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 first1
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- 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)
- When used during outbreaks of other novel coronavirus infections (i.e., MERS and SARS), corticosteroid therapy was associated with delayed virus clearance.2,3
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- 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 (e.g., patients from tropical, subtropical, or warm temperate regions or who engage in agricultural activities) or fulminant reactivations of HBV.4-6
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-
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).
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For the Panel’s recommendations on the use of corticosteroids, please see Therapeutic Management of Patients With COVID-19.
- If dexamethasone is not available, an alternative corticosteroid such as prednisone, methylprednisolone, or 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
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Interferons |
Interferon Alfa |
PegIFN Alfa-2a
Dose for MERS:
- PegIFN alfa-2a 180 mcg SQ once weekly for 2 weeks7,8
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)9
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- Flu-like symptoms (e.g., fever, fatigue, myalgia)10
- Injection site reactions
- Liver function abnormalities
- Decreased blood counts
- Worsening depression
- Insomnia
- Irritability
- Nausea
- Vomiting
- Hypertension
- Induction of autoimmunity
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-
CBC with differential
- Liver enzymes; avoid if Child-Pugh Score >6
- Depression, psychiatric symptoms
- Reduce dose in patients with CrCl <30 mL/min.
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- Low potential for drug interactions
- Inhibition of CYP1A2
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- The Panel recommends against the use of IFNs for the treatment of patients with severe and critical COVID-19, except in a clinical trial (AIII).
- For COVID-19, IFN alfa has primarily been used as nebulization and usually as part of a combination regimen.
- Neither nebulized IFN alfa-2b nor IFN alfa-1b are FDA-approved for use in the United States.
- 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
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Interferon Beta |
IFN Beta-1a
Dose for MERS:
- IFN beta-1a 44 mcg SQ 3 times weekly8
Dose for COVID-19:
- Dose and duration un-known
IFN Beta-1b Dose for COVID-19:
- IFN beta-1b 8 million international units SQ every other day, up to 7 days total11
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-
Flu-like symptoms (e.g., fever, fatigue, myalgia)12
- Leukopenia, neutropenia, thrombocytopenia, lymphopenia
- Liver function abnormalities (ALT > AST)
- Injection site reactions
- Headache
- Hypertonia
- Pain
- Rash
- Worsening depression
- Induction of autoimmunity
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-
Liver enzymes
- CBC with differential
- Worsening CHF
- Depression, suicidal ideation
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-
Low potential for drug interactions
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-
The Panel recommends against the use of IFNs for the treatment of patients with severe or critical COVID-19, except in a clinical trial (AIII).
- There are insufficient data to recommend either for or against the use of IFN beta for the treatment of early (i.e., <7 days from symptom onset) mild to moderate COVID-19.
- 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:
IFN Beta-1b Products:
|
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
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-
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
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-
CBC with differential
- Renal function (reduce dose in patients with CrCl <30 mL/min)
- Liver enzymes
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-
Use with TNF-blocking agents is not recommended due to increased risk of infection.
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-
There are insufficient data for the Panel to recommend either for or against the use of IL-1 inhibitors (e.g., anakinra) for the treatment of COVID-19.
- A list of clinical trials is available: Anakinra
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Interleukin-6 Inhibitors |
Anti-Interleukin-6 Receptor Monoclonal Antibodies |
Sarilumab13 |
Dose for COVID-19 in Clinical Trial (See ClinicalTrials.gov Identifier NCT04315298):
- Sarilumab 400 mg IV (single dose)14
- REMAP-CAP evaluated sarilumab for IV administration, which is not the approved formulation in the United States.
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Neutropenia, thrombocytopenia
- Gastrointestinal perforation
- HSR
- Increased liver enzymes
- HBV reactivation
- Infusion reaction possible
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- Monitor for HSR
- Monitor for infusion reactions
- Neutrophils
- Platelets
- Liver enzymes
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-
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.
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-
For patients who are within 24 hours of admission to the ICU and who require invasive or noninvasive mechanical ventilation or high-flow oxygen (>0.4 FiO2/30 L/min of oxygen flow), there are insufficient data to recommend either for or against the use of sarilumab for the treatment of COVID-19.
- For patients who do not require ICU-level care or who are admitted to the ICU but do not meet the above criteria, the Panel recommends against the use of sarilumab for the treatment of COVID-19, except in a clinical trial (BIIa).
- 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
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Tocilizumab15 |
Dose for COVID-19 in Clinical Trial:
- Tocilizumab 8 mg/kg IV once
- Dose should not exceed tocilizumab 800 mg.
- If tocilizumab is used, administer with a course of dexamethasone therapy.
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-
Infusion-related reactions
- HSR
- Gastrointestinal perforation
- Hepatotoxicity
- Treatment-related changes in neutrophils, platelets, lipids, and liver enzymes
- HBV reactivation
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-
Monitor for HSR
- Monitor for infusion reactions
- Neutrophils
- Platelets
- Liver enzymes
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-
Elevated IL-6 may downregulate CYP enzymes; use of tocilizumab may lead to in-creased metabo-lism of drugs that are CYP450 substrates.
- Effects on CYP450 may persist for weeks after therapy.
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-
For patients who are within 24 hours of admission to the ICU and who require invasive or noninvasive mechanical ventilation or high-flow oxygen (>0.4 FiO2/30 L/min of oxygen flow), there are insufficient data to recommend either for or against the use of tocilizumab for the treatment of COVID-19.
- Some Panel members would administer a single dose of tocilizumab (8 mg/kg actual body weight up to 800 mg) in addition to dexamethasone to patients who meet the above criteria and who are also exhibiting rapid progression of respiratory failure.
- For patients who do not require ICU-level care or who are admitted to the ICU but do not meet the above criteria, the Panel recommends against the use of tocilizumab for the treatment of COVID-19, except in a clinical trial (BIIa).
- 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
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Anti-Interleukin-6 Monoclonal Antibody |
Siltuximab |
Dose for Multicentric Castleman Disease:
- Siltuximab 11 mg/kg administered over 1 hour by IV infusion every 3 weeks16
Dose for COVID-19:
- Dose and duration unknown
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-
Infusion-related reaction
- HSR
- Gastrointestinal perforation
- Neutropenia
- Hypertension
- Dizziness
- Rash
- Pruritus
- Hyperuricemia
|
-
Monitor for HSR
- Monitor for infusion reactions
- Neutrophils
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-
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.
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-
The Panel recommends against the use of siltuximab for the treatment of COVID-19, except in a clinical trial (AIIa).
- May mask signs of acute inflammation or infection (i.e., by suppressing fever and CRP levels).
- A list of clinical trials is available: Siltuximab
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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
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- Hemorrhage
- Cytopenias (neutropenia, anemia, thrombocytopenia, lymphopenia)
- Atrial fibrillation and flutter
- Infection
- Headache
- Diarrhea
- Fatigue
- Myalgia
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-
CBC with differential
- Signs and symptoms of bleeding (particularly when coadministered with anticoagulant or antiplatelet therapy)
- Monitor for cardiac arrhythmias
- Monitor for new infections
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-
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.
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-
The Panel recommends against the use of BTK inhibitors for the treatment of COVID-19, except in a clinical trial (AIII).
- 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
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-
Hemorrhage
- Cardiac arrhythmias
- Serious infections
- Cytopenias (thrombocytopenia, neutropenia, anemia)
- Hypertension
- Diarrhea
- Musculoskeletal pain
- Rash
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-
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
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-
Avoid concomitant use with strong CYP3A inhibitors or inducers.
- Dose reduction may be necessary with moderate CYP3A4 inhibitors.
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-
The Panel recommends against the use of BTK inhibitors for the treatment of COVID-19, except in a clinical trial (AIII).
- 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, hypertension, or acute infections may be predisposed to cardiac arrhythmias.
- A list of clinical trials is available: Ibrutinib
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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
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-
Hemorrhage
- Cytopenias (neutropenia, thrombocytopenia, anemia, leukopenia)
- Atrial fibrillation and flutter
- Infection
- Rash
- Bruising
- Diarrhea
- Cough
- Musculoskeletal pain
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-
CBC with differential
- Signs and symptoms of bleeding
- Monitor for cardiac arrhythmias
- Monitor for new infections
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-
Avoid concomitant use with moderate or strong CYP3A inducers.
- Dose reduction required with moderate and strong CYP3A4 inhibitors.
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-
The Panel recommends against the use of BTK inhibitors for the treatment of COVID-19, except in a clinical trial (AIII).
- Dose reduction required in patients with severe hepatic impairment.
- A list of clinical trials is available: Zanubrutinib
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Janus Kinase Inhibitors |
Baricitinib17 |
Dose for Rheumatoid Arthritis:
- Adults: Baricitinib 2 mg PO once daily
Dose for COVID-19:18
- 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 dosage recommendations in patients with renal impairment or hepatic impairment.17
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Lymphoma and other malignancies
- Thrombosis
- Gastrointestinal perforation
- Treatment-related changes in lymphocytes, neutrophils, Hgb, liver enzymes
- HSV
- Herpes zoster
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-
CBC with differential
- Renal function
- Liver enzymes
- Monitor for new infections
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-
Dose modification is recommended when concurrently administering with a strong OAT3 inhibitor.
- Avoid administration of live vaccines.
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- There are insufficient data for the Panel to recommend either for or against the use of baricitinib in combination with RDV for the treatment of COVID-19 in hospitalized patients, when corticosteroids can be used.
- In the rare circumstance when corticosteroids cannot be used, the Panel recommends baricitinib in combination with RDV for the treatment of COVID-19 in hospitalized nonintubated patients who require oxygen supplementation (BIIa).
- The Panel recommends against the use of baricitinib without RDV, except in a clinical trial (AIII).
- There are insufficient data for the Panel to recommend either for or against the use of baricitinib in combination with corticosteroids for the treatment of COVID-19. Because both agents are potent immunosuppressants, there is a potential for an additive risk of infection.
- Baricitinib is not recommended for patients with severe hepatic or renal impairment.
- Baricitinib is available through the FDA EUA for the treatment of COVID-19 in combination with RDV for hospitalized adults and pediatric patients aged ≥2 years who require supple-mental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation.18
- A list of clinical trials is available: Baricitinib
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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
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-
Thrombocytopenia
- Anemia
- Neutropenia
- Liver enzyme elevations
- Risk of infection
- Dizziness
- Headache
- Diarrhea
- CPK elevation
- Herpes zoster
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-
CBC with differential
- Liver enzymes
- Monitor for new infections
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-
Dose modifications required when administered with strong CYP3A4 inhibitors.
- Avoid use with doses of fluconazole >200 mg.
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-
The Panel recommends against the use of JAK inhibitors (other than baricitinib) for the treatment of COVID-19, except in a clinical trial (AIII).
- Dose modification may be required in patients with moderate or severe renal impairment, hepatic impairment, or thrombocytopenia.
- A list of clinical trials is available: Ruxolitinib
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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:
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-
Thrombotic events (pulmonary embolism, DVT, arterial thrombosis)
- Anemia
- Risk of infection
- Gastrointestinal perforation
- Diarrhea
- Headache
- Herpes zoster
- Lipid elevations
- Liver enzyme elevations
- Lymphoma and other malignancies
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-
CBC with differential
- Liver enzymes
- Monitor for new infections
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-
Dose modifications required when administered with strong CYP3A4 inhibitors or when used with a moderate CYP3A4 inhibitor coadministered with a strong CYP2C19 inhibitor.
- Avoid administration of live vaccines.
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-
The Panel recommends against the use of JAK inhibitors (other than baricitinib) for the treatment of COVID-19, except in a clinical trial (AIII).
- 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
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Non-SARS-CoV-2 Specific Immunoglobulin |
Non-SARS-CoV-2 Specific Immunoglobulin |
-
Dose varies based on indication and formulation.
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-
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.
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-
Monitor for transfusion-related reactions
- Monitor vital signs at baseline and during and after infusion
- Discontinue if renal function deteriorates during treatment.
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-
IVIG may interfere with immune response to certain vaccines.
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-
The Panel recommends against the use of non-SARS-CoV-2 specific IVIG for the treatment of COVID-19, except in a clinical trial (AIII). This recommendation should not preclude the use of IVIG when otherwise indicated for the treatment of complications that arise during the course of COVID-19.
- A list of clinical trials is available: Intravenous Immunoglobulin
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