Skip to main content
U.S. flag

An official website of the United States government

Dot gov

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Https

Secure .gov websites use HTTPS
A lock () or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

Table 5f. Characteristics of Immunomodulators

Last Updated: January 26, 2023

  • The information in this table is derived from data on the use of these drugs for FDA-approved indications or from clinical trials on their use in patients with COVID-19.
  • For dose modifications in patients with organ failure or those who require extracorporeal devices, please refer to product labels or EUAs, when available.
  • There are currently not enough data to determine whether certain medications can be safely coadministered with therapies for the treatment of COVID-19. When using concomitant medications with similar toxicity profiles, consider performing additional safety monitoring.
  • The potential additive, antagonistic, or synergistic effects and the safety of using certain combination therapies for the treatment of COVID-19 are unknown. Clinicians are encouraged to report AEs to the FDA Medwatch program.
  • For drug interaction information, please refer to product labels and visit the Liverpool COVID-19 Drug Interactions website.
  • For the Panel’s recommendations on using the drugs listed in this table, please refer to the drug-specific sections of the Guidelines, Therapeutic Management of Nonhospitalized Adults With COVID-19, and Therapeutic Management of Hospitalized Adults With COVID-19.
Table 5f. Characteristics of Immunomodulators
Drug NameDosing Regimens
Adverse Events Monitoring Parameters Drug-Drug Interaction Potential Comments
Corticosteroid (Systemic)
Recommended by the Panel for the treatment of COVID-19 in certain hospitalized patients.
DexamethasoneDose for COVID-19
  • DEX 6 mg IV or PO once daily for up to 10 days or until hospital discharge, whichever comes first1
  • Hyperglycemia
  • Secondary infections
  • Reactivation of latent infections (e.g., HBV, HSV, strongyloidiasis, TB)
  • Cases of disseminated strongyloidiasis have been reported in patients with COVID-19 during treatment with corticosteroids and tocilizumab.
  • Psychiatric disturbances
  • Avascular necrosis
  • Adrenal insufficiency
  • Increased BP
  • Peripheral edema
  • Myopathy (particularly if used with NMBAs)
  • Blood glucose
  • BP
  • Signs and symptoms of new infection
  • Moderate CYP3A4 inducer
  • CYP3A4 substrate
  • If DEX is not available, an alternative corticosteroid (e.g., prednisone, methylprednisolone, hydrocortisone) can be used.
  • The approximate total daily dose equivalencies for these glucocorticoids to DEX 6 mg (PO or IV) are:
    • Prednisone 40 mg
    • Methylprednisolone 32 mg
    • Hydrocortisone 160 mg
Janus Kinase Inhibitors
Baricitinib and tofacitinib: Recommended by the Panel for the treatment of COVID-19 in certain hospitalized patients.
Ruxolitinib: Not recommended by the Panel for the treatment of COVID-19. Currently under investigation in clinical trials.
Baricitinib2

FDA-Approved Doses for COVID-19 in Adults Aged ≥18 Years2

eGFR ≥60 mL/min/1.73 m2
  • Baricitinib 4 mg PO once daily
eGFR 30 to <60 mL/min/1.73 m2
  • Baricitinib 2 mg PO once daily
eGFR 15 to <30 mL/min/1.73 m2
  • Baricitinib 1 mg PO once daily
eGFR <15 mL/min/1.73 m2
  • Not recommended
FDA EUA Dose for Children Aged 9–17 Years3
  • Same as adults 
FDA EUA Doses for Children Aged 2 to <9 Years3
eGFR ≥60 mL/min/1.73m2
  • Baricitinib 2 mg PO once daily
eGFR 30 to <60 mL/min/1.73m2
  • Baricitinib 1 mg PO once daily
eGFR <30 mL/min/1.73m2
  • Not recommended
Duration of Therapy
  • Up to 14 days or until hospital discharge
  • Lymphoma and other malignancies
  • Thrombosis
  • GI perforation
  • Treatment-related changes in lymphocytes, neutrophils, Hgb, liver enzymes
  • HSV reactivation
  • Herpes zoster
  • Secondary infections
  • Serious cardiac-related events (e.g., MI, stroke)
  • CBC with differential
  • Renal function
  • Liver enzymes
  • New infections
  • Dose modification is recommended when administering concurrently with a strong OAT3 inhibitor.
  • See the FDA label2 and EUA3 for dosing guidance for patients with:
    • ALC <200 cells/µL
    • ANC <500 cells/µL
  • If increases in ALT or AST are observed and DILI is suspected, interrupt baricitinib treatment until the diagnosis of DILI is excluded.
  • Baricitinib tablets can be taken orally or crushed, dispersed in water, and given via gastrostomy tube.2

Availability

  • Baricitinib is approved by the FDA for the treatment of COVID-19 in adults aged ≥18 years.2
  • Baricitinib is available through an FDA EUA for children aged 2–17 years who require supplemental oxygen, NIV, MV, or ECMO.3
Ruxolitinib

Dose for FDA-Approved Indications

  • Ruxolitinib 5–20 mg PO twice daily

Dose for COVID-19 in Clinical Trials

  • Ruxolitinib 5 mg PO twice daily for 14 days4
  • Thrombocytopenia
  • Anemia
  • Neutropenia
  • Liver enzyme elevations
  • Risk of infection
  • Dizziness
  • Headache
  • Diarrhea
  • CPK elevation
  • Herpes zoster
  • CBC with differential
  • Liver enzymes
  • New infections
  • Requires dose modification when administered with strong CYP3A4 inhibitor
  • Avoid use with fluconazole doses >200 mg.
  • May require dose modification in patients with hepatic impairment, moderate or severe renal impairment, or thrombocytopenia
Tofacitinib

Dose for COVID-19 in Clinical Trials

  • Tofacitinib 10 mg PO twice daily for up to 14 days or until hospital discharge5
  • Thrombotic events (e.g., PE, DVT, arterial thrombosis)
  • Anemia
  • Risk of infection
  • GI perforation
  • Diarrhea
  • Headache
  • Herpes zoster
  • Lipid elevations
  • Liver enzyme elevations
  • Lymphoma and other malignancies
  • Serious cardiac-related events (e.g., MI, stroke)
  • CBC with differential
  • Liver enzymes
  • New infections
  • Requires dose modification when administered with strong CYP3A4 inhibitors or when used with a moderate CYP3A4 inhibitor that is coadministered with a strong CYP2C19 inhibitor
  • Coadministration with strong CYP3A4 inducers is not recommended.
  • Avoid use in patients with ALC <500 cells/mm3, ANC <1,000 cells/mm3, or Hgb <9 grams/dL.
  • May require dose modification in patients with moderate or severe renal impairment or moderate hepatic impairment
Interleukin-6 Inhibitors
Anti-Interleukin-6 Receptor Monoclonal Antibodies
Recommended by the Panel for the treatment of COVID-19 in certain hospitalized patients.
Sarilumab6

Dose for COVID-19 in Clinical Trials

  • Single dose of sarilumab 400 mg IV7,8
  • Neutropenia
  • Thrombocytopenia
  • GI perforation
  • HSR
  • Increased liver enzymes
  • HBV reactivation
  • Infusion-related reaction
  • HSR
  • Infusion reactions
  • Neutrophils
  • PLT
  • Liver enzymes
  • Elevated IL-6 may downregulate CYP enzymes; thus, use of sarilumab may lead to increased metabolism of drugs that are CYP substrates.
  • The effects of sarilumab on CYP enzymes may persist for weeks after the drug is stopped.
  • Sarilumab is not recommended in patients with ALT or AST >1.5 times the upper limit of the reference range, ANC <2,000 cells/mm3, or PLT <150,000 cells/mm3.6
  • Treatment with sarilumab may mask signs of acute inflammation or infection by suppressing fever and CRP levels.

Availability

  • An IV formulation of sarilumab is not approved by the FDA, but in clinical trials, a single SUBQ dose (using the prefilled syringes, not the prefilled pen) of sarilumab 400 mg was reconstituted in 100 cc 0.9% NaCl and given as an IV infusion over 1 hour.8,9
  • IV infusion of sarilumab should occur within 4 hours of its preparation; it can be stored at room temperature until administered. 
Tocilizumab10

FDA-Approved Doses for COVID-19 in Hospitalized Adults 

  • Tocilizumab 8 mg/kg (maximum 800 mg) by IV infusion over 1 hour

FDA EUA Dose for COVID-19 in Hospitalized Children

Body Weight ≥30 kg

  • Tocilizumab 8 mg/kg by IV infusion over 1 hour

Body Weight <30 kg

  • Tocilizumab 12 mg/kg by IV infusion over 1 hour
For All Doses
  • If clinical signs or symptoms worsen or do not improve following the first infusion, 1 additional dose may be administered at least 8 hours after the first dose.
  • Infusion-related reaction
  • HSR
  • GI perforation
  • Hepatotoxicity
  • Treatment-related changes on laboratory tests for neutrophils, PLT, lipids, and liver enzymes
  • HBV reactivation
  • Secondary infections
  • Cases of disseminated strongyloidiasis have been reported in patients with COVID-19 during treatment with tocilizumab and corticosteroids.
  • HSR
  • Infusion reactions
  • Neutrophils
  • PLT
  • Liver enzymes
  • Inhibition of IL-6 may lead to increased metabolism of coadministered drugs that are CYP450 substrates.
  • The effects of tocilizumab on CYP enzymes may persist for weeks after the drug is stopped.
  • Tocilizumab is not recommended in patients with ALT or AST >10 times the upper limit of the reference range, ANC <1,000 cells/mm3, or PLT <50,000 cells/mm3.11
  • The SUBQ formulation of tocilizumab is not intended for IV administration.
Availability
  • IV tocilizumab is approved by the FDA for the treatment of COVID-19 in hospitalized adults aged ≥18 years.10
  • Tocilizumab is available through an FDA EUA for the treatment of COVID-19 in certain hospitalized children aged 2–17 years.11
Anti-Interleukin-6 Monoclonal Antibody
Not recommended by the Panel for the treatment of COVID-19. Currently under investigation in clinical trials.
Siltuximab

FDA-Approved Dose for Multicentric Castleman Disease

  • Siltuximab 11 mg/kg by IV infusion over 1 hour every 3 weeks12

Dose for COVID-19

  • Dose and duration unknown
  • Infusion-related reaction
  • HSR
  • GI perforation
  • Neutropenia
  • HTN
  • Dizziness
  • Rash
  • Pruritus
  • Hyperuricemia
  • Neutrophils
  • HSR
  • Infusion reactions
  • Elevated IL-6 may downregulate CYP enzymes; use of siltuximab may lead to increased metabolism of drugs that are CYP substrates.
  • The effects of siltuximab on CYP enzymes may persist for weeks after therapy is stopped.
  • Siltuximab is not recommended in patients with ANC <1,000 cells/mm3, Hgb >17 g/dL, or PLT <75,000 cells/mm3.12
  • Treatment with siltuximab may mask signs of acute inflammation or infection by suppressing fever and CRP levels.
Interleukin-1 Inhibitors
Anakinra: Received an FDA EUA for the treatment of COVID-19 in certain hospitalized adults. There is insufficient evidence for the Panel to recommend either for or against its use.
Canakinumab: Not recommended by the Panel for the treatment of COVID-19.
Anakinra

FDA EUA Dose for COVID-19 in Hospitalized Patients Aged ≥18 Years

  • Anakinra 100 mg SUBQ once daily for 10 days

Dose for CrCl <30 mL/min

  • Anakinra 100 mg SUBQ every other day for 5 total doses over 10 days.13
  • Neutropenia (particularly when used concomitantly with other agents that can cause neutropenia)
  • HSR, including anaphylaxis and angioedema
  • Secondary infections
  • Injection site reactions
  • Liver enzyme elevations
  • Hyperkalemia
  • Hypernatremia
  • Rash
  • CBC with differential; assess neutrophils before starting treatment and during therapy.
  • BMP
  • Liver enzymes
  • Renal function
  • Use with TNF-blocking agents is not recommended due to increased risk of infection.
  • Contraindicated in patients with known hypersensitivity to proteins derived from Escherichia coli, anakinra, or any component of the product13
  • Patients with <1,500 neutrophils/mm3 were excluded from participation in the SAVE-MORE study.14
Availability
  • SUBQ anakinra is available through an FDA EUA.13 
 
Canakinumab

FDA-Approved Dose for Systemic JIA

  • Canakinumab 4 mg/kg (maximum 300 mg) SUBQ every 4 weeks15
  • HSR
  • Neutropenia
  • Nasopharyngitis
  • Diarrhea
  • Respiratory tract infections
  • Bronchitis
  • Gastroenteritis
  • Pharyngitis
  • Musculoskeletal pain
  • Vertigo
  • Abdominal pain
  • Injection site reactions
  • Liver enzyme elevations
  • HSR
  • CBC with differential
  • Liver enzymes
  • Binding of canakinumab to IL-1 may increase formation of CYP enzymes and alter metabolism of drugs that are CYP substrates.
  • Use with TNF-blocking agents is not recommended due to potential increased risk of infection.
  • Canakinumab for IV administration is not an approved formulation in the United States.15
Corticosteroids (Inhaled)
Not recommended by the Panel for the treatment of COVID-19. Currently under investigation in clinical trials.
Budesonide (Inhaled)Dose for COVID-19 in Clinical Trials
  • Budesonide 800 mcg oral inhalation twice daily until symptom resolution or up to 14 days16,17
  • Secondary infections
  • Oral thrush
  • Systemic AEs (less common)
  • Signs of AEs involving the oral mucosa or throat, including thrush
  • Signs of systemic corticosteroid effects (e.g., adrenal suppression)
  • CYP3A4 substrate
  • Do not use with strong CYP3A4 inhibitors.
  • No comments
Ciclesonide (Inhaled)Dose for COVID-19 in Clinical Trials
  • Ciclesonide 160 mcg as 2 MDI inhalations twice daily for 30 days18
  • Secondary infections
  • Oral thrush
  • Systemic AEs (less common)
  • Signs of AEs involving the oral mucosa or throat, including thrush
  • Signs of systemic corticosteroid effects (e.g., adrenal suppression)
  • CYP3A4 substrate
  • Strong CYP3A4 inhibitors are expected to have less effect on ciclesonide exposure than on budesonide exposure.
  • No comments

References

  1. Randomised Evaluation of COVID-19 Therapy (RECOVERY). Low-cost dexamethasone reduces death by up to one third in hospitalised patients with severe respiratory complications of COVID-19. 2020. Available at: https://www.recoverytrial.net/news/low-cost-dexamethasone-reduces-death-by-up-to-one-third-in-hospitalised-patients-with-severe-respiratory-complications-of-covid-19. Accessed January 20, 2023.
  2. Baricitinib (Olumiant) [package insert]. Food and Drug Administration. 2022. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/207924s006lbl.pdf.
  3. Food and Drug Administration. Fact sheet for healthcare providers: Emergency Use Authorization (EUA) of baricitinib. 2022. Available at: https://www.fda.gov/media/143823/download.
  4. Cao Y, Wei J, Zou L, et al. Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): a multicenter, single-blind, randomized controlled trial. J Allergy Clin Immunol. 2020;146(1):137-146.e3. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32470486.
  5. Guimarães PO, Quirk D, Furtado RH, et al. Tofacitinib in patients hospitalized with COVID-19 pneumonia. N Engl J Med. 2021;385(5):406-415. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34133856.
  6. Sarilumab (Kevzara) [package insert]. Food and Drug Administration. 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761037s001lbl.pdf.
  7. REMAP-CAP Investigators. Effectiveness of tocilizumab, sarilumab, and anakinra for critically ill patients with COVID-19: the REMAP-CAP COVID-19 immune modulation therapy domain randomized clinical trial. medRxiv. 2021;Preprint. Available at: https://www.medrxiv.org/content/10.1101/2021.06.18.21259133v2.
  8. Sivapalasingam S, Lederer DJ, Bhore R, et al. Efficacy and safety of sarilumab in hospitalized patients with COVID-19: a randomized clinical trial. Clin Infect Dis. 2022;75(1):e380-e388. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35219277.
  9. REMAP-CAP Investigators. Interleukin-6 receptor antagonists in critically ill patients with COVID-19. N Engl J Med. 2021;384(16):1491-1502. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33631065.
  10. Tocilizumab (Actemra) [package insert]. Food and Drug Administration. 2022. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125276s138lbl.pdf.
  11. Food and Drug Administration. Fact sheet for healthcare providers: Emergency Use Authorization for Actemra (tocilizumab). 2021. Available at: https://www.fda.gov/media/150321/download.
  12. Siltuximab (Sylvant) [package insert]. Food and Drug Administration. 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125496s018lbl.pdf.
  13. Food and Drug Administration. Fact sheet for healthcare providers: Emergency Use Authorization for Kineret. 2022. Available at: https://www.fda.gov/media/163075/download.
  14. Kyriazopoulou E, Poulakou G, Milionis H, et al. Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled Phase 3 trial. Nat Med. 2021;27(10):1752-1760. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34480127.
  15. Canakinumab (Ilaris) [package insert]. Food and Drug Administration. 2020. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125319s100lbl.pdf.
  16. Ramakrishnan S, Nicolau DV Jr, Langford B, et al. Inhaled budesonide in the treatment of early COVID-19 (STOIC): a Phase 2, open-label, randomised controlled trial. Lancet Respir Med. 2021;9(7):763-772. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33844996.
  17. Yu LM, Bafadhel M, Dorward J, et al. Inhaled budesonide for COVID-19 in people at high risk of complications in the community in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Lancet. 2021;398(10303):843-855. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34388395.
  18. Clemency BM, Varughese R, Gonzalez-Rojas Y, et al. Efficacy of inhaled ciclesonide for outpatient treatment of adolescents and adults with symptomatic COVID-19: a randomized clinical trial. JAMA Intern Med. 2022;182(1):42-49. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34807241.