Baricitinib

by Editorial Board last updated 2021-01-25 21:23:06.467710-05:00
Baricitinib (Lilly)
Olumiant
  • Baricitinib (Lilly) is a Janus Kinase inhibitor (JAK), specifically a JAK-1 and JAK-2 inhibitor.
  • EUA issued by US FDA on 19 Nov 2020 based on ACTT-2 trial that showed modest improvement when administered in combination with remdesivir in hospitalized adults and children aged ≥2 years with COVID-19 who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)
    • The primary endpoint was time to recovery during the first 28 days:  The median time to recovery was shorter in the baricitinib plus remdesivir group (7 days) than in the placebo plus remdesivir group (8 days) in the overall cohort (rate ratio 1.16; 95% CI, 1.01–1.32; P = 0.03). 
    • Recovery time was improved by 8 days in the subset of patients receiving non-invasive ventilation of high-flow oxygen devices at baseline (10 days versus 18 days).
    • Rate of progression to death or invasive ventilation was lower in the combination therapy group (12.2% vs. 17.2%; rate ratio, 0.69; 95% CI, 0.50 to 0.95).
    • Trend toward lower 28-day mortality in the combination therapy group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09), which did not achieve statistical significance. 

    • Patients were excluded from the trial if they were receiving corticosteroids: Risks and benefits of baricirinib vis-a-vis dexamethasone, the latter having been shown in the RECOVERY trial to improve survival, are unknown and will require further study. Accordingly, remdesivir plus dexamethasone is preferred over bariticinib + remdesivir, which should be used only in situations where corticosteroids cannot be used.

  • Baricitinib exposure is increased when co-administered with strong OAT3 inhibitors, such as probenecid. See dosing recommendations in Major Drug Interactions below.
  • BLACK BOX warning: serious infections (TB, fungal infections, other opportunistic infections), lymphoma and other malignancies, thrombosis including deep vein thrombosis and pulmonary embolism.
  • Recommended dosing for COVID-19 under the EUA: 4 mg once daily, with or without food.
  • Duration of treatment: 14 days or until hospital discharge, whichever comes first.
  • Recommended dosing for COVID-19 under the EUA:
    • Age ≥9 years: 4 mg once daily, with or without food.
    • Age 2 to <9 years: 2 mg once daily, with or without food.
    • Age <2 years: not authorized.
  • Duration of treatment: 14 days or until hospital discharge, whichever comes first.
  • Dosing adjustments are based on eGFR.
eGFR (mL/min/1.73 m2) Age ≥9 years Age 2 to <9 years
≥60 4 mg q24h 2 mg q24h
30 to <60 2 mg q24h 1 mg q24h
15 to <30 1 mg q24h Not recommended
<15 Not recommended Not recommended
  • No dosage adjustment necessary in mild or moderate hepatic impairment.
  • Not recommended in severe hepatic impairment (no data).
  • Serious infections (TB, fungal infections, other opportunistic infections).
  • Lymphoma, other malignancies.
  • Thrombosis, including deep vein thrombosis and pulmonary embolism.
  • Gastrointestinal perforations.
  • Hypersensitivity reactions (angioedema, urticaria, rash).
  • AST, ALT elevations.
  • Neutropenia, lymphopenia, anemia.
  • Lipid elevations (total cholesterol, LDL, HDL).
Class  JAK inhibitor
PK/PD Index No data
Pharmaceutical
Preparation		  1 mg, 2 mg tablets
COVID-19 Adult Dose  4 mg q24h
Pregnancy
Category		 Insufficient data in humans, toxic in animals
Food Effect1  Take with or without food
Oral
Absorption2 (%)		  80
Tmax (hr) 1
Peak Serum Level3
(μg/mL)		 No data
Protein Binding
(%)		  50
Average Serum
Half-life4 (hr)		 12
Elimination Primarily renal
Biliary Penetration5 (%)  No data
CSF/Blood
Penetration6 (%)		 No data
Therapeutic Levels in CSF7  No data
Volume of Distribution8
(Vd)		  76 L
AUC9
(μg*hr/mL)		 No data
CYP450, Transporter
Interactions		  Substrate for OAT3, PGP, BCRP, MATE2-K
  • Notes:
    • 1 Adult preparations unless otherwise noted.
    • 2 Absorption under optimal conditions.
    • 3 Total drug; adjust for protein binding to determine free drug concentration.
      • SD = after single dose
      • SS = steady state after multiple doses
    • 4 Assumes CrCl > 80 mL/min
    • 5 Peak concentration in bile/peak concentration in serum x 100
    • 6 CSF levels with inflammation
    • 7 Judgment based on drug dose & organism susceptibility. CSF concentration ideally ≥10x above MIC.
    • 8 Volume of Distribution (Vd):
      • V/F = Vd/oral bioavailability
      • Vss = Vd at steady state
      • Vss/F = Vd at steady state/oral bioavailability
    • 9 Area under the plasma concentration versus time curve
Drug Effect on concentration Suggested management
Strong OAT3 inhibitors ↑ baricitinib
If dose is 2-4 mg q24h, ↓dose by 50%.
If dose is 1 mg q24h, consider stopping OAT3 inhibitor.
  • Baricitinib is considered an alternative treatment for hospitalized patients who are hyperemic with severe COVID disease; its use in combination with dexamethasone has not been studied