Oseltamivir Phosphate

Oseltamivir phosphate for oral suspension is an influenza neuraminidase inhibitor (NAI) indicated for:

• Treatment of acute, uncomplicated influenza A and B in patients 2 weeks of age and older who have been symptomatic for no more than 48 hours.  (
  1.1 Treatment of Influenza

  Oseltamivir phosphate for oral suspension is indicated for the treatment of acute, uncomplicated illness due to influenza A and B infection in patients 2 weeks of age and older who have been symptomatic for no more than 48 hours.
  )
• Prophylaxis of influenza A and B in patients 1 year and older. (
  1.2 Prophylaxis of Influenza

  Oseltamivir phosphate for oral suspension is indicated for the prophylaxis of influenza A and B in patients 1 year and older.
  )

• Not a substitute for annual influenza vaccination. (
  1.3 Limitations of Use

  • Oseltamivir phosphate for oral suspension is not a substitute for early influenza vaccination on an annual basis as recommended by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices.
  • Influenza viruses change over time. Emergence of resistance substitutions could decrease drug effectiveness. Other factors (for example, changes in viral virulence) might also diminish clinical benefit of antiviral drugs. Prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use oseltamivir phosphate for oral suspension
    [see Microbiology (12.4)]
    .
  • Oseltamivir phosphate for oral suspension is not recommended for patients with end‐stage renal disease not undergoing dialysis
    [see Dosage and Administration (2.4)and Use in Specific Populations (8.6)].
  )
• Consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use. (
  1.3 Limitations of Use

  • Oseltamivir phosphate for oral suspension is not a substitute for early influenza vaccination on an annual basis as recommended by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices.
  • Influenza viruses change over time. Emergence of resistance substitutions could decrease drug effectiveness. Other factors (for example, changes in viral virulence) might also diminish clinical benefit of antiviral drugs. Prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use oseltamivir phosphate for oral suspension
    [see Microbiology (12.4)]
    .
  • Oseltamivir phosphate for oral suspension is not recommended for patients with end‐stage renal disease not undergoing dialysis
    [see Dosage and Administration (2.4)and Use in Specific Populations (8.6)].
  )
• Not recommended for patients with end‐stage renal disease not undergoing dialysis. (
  1.3 Limitations of Use

  • Oseltamivir phosphate for oral suspension is not a substitute for early influenza vaccination on an annual basis as recommended by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices.
  • Influenza viruses change over time. Emergence of resistance substitutions could decrease drug effectiveness. Other factors (for example, changes in viral virulence) might also diminish clinical benefit of antiviral drugs. Prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use oseltamivir phosphate for oral suspension
    [see Microbiology (12.4)]
    .
  • Oseltamivir phosphate for oral suspension is not recommended for patients with end‐stage renal disease not undergoing dialysis
    [see Dosage and Administration (2.4)and Use in Specific Populations (8.6)].
  )

• Adults and adolescents (13 years and older): 75 mg twice daily for 5 days (
  2.2 Recommended Dosage for Treatment of Influenza

  Initiate treatment with oseltamivir phosphate for oral suspension within 48 hours of influenza symptom onset.

  
  
  

  Adults and Adolescents (13 years of age and older)

  
  
  

  The recommended oral dosage of oseltamivir phosphate for oral suspension for treatment of influenza in adults and adolescents 13 years and older is 75 mg twice daily (12.5 mL of oral suspension twice daily) for 5 days.

  
  
  

  Pediatric Patients (2 weeks of age through 12 years of age)

  
  
  

  Table 1 displays the recommended oral dosage of oseltamivir phosphate for oral suspension for treatment of influenza in pediatric patients 2 weeks of age through 12 years of age and provides information about prescribing the formulation for oral suspension.
  )
• Pediatric patients 1 to 12 years of age: Based on weight twice daily for 5 days (
  2.2 Recommended Dosage for Treatment of Influenza

  Initiate treatment with oseltamivir phosphate for oral suspension within 48 hours of influenza symptom onset.

  
  
  

  Adults and Adolescents (13 years of age and older)

  
  
  

  The recommended oral dosage of oseltamivir phosphate for oral suspension for treatment of influenza in adults and adolescents 13 years and older is 75 mg twice daily (12.5 mL of oral suspension twice daily) for 5 days.

  
  
  

  Pediatric Patients (2 weeks of age through 12 years of age)

  
  
  

  Table 1 displays the recommended oral dosage of oseltamivir phosphate for oral suspension for treatment of influenza in pediatric patients 2 weeks of age through 12 years of age and provides information about prescribing the formulation for oral suspension.
  )
• Pediatric patients 2 weeks to less than 1 year of age: 3mg/kg twice daily for 5 days (
  2.2 Recommended Dosage for Treatment of Influenza

  Initiate treatment with oseltamivir phosphate for oral suspension within 48 hours of influenza symptom onset.

  
  
  

  Adults and Adolescents (13 years of age and older)

  
  
  

  The recommended oral dosage of oseltamivir phosphate for oral suspension for treatment of influenza in adults and adolescents 13 years and older is 75 mg twice daily (12.5 mL of oral suspension twice daily) for 5 days.

  
  
  

  Pediatric Patients (2 weeks of age through 12 years of age)

  
  
  

  Table 1 displays the recommended oral dosage of oseltamivir phosphate for oral suspension for treatment of influenza in pediatric patients 2 weeks of age through 12 years of age and provides information about prescribing the formulation for oral suspension.
  )
• Renally impaired adult patients (creatinine clearance >30 to 60 mL/min): Reduce to 30 mg twice daily for 5 days (
  2.4 Dosage in Patients with Renal Impairment

  Table 2 displays the dosage recommendations for the treatment and prophylaxis of influenza in adults with various stages of renal impairment (estimated creatinine clearance of less than or equal to 90 mL per minute). Dosage modifications are recommended in adults with an estimated creatinine clearance less than or equal to 60 mL per minute

  [see Use in Specific Population (8.6)and Clinical Pharmacology (12.3)]

  .

  
  
  

  Table 2 Recommended Dosage Modifications for

  Treatment

  and

  Prophylaxis

  of Influenza in Adults with Renal Impairment or End Stage Renal Disease (ESRD) on Dialysis

  Renal Impairment (Creatinine Clearance)	Recommended Treatment Regimen*	Recommended Prophylaxis Regimen* †
  Mild (>60 to 90 mL/minute)	75 mg twice daily for 5 days	75 mg once daily
  Moderate (>30 to 60 mL/minute)	30 mg twice daily for 5 days	30 mg once daily
  Severe (>10 to 30 mL/minute)	30 mg once daily for 5 days	30 mg every other day
  ESRD Patients on Hemodialysis (≤ 10 mL/minute)	30 mg immediately and then 30 mg after every hemodialysis cycle (treatment duration not to exceed 5 days)	30 mg immediately and then 30 mg after alternate hemodialysis cycles
  ESRD Patients on Continuous Ambulatory Peritoneal Dialysis‡ (≤10 mL/minute)	A single 30 mg dose administered immediately	30 mg immediately and then 30 mg once weekly
  ESRD Patients not on Dialysis	Oseltamivir phosphate for oral suspension is not recommended	Oseltamivir phosphate for oral suspension is not recommended

  *   Oral suspension can be used for 30 mg dosing.

  †   The recommended duration for post-exposure prophylaxis is at least 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients).

  ‡   Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients.
  )
• Renally impaired adult patients (creatinine clearance >10 to 30 mL/min): Reduce to 30 mg once daily for 5 days (
  2.4 Dosage in Patients with Renal Impairment

  Table 2 displays the dosage recommendations for the treatment and prophylaxis of influenza in adults with various stages of renal impairment (estimated creatinine clearance of less than or equal to 90 mL per minute). Dosage modifications are recommended in adults with an estimated creatinine clearance less than or equal to 60 mL per minute

  [see Use in Specific Population (8.6)and Clinical Pharmacology (12.3)]

  .

  
  
  

  Table 2 Recommended Dosage Modifications for

  Treatment

  and

  Prophylaxis

  of Influenza in Adults with Renal Impairment or End Stage Renal Disease (ESRD) on Dialysis

  Renal Impairment (Creatinine Clearance)	Recommended Treatment Regimen*	Recommended Prophylaxis Regimen* †
  Mild (>60 to 90 mL/minute)	75 mg twice daily for 5 days	75 mg once daily
  Moderate (>30 to 60 mL/minute)	30 mg twice daily for 5 days	30 mg once daily
  Severe (>10 to 30 mL/minute)	30 mg once daily for 5 days	30 mg every other day
  ESRD Patients on Hemodialysis (≤ 10 mL/minute)	30 mg immediately and then 30 mg after every hemodialysis cycle (treatment duration not to exceed 5 days)	30 mg immediately and then 30 mg after alternate hemodialysis cycles
  ESRD Patients on Continuous Ambulatory Peritoneal Dialysis‡ (≤10 mL/minute)	A single 30 mg dose administered immediately	30 mg immediately and then 30 mg once weekly
  ESRD Patients not on Dialysis	Oseltamivir phosphate for oral suspension is not recommended	Oseltamivir phosphate for oral suspension is not recommended

  *   Oral suspension can be used for 30 mg dosing.

  †   The recommended duration for post-exposure prophylaxis is at least 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients).

  ‡   Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients.
  )
• ESRD patients on hemodialysis: Reduce to 30 mg immediately and then 30 mg after every hemodialysis cycle. Treatment duration not to exceed 5 days (
  2.4 Dosage in Patients with Renal Impairment

  Table 2 displays the dosage recommendations for the treatment and prophylaxis of influenza in adults with various stages of renal impairment (estimated creatinine clearance of less than or equal to 90 mL per minute). Dosage modifications are recommended in adults with an estimated creatinine clearance less than or equal to 60 mL per minute

  [see Use in Specific Population (8.6)and Clinical Pharmacology (12.3)]

  .

  
  
  

  Table 2 Recommended Dosage Modifications for

  Treatment

  and

  Prophylaxis

  of Influenza in Adults with Renal Impairment or End Stage Renal Disease (ESRD) on Dialysis

  Renal Impairment (Creatinine Clearance)	Recommended Treatment Regimen*	Recommended Prophylaxis Regimen* †
  Mild (>60 to 90 mL/minute)	75 mg twice daily for 5 days	75 mg once daily
  Moderate (>30 to 60 mL/minute)	30 mg twice daily for 5 days	30 mg once daily
  Severe (>10 to 30 mL/minute)	30 mg once daily for 5 days	30 mg every other day
  ESRD Patients on Hemodialysis (≤ 10 mL/minute)	30 mg immediately and then 30 mg after every hemodialysis cycle (treatment duration not to exceed 5 days)	30 mg immediately and then 30 mg after alternate hemodialysis cycles
  ESRD Patients on Continuous Ambulatory Peritoneal Dialysis‡ (≤10 mL/minute)	A single 30 mg dose administered immediately	30 mg immediately and then 30 mg once weekly
  ESRD Patients not on Dialysis	Oseltamivir phosphate for oral suspension is not recommended	Oseltamivir phosphate for oral suspension is not recommended

  *   Oral suspension can be used for 30 mg dosing.

  †   The recommended duration for post-exposure prophylaxis is at least 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients).

  ‡   Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients.
  )
• ESRD patients on CAPD: Reduce to a single 30 mg dose immediately (
  2.4 Dosage in Patients with Renal Impairment

  Table 2 displays the dosage recommendations for the treatment and prophylaxis of influenza in adults with various stages of renal impairment (estimated creatinine clearance of less than or equal to 90 mL per minute). Dosage modifications are recommended in adults with an estimated creatinine clearance less than or equal to 60 mL per minute

  [see Use in Specific Population (8.6)and Clinical Pharmacology (12.3)]

  .

  
  
  

  Table 2 Recommended Dosage Modifications for

  Treatment

  and

  Prophylaxis

  of Influenza in Adults with Renal Impairment or End Stage Renal Disease (ESRD) on Dialysis

  Renal Impairment (Creatinine Clearance)	Recommended Treatment Regimen*	Recommended Prophylaxis Regimen* †
  Mild (>60 to 90 mL/minute)	75 mg twice daily for 5 days	75 mg once daily
  Moderate (>30 to 60 mL/minute)	30 mg twice daily for 5 days	30 mg once daily
  Severe (>10 to 30 mL/minute)	30 mg once daily for 5 days	30 mg every other day
  ESRD Patients on Hemodialysis (≤ 10 mL/minute)	30 mg immediately and then 30 mg after every hemodialysis cycle (treatment duration not to exceed 5 days)	30 mg immediately and then 30 mg after alternate hemodialysis cycles
  ESRD Patients on Continuous Ambulatory Peritoneal Dialysis‡ (≤10 mL/minute)	A single 30 mg dose administered immediately	30 mg immediately and then 30 mg once weekly
  ESRD Patients not on Dialysis	Oseltamivir phosphate for oral suspension is not recommended	Oseltamivir phosphate for oral suspension is not recommended

  *   Oral suspension can be used for 30 mg dosing.

  †   The recommended duration for post-exposure prophylaxis is at least 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients).

  ‡   Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients.
  )

• Adults and adolescents (13 years and older): 75 mg once daily for at least 10 days (
  2.3 Recommended Dosage for Prophylaxis of Influenza

  Initiate post‐exposure prophylaxis with oseltamivir phosphate for oral suspension within 48 hours following close contact with an infected individual. Initiate seasonal prophylaxis with oseltamivir phosphate for oral suspension during a community outbreak.

  
  
  

  Adults and Adolescents (13 years of age and older)

  
  
  

  The recommended dosage of oseltamivir phosphate for oral suspension for prophylaxis of influenza in adults and adolescents 13 years and older is 75 mg orally once daily (12.5 mL of oral suspension once daily) for at least 10 days following close contact with an infected individual and up to 6 weeks during a community outbreak. In immunocompromised patients, oseltamivir phosphate for oral suspension may be continued for up to 12 weeks

  [see Use in Specific Populations (8.9)]

  . The duration of protection lasts for as long as oseltamivir phosphate for oral suspension dosing is continued.

  
  
  

  Pediatric Patients (1 year to 12 years of age)

  
  
  

  Table 1 displays the recommended oral dosage of oseltamivir phosphate for oral suspension for prophylaxis of influenza in pediatric patients 1 year to 12 years of age based on body weight and provides information about prescribing the formulation for oral suspension. Prophylaxis in pediatric patients is recommended for 10 days following close contact with an infected individual and up to 6 weeks during a community outbreak

  [see Use in Specific Populations (8.4)and Clinical Studies (14.2)]

  .

  Table 1

  Oseltamivir Phosphate

  for Oral

  Suspension Dosage Recommendations in Pediatric Patients for

  Treatment

  and

  Prophylaxis

  of Influenza

  Weight	Treatment Dosage for 5 days	Prophylaxis Dosage for 10 days*	Volume of Oral Suspension (6 mg/mL) for each Dose †	Number of Bottles of Oral Suspension to Dispense
  Patients from 2 Weeks to less than 1 Year of Age
  Any weight	3 mg/kg twice daily	Not applicable	0.5 mL/kg§	1 bottle
  Patients 1 to 12 Years of Age Based on Body Weight
  15 kg or less	30 mg twice daily	30 mg once daily	5 mL	1 bottle
  15.1 kg to 23 kg	45 mg twice daily	45 mg once daily	7.5 mL	2 bottles
  23.1 kg to 40 kg	60 mg twice daily	60 mg once daily	10 mL	2 bottles
  40.1 kg or more	75 mg twice daily	75 mg once daily	12.5 mL	3 bottles

  *  The recommended duration for post-exposure prophylaxis is 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients). The amount supplied (e.g., number of bottles) for seasonal prophylaxis may be greater than for post‐exposure prophylaxis.

  †   Use an oral dosing dispensing device that measures the appropriate volume in mL with the oral suspension.

  §  For patients less than 1 year of age, provide an appropriate dosing device that can accurately measure and   administer small volumes.
  )

-       Community outbreak: 75 mg once daily for up to 6 weeks (

• Pediatric patients 1 to 12 years of age: Based on weight once daily for 10 days (
  2.3 Recommended Dosage for Prophylaxis of Influenza

  Initiate post‐exposure prophylaxis with oseltamivir phosphate for oral suspension within 48 hours following close contact with an infected individual. Initiate seasonal prophylaxis with oseltamivir phosphate for oral suspension during a community outbreak.

  
  
  

  Adults and Adolescents (13 years of age and older)

  
  
  

  The recommended dosage of oseltamivir phosphate for oral suspension for prophylaxis of influenza in adults and adolescents 13 years and older is 75 mg orally once daily (12.5 mL of oral suspension once daily) for at least 10 days following close contact with an infected individual and up to 6 weeks during a community outbreak. In immunocompromised patients, oseltamivir phosphate for oral suspension may be continued for up to 12 weeks

  [see Use in Specific Populations (8.9)]

  . The duration of protection lasts for as long as oseltamivir phosphate for oral suspension dosing is continued.

  
  
  

  Pediatric Patients (1 year to 12 years of age)

  
  
  

  Table 1 displays the recommended oral dosage of oseltamivir phosphate for oral suspension for prophylaxis of influenza in pediatric patients 1 year to 12 years of age based on body weight and provides information about prescribing the formulation for oral suspension. Prophylaxis in pediatric patients is recommended for 10 days following close contact with an infected individual and up to 6 weeks during a community outbreak

  [see Use in Specific Populations (8.4)and Clinical Studies (14.2)]

  .

  Table 1

  Oseltamivir Phosphate

  for Oral

  Suspension Dosage Recommendations in Pediatric Patients for

  Treatment

  and

  Prophylaxis

  of Influenza

  Weight	Treatment Dosage for 5 days	Prophylaxis Dosage for 10 days*	Volume of Oral Suspension (6 mg/mL) for each Dose †	Number of Bottles of Oral Suspension to Dispense
  Patients from 2 Weeks to less than 1 Year of Age
  Any weight	3 mg/kg twice daily	Not applicable	0.5 mL/kg§	1 bottle
  Patients 1 to 12 Years of Age Based on Body Weight
  15 kg or less	30 mg twice daily	30 mg once daily	5 mL	1 bottle
  15.1 kg to 23 kg	45 mg twice daily	45 mg once daily	7.5 mL	2 bottles
  23.1 kg to 40 kg	60 mg twice daily	60 mg once daily	10 mL	2 bottles
  40.1 kg or more	75 mg twice daily	75 mg once daily	12.5 mL	3 bottles

  *  The recommended duration for post-exposure prophylaxis is 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients). The amount supplied (e.g., number of bottles) for seasonal prophylaxis may be greater than for post‐exposure prophylaxis.

  †   Use an oral dosing dispensing device that measures the appropriate volume in mL with the oral suspension.

  §  For patients less than 1 year of age, provide an appropriate dosing device that can accurately measure and   administer small volumes.
  )

-       Community outbreak: Based on weight once daily for up to 6 weeks (

• Renally impaired adult patients (creatinine clearance >30 to 60 mL/min): Reduce to 30 mg once daily (
  2.4 Dosage in Patients with Renal Impairment

  Table 2 displays the dosage recommendations for the treatment and prophylaxis of influenza in adults with various stages of renal impairment (estimated creatinine clearance of less than or equal to 90 mL per minute). Dosage modifications are recommended in adults with an estimated creatinine clearance less than or equal to 60 mL per minute

  [see Use in Specific Population (8.6)and Clinical Pharmacology (12.3)]

  .

  
  
  

  Table 2 Recommended Dosage Modifications for

  Treatment

  and

  Prophylaxis

  of Influenza in Adults with Renal Impairment or End Stage Renal Disease (ESRD) on Dialysis

  Renal Impairment (Creatinine Clearance)	Recommended Treatment Regimen*	Recommended Prophylaxis Regimen* †
  Mild (>60 to 90 mL/minute)	75 mg twice daily for 5 days	75 mg once daily
  Moderate (>30 to 60 mL/minute)	30 mg twice daily for 5 days	30 mg once daily
  Severe (>10 to 30 mL/minute)	30 mg once daily for 5 days	30 mg every other day
  ESRD Patients on Hemodialysis (≤ 10 mL/minute)	30 mg immediately and then 30 mg after every hemodialysis cycle (treatment duration not to exceed 5 days)	30 mg immediately and then 30 mg after alternate hemodialysis cycles
  ESRD Patients on Continuous Ambulatory Peritoneal Dialysis‡ (≤10 mL/minute)	A single 30 mg dose administered immediately	30 mg immediately and then 30 mg once weekly
  ESRD Patients not on Dialysis	Oseltamivir phosphate for oral suspension is not recommended	Oseltamivir phosphate for oral suspension is not recommended

  *   Oral suspension can be used for 30 mg dosing.

  †   The recommended duration for post-exposure prophylaxis is at least 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients).

  ‡   Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients.
  )
• Renally impaired adult patients (creatinine clearance >10 to 30 mL/min): Reduce to 30 mg once every other day (
  2.4 Dosage in Patients with Renal Impairment

  Table 2 displays the dosage recommendations for the treatment and prophylaxis of influenza in adults with various stages of renal impairment (estimated creatinine clearance of less than or equal to 90 mL per minute). Dosage modifications are recommended in adults with an estimated creatinine clearance less than or equal to 60 mL per minute

  [see Use in Specific Population (8.6)and Clinical Pharmacology (12.3)]

  .

  
  
  

  Table 2 Recommended Dosage Modifications for

  Treatment

  and

  Prophylaxis

  of Influenza in Adults with Renal Impairment or End Stage Renal Disease (ESRD) on Dialysis

  Renal Impairment (Creatinine Clearance)	Recommended Treatment Regimen*	Recommended Prophylaxis Regimen* †
  Mild (>60 to 90 mL/minute)	75 mg twice daily for 5 days	75 mg once daily
  Moderate (>30 to 60 mL/minute)	30 mg twice daily for 5 days	30 mg once daily
  Severe (>10 to 30 mL/minute)	30 mg once daily for 5 days	30 mg every other day
  ESRD Patients on Hemodialysis (≤ 10 mL/minute)	30 mg immediately and then 30 mg after every hemodialysis cycle (treatment duration not to exceed 5 days)	30 mg immediately and then 30 mg after alternate hemodialysis cycles
  ESRD Patients on Continuous Ambulatory Peritoneal Dialysis‡ (≤10 mL/minute)	A single 30 mg dose administered immediately	30 mg immediately and then 30 mg once weekly
  ESRD Patients not on Dialysis	Oseltamivir phosphate for oral suspension is not recommended	Oseltamivir phosphate for oral suspension is not recommended

  *   Oral suspension can be used for 30 mg dosing.

  †   The recommended duration for post-exposure prophylaxis is at least 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients).

  ‡   Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients.
  )
• ESRD patients on hemodialysis: Reduce to 30 mg immediately and then 30 mg after alternate hemodialysis cycles for the recommended duration of prophylaxis (
  2.4 Dosage in Patients with Renal Impairment

  Table 2 displays the dosage recommendations for the treatment and prophylaxis of influenza in adults with various stages of renal impairment (estimated creatinine clearance of less than or equal to 90 mL per minute). Dosage modifications are recommended in adults with an estimated creatinine clearance less than or equal to 60 mL per minute

  [see Use in Specific Population (8.6)and Clinical Pharmacology (12.3)]

  .

  
  
  

  Table 2 Recommended Dosage Modifications for

  Treatment

  and

  Prophylaxis

  of Influenza in Adults with Renal Impairment or End Stage Renal Disease (ESRD) on Dialysis

  Renal Impairment (Creatinine Clearance)	Recommended Treatment Regimen*	Recommended Prophylaxis Regimen* †
  Mild (>60 to 90 mL/minute)	75 mg twice daily for 5 days	75 mg once daily
  Moderate (>30 to 60 mL/minute)	30 mg twice daily for 5 days	30 mg once daily
  Severe (>10 to 30 mL/minute)	30 mg once daily for 5 days	30 mg every other day
  ESRD Patients on Hemodialysis (≤ 10 mL/minute)	30 mg immediately and then 30 mg after every hemodialysis cycle (treatment duration not to exceed 5 days)	30 mg immediately and then 30 mg after alternate hemodialysis cycles
  ESRD Patients on Continuous Ambulatory Peritoneal Dialysis‡ (≤10 mL/minute)	A single 30 mg dose administered immediately	30 mg immediately and then 30 mg once weekly
  ESRD Patients not on Dialysis	Oseltamivir phosphate for oral suspension is not recommended	Oseltamivir phosphate for oral suspension is not recommended

  *   Oral suspension can be used for 30 mg dosing.

  †   The recommended duration for post-exposure prophylaxis is at least 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients).

  ‡   Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients.
  )
• ESRD patients on CAPD: Reduce to 30 mg immediately and then 30 mg once weekly for the recommended duration of prophylaxis (
  2.4 Dosage in Patients with Renal Impairment

  Table 2 displays the dosage recommendations for the treatment and prophylaxis of influenza in adults with various stages of renal impairment (estimated creatinine clearance of less than or equal to 90 mL per minute). Dosage modifications are recommended in adults with an estimated creatinine clearance less than or equal to 60 mL per minute

  [see Use in Specific Population (8.6)and Clinical Pharmacology (12.3)]

  .

  
  
  

  Table 2 Recommended Dosage Modifications for

  Treatment

  and

  Prophylaxis

  of Influenza in Adults with Renal Impairment or End Stage Renal Disease (ESRD) on Dialysis

  Renal Impairment (Creatinine Clearance)	Recommended Treatment Regimen*	Recommended Prophylaxis Regimen* †
  Mild (>60 to 90 mL/minute)	75 mg twice daily for 5 days	75 mg once daily
  Moderate (>30 to 60 mL/minute)	30 mg twice daily for 5 days	30 mg once daily
  Severe (>10 to 30 mL/minute)	30 mg once daily for 5 days	30 mg every other day
  ESRD Patients on Hemodialysis (≤ 10 mL/minute)	30 mg immediately and then 30 mg after every hemodialysis cycle (treatment duration not to exceed 5 days)	30 mg immediately and then 30 mg after alternate hemodialysis cycles
  ESRD Patients on Continuous Ambulatory Peritoneal Dialysis‡ (≤10 mL/minute)	A single 30 mg dose administered immediately	30 mg immediately and then 30 mg once weekly
  ESRD Patients not on Dialysis	Oseltamivir phosphate for oral suspension is not recommended	Oseltamivir phosphate for oral suspension is not recommended

  *   Oral suspension can be used for 30 mg dosing.

  †   The recommended duration for post-exposure prophylaxis is at least 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients).

  ‡   Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients.
  )

Oseltamivir Phosphate for Oral Suspension: 6 mg per mL (final concentration when constituted)

• White to off-white granular powder blend for constitution.

There are no adequate and well-controlled studies with oseltamivir phosphate in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Available published epidemiological data suggest that oseltamivir phosphate, taken in any trimester, is not associated with an increased risk of birth defects. However, these studies individually are limited by small sample sizes, use of different comparison groups, and some lacked information on dose, which preclude a definitive assessment of the risk

The background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage is 2 to 4% and 15 to 20%, respectively.

Pregnant women are at higher risk of severe complications from influenza, which may lead to adverse pregnancy and/or fetal outcomes including maternal death, still births, birth defects, preterm delivery, low birth weight and small for gestational age.

Published prospective and retrospective observational studies of more than 5,000 women exposed to oseltamivir phosphate during pregnancy, including more than 1,000 women exposed in the first trimester, suggest that the observed rate of congenital malformations was not increased above the rate in the general comparison population, regardless of when therapy was administered during the gestational period. However, individually, none of these studies had adequate sample sizes and some lacked information on dose, which preclude a definitive assessment of the risk.

Oseltamivir was administered orally during organogenesis to pregnant rats (at 50, 250, or 1500 mg/kg/day on gestation days 6 to 17) and rabbits (at 50, 150, or 500 mg/kg/day on gestation days 6 to 18). In rats, embryo-fetal effects consisting of an increased incidence of minor skeletal malformations were observed at a maternally toxic dose (1500 mg/kg/day), resulting in systemic drug exposures (based on AUC for oseltamivir carboxylate) 190 times human exposures at the maximum recommended human dose (MRHD) of oseltamivir phosphate (75 mg twice a day). In the rabbit study, embryo-fetal effects consisting of an increased incidence of minor skeletal abnormalities and variants were observed at maternally toxic doses (≥150 mg/kg/day) resulting in systemic exposures (based on AUC for oseltamivir carboxylate) ≥8 times human exposures at the MRHD of oseltamivir phosphate.

In prenatal and postnatal development studies in rats, oseltamivir was administered orally (at 50, 250, 500, or 1500 mg/kg/day) from organogenesis through late gestation, delivery, and lactation (gestation day 6 to postpartum/lactation day 20). Prolonged parturition duration and reduced offspring viability were observed at a maternally toxic dose (1500 mg/kg/day). No adverse maternal or offspring effects were observed at doses ≤500 mg/kg/day, resulting in systemic drug exposures (based on AUC for oseltamivir carboxylate) 44 times human exposures at the MRHD of oseltamivir phosphate.

• Serious skin/hypersensitivity reactions such as Stevens‐Johnson syndrome, toxic epidermal necrolysis and erythema multiforme: Discontinue oseltamivir phosphate and initiate appropriate treatment if allergic‐like reactions occur or are suspected. (
  5.1 Serious Skin/Hypersensitivity Reactions

  Cases of anaphylaxis and serious skin reactions including toxic epidermal necrolysis, Stevens‐Johnson syndrome, and erythema multiforme have been reported in postmarketing experience with oseltamivir phosphate. Stop oseltamivir phosphate and institute appropriate treatment if an allergic‐like reaction occurs or is suspected. The use of oseltamivir phosphate for oral suspension is contraindicated in patients with known serious hypersensitivity to oseltamivir phosphate

  [see Contraindications (4)and Adverse Reactions (6.2)]

  .
  )
• Neuropsychiatric events: Patients with influenza, including those receiving oseltamivir phosphate, particularly pediatric patients, may be at an increased risk of confusion or abnormal behavior early in their illness. Monitor for signs of abnormal behavior. (
  5.2 Neuropsychiatric Events

  There have been postmarketing reports of delirium and abnormal behavior leading to injury, and in some cases resulting in fatal outcomes, in patients with influenza who were receiving oseltamivir phosphate

  [see Adverse Reactions (6.2)]

  . Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made but they appear to be uncommon based on oseltamivir phosphate usage data. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of oseltamivir phosphate to these events has not been established.

  
  
  

  Influenza can be associated with a variety of neurologic and behavioral symptoms that can include events such as hallucinations, delirium, and abnormal behavior, in some cases resulting in fatal outcomes. These events may occur in the setting of encephalitis or encephalopathy but can occur without obvious severe disease. Closely monitor oseltamivir phosphate-treated patients with influenza for signs of abnormal behavior. If neuropsychiatric symptoms occur, evaluate the risks and benefits of continuing oseltamivir phosphate for each patient.
  )