Table 5e. Characteristics of Immunomodulators

Last Updated: July 21, 2023

The information in this table is derived from data on the use of these drugs for FDA-approved indications or from clinical trials that evaluated 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; Therapeutic Management of Hospitalized Adults With COVID-19; Therapeutic Management of Hospitalized Children With COVID-19; and Pregnancy, Lactation, and COVID-19 Therapeutics.

Table 5e. Characteristics of Immunomodulators
Drug Name	Dosing 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.
Dexamethasone	Dose 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 (IV or PO) are: Prednisone 40 mg Methylprednisolone 32 mg Hydrocortisone 160 mg
Janus Kinase Inhibitors Recommended by the Panel for the treatment of COVID-19 in certain hospitalized patients.
Baricitinib²	FDA-Approved Doses for COVID-19 in Adults Aged ≥18 Years, per eGFR² ≥60 mL/min/1.73 m² BAR 4 mg PO once daily for 14 days or until hospital discharge, whichever comes first 30 to <60 mL/min/1.73 m² BAR 2 mg PO once daily for 14 days or until hospital discharge, whichever comes first 15 to <30 mL/min/1.73 m² BAR 1 mg PO once daily for 14 days or until hospital discharge, whichever comes first <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 Years, per eGFR³ ≥60 mL/min/1.73 m² BAR 2 mg PO once daily for 14 days or until hospital discharge, whichever comes first 30 to <60 mL/min/1.73 m² BAR 1 mg PO once daily for 14 days or until hospital discharge, whichever comes first <30 mL/min/1.73 m² Not recommended	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 Signs and symptoms of 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 BAR treatment until the diagnosis of DILI is excluded. BAR tablets can be taken PO or crushed, dispersed in water, and given via gastrostomy tube.² Availability BAR is approved by the FDA for the treatment of COVID-19 in adults aged ≥18 years.² BAR is available through an FDA EUA for children aged 2–17 years who require supplemental oxygen, NIV, MV, or ECMO.³
Tofacitinib	Dose for COVID-19 in Clinical Trials Tofacitinib 10 mg PO twice daily for up to 14 days or until hospital discharge, whichever comes first⁴	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.
Sarilumab⁵	Dose for COVID-19 in Clinical Trials Single dose of sarilumab 400 mg IV^6,7	Neutropenia Thrombocytopenia GI perforation HSRs Increased liver enzymes HBV reactivation Infusion-related reactions	HSRs Infusion-related 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/mm³.⁵ Treatment with sarilumab may mask signs of acute inflammation or infection by suppressing fever and CRP levels. Availability 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.^7,8 IV infusion of sarilumab should occur within 4 hours of its preparation; it can be stored at room temperature until administered.
Tocilizumab⁹	FDA-Approved Dose for COVID-19 in Hospitalized Adults Tocilizumab 8 mg/kg (maximum 800 mg) by IV infusion over 1 hour FDA EUA Doses 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.	HSRs Infusion-related reactions 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.	HSRs Infusion-related 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/mm³.¹⁰ 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.⁹ Tocilizumab is available through an FDA EUA for the treatment of COVID-19 in certain hospitalized children aged 2–17 years.¹⁰
Anti-C5a Monoclonal Antibody Received an FDA EUA for the treatment of COVID-19 when initiated within 48 hours of receiving MV or ECMO. There is insufficient evidence for the Panel to recommend either for or against its use.
Vilobelimab	FDA EUA Dose for COVID-19 in Hospitalized Adults Receiving MV or ECMO 800 mg IV infusion after dilution, for a maximum of 6 doses; start treatment within 48 hours of intubation (Day 1) followed by administration on Days 2, 4, 8, 15, and 22 if patient is still hospitalized (even if discharged from ICU)	Secondary infections Delirium PE HTN Pneumothorax DVT Liver enzyme elevations Hypoxemia Thrombocytopenia Pneumomediastinum Supraventricular tachycardia Constipation Rash	CBC Liver enzymes Infusion-related reactions New infections	None	Availability Vilobelimab is not FDA approved, but it is commercially available for use in hospitalized adults with COVID-19, as authorized in the EUA.
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 days¹¹	Neutropenia (particularly when used concomitantly with other agents that can cause neutropenia) HSRs, 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 product¹¹ Patients with <1,500 neutrophils/mm³ were excluded from participation in the SAVE-MORE study.¹² Availability SUBQ anakinra is available through an FDA EUA.¹¹
Canakinumab	FDA-Approved Dose for Systemic JIA Canakinumab 4 mg/kg (maximum 300 mg) SUBQ every 4 weeks¹³	HSRs Neutropenia Nasopharyngitis Diarrhea Respiratory tract infections Bronchitis Gastroenteritis Pharyngitis Musculoskeletal pain Vertigo Abdominal pain Injection site reactions Liver enzyme elevations	HSRs 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.	Availability IV canakinumab is not an approved formulation in the United States.¹³
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 µg oral inhalation twice daily until symptom resolution or up to 14 days^14,15	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 µg as 2 MDI inhalations twice daily for 30 days¹⁶	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
Key: AE = adverse event; ALC = absolute lymphocyte count; ALT = alanine transaminase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; BAR = baricitinib; BMP = basic metabolic panel; BP = blood pressure; CBC = complete blood count; CrCl = creatinine clearance; CRP = C-reactive protein; CYP = cytochrome P450; DEX = dexamethasone; DILI = drug-induced liver injury; DVT = deep vein thrombosis; ECMO = extracorporeal membrane oxygenation; eGFR = estimated glomerular filtration rate; EUA = Emergency Use Authorization; FDA = Food and Drug Administration; GI = gastrointestinal; HBV = hepatitis B virus; Hgb = hemoglobin; HSR = hypersensitivity reaction; HSV = herpes simplex virus; HTN = hypertension; ICU = intensive care unit; IL = interleukin; IV = intravenous; JIA = juvenile idiopathic arthritis; MDI = metered dose inhaler; MI = myocardial infarction; MV = mechanical ventilation; NaCl = sodium chloride; NIV = noninvasive ventilation; NMBA = neuromuscular blocking agent; OAT = organic anion transporter; the Panel = the COVID-19 Treatment Guidelines Panel; PE = pulmonary embolism; PLT = platelet count; PO = oral; SUBQ = subcutaneous; TB = tuberculosis; TNF = tumor necrosis factor

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