Table 1.

Characteristics of Proposed Therapies for the Treatment of COVID-19.2022.

Class and Agent	Dosing	● Place in Therapy	Drug-Drug Interactions	Adverse Effects	Special Considerations for Transplant Recipients
Antivirals
Remdesivir	200 mg IV for 1 d, followed by 100 mg for 5–10 d	NIH Guidelines [9]: Recommended for pts hospitalized and requiring supplemental oxygen (alone BIIa, with dexamethasone BIII) Recommended for pts hospitalized and requiring high-flow oxygen or noninvasive ventilation with dexamethasone (BIII) WHO Guidelines [32]: Recommend against remdesivir in addition to usual care for any disease severity (conditional recommendation against) IDSA Guidelines [33]: Recommended for pts hospitalized with SpO2 ≤94% on room air, requiring supplemental oxygen, mechanical ventilation, or ECMO (5 d course) (conditional recommendation, moderate certainty of evidence)	Substrate of CYP3A4, OATP1B1, and P-gp and an inhibitor of CYP3A4, OATP1B1, OATP1B3, and MATE1 Hydroxychloroquine and chloroquine may diminish the effects of remdesivir; combined use is not recommended Formal drug interactions studies have not been conducted	Bradycardia Hypotension Increased serum ALT and AST Hypersensitivity reactions Prolonged prothrombin time Nausea	Monitor closely for drug interactions Not recommended if eGFR <30 mL/min due to concern for vehicle (SBECD) accumulation leading to renal or liver injury, however, toxicity was not observed in a retrospective study [34] Discontinue if ALT levels increase to >10 times the upper limit of normal, or if ALT elevation with signs/symptoms of liver injury Most patients should receive a 5 d course; no difference in outcomes with 10 d vs. 5 d
Chloroquine or Hydroxychloroquine (with or without azithromycin)	Hydroxychloroquine a: 800 mg q6h for 2 doses, followed by 400 mg q12h for 9 days or until discharge   Chloroquine: 500 mg PO q12h for 7–14 d   Azithromycin: 500 mg on d 1, then 250 mg once daily on d 2–5 or 500 mg once daily for 7 d	NIH Guidelines: Recommend against use in hospitalized pts (AI) Recommend against use in nonhospitalized pts, except in clinical trial (AIIa) WHO Guidelines: Strongly recommend against for prophylaxis or treatment of COVID-19 (recommendation against) IDSA Guidelines: Recommend against use in hospitalized pts (strong recommendation, moderate certainty) Recommend against use in nonhospitalized pts (strong recommendation, low certainty)	Minor substrate of CYP2D6 QT prolongation with other medications that prolong QT interval May decrease therapeutic effects of remdesivir; avoid combination Increased risk of hemolytic reactions with dapsone May increase levels of digoxin and cyclosporin	QT prolongation Cardiomyopathy Hypersensitivity reactions Hypoglycemia Myopathy Neuropsychiatric effects Retinopathy	Should not be used for hospitalized patients with COVID-19
Ivermectin	100–400 µg/kg daily for up to 5 d	NIH Guidelines: Insufficient data to recommend for or against use for the treatment of COVID-19 WHO Guidelines: Recommend against for treatment of COVID-19 outside of a clinical trial (only in research setting) IDSA Guidelines: Recommend against use in nonhospitalized and hospitalized pts outside of a clinical trial (conditional recommendation, very low certainty)	Minor CYP3A4 and P-glycoprotein substrate	Mazzotti reaction associated with onchocerciasis Cardiovascular (tachycardia, edema) Dizziness Gastrointestinal upset AST/ALT elevations Blood dyscrasias	May be used in patients with COVID-19 receiving immunosuppressive therapy from countries with high prevalence of strongyloidiasis as antihelminthic
Lopinavir/ritonavir	400 mg/100 mg PO q12h for 7–14 d	NIH Guidelines: Recommend against use for nonhospitalized (AIII) and hospitalized (AI) pts WHO Guidelines: Recommend against for treatment of COVID-19 (recommendation against) IDSA Guidelines: Recommend against use in hospitalized pts (strong recommendation, moderate certainty)	Extensive and significant drug interactions exist; review of full drug regimen is recommended prior to use Strong CYP3A4 inhibitor; concentrations of drugs metabolized by CYP3A4 may be increased Anticoagulants Antiplatelet Azole antifungals Calcineurin inhibitors	Gastrointestinal upset Hepatotoxicity Dermatologic Endocrine and metabolic abnormalities CNS adverse effects	Should not be used in the treatment of COVID-19
Anti-SARS-CoV-2 Antibody Products
Monoclonal Antibodies	Bamlanivimab 700 mg plus etesevimab 1400 mg IV as a single dose   Casirivimab 600 mg plus imdevimab 600 mg IV/SQ as a single dose   Sotrovimab 500 mg IV as a single dose	NIH Guidelines: Casirivimab plus imdevimab or sotrovimab recommended for outpatients with mild to moderate COVID-19 who are high-risk as defined by EUA criteria (AIIa for casirivimab plus imdevimab) Recommend against use of bamlanivimab plus etesevimab (AIII) Recommend against use in hospitalized patients outside of a clinical trial (AIIa) WHO Guidelines: Class not addressed IDSA Guidelines: Recommended for ambulatory pts with mild to moderate COVID-19 at high risk for progression to severe disease (conditional recommendation, low certainty)	May decrease the effects of COVID-19 vaccine; postpone administration of COVID-19 vaccine until at least 90 days after treatment	Hypersensitivity reactions Pruritis Injection site reactions Fever	Authorized under FDA EUA Administer in healthcare settings by qualified healthcare professional with access to medications to treat infusion reactions Monitor patient for at least 1-h post-administration Use of bamlanivimab alone and bamlanivimab plus etesevimab is not recommended due to decreased susceptibility of SARS-CoV-2 variants
Convalescent Plasma (CP)	1 unit (approximately 200 mL) of high-titer b CP IV as a single dose; an additional unit may be considered based on prescriber judgement	NIH Guidelines: For hospitalized pts without impaired immunity: recommend against use (AI) For hospitalized pts with impaired immunity: insufficient data to recommend for or against use of high-titer CP For nonhospitalized pts: insufficient data to recommend either for or against use outside of a clinical trial Recommend against use of low-titer CP in any setting WHO Guidelines: Class not addressed IDSA Guidelines: Recommend against use for hospitalized pts (conditional recommendation, low certainty) Recommend only in the context of a clinical trial for ambulatory pts with mild to moderate COVID-19 (knowledge gap)	May decrease the effects of COVID-19 vaccine; postpone administration of COVID-19 vaccine until at least 90 days after treatment	Transfusion reactions	Authorized under the EUA for the treatment of hospitalized patients with COVID-19 and impaired immunity Careful history should be taken for previous transfusion reactions Monitor vital signs before, during, and after infusion Patients with cardiac disease may require lower volume and slower infusion Low-titer CP should not be used
Immunomodulators
Corticosteroids	Dexamethasone: 6 mg IV/PO q24h for 10 d or until hospital discharge   Equivalent daily doses: Prednisone 40 mg Methylprednisolone 32 mg Hydrocortisone 160 mg	NIH Guidelines: Recommended for pts hospitalized and requiring supplemental oxygen (alone BI, with remdesivir BIII) Recommended for pts hospitalized and requiring high-flow oxygen or noninvasive ventilation (alone AI, with remdesivir BIII) Recommended for pts hospitalized and requiring mechanical ventilation or ECMO (AI) WHO Guidelines: Recommended for pts with severe or critical COVID-19 (recommended) Recommended against use for pts with non-severe COVID-19 (conditional recommendation against) IDSA Guidelines: Recommended for pts hospitalized with SpO2 ≤94% on room air or requiring supplemental oxygen (conditional recommendation, moderate certainty) Recommended for pts hospitalized on mechanical ventilation or ECMO (strong recommendation, moderate certainty) Recommend against use for pts with SpO2 >94% not requiring supplemental O2 (conditional recommendation, low certainty)	Major substrate of CYP3A4 Minor substrate of P-gp/ABCB1 Weak inducer of CYP3A4 May decrease the concentration of tacrolimus	Immunosuppression Adrenal insufficiency and suppression Psychiatric disturbances Gastrointestinal issues (increased appetite, peptic ulcers, esophagitis)	Risk of reactivation of latent infections such as strongyloidiasis, HBV, HSV, TB Monitor closely for new secondary infections Co-management of immunosuppression for transplant recipients and COVID19 therapy necessitates a careful balance of minimizing maintenance medications and utilizing evidence based primary treatment Corticosteroids have historically been mainstays of maintenance immunosuppression for transplant recipients and when used to manage pulmonary manifestations of SARS-CoV-2, may also serve as prophylaxis against allograft rejection
Immunoglobulins	500 mg/kg daily for 5 d	NIH Guidelines: Recommend against use of non-SARS-CoV-2-specific IVIG for COVID-19 outside of a clinical trial (AIII) WHO Guidelines: Agent not addressed IDSA Guidelines: Agent not addressed	May interfere with response to COVID-19 vaccination	Thrombosis Hemolysis Renal failure Hypertension Transfusion-related lung injury Flu-like symptoms	Monitor closely for transfusion-related reactions Use of IVIG is appropriate if being used for other indications during COVID-19 illness
Interleukin-6 Inhibitors	Tocilizumab: 8 mg/kg (maximum 800 mg) IV as a single dose	NIH Guidelines: Either baricitinib or tocilizumab is recommended in conjunction with dexamethasone in pts within 3 d of hospitalization who have rapid respiratory decompensation (admitted to ICU within 24 h and require mechanical ventilation, noninvasive ventilation, or high-flow, or have rapidly escalating O2 needs and require noninvasive ventilation or high-flow with a CRP ≥ 75 mg/L) (BIIa) Insufficient evidence to recommend for or against use in hospitalized pts on conventional O2 WHO Guidelines: Agent not addressed IDSA Guidelines: Suggested for pts with progressive severe or critical COVID-19 who have elevated inflammatory markers (i.e., CRP ≥75 mg/L) with corticosteroid (conditional recommendation, low certainty)	May enhance immunosuppressive effects with other immunosuppressive medications May interfere with response to COVID-19 vaccination	Neutropenia Hepatotoxicity Infusion-related reactions Hypertension Headache	The safety of IL-6 inhibitors is unknown in patients who are significantly immunosuppressed; the NIH guidelines recommend against use in this population Serious infections (fungal, bacterial, TB, viral, opportunistic) have occurred in patients receiving long courses of IL-6 inhibitors Consider ivermectin in patients who are receiving tocilizumab and corticosteroid in areas where strongyloidiasis is endemic Drug labeling recommends to avoid in ANC <2000/mm3, plt <100,000/mm3, and AST or ALT >1.5 times ULN
Interleukin-1 Inhibitors	Anakinra 100 mg SQ q12h for 72 h, followed by 100 mg SQ daily for 7 d	NIH Guidelines: Insufficient evidence to recommend for or against use WHO Guidelines: Agent not addressed IDSA Guidelines: Agent not addressed	Additive immunosuppression when used with other immunosuppressive agents	Flu-like symptoms Injection site reactions Gastrointestinal upset Hepatoxicity Anaphylaxis	Avoid in patients on TNF-alpha inhibitors due to increased risk of infection
Kinase Inhibitors	Baricitinib 4 mg PO daily for up to 14 d   Ruxolitinib 5–20 mg PO twice daily, for 14 days	NIH Guidelines: Baricitinib recommended in combination with remdesivir in hospitalized, nonventilated pts on supplemental O2 only if corticosteroids cannot be used (BIIa) Either baricitinib or tocilizumab is recommended in conjunction with dexamethasone in pts within 3 d of hospitalization who have rapid respiratory decompensation (admitted to ICU within 24 h and require mechanical ventilation, noninvasive ventilation, or high-flow, or have rapidly escalating O2 needs and require noninvasive ventilation or high-flow with a CRP ≥ 75 mg/L) (BIIa) Recommend against use of other kinase inhibitors outside of a clinical trial (AIII) WHO Guidelines: Agent not addressed IDSA Guidelines: Baricitinib recommended with remdesivir in pts with severe COVID-19 who cannot receive a corticosteroid (conditional recommendation, low certainty)	Substrate of CYP3A4 (minor), OAT1/3, P-gp/ABCB1 (minor)	Upper respiratory tract infections Herpes simplex and Herpes zoster Nausea Thrombosis Neutropenia, lymphopenia, anemia	Authorized for use with remdesivir under FDA EUA for pts meeting specific criteria Not recommended in patients with severe hepatic impairment Renal dosing required Drug should be discontinued if ALC <200 cells/µL, ANC <500 cells/µL, eGFR <15 mL/min/1.73 m2, or drug-induced liver injury develops Tablets can be dispersed in water
Interferons	Interferon alpha, interferon beta	NIH Guidelines: Recommends against use in pts with severe or critical COVID-19 outside of a clinical trial (AIII) Insufficient data to recommend either for or against use for the treatment of early mild or moderate COVID-19 WHO Guidelines: Agent not addressed IDSA Guidelines: Agent not addressed	No clinically significant drug interactions	Flu-like symptoms Headache Fatigue Myalgia Hepatic injury Psychiatric problems Hematologic abnormalities	Among SOT recipients, the enhancing of the immune response may result in allograft rejection and should be considered a potential risk for this population Mostly studied as nebulization for COVID-19; formulation not approved for use in US

Abbreviations: ALT, alanine aminotransferase; ANC, absolute neutrophil count; AST, aspartate aminotransferase; d, day; ECMO, Extracorporeal membrane oxygenation; eGFR, estimated glomerular filtration rate; EUA, emergency use authorization; FDA, U.S. Food and Drug Administration; GI, gastrointestinal; HBV, Hepatitis B virus; HSV, Herpes Simplex virus; IDSA, Infectious Diseases Society of America; IV, intravenously; NIH, U.S. National Institutes of Health; P-gp, P-glycoprotein; PO, per os (by mouth); pt, patient; SOT, solid organ transplant; TB, tuberculosis; ULN, upper limit of normal; WHO, World Health Organization. Data updated as of August 12, 2021. ^a Mutiple strategies exist. Dosing from RECOVERY Trial is listed in table. ^b High-titer convalescent plasma is defined as a neutralizing antibody titer of ≥250 in the Broad Institute’s neutralizing antibody assay or an S/C cutoff of ≥12 in the Ortho VITROS IgG assay.