Treating influenza using substituted polycyclic pyridone derivatives and prodrugs thereof in a subject having influenza and a severe influenza condition

A method for treating an influenza virus infection, comprising:

• reading a dosage instruction on a package insert or in a package of a pharmaceutical formulation comprising a compound (A) having one of following formula (1) or formula (2):
• or a pharmaceutically acceptable salt thereof, and a compound (B) that is at least one neuraminidase inhibitor;
• and
• administering the pharmaceutical formulation to a subject that:
• (1) has an influenza virus infection,
• (2) has been symptomatic of the influenza virus infection for no more than 96 hours, and
• (3) further has at least one severe influenza condition selected from the group consisting of:
• (a) being hospitalized due to the influenza virus infection,
• (b) requiring an extension of hospitalization because of acquiring the influenza virus infection during the hospitalization,
• (c) having a National Early Warning Score 2 of four or more,
• (d) being on support for respiration, and
• (e) having at least one complication attributable to the influenza virus infection that necessitates hospitalization.

A pharmaceutical composition for treating a subject that:

• (1) has an influenza virus infection,
• (2) has been symptomatic of the influenza virus infection for no more than 96 hours, and
• (3) further has at least one severe influenza condition selected from the group consisting of:
• (a) being hospitalized due to influenza virus infection,
• (b) requiring an extension of hospitalization because of acquiring the influenza virus infection during the hospitalization,
• (c) having a National Early Warning Score 2 of four or more,
• (d) being on support for respiration, and
• (e) having at least one complication attributable to the influenza virus infection that necessitates hospitalization
• wherein the pharmaceutical composition comprises the compound (A) and the compound (B),
• the treatment comprises administering an effective amount of a compound (A) and an effective amount of a compound (B) to the subject,
• the compound (A) has one of following formula (1) or formula (2):
• or a pharmaceutically acceptable salt thereof, and
• the compound (B) is at least one neuraminidase inhibitor.

A package, comprising:

• a pharmaceutical formulation comprising a compound (A) having one of following formula (1) or formula (2):
• or a pharmaceutically acceptable salt thereof, and a compound (B) that is at least one neuraminidase inhibitor;
• and
• a dosage instruction on a package insert or in the package for administering the pharmaceutical formulation to a subject that:
• (1) has an influenza virus infection,
• (2) has been symptomatic of the influenza virus infection for no more than 96 hours, and
• (3) further has at least one severe influenza condition selected from the group consisting of:
• (a) being hospitalized due to the influenza virus infection,
• (b) requiring an extension of hospitalization because of acquiring the influenza virus infection during the hospitalization,
• (c) having a National Early Warning Score 2 of four or more,
• (d) being on support for respiration, and
• (e) having at least one complication attributable to the influenza virus infection that necessitates hospitalization.