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

Last Updated: June 16, 2020

Table 2b. 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
(When Used with Hydroxychloroquine)
 500 mg PO once on Day 1, then 250 mg PO daily on Days 2–5
  • Gastrointestinal effects (e.g., diarrhea, nausea, vomiting)
  • Hepatotoxicity
  • Baseline/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 the use of HCQ plus AZM for the treatment 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:
  • 1 gm PO once on Day 1, then 500 mg PO once daily for 4–7 days of total treatment 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/follow-up ECG if CQ is given with concomitant 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, except in a clinical trial (AII).
  • 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
  • CQ is not commercially available in the United States
  • 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:
  • 800 mg PO once on Day 1, then 400 mg PO once daily for 4–7 days of total treatment 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 the use of 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 concomitant QTc-prolonging drugs (e.g., AZM) or if the patient has underlying cardiac diseases
  • Additive effect with other drugs that prolong the QTc interval (including AZM) or cause hypoglycemia
  • CYP2D6 inhibitor (moderate)
  • P-gp inhibitor
  • The Panel recommends against HCQ for the treatment of COVID-19, except in a clinical trial (AII).
  • The Panel recommends against the use of HCQ plus AZM for the treatment of 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/r 400 mg/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/r 400 mg/100 mg per dose) PO twice daily for a total of 7 days
  • 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/r is given with other QTc-prolonging medications.
High Drug Interaction Potential
Lopinavir:
  • CYP3A4 inhibitor and substrate
Ritonavir:
  • CYP3A4 > 2D6 substrate
  • Potent CYP3A4 and 2D6 inhibitor
  • Inducer of UGT1A1 and CYPs 1A2, 2C8, 2C9, and 2C19
  • The Panel recommends against the use of LPV/r and other HIV PIs for the treatment of COVID-19, except in a clinical trial setting (AI).
  • Liquid formulation is commercially available. Crushing LPV/r 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
Investigational drug.

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

In Patients Who are Participating in Clinical Trials:
  • Dose according to 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 one 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 EUAb for Pediatric Patients Weighing 3.5 to <40 kg
Requiring Invasive Mechanical Ventilation and/or ECMO:

  • RDV 5 mg/kg mg IV over 30–120 minutes for one dose on Day 1, followed by RDV 2.5 mg/kg IV daily over 30–120 minutes on Day 2 through Day 10
Not Requiring Invasive Mechanical Ventilation and/or ECMO:
  • RDV 5 mg/kg mg IV over 30–120 minutes for one dose on Day 1, followed by RDV 2.5 mg/kg IV daily over 30–120 minutes on Day 2 through Day 5. If no clinical improvement, may extend treatment 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. Potential for SBECD accumulation in patients with moderate to severe renal impairment
  • Gastrointestinal symptoms (e.g., nausea, vomiting)
  • Monitor for infusion reactions.
  • Renal and hepatic function
  • Do not administer RDV if eGFR <30 mL/min (or if patient is receiving dialysis), or if ALT or AST is >5 times ULN
  • RDV levels are unlikely to be markedly 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 of P-gp is expected to modestly reduce RDV levels. The clinical relevance of lower RDV levels is unknown. The use of RDV with known inducers of P-gp (e.g., rifampin) is not recommended.
For Patients with Severe COVID-19:
  • The Panel recommends RDV for treatment of COVID-19 in hospitalized patients with SpO2 ≤94% on ambient air (at sea level) or those who require supplemental oxygen (AI), and in patients who are on mechanical ventilation or ECMO (BI).
For Patients with Mild to Moderate COVID-19:
  • There are insufficient data to recommend for or against RDV for the treatment of patients with mild or moderate COVID-19.
Availability:
  • RDV is available through an EUAb for the treatment of hospitalized adults and children with severe COVID-19.
  • RDV is also available for other patient populations through expanded access and compassionate use programs.
  • A list of clinical trials is available here: Remdesivir