KEY CLINICAL UPDATE IN ANTIVIRAL CHEMOTHERAPY
Several compounds can influence viral replication and the development of viral disease. For current information about the treatment of SARS-CoV-2, see Chapter 32.
AGENTS FOR INFLUENZA AND OTHER RESPIRATORY VIRAL INFECTIONS
Amantadine (and rimantadine) are active against influenza A (but not influenza B) and previously have been effective both as prophylaxis and therapy. However, the high rate of emerged influenza resistance has resulted in amantadine (and rimantadine) being no longer recommended in the treatment of influenza. Yearly immunization against influenza is the primary intervention for disease prevention.
Neuraminidase inhibitors, including zanamivir inhalation and oseltamivir tablets, are effective in the prevention and treatment of influenza A and B and are also active against the avian influenza virus. Peramivir is an intravenous neuraminidase inhibitor approved for the treatment of influenza. Insufficient data exist to evaluate the clinical efficacy of peramivir against influenza B. The majority of influenza A H1N1 viruses tested for drug resistance have been susceptible to oseltamivir, zanamivir, and peramivir but resistant to the adamantanes (amantadine, rimantadine). Thus, choices for oral therapy center upon oseltamivir and zanamivir. To date, all oseltamivir-resistant isolates have been zanamivir-susceptible. As with amantadine and rimantadine, the neuraminidase inhibitors must be administered soon (within 48 hours) after the onset of symptoms to be effective. Zanamivir inhalers are difficult to use for some patients, especially those with asthma and chronic obstructive pulmonary disease, in whom bronchospasm has been reported.
Gastrointestinal adverse events are the most commonly observed side effects with oseltamivir. In addition, while cause and effect are not well-established, neuropsychiatric disorders, including suicidal ideation, have been associated with oseltamivir. Both medications are administered twice daily (oseltamivir 75 mg orally; zanamivir 10 mg inhalation) for 5 days when used for therapy; however, up to 150 mg of oseltamivir twice daily has been recommended for more severe disease. Both agents reduce the duration of symptoms by only 1 day and viral shedding by 2 days. However, treatment of critically ill patients initiated within 5 days after symptom onset has been associated with decreased mortality. Both agents also effectively prevent disease in household contacts when administered prophylactically (oseltamivir 75 mg orally once daily, zanamivir 10 mg inhaled once daily) for 7 days. Critically ill patients, in most instances, are unable to receive antiviral agents via the oral or inhaled route of administration. Peramivir, an intravenous antiviral, is available as a single dose. It is as effective as, but more expensive than, oral oseltamivir.
Baloxavir marboxil is a small-molecule prodrug approved for the treatment of uncomplicated influenza and postexposure prophylaxis of influenza A or B. Baloxavir marboxil is hydrolyzed to an active form, baloxavir, which inhibits influenza polymerase acidic endonuclease to halt replication of influenza A and B. With this unique mechanism of action, baloxavir is not influenced by adamantane or neuraminidase resistance. However, resistance to baloxavir has been detected. Baloxavir marboxil is ...