Table 2. Characteristics of Potential Antiviral Agents Under Evaluation for Treatment of COVID-19

Last Updated: August 27, 2020

Table 2. Characteristics of Potential Antiviral Agents Under Evaluation for Treatment of COVID-19
Drug Name Dosing Regimens
There are no approved doses for the treatment of COVID-19. 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
Azithromycin
Note: Most studies of COVID-19 use AZM with HCQ.
 AZM 500 mg PO once on Day 1, then AZM 250 mg PO daily on Days 2–5
  • Gastrointestinal effects (e.g., diarrhea, nausea, vomiting)
  • Hepatotoxicity
  • Baseline ECG and follow- up ECG
  • Hepatic panel, SCr, potassium, magnesium

Additive effect with other drugs that prolong the QTc interval (including HCQ and CQ)

  • The Panel recommends against using HCQ plus AZM to treat of COVID-19 except in a clinical trial setting (AIII).
  • Half-life of up to 72 hours
  • A list of clinical trials is available here: Azithromycin
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
  • Gastrointestinal 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
  • Perform G6PD testing; CQ is not recommended in patients with G6PD deficiency. Consider using HCQ instead of CQ while awaiting G6PD test results.
  • 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 for the treatment of COVID-19 in hospitalized patients (AI).
  • In nonhospitalized patients, the Panel recommends against the use of CQ for the treatment of COVID-19, except in a clinical trial (AI).
  • The Panel recommends against using 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
  • Gastrointestinal 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 for to treat COVID-19 outside the setting 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 for the treatment of COVID-19 in hospitalized patients (AI).
  • In nonhospitalized patients, the Panel recommends against the use of HCQ for the treatment of COVID-19, except in a clinical trial (AI).
  • The Panel recommends against using HCQ plus AZM to treat COVID-19, except in a clinical trial (AIII).
  • Long elimination; half-life is 40–55 days.
  • Dose-dependent toxicity
  • A list of clinical trials is available here: Hydroxychloroquine
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 LPV 400 mg/RTV 100 mg per dose) PO twice daily for a total of 7 days
  • Gastrointestinal 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 using LPV/RTV or other HIV PIs to treat COVID-19, except in a clinical trial setting (AI).
  • Liquid formulation is commercially available. Crushing LPV/RTV tablets may result in significantly decreased drug exposure (AUC ↓ 45%).2
  • Use with caution in patients with hepatic impairment.
  • A list of clinical trials is available here: Lopinavir/Ritonavir
Remdesivir

Note: RDV is not approved by the FDA; however, it is available through an EUA,a a clinical trial, or the manufacturer’s emergency access program.

In Patients Who Are Participating in Clinical Trials:
  • Dose according to the clinical trial protocol.

Panel's Recommendations for Adult and Pediatric Patients Weighing ≥40 kg

For Patients With Severe COVID-19 Who Are Not Intubated: 

  • RDV 200 mg IV over 30–120 minutes for 1 dose, followed by RDV 100 mg IV on Day 2 through Day 5 (AI).
For Mechanically Ventilated Patients, Patients on ECMO, and Patients Who Have Not Shown Adequate Improvement After 5 Days of Therapy:
  • There are insufficient data on the optimal duration of therapy for mechanically ventilated patients, patients on ECMO, and patients who have not shown adequate improvement after 5 days of therapy. Some experts extend the total RDV treatment duration to up to 10 days (CIII).

Note: The EUA recommends 10-day therapy for patients on mechanical ventilation or ECMO.

Suggested Dose in EUAa for Pediatric Patients Weighing 3.5 to <40 kg
For Patients Who Require Invasive Mechanical Ventilation and/or ECMO:

  • RDV 5 mg/kg IV over 30–120 minutes for 1 dose on Day 1, followed by RDV 2.5 mg/kg IV daily over 30–120 minutes on Day 2 through Day 10
For Patients Who Do Not Require Invasive Mechanical Ventilation and/or ECMO:
  • RDV 5 mg/kg IV over 30–120 minutes for 1 dose on Day 1, followed by RDV 2.5 mg/kg IV daily over 30–120 minutes on Day 2 through Day 5. If there is no clinical improvement,  treatment may be extended for up to 5 additional days (for a total treatment duration of 10 days).
  • Transient elevations in ALT or AST levels (Grade 1 or 2), typically after multiple days of therapy3
  • Mild, reversible PT prolongation without INR change or hepatic effects3
  • Drug vehicle is SBECD, which has been associated with renal toxicity. SBECD accumulation may occur in patients with moderate or severe renal impairment.
  • Gastrointestinal symptoms (e.g., nausea, vomiting)
  • Monitor for infusion reactions.
  • Renal and hepatic function
  • Do not administer RDV if eGFR is <30 mL/min (or if patient is receiving dialysis), or if ALT or AST is >5 times ULN
  • Clinical studies of drug-drug interactions for RDV have not been conducted.
  • RDV levels are unlikely to be substantially altered by CYP2C8, CYP2D6, or CYP3A4 enzymes, or by P-gp or OATP drug transporters.
  • RDV may be administered with weak to moderate inducers or with strong inhibitors of CYP450, OATP, or P-gp.
  • Strong induction may modestly reduce RDV levels. The clinical relevance of lower RDV levels is unknown. Based on information provided by Gilead (written communication, July 2020), the use of RDV with strong inducers (e.g., rifampin) is not recommended.
  • Minimal to no reduction in RDV exposure is expected when RDV is coadministered with dexamethasone.
  • CQ or HCQ may decrease the antiviral activity of RDV; coadministration of these drugs is not recommended.
Recommendation for Prioritizing Limited Supplies of RDV:
  • Because RDV supplies are limited, the Panel recommends prioritizing RDV for use in hospitalized patients with COVID-19 who require supplemental oxygen but who do not require oxygen delivery through a high-flow device, noninvasive ventilation, invasive mechanical ventilation, or ECMO (BI).
Recommendation for Patients with Mild or Moderate COVID-19:
  • There are insufficient data for the Panel to recommend either for or against the use of RDV in patients with mild or moderate COVID-19.
Recommendations for Patients With COVID-19 Who Require Supplemental Oxygen:
For Patients Who Do Not Require Oxygen Delivery Through a High-Flow Device, Noninvasive Ventilation, Invasive Mechanical Ventilation, or ECMO:
  • The Panel recommends using RDV for 5 days or until hospital discharge, whichever comes first (AI).
  • If a patient who is on supplemental oxygen while receiving RDV progresses to requiring delivery of oxygen through a high-flow device, noninvasive ventilation, invasive mechanical ventilation, or ECMO, the course of RDV should be completed.
For Patients Who Require Oxygen Delivery Through a High-Flow Device, Noninvasive Ventilation, Invasive Mechanical Ventilation, or ECMO:
  • Because there is uncertainty regarding whether starting RDV confers clinical benefit in these groups of patients, the Panel cannot make a recommendation either for or against starting RDV.
Duration of Therapy for Patients Who Have Not Shown Clinical Improvement After 5 Days of Therapy:
  • There are insufficient data on the optimal duration of RDV therapy for patients with COVID-19 who have not shown clinical improvement after 5 days of therapy. In this group, some experts extend the total RDV treatment duration to up to 10 days (CIII).
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