Table 2d. Characteristics of Antiviral Agents That Are Approved or Under Evaluation for the Treatment of COVID-19

Last Updated: February 11, 2021

Table 2d. Characteristics of Antiviral Agents That Are Approved or Under Evaluation for Treatment of COVID-19
Dosing Regimens
The doses listed here are for approved indications or from reported experiences or clinical trials.
Adverse Effects Monitoring Parameters Drug-Drug Interaction Potential Panel’s Recommendations, Comments, and Links to Clinical Trials
Chloroquine
Dose Previously Suggested in an EUA for Adults and Adolescents Weighing ≥50 kg:
  • CQ 1 g PO once on Day 1, then CQ 500 mg PO once daily for 4–7 days of total treatment. Treatment duration should be based on clinical evaluation.
  • Prolonged QTc interval, Torsades de Pointes, AV block, ventricular arrhythmia
  • GI effects (e.g., nausea, vomiting, diarrhea)
  • Hepatitis
  • Hypoglycemia
  • Hemolysis (especially in patients with G6PD deficiency)
  • Myopathy
  • Rash
  • Given the risk of heart rhythm problems, the FDA cautions against using CQ to treat COVID-19 outside of a hospital or a clinical trial.1
  • CBC, hepatic panel, blood glucose, SCr, potassium, magnesium
  • Baseline ECG
  • Follow-up ECG if CQ is given with QTc-prolonging drugs or if the patient has underlying cardiac disease
  • Additive effect with other drugs that prolong the QTc interval (including AZM) or that cause hypoglycemia
  • CYP2D6 inhibitor (moderate)
  • P-gp inhibitor
  • The Panel recommends against the use of CQ with or without AZM for the treatment of COVID-19 in hospitalized patients (AI).
  • In nonhospitalized patients, the Panel recommends against the use of CQ with or without AZM for the treatment of COVID-19, except in a clinical trial (AIIa).
  • The Panel recommends against the use of high-dose CQ (600 mg twice daily for 10 days) for the treatment of COVID-19 (AI).
  • Dose-dependent toxicity
  • A list of clinical trials is available here: Chloroquine
Hydroxychloroquine
Adults:
  • Various loading and maintenance doses have been reported in studies or in clinical care.
Dose Previously Suggested in an EUA for Hospitalized Adults and Adolescents Weighing ≥50 kg:
  • HCQ 800 mg PO once on Day 1, then HCQ 400 mg PO once daily for 4–7 days of total treatment. Treatment duration should be based on clinical evaluation.
  • Prolonged QTc interval, Torsades de Pointes, AV block, ventricular arrhythmia
  • GI effects (e.g., nausea, vomiting, diarrhea)
  • Hepatitis
  • Hypoglycemia
  • Myopathy
  • Anxiety, agitation, hallucinations, psychosis
  • Allergic reaction/rash
  • Given the risk of heart rhythm problems, the FDA cautions against using HCQ to treat COVID-19 outside of a hospital or a clinical trial.1
  • CBC, hepatic panel, blood glucose, SCr, potassium, magnesium
  • Baseline ECG
  • Follow-up ECG if HCQ is given with QTc-prolonging drugs (e.g., AZM) or if the patient has underlying cardiac disease
  • Additive effect with other drugs that prolong the QTc interval (including AZM) or that cause hypoglycemia
  • CYP2D6 inhibitor (moderate)
  • P-gp inhibitor
  • The Panel recommends against the use of HCQ with or without AZM for the treatment of COVID-19 in hospitalized patients (AI).
  • In nonhospitalized patients, the Panel recommends against the use of HCQ with or without AZM for the treatment of COVID-19, except in a clinical trial (AIIa).
  • Long elimination; half-life is 40–55 days.
  • Dose-dependent toxicity
  • A list of clinical trials is available here: Hydroxychloroquine
Ivermectin
Adults:
  • The dose most commonly used in clinical trials is IVM 0.2–0.6 mg/kg given as a single dose or as a once-daily dose for up to 5 days.
  • Generally well tolerated
  • Dizziness
  • Pruritis
  • GI effects (e.g., nausea, diarrhea)
  • Neurological AEs have been reported with the use of IVM for the treatment of parasitic diseases, but it is not clear whether these AEs were caused by IVM or the underlying conditions.
  • Monitor for potential AEs.
  • Minor CYP3A4 substrate
  • P-gp substrate
  • There are insufficient data for the Panel to recommend either for or against the use of IVM for the treatment of COVID-19.
  • Generally given on an empty stomach with water; however, administering IVM with food increases its bioavailability.2
  • A list of clinical trials is available here: Ivermectin
Lopinavir/Ritonavir
Adults:
  • LPV 400 mg/RTV 100 mg PO twice daily for 10–14 days
Neonates Aged ≥14 Days with a PMA ≥42 Weeks and Children Aged <18 Years:
  • LPV 300 mg/m2 plus RTV 75 mg/m2 (maximum dose LPV 400 mg/RTV 100 mg) PO twice daily for a total of 7 days
  • GI effects (e.g., nausea, vomiting, diarrhea)
  • Transaminase elevation
  • QTc interval prolongation and Torsades de Pointes have been reported.
  • PR interval prolongation
  • HIV antigen/antibody testing at baseline
  • Serum transaminase levels
  • Consider monitoring ECG when LPV/RTV is given with other QTc-prolonging medications.
High Drug-Drug Interaction Potential
Lopinavir:
  • CYP3A4 inhibitor and substrate
Ritonavir:
  • CYP3A4 > CYP2D6 substrate
  • Potent CYP3A4 and CYP2D6 inhibitor
  • Inducer of UGT1A1 and CYP1A2, CYP2C8, CYP2C9, and CYP2C19
  • The Panel recommends against the use of LPV/RTV for the treatment of COVID-19 in hospitalized patients (AI).
  • The Panel recommends against the use of LPV/RTV for the treatment of COVID-19 in nonhospitalized patients (AIII).
  • Liquid formulation is commercially available. Crushing LPV/RTV tablets may result in significantly decreased drug exposure (AUC ↓ 45%).3
  • Use with caution in patients with hepatic impairment.
  • A list of clinical trials is available here: Lopinavir/Ritonavir
Remdesivir

For Hospitalized Adult and Pediatric Patients (Aged ≥12 Years and Weighing ≥40 kg)

For Patients Who Are Not Mechanically Ventilated and/or on ECMO:

  • RDV 200 mg IV over 30–120 minutes on Day 1, followed by RDV 100 mg IV on Day 2 through Day 5
  • In patients who have not shown clinical improvement after 5 days of therapy, treatment may be extended up to 10 days.

For Mechanically Ventilated Patients and/or Patients on ECMO:

  • RDV 200 mg IV over 30–120 minutes on Day 1, followed by RDV 100 mg IV on Day 2 through Day 10

Suggested Dose in EUAa for Hospitalized Pediatric Patients Weighing 3.5 kg to <40 kg or Aged <12 Years and Weighing ≥3.5 kg

For Patients Weighing 3.5 kg to <40 kg:

  • RDV 5 mg/kg IV over 30–120 minutes on Day 1, followed by RDV 2.5 mg/kg once daily starting on Day 2
  • For patients who are not mechanically ventilated and/or on ECMO, the recommended treatment duration is 5 days. If patients have not shown clinical improvement after 5 days of therapy, treatment may be extended up to 10 days.
  • For mechanically ventilated patients and/or patients on ECMO, the recommended treatment duration is 10 days.

For Patients Aged <12 Years and Weighing ≥40 kg:

  • Same dose as for adults and children aged ≥12 years and weighing >40 kg
  • Nausea
  • ALT and AST elevations
  • Hypersensitivity
  • Increases in prothrombin time
  • Drug vehicle is SBECD, which has been associated with renal toxicity. SBECD accumulation may occur in patients with moderate or severe renal impairment.
  • Each 100 mg vial of RDV lyophilized powder contains 3 g of SBECD and each 100 mg/20 mL vial of RDV solution contains 6 g of SBECD.
  • Infusion reactions
  • Renal function, hepatic function, and prothrombin time should be monitored before and during treatment as clinically indicated.
  • Not recommended if eGFR is <30 mL/min
  • RDV may need to be discontinued if ALT levels increase to >10 times the ULN and should be discontinued if there is an increase in ALT level and signs or symptoms of liver inflammation are observed.4
  • Clinical drug-drug interaction studies of RDV have not been conducted.
  • In vitro, RDV is a substrate of CYP3A4, OATP1B1, and P-gp and an inhibitor of CYP3A4, OATP1B1, OATP1B3, and MATE1.4
  • Minimal to no reduction in RDV exposure is expected when RDV is coadministered with dexamethasone (Gilead Sciences, written communication, July 2020).
  • CQ or HCQ may decrease the antiviral activity of RDV; coadministration of these drugs is not recommended.4
  • No significant interaction is expected between RDV and oseltamivir or baloxavir (Gilead Sciences, personal and written communications, August and September 2020).
  • See Therapeutic Management of Patients with COVID-19 for recommendations on using RDV with or without dexamethasone.
  • RDV should be administered in a hospital or a health care setting that can provide a similar level of care to an inpatient hospital.
Availability:
  • RDV is approved by the FDA for the treatment of COVID-19 in hospitalized adult and pediatric patients (aged ≥12 years and weighing ≥40 kg).
  • An EUAa is available for hospitalized pediatric patients weighing 3.5 kg to <40 kg or aged <12 years and weighing ≥3.5 kg.
  • A list of clinical trials is available here: Remdesivir