malignancies reported.

  • 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.

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

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

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

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). 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 being investigated and used for the treatment of COVID-19 caused by SARS-CoV-2 in hospitalized adults and pediatric patients ≥2 years of age requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Although efficacy and safety of baricitinib have not been definitively established for the treatment of COVID-19, it is available under an FDA emergency use authorization (EUA) for treatment of COVID-19.

On November 19, 2020, FDA issued the initial EUA for baricitinib that permitted its use in combination with remdesivir for the treatment of suspected or laboratory confirmed COVID-19 in certain hospitalized patients requiring supplemental oxygen, invasive mechanical ventilation, or ECMO. On July 28, 2020, FDA revised the EUA to authorize use of the drug as monotherapy.

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.

Baricitinib Dosage and Administration

General

Pretreatment Screening

  • Evaluate for active or latent tuberculosis infection prior to initiation of therapy; initiate antimycobacterial therapy if indicated.

  • 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 in patients with an absolute lymphocyte count of less than 500/mm3, an absolute neutrophil count (ANC) of less than 1000/mm3, or hemoglobin concentration of less than 8 g/dL.

  • Screen for viral hepatitis infection before initiating therapy.

  • Evaluate liver function tests at baseline.

  • In patients with COVID-19, assess baseline estimated glomerular filtration rate (GFR).

  • Consider benefits and risks of all-cause mortality prior to initiating therapy with baricitinib.

  • Consider benefits and 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.

  • Routinely monitor liver function tests 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.

  • Monitor for onset of new abdominal symptoms.

  • Monitor for thrombosis.

  • In patients with COVID-19, closely monitor patients with baseline and post-baseline laboratory abnormalities.

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

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

Dispensing and Administration Precautions

    Handling and Disposal
  • The EUA for baricitinib that permits use of the drug for the treatment of COVID-19 states 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.

  • Update immunizations according to current immunization guidelines prior to initiating therapy.

Administration

Oral Administration

Administer orally without regard to food.

Alternative Administration in Patients with COVID-19†

The EUA that permits use of baricitinib for the treatment of COVID-19 in hospitalized adults and pediatric patients ≥2 years of age requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) provides information on alternative administration of the drug via oral dispersion, gastrostomy tube, or nasogastric 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 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.

Administration via gastrostomy feeding tube: Place tablets 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.

Administration via nasogastric feeding tube: Place tablets 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.

Dosage

Pediatric Patients

Treatment of COVID-19†
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 OAT3 (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 patients with COVID-19 who develop laboratory abnormalities, dosage modification may be necessary (see Table 1).

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

Laboratory Abnormality

Dosage Modification

Absolute lymphocyte count <200 cells/mm3

Consider interrupting baricitinib therapy until absolute lymphocyte count ≥200 cells/mm3

Absolute neutrophil count <500 cells/mm3

Consider interrupting baricitinib therapy until absolute neutrophil count ≥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.

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

In patients receiving concomitant therapy with potent inhibitors of OAT3 (e.g., probenecid), reduce dosage of baricitinib to 1 mg once daily.

Treatment of COVID-19†
Oral

For treatment of COVID-19 in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or ECMO with an estimated GFR ≥60 mL/min per 1.73 m2, EUA permits baricitinib is 4 mg once daily for a total duration of 14 days or until hospital discharge, whichever occurs first. In hospitalized patients with COVID-19, prophylaxis for venous thromboembolism is recommended unless contraindicated.

In patients receiving concomitant therapy with potent inhibitors of OAT3 (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
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 who experience absolute lymphocyte count <500/mm3, interrupt treatment until lymphocyte count ≥500/mm3, then resume baricitinib 2 mg daily.

In patients with rheumatoid arthritis, who experience ANC <1000/mm3, interrupt treatment until ANC ≥1000/mm3, then resume baricitinib 2 mg daily.

In patients with rheumatoid arthritis, who experience hemoglobin concentration <8 g/dL, interrupt treatment until hemoglobin concentration ≥8 g/dL, then resume baricitinib 2 mg daily.

In patients with COVID-19 who develop laboratory abnormalities, dosage modification may be necessary (see Table 2).

Table 2. Recommended Dosage Modification for Laboratory Abnormalities in Patients with COVID-19†20

Laboratory Abnormality

Dosage Modification

Absolute lymphocyte count <200 cells/mm3

Consider interrupting baricitinib therapy until absolute lymphocyte count ≥200 cells/mm3

Absolute neutrophil count <500 cells/mm3

Consider interrupting baricitinib therapy until absolute neutrophil count ≥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

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment: No dosage adjustment needed in patients with rheumatoid arthritis.

Severe hepatic impairment: Not studied. Use not recommended in patients with rheumatoid arthritis. Use in patients with COVID-19 and severe hepatic impairment only if potential benefit outweighs the potential risk.

Renal Impairment

Moderate renal impairment (eGFR 30–60 mL/minute per 1.73 m2): Reduce dosage to 1 mg once daily in patients with rheumatoid arthritis.

Severe renal impairment (eGFR <30 mL/minute per 1.73 m2): Use not recommended in patients with rheumatoid arthritis.

COVID-19: Adjust dosage based on eGFR (see Table 3).

Table 3. Recommended Dosage Modification for Renal Impairment in Patients with COVID-19†1

eGFR Value

Adults and Pediatric Patients ≥9 years of age

Pediatric Patients 2 to <9 years of age

30 to <60 mL/min per 1.73 m2

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 1mg once daily

Use not recommended

<15 mL/min per 1.73 m2

Use not recommended

Use not recommended

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

  • Manufacturer states none known.

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

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 lymphocyte count <500/mm3, ANC <1000/mm3, or hemoglobin concentration <8 g/dL.

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. Manage dyslipidemia according to current standards of care.

Immunization

Avoid live vaccines. Update immunizations according to current administration guidelines prior to initiation of baricitinib.

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.

Specific Populations

Pregnancy

No adequate data in pregnant women.

Skeletal malformations, reduced fetal body weight, and embryolethality observed in animal studies at exposures ≥20 times the exposure at the maximum recommended human dosage. No evidence of developmental toxicity at exposures 5–13 times the exposure at the maximum recommended human dosage.

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.

Pediatric Use

Safety and efficacy not established with rheumatoid arthritis.

EUA for use of baricitinib for the treatment of COVID-19 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, but increased sensitivity cannot be ruled out. 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 in patients with rheumatoid arthritis.

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

When used for the treatment of COVID-19, 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.

Not recommended in patients with moderate to severe renal impairment (eGFR <30 mL/minute 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 patients with COVID-19: Urinary tract infection, pulmonary embolism, deep vein thrombosis, thrombocytosis, neutropenia, and increased serum creatine phosphokinase, ALT, and AST concentrations.

Interactions for Baricitinib

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 with rheumatoid arthritis receiving concomitant therapy with potent inhibitors of OAT3 (e.g., probenecid), reduce dosage of baricitinib to 1 mg once daily. In patients with COVID-19 receiving concomitant therapy with potent inhibitors of OAT3 (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.

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

Drug

Interaction

Comments

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

No clinically important effect on pharmacokinetics of baricitinib

Dosage adjustment of baricitinib not necessary

Azathioprine

Possible increased risk of serious infection

Concomitant use not recommended

Contraceptives, oral

No clinically important effects on pharmacokinetics of ethinyl estradiol or levonorgestrel

Cyclosporine

Possible increased risk of serious infection

No clinically important effect on pharmacokinetics of baricitinib

Concomitant use not recommended

Diclofenac

Clinically important pharmacokinetic interactions not expected

No dosage adjustment required

Digoxin

No clinically important effect on pharmacokinetics of digoxin

Dosage adjustment of digoxin not necessary

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

Concomitant use not recommended

Ibuprofen

Clinically important pharmacokinetic interactions not expected

No dosage adjustment required

Methotrexate

No clinically important effect on pharmacokinetics of either drug

Dosage adjustments not necessary

Omeprazole

No clinically important effect on pharmacokinetics of baricitinib

Dosage adjustment of baricitinib not necessary

Probenecid

Approximately twofold increase in AUC of baricitinib

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

Rheumatoid arthritis: Reduce dosage of baricitinib to 1 mg once daily

COVID-19: 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; however, if recommended baricitinib dosage is 1 mg once daily, consider discontinuing probenecid

Rifampin

No clinically important effect on pharmacokinetics of baricitinib

Dosage adjustment of baricitinib not necessary

Simvastatin

No clinically important effect on pharmacokinetics of simvastatin

Dosage adjustment of simvastatin not necessary

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 hours in patients with rheumatoid arthritis.

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.

  • 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 promptly notifying clinicians of persistent fever and abdominal pain or changes in bowel function.

  • Importance of periodic laboratory monitoring.

  • Importance of women 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, 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, which is an investigational treatment that has not received FDA approval, for use in adults and pediatric patients 2 years of age and older. 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.

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 is restricted.

Baricitinib

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

2 mg

Olumiant

Lilly

AHFS DI Essentials™. © Copyright 2022, Selected Revisions April 28, 2022. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

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Frequently asked questions