Table 4f. Characteristics of Immunomodulators
Last Updated: December 16, 2021
- The information in this table is derived from data on the use of these drugs for FDA-approved indications or in investigational trials, and it is supplemented with data on their use in patients with COVID-19, when available.
- For dose modifications for patients with organ failure or those who require extracorporeal devices, please refer to product labels, 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.
Drug Name | Dosing Regimen The doses listed are for approved indications or from clinical trials or clinical experience in patients with COVID-19. | Adverse Events | Monitoring Parameters | Drug-Drug Interaction Potential | Comments and Links to Clinical Trials |
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Colchicine Not approved by the FDA and not recommended by the Panel for the treatment of COVID-19. Currently under investigation in clinical trials. | |||||
Colchicine | Dose for COVID-19 in COLCORONA Trial:
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Corticosteroids (Inhaled) Not approved by the FDA and 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:
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Ciclesonide (Inhaled) | Dose for COVID-19 in Clinical Trials:
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Corticosteroids (Systemic) Recommended by the Panel for the treatment of COVID-19 in certain nonhospitalized and hospitalized patients. | |||||
Dexamethasone (Systemic) | Dose for COVID-19:
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Fluvoxamine Not approved by the FDA and not recommended by the Panel for the treatment of COVID-19. Currently under investigation in clinical trials. | |||||
Fluvoxamine | Dose for COVID-19 in Clinical Trials:
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Interleukin-1 Inhibitors Not approved by the FDA and not recommended by the Panel for the treatment of COVID-19. Currently under investigation in clinical trials. | |||||
Anakinra | FDA-Approved Dose for Rheumatoid Arthritis:
Dose for COVID-19 in Clinical Trials:
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Canakinumab | FDA-Approved Dose for Systemic Juvenile Idiopathic Arthritis:
Dose for COVID-19 in Clinical Trials:
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Interleukin-6 Inhibitors | |||||
Anti-Interleukin-6 Receptor Monoclonal Antibodies Recommended by the Panel for the treatment of COVID-19 in certain nonhospitalized and hospitalized patients. | |||||
Sarilumab11 | Dose for COVID-19 in Clinical Trials:
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Availability:
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Tocilizumab13 | EUA Dose for COVID-19 For Hospitalized Patients Aged ≥2 Years Based on Body Weight:
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Anti-Interleukin-6 Monoclonal Antibody Not approved by the FDA and 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:
Dose for COVID-19:
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Kinase Inhibitors | |||||
Janus Kinase Inhibitors Baricitinib and Tofacitinib: Recommended by the Panel for the treatment of COVID-19 in certain nonhospitalized and hospitalized patients. Ruxolitinib: Not approved by the FDA and not recommended by the Panel for the treatment of COVID-19. Currently under investigation in clinical trials. | |||||
Baricitinib16 | EUA Dose for COVID-1917
For Children Aged 2 to <9 Years Based on eGFR:
Duration of Therapy:
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Availability:
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Ruxolitinib | Dose for FDA-Approved Indications:
Dose for COVID-19 in Clinical Trials:
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Tofacitinib | Dose for COVID-19 in Clinical Trial:
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Non-SARS-CoV-2 Specific Immunoglobulin Primarily used for the treatment of multi-system inflammatory syndrome in children (MIS-C). Currently under investigation in clinical trials. | |||||
Non-SARS-CoV-2 Specific Immunoglobulin |
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Key: AE = adverse event; ALC = absolute lymphocyte count; ALT = alanine transaminase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; BP = blood pressure; CBC = complete blood count; CPK = creatine phosphokinase; 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; Hgb = hemoglobin; HSR = hypersensitivity reaction; HSV = herpes simplex virus; HTN = hypertension; IL = interleukin; IV = intravenous; IVIG = intravenous immunoglobulin; IVM = ivermectin; MAOI = monoamine oxidase inhibitor; MDI = metered dose inhaler; MI= myocardial infarction; MV = mechanical ventilation; NaCl = sodium chloride; NIV = noninvasive ventilation; OAT = organic anion transporter; the Panel = the COVID-19 Treatment Guidelines Panel; PE = pulmonary embolism; P-gp= P-glycoprotein; PK = pharmacokinetic; PO = orally; RDV = remdesivir; SQ = subcutaneous; TB = tuberculosis; TNF = tumor necrosis factor; TRALI = transfusion-related acute lung injury |
References
- Tardif JC, Bouabdallaoui N, L'Allier PL, et al. Colchicine for community-treated patients with COVID-19 (COLCORONA): a Phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial. Lancet Respir Med. 2021;9(8):924-932. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34051877.
- Colchicine (Colcrys) [package insert]. Food and Drug Administration. 2012. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022352s017lbl.pdf.
- 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.
- 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 Sep 4;398(10303):843-855. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34388395.
- 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. 2021;Published online ahead of print. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34807241.
- 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 February 9, 2021.
- Stauffer WM, Alpern JD, Walker PF. COVID-19 and dexamethasone: a potential strategy to avoid steroid-related strongyloides hyperinfection. JAMA. 2020;324(7):623-624. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32761166.
- Anakinra (Kineret) [package insert]. Food and Drug Administration. 2012. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/103950s5136lbl.pdf.
- Canakinumab (Ilaris) [package insert]. Food and Drug Administration. 2020. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125319s100lbl.pdf.
- Caricchio R, Abbate A, Gordeev I, et al. Effect of canakinumab vs placebo on survival without invasive mechanical ventilation in patients hospitalized with severe COVID-19: a randomized clinical trial. JAMA. 2021;326(3):230-239. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34283183.
- Sarilumab (Kevzara) [package insert]. Food and Drug Administration. 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761037s001lbl.pdf.
- Regeneron and Sanofi provide update on U.S. Phase 2/3 adaptive-designed trial of KEVZARA® (sarilumab) in hospitalized COVID-19 patients [press release]. 2020.
- Tocilizumab (Actemra) [package insert]. Food and Drug Administration. 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125276s131lbl.pdf.
- 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.
- Siltuximab (Sylvant) [package insert]. Food and Drug Administration. 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125496s018lbl.pdf.
- Baricitinib (Olumiant) [package insert]. Food and Drug Administration. 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/207924s001lbl.pdf.
- Food and Drug Administration. Fact sheet for healthcare providers: Emergency Use Authorization (EUA) of baricitinib. 2021. Available at: https://www.fda.gov/media/143823/download.
- 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. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32470486.
- Guimaraes 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.