Mechanism of action Target Virus Resistance Formulation Applicability to critically ill patients
Amantadine M2 ion channel blockers Influenza A High levels of resistance Oral Not recommended
Rimantadine M2 ion channel blockers Influenza A High levels of resistance Oral Not recommended
Oseltamivir Neuraminidase inhibitor(NAI) Influenza A and B Uncommon (1-3% of circulating isolates) but higher for treatment-emergent in critically ill and immunocompromised Oral Needs dose adjustment in patients with renal impairment
No dose adjustment is necessary in patients with mild to moderate hepatic impairment
Extemporaneous formulation possible or gastric delivery in intubated patients
Zanamivir NAI Influenza A and B Rare Intravenous; nebulized solution (investigational); inhaled dry powder (commercial formulation) Inhibitory for most strains resistant to oseltamivir
Nebulized formulation (investigational) with limited use in severely ill patients
Limited systemic absorption and distribution to extrapulmonary sites of inhaled commercial product
Lactose-containing powder commercial preparation with lactose carrier should not be given nebulized as it may cause ventilator circuit obstruction
Intravenous formulation similar in efficacy to oseltamivir in hospitalized patients.
Intravenous zanamivir is approved by the European Medicines Agency (EMA)
Peramivir NAI Influenza A and B Uncommon (see oseltamivir above) Intravenous Intravenous formulation (multiple doses) similar in efficacy to oseltamivir in hospitalized patients
Peramivir is approved by the FDA and EMA for uncomplicated influenza
Laninamivir NAI Influenza A and B Rare Inhaled, single dose, long acting Not suitable for mechanically ventilated patients.
Approved in Japan only
Favipiravir Polymerase inhibitor (PB1 transcriptase), viral mutagen Influenza A, B and other RNA viruses Not seen in clinical strains Oral Under study in hospitalized patients in combination with NAIs
Teratogenicity risk
PK altered in critically ill with reduced drug exposure– appropriate dose regimen uncertain
Approved only for stockpiling in Japan
Baloxavir Polymerase inhibitor (PA cap-dependent endonuclease) Influenza A, B Treatment-emergence resistance common with monotherapy Oral Under study (multiple-dose) in combination with NAIs in hospitalized patients
Not studied and PK uncertain in critically ill patients
Inhibitory for strains resistant to M2Is and/or NAIs
At present, baloxavir is approved in the US, Japan, and over eight other countries
Nitazoxanide Host-directed and influenza HA Influenza and other RVIs Not seen in clinical strains Oral Not effective in hospitalized SARI patients. Not recommended.
Ribavirin Host-directed effects, transcriptase inhibitor, viral mutagen RSV, influenza, measles other RVIs Not seen in clinical strains Aerosolized, oral, intravenous (investigational) Aerosol formulation approved in RSV-infected children but of uncertain value.
All 3 formulations have been used in treating RSV-infected HSCT and SOT patients
Anecdotal use of systemic ribavirin in severe measles and other paramyxovirus infections
Not recommended in combination with interferons for MERS
Teratogenicity risk
Aerosol delivery presents risk of healthcare worker exposure
Cidofovir DNA polymerase inhibitor Adenovirus Intravenous Anecdotal use in severe adenovirus infections and in immunocompromised patients
Acyclovir DNA polymerase inhibitor VZV, HSV Uncommon except in immunocompromised Intravenous, oral Intravenous recommended in VZV pneumonia; addition of systemic corticosteroids recommended by some experts