Summary of different COVID-19 therapeutic modalities
| Drug . | Indication . | Mechanism of action . | Dosage and administration . | Special consideration . |
|---|---|---|---|---|
| Baricitinib | Hospitalized with increasing oxygen requirement and increased inflammatory markers | JAK inhibitor | 4 mg PO once daily up to 14 d or until hospital discharge | • Needs to be dose-adjusted according to creatinine clearance • Administer in conjunction with corticosteroids • Avoid combination with IL-6/IL-6 receptor inhibitors because of increased risk of infections |
| Bebtelovimab | Nonhospitalized patients with mild to moderate infection | Recombinant neutralizing human mAb that binds to the spike protein of SARS-CoV-2 | 175 mg IV as a single dose | • Administer as soon as possible after a positive SARS-CoV-2 test and within 7 d of symptoms |
| Dexamethasone | Hospitalized with hypoxia (oxygen saturation <94% on room air) | Decreases inflammation and inflammatory mediators | 6 mg IV or PO once daily for up to 10 d or until hospital discharge | • If dexamethasone is not available, an equivalent dose of other corticosteroids may be used |
| Molnupiravir | Nonhospitalized patients at high risk of disease progression | Nucleoside analog prodrug of N-hydroxycytidine, which is incorporated into the viral RNA and leads to the accumulation of deleterious errors in the viral genome and inhibition of viral replication | 800 mg every 12 h for 5 d | • Limited efficacy; consider using if ritonavir-boosted nirmatrelvir or remdesivir are unavailable • Initiate as soon as possible after COVID-19 diagnosis and within 5 d of symptom onset |
| Remdesivir | Hospitalized and nonhospitalized patients at high risk of disease progression | Nucleotide prodrug of an adenosine analog that binds to the viral RNA-dependent RNA polymerase and inhibits viral replication by terminating RNA transcription prematurely | Nonhospitalized patients: 200 mg IV once, followed by 100 mg once daily on days 2 and 3 Hospitalized patients: 200 mg IV once, followed by 100 mg IV once daily for a total duration of 5 d or until hospital discharge, whichever is first, but may extend to up to 10 d in certain patients without substantial clinical improvement by day 5 | • Complete 10-d course for more severe illness • Consider using remdesivir solution over the lyophilized powder formulation in patients with renal impairment (the former contains less SBECD, which is primarily eliminated by the kidneys) |
| Ritonavir-boosted nirmatrelvir | Nonhospitalized patients at high risk of disease progression | Protease inhibitor active against MPRO, the main SARS-CoV-2 protease, resulting in inhibition of viral replication | 300 mg of nirmatrelvir with 100 mg of ritonavir, administered together twice daily for 5 d* | • Extensive drug–drug interactions • Initiate as soon as possible after COVID-19 diagnosis and within 5 d of symptom onset |
| Sarilumab | Hospitalized with increasing oxygen requirement and increased inflammatory markers | Anti–IL-6 receptor inhibitor leading to a reduction in cytokines and acute phase reactant production | Reconstitute the 400-mg single-dose prefilled subcutaneous syringe in 100 cc 0.9% NaCl IV infusion over 1 h | • Use as an alternative drug if tocilizumab is not available • Use the single-dose, prefilled syringe (not the prefilled pen) |
| Tixagevimab and cilgavimab | Preexposure prophylaxis | Combination of 2 human mAbs targeted against the surface spike protein of SARS-CoV-2 | 300 mg/300 mg of tixagevimab and cilgavimab as a single dose (administered in 2 separate IM syringes consecutively) | • Platelet count preferably >20 K/mcL since it is an IM injection |
| Tocilizumab | Hospitalized with increasing oxygen requirement and increased inflammatory markers | Anti–IL-6 receptor inhibitor leading to a reduction in cytokines and acute phase reactant production | 8 mg/kg actual body weight (up to 800 mg) as a single IV dose | • Avoid combination with JAK inhibitors • Consider a second dose 8 h after the first dose if no clinical improvement |
| Tofacitinib | Hospitalized with increasing oxygen requirements and increased inflammatory markers | JAK inhibitor | 10 mg PO twice daily up to 14 d or until hospital discharge | • Use as an alternative drug if baricitinib is not available • Needs to be dose-adjusted according to creatinine clearance |
| Drug . | Indication . | Mechanism of action . | Dosage and administration . | Special consideration . |
|---|---|---|---|---|
| Baricitinib | Hospitalized with increasing oxygen requirement and increased inflammatory markers | JAK inhibitor | 4 mg PO once daily up to 14 d or until hospital discharge | • Needs to be dose-adjusted according to creatinine clearance • Administer in conjunction with corticosteroids • Avoid combination with IL-6/IL-6 receptor inhibitors because of increased risk of infections |
| Bebtelovimab | Nonhospitalized patients with mild to moderate infection | Recombinant neutralizing human mAb that binds to the spike protein of SARS-CoV-2 | 175 mg IV as a single dose | • Administer as soon as possible after a positive SARS-CoV-2 test and within 7 d of symptoms |
| Dexamethasone | Hospitalized with hypoxia (oxygen saturation <94% on room air) | Decreases inflammation and inflammatory mediators | 6 mg IV or PO once daily for up to 10 d or until hospital discharge | • If dexamethasone is not available, an equivalent dose of other corticosteroids may be used |
| Molnupiravir | Nonhospitalized patients at high risk of disease progression | Nucleoside analog prodrug of N-hydroxycytidine, which is incorporated into the viral RNA and leads to the accumulation of deleterious errors in the viral genome and inhibition of viral replication | 800 mg every 12 h for 5 d | • Limited efficacy; consider using if ritonavir-boosted nirmatrelvir or remdesivir are unavailable • Initiate as soon as possible after COVID-19 diagnosis and within 5 d of symptom onset |
| Remdesivir | Hospitalized and nonhospitalized patients at high risk of disease progression | Nucleotide prodrug of an adenosine analog that binds to the viral RNA-dependent RNA polymerase and inhibits viral replication by terminating RNA transcription prematurely | Nonhospitalized patients: 200 mg IV once, followed by 100 mg once daily on days 2 and 3 Hospitalized patients: 200 mg IV once, followed by 100 mg IV once daily for a total duration of 5 d or until hospital discharge, whichever is first, but may extend to up to 10 d in certain patients without substantial clinical improvement by day 5 | • Complete 10-d course for more severe illness • Consider using remdesivir solution over the lyophilized powder formulation in patients with renal impairment (the former contains less SBECD, which is primarily eliminated by the kidneys) |
| Ritonavir-boosted nirmatrelvir | Nonhospitalized patients at high risk of disease progression | Protease inhibitor active against MPRO, the main SARS-CoV-2 protease, resulting in inhibition of viral replication | 300 mg of nirmatrelvir with 100 mg of ritonavir, administered together twice daily for 5 d* | • Extensive drug–drug interactions • Initiate as soon as possible after COVID-19 diagnosis and within 5 d of symptom onset |
| Sarilumab | Hospitalized with increasing oxygen requirement and increased inflammatory markers | Anti–IL-6 receptor inhibitor leading to a reduction in cytokines and acute phase reactant production | Reconstitute the 400-mg single-dose prefilled subcutaneous syringe in 100 cc 0.9% NaCl IV infusion over 1 h | • Use as an alternative drug if tocilizumab is not available • Use the single-dose, prefilled syringe (not the prefilled pen) |
| Tixagevimab and cilgavimab | Preexposure prophylaxis | Combination of 2 human mAbs targeted against the surface spike protein of SARS-CoV-2 | 300 mg/300 mg of tixagevimab and cilgavimab as a single dose (administered in 2 separate IM syringes consecutively) | • Platelet count preferably >20 K/mcL since it is an IM injection |
| Tocilizumab | Hospitalized with increasing oxygen requirement and increased inflammatory markers | Anti–IL-6 receptor inhibitor leading to a reduction in cytokines and acute phase reactant production | 8 mg/kg actual body weight (up to 800 mg) as a single IV dose | • Avoid combination with JAK inhibitors • Consider a second dose 8 h after the first dose if no clinical improvement |
| Tofacitinib | Hospitalized with increasing oxygen requirements and increased inflammatory markers | JAK inhibitor | 10 mg PO twice daily up to 14 d or until hospital discharge | • Use as an alternative drug if baricitinib is not available • Needs to be dose-adjusted according to creatinine clearance |
IM, intramuscular; JAK, Janus kinase; PO, by mouth; SBECD, sulfobutylether-beta-cyclodextrin sodium.
Refer to the ritonavir-boosted nirmatrelvir package insert for dose adjustment for renal and hepatic impairment.91