Table 4c. Characteristics of Immunomodulators Under Evaluation for the Treatment of COVID-19

Last Updated: April 21, 2021

Table 4c. Characteristics of Immunomodulators Under Evaluation for the Treatment of COVID-19
Drug Name Dosing Regimen
There are no approved doses for the treatment of COVID-19. The doses listed here are for approved indications or from reported experiences or clinical trials.
Adverse Effects Monitoring Parameters Drug-Drug Interaction Potential Comments and Links to Clinical Trials
Colchicine
Colchicine Dose for COVID-19 in Clinical Trial
COLCORONA:
  • Colchicine 0.5 mg twice daily for 3 days then once daily for 27 days
  • Diarrhea
  • Nausea
  • Vomiting
  • Cramping
  • Abdominal pain
  • Bloating
  • Loss of appetite
  • Neuromyotoxicity (rare)1
  • Blood dyscrasias (rare)
  • CBC
  • Renal function
  • Hepatic function
  • P-gp and CYP3A4 substrate
  • The risk of myopathy may be increased with the concomitant use of certain HMG-CoA reductase inhibitors (e.g., atorvastatin, lovastatin, simvastatin) due to potential competitive interactions mediated by P-gp and CYP3A4 pathways.
  • Fatal colchicine toxicity has been reported in individuals with renal or hepatic impairment who used colchicine in conjunction with P-gp inhibitors or strong CYP3A4 inhibitors.
  • Colchicine should be avoided in patients with severe renal insufficiency, and those with moderate renal insufficiency should be monitored for AEs.
  • A list of clinical trials is available: Colchicine
Availability:
  • COLCORONA used 0.5 mg tablets for dosing; in the United States, colchicine is available as 0.6 mg tablets.
Corticosteroids
Dexamethasone Dose for COVID-19:
  • Dexamethasone 6 mg IV or PO once daily, for up to 10 days or until hospital discharge, whichever comes first2
  • Hyperglycemia
  • Secondary infections
  • Reactivation of latent infections (e.g., HBV, HSV, strongyloidiasis, TB)
  • Psychiatric disturbances
  • Avascular necrosis
  • Adrenal insufficiency
  • Increased blood pressure
  • Peripheral edema
  • Myopathy (particularly if used with neuromuscular blocking agents)
  • Blood glucose
  • Blood pressure
  • Signs and symptoms of new infection
  • When initiating dexamethasone, consider appropriate screening and treatment to reduce the risk of Strongyloides hyperinfection in patients at high risk of strongyloidiasis or fulminant reactivations of HBV.3-5
  • Moderate CYP3A4 inducer
  • CYP3A4 substrate
  • Although coadministration of RDV and dexamethasone has not been formally studied, a clinically significant PK interaction is not predicted (Gilead, written communication, August 2020).
  • If dexamethasone is not available, an alternative corticosteroid (e.g., prednisone, methylprednisolone, hydrocortisone) can be used.
  • The approximate total daily dose equivalencies for these glucocorticoids to dexamethasone 6 mg (PO or IV) are: prednisone 40 mg, methylprednisolone 32 mg, and hydrocortisone 160 mg.
  • A list of clinical trials is available: Dexamethasone
Fluvoxamine
Fluvoxamine

Dose for COVID-19 in Clinical Trials:

  • Various dosing regimens used
  • Nausea
  • Diarrhea
  • Dyspepsia
  • Asthenia
  • Insomnia
  • Somnolence
  • Sweating
  • Suicidal ideation (rare)
  • Assess for drug interactions.
  • Hepatic function
  • Monitor for withdrawal symptoms when tapering dose.
  • Fluvoxamine is a CYP2D6 substrate.
  • Fluvoxamine inhibits several CYP450 isoenzymes (CYP1A2, CYP2C9, CYP3A4, CYP2C19, CYP2D6).
  • Coadministration of tizanidine, thioridazine, alosetron, or pimozide with fluvoxamine is contraindicated.
  • Fluvoxamine may enhance anticoagulant effects of antiplatelets and anticoagulants; consider additional monitoring when these drugs are used concomitantly with fluvoxamine.
  • The use of MAOIs concomitantly with fluvoxamine or within 14 days of treatment with fluvoxamine is contraindicated.
  • A list of clinical trials is available: Fluvoxamine
Interferons
Interferon Alfa

Peg-IFN Alfa-2a
Dose for MERS:

  • Peg-IFN alfa-2a 180 µg SQ once weekly for 2 weeks6,7

IFN Alfa-2b
Dose for COVID-19 in Clinical Trials:

  • Nebulized IFN alfa-2b 5 million international units twice daily (no duration listed in the study methods)8
  • Flu-like symptoms (e.g., fever, fatigue, myalgia)9
  • Injection site reactions
  • Liver function abnormalities
  • Decreased blood counts
  • Worsening depression
  • Insomnia
  • Irritability
  • Nausea
  • Vomiting
  • HTN
  • Induction of autoimmunity
  • CBC with differential
  • Liver enzymes; avoid if Child-Pugh Score >6
  • Depression, psychiatric symptoms
  • Reduce dose in patients with CrCl <30 mL/min.
  • Low potential for drug-drug interactions
  • Inhibition of CYP1A2
  • For COVID-19, IFN alfa has primarily been used as nebulization and usually as part of a combination regimen.
  • Use with caution with other hepatotoxic agents.
  • Reduce dose if ALT >5 times ULN; discontinue if bilirubin level also increases.
  • Reduce dose or discontinue if neutropenia or thrombocytopenia occur.
  • A list of clinical trials is available: Interferon
Availability:
  • Neither nebulized IFN alfa-2b nor IFN alfa-1b are FDA-approved for use in the United States.
Interferon Beta

IFN Beta-1a
Dose for MERS:

  • IFN beta-1a 44 mcg SQ 3 times weekly7

Dose for COVID-19:

  • Dose and duration unknown

IFN Beta-1b
Dose for COVID-19:

  • IFN beta-1b 8 million international units SQ every other day, up to 7 days total10
  • Flu-like symptoms (e.g., fever, fatigue, myalgia)11
  • Leukopenia, neutropenia, thrombocytopenia, lymphopenia
  • Liver function abnormalities (ALT > AST)
  • Injection site reactions
  • Headache
  • Hypertonia
  • Pain
  • Rash
  • Worsening depression
  • Induction of autoimmunity
  • Liver enzymes
  • CBC with differential
  • Worsening CHF
  • Depression, suicidal ideation
  • Low potential for drug-drug interactions
  • Use with caution with other hepatotoxic agents.
  • Reduce dose if ALT >5 times ULN.
  • A list of clinical trials is available: Interferon

Availability:

  • Several products are available in the United States; product doses differ.
IFN Beta-1a Products:
  • Avonex, Rebif
IFN Beta-1b Products:
  • Betaseron, Extavia
Interleukin-1 Inhibitor
Anakinra

Dose for Rheumatoid Arthritis:

  • Anakinra 100 mg SQ once daily

Dose for COVID-19:

  • Dose and duration vary by study
  • Has also been used as IV infusion
  • Neutropenia (particularly with concomitant use of other agents that can cause neutropenia)
  • Anaphylaxis
  • Headache
  • Nausea
  • Diarrhea
  • Sinusitis
  • Arthralgia
  • Flu-like symptoms
  • Abdominal pain
  • Injection site reactions
  • Liver enzyme elevations
  • CBC with differential
  • Renal function (reduce dose in patients with CrCl <30 mL/min)
  • Liver enzymes
  • Use with TNF-blocking agents is not recommended due to increased risk of infection.
  • A list of clinical trials is available: Anakinra
Interleukin-6 Inhibitors
Anti-Interleukin-6 Receptor Monoclonal Antibodies
Sarilumab12

Dose for COVID-19 in Clinical Trial (See ClinicalTrials.gov Identifier NCT04315298):

  • Sarilumab 400 mg IV (single dose)13
  • Neutropenia, thrombocytopenia
  • GI perforation
  • HSR
  • Increased liver enzymes
  • HBV reactivation
  • Infusion-related reaction
  • Monitor for HSR.
  • Monitor for infusion reactions.
  • Neutrophils
  • Platelets
  • Liver enzymes
  • Elevated IL-6 may downregulate CYP enzymes; use of sarilumab may lead to increased metabolism of drugs that are CYP450 substrates.
  • Effects on CYP450 may persist for weeks after therapy.
  • Treatment with sarilumab may mask signs of acute inflammation or infection (i.e., by suppressing fever and CRP levels).
  • A list of clinical trials is available: Sarilumab

Availability:

  • Sarilumab for IV administration is not an approved formulation in the United States.
Tocilizumab14

Dose for COVID-19 in Clinical Trial:

  • Single dose of tocilizumab 8 mg/kg actual body weight IV
  • Dose should not exceed tocilizumab 800 mg.
  • Administer in combination with dexamethasone.
  • In clinical trials, some patients received a second dose of tocilizumab at the discretion of treating physicians; however, there are insufficient data to determine which patients, if any, would benefit from an additional dose of the drug.
  • Infusion-related reaction
  • HSR
  • GI perforation
  • Hepatotoxicity
  • Treatment-related changes on laboratory tests for neutrophils, platelets, lipids, and liver enzymes
  • HBV reactivation
  • Monitor for HSR.
  • Monitor for infusion reactions.
  • Neutrophils
  • Platelets
  • Liver enzymes
  • Cases of severe and disseminated strongyloidiasis have been reported with the use of tocilizumab and corticosteroids in patients with COVID-19.15,16 Prophylactic treatment with ivermectin should be considered for persons who are from areas where strongyloidiasis is endemic.3
  • Elevated IL-6 may downregulate CYP enzymes; use of tocilizumab may lead to increased metabolism of drugs that are CYP450 substrates.
  • Effects on CYP450 may persist for weeks after therapy.
  • Tocilizumab use should be avoided in patients who are significantly immunocompromised. The safety of using tocilizumab plus a corticosteroid in immunocompromised patients is unknown.
  • May mask signs of acute inflammation or infection (i.e., by suppressing fever and CRP levels).
  • The SQ formulation of tocilizumab is not intended for IV administration.
  • A list of clinical trials is available: Tocilizumab
Anti-Interleukin-6 Monoclonal Antibody
Siltuximab

Dose for Multicentric Castleman Disease:

  • Siltuximab 11 mg/kg administered over 1 hour by IV infusion every 3 weeks17

Dose for COVID-19:

  • Dose and duration unknown
  • Infusion-related reaction
  • HSR
  • GI perforation
  • Neutropenia
  • HTN
  • Dizziness
  • Rash
  • Pruritus
  • Hyperuricemia
  • Monitor for HSR.
  • Monitor for infusion reactions.
  • Neutrophils
  • Elevated IL-6 may downregulate CYP enzymes; use of siltuximab may lead to increased metabolism of drugs that are CYP450 substrates.
  • Effects on CYP450 may persist for weeks after therapy.
  • May mask signs of acute inflammation or infection (i.e., by suppressing fever and CRP levels).
  • A list of clinical trials is available: Siltuximab
Kinase Inhibitors
Bruton’s Tyrosine Kinase Inhibitors
Acalabrutinib

Dose for FDA-Approved Indications:

  • Acalabrutinib 100 mg PO every 12 hours

Dose for COVID-19:

  • Dose and duration unknown
  • Hemorrhage
  • Cytopenias (neutropenia, anemia, thrombocytopenia, lymphopenia)
  • Atrial fibrillation and flutter
  • Infection
  • Headache
  • Diarrhea
  • Fatigue
  • Myalgia
  • CBC with differential
  • Signs and symptoms of bleeding (particularly when coadministered with anticoagulant or antiplatelet therapy)
  • Monitor for cardiac arrhythmias.
  • Monitor for new infections.
  • Avoid concomitant use with strong CYP3A inhibitors or inducers.
  • Dose reduction may be necessary with moderate CYP3A4 inhibitors.
  • Avoid concomitant PPI use.
  • H2-receptor antagonist should be administered 2 hours after acalabrutinib.
  • Avoid use in patients with severe hepatic impairment.
  • Patients with underlying cardiac risk factors, hypertension, or acute infections may be predisposed to atrial fibrillation.
  • A list of clinical trials is available: Acalabrutinib
Ibrutinib

Dose for FDA-Approved Indications:

  • Ibrutinib 420 mg or 560 mg PO once daily

Dose for COVID-19:

  • Dose and duration unknown
  • Hemorrhage
  • Cardiac arrhythmias
  • Serious infections
  • Cytopenias (thrombocytopenia, neutropenia, anemia)
  • HTN
  • Diarrhea
  • Musculoskeletal pain
  • Rash
  • CBC with differential
  • Blood pressure
  • Signs and symptoms of bleeding (particularly when coadministered with anticoagulant or antiplatelet therapy)
  • Monitor for cardiac arrhythmias.
  • Monitor for new infections.
  • Avoid concomitant use with strong CYP3A inhibitors or inducers.
  • Dose reduction may be necessary with moderate CYP3A4 inhibitors.
  • Avoid use in patients with severe baseline hepatic impairment. Dose modifications required in patients with mild or moderate hepatic impairment.
  • Patients with underlying cardiac risk factors, HTN, or acute infections may be predisposed to cardiac arrhythmias.
  • A list of clinical trials is available: Ibrutinib
Zanubrutinib

Dose for FDA-Approved Indications:

  • Zanubrutinib 160 mg PO twice daily or 320 mg PO once daily

Dose for COVID-19:

  • Dose and duration unknown
  • Hemorrhage
  • Cytopenias (neutropenia, thrombocytopenia, anemia, leukopenia)
  • Atrial fibrillation and flutter
  • Infection
  • Rash
  • Bruising
  • Diarrhea
  • Cough
  • Musculoskeletal pain
  • CBC with differential
  • Signs and symptoms of bleeding
  • Monitor for cardiac arrhythmias.
  • Monitor for new infections.
  • Avoid concomitant use with moderate or strong CYP3A inducers.
  • Dose reduction required with moderate and strong CYP3A4 inhibitors.
  • Dose reduction required in patients with severe hepatic impairment.
  • A list of clinical trials is available: Zanubrutinib
Janus Kinase Inhibitors
Baricitinib18

Dose for Rheumatoid Arthritis:
Adults:

  • Baricitinib 2 mg PO once daily

Dose for COVID-19:19
Adults:

  • Baricitinib 4 mg PO once daily for 14 days or until hospital discharge

Children:

  • Limited data are available. Dose per the FDA EUA:
    • Aged ≥9 years: Baricitinib 4 mg PO once daily for 14 days or until hospital discharge
    • Aged ≥2 years to <9 years: Baricitinib 2 mg PO once daily for 14 days or until hospital discharge
  • See full prescribing information for dosing recommendations in patients with renal or hepatic impairment.18
  • Lymphoma and other malignancies
  • Thrombosis
  • GI perforation
  • Treatment-related changes in lymphocytes, neutrophils, Hgb, liver enzymes
  • HSV reactivation
  • Herpes zoster
  • CBC with differential
  • Renal function
  • Liver enzymes
  • Monitor for new infections.
  • Dose modification is recommended when concurrently administering a strong OAT3 inhibitor.
  • Avoid concomitant administration of live vaccines.
  • Baricitinib is not recommended for patients with severe hepatic or renal impairment.
  • A list of clinical trials is available: Baricitinib

Availability:

  • Baricitinib is available through an FDA EUA. The EUA allows for the use of baricitinib, in combination with RDV, for the treatment of COVID-19 for hospitalized adults and pediatric patients aged ≥2 years who require supplemental oxygen, IMV, or ECMO.19
Ruxolitinib

Dose for FDA-Approved Indications:

  • Ruxolitinib 5 mg–20 mg PO twice daily

Dose for COVID-19 in Clinical Trials:

  • Ruxolitinib 5 mg–20 mg PO twice daily, for 14 days
  • Thrombocytopenia
  • Anemia
  • Neutropenia
  • Liver enzyme elevations
  • Risk of infection
  • Dizziness
  • Headache
  • Diarrhea
  • CPK elevation
  • Herpes zoster
  • CBC with differential
  • Liver enzymes
  • Monitor for new infections.
  • Dose modifications required when administered with strong CYP3A4 inhibitors.
  • Avoid use with doses of fluconazole >200 mg.
  • Dose modification may be required in patients with hepatic impairment, moderate or severe renal impairment, or thrombocytopenia.
  • A list of clinical trials is available: Ruxolitinib
Tofacitinib

Dose for FDA-Approved Indications:

  • Tofacitinib 5 mg PO twice daily for rheumatoid and psoriatic arthritis
  • Tofacitinib 10 mg PO twice daily for ulcerative colitis

Dose for COVID-19:

  • Thrombotic events (pulmonary embolism, DVT, arterial thrombosis)
  • Anemia
  • Risk of infection
  • GI perforation
  • Diarrhea
  • Headache
  • Herpes zoster
  • Lipid elevations
  • Liver enzyme elevations
  • Lymphoma and other malignancies
  • CBC with differential
  • Liver enzymes
  • Monitor for new infections.
  • Dose modifications required when administered with strong CYP3A4 inhibitors or when used with a moderate CYP3A4 inhibitor that is coadministered with a strong CYP2C19 inhibitor.
  • Avoid administration of live vaccines.
  • Avoid use in patients with ALC <500 cells/mm3, ANC <1,000 cells/mm3, or Hgb <9 grams/dL.
  • Dose modification may be required in patients with moderate or severe renal impairment or moderate hepatic impairment.
  • A list of clinical trials is available: Tofacitinib
Non-SARS-CoV-2 Specific Immunoglobulin
Non-SARS-CoV-2 Specific Immunoglobulin
  • Dose varies based on indication and formulation.
  • Allergic reactions, including anaphylaxis
  • Renal failure
  • Thrombotic events
  • Aseptic meningitis syndrome
  • Hemolysis
  • TRALI
  • Transmission of infectious pathogens
  • AEs may vary by formulation.
  • AEs may be increased with high-dose, rapid infusion, or in patients with underlying conditions.
  • Monitor for transfusion-related reactions.
  • Monitor vital signs at baseline and during and after infusion.
  • Discontinue if renal function deteriorates during treatment.
  • IVIG may interfere with immune response to certain vaccines.