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Anti-Influenza Agents

Infectious Disease -ALL Agents (INDEX)

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Amantadine (symmetrel ®) 

Dosing (Adults):
Influenza A treatment: Oral: 100 mg twice daily; initiate within 24-48 hours after onset of symptoms; discontinue as soon as possible based on clinical response (generally within 3-5 days or within 24-48 hours after symptoms disappear).

Influenza A prophylaxis: Oral: 100 mg twice daily; continue treatment throughout the peak influenza activity in the community or throughout the entire influenza season in patients who cannot be vaccinated. Development of immunity following vaccination takes ~2 weeks; amantadine therapy should be considered for high-risk patients from the time of vaccination until immunity has developed.

Drug-induced extrapyramidal symptoms: Oral: 100 mg twice daily; may increase to 300-400 mg/day, if needed.

Parkinson's disease: Oral: 100 mg twice daily as sole therapy; may increase
to 400 mg/day if needed with close monitoring; initial dose: 100 mg/day if with other serious illness or with high doses of other anti-Parkinson drugs.

Elderly: Influenza A prophylaxis or treatment: 100 mg/day in patients over 65 years.

Renal Dosing:
CrCl 30-50 mL/minute: Administer 200 mg on day 1, then 100 mg/day.
CrCl 15-29 mL/minute: Administer 200 mg on day 1, then 100 mg on alternate days.
CrCl <15 mL/minute: Administer 200 mg every 7 days.
Hemodialysis: Administer 200 mg every 7 days.

Supplied: 100 mg capsule / tablet. Syrup: 50 mg/5 ml.

Oseltamivir phosphate (tamiflu ®) 

INDICATIONS
TAMIFLU is an influenza neuraminidase inhibitor indicated for:

  • Treatment of acute, uncomplicated influenza in patients 2 weeks of age and older who have been symptomatic for no more than 2 days.
  • Prophylaxis of influenza in patients 1 year and older.

Important Limitations of Use:

  • Efficacy not established in patients who begin therapy after 48 hours of symptoms.
  • Not a substitute for annual influenza vaccination.
  • No evidence of efficacy for illness from agents other than influenza viruses types A and B.
  • CConsider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use.

Treatment of Influenza
Dose adjustment is recommended for adult patients with creatinine clearance between 10 and 60 mL/min and patients with end-stage renal disease (ESRD) undergoing hemodialysis or continuous peritoneal dialysis receiving TAMIFLU for the treatment of influenza. TAMIFLU is not recommended for patients with ESRD not undergoing dialysis. The recommended doses are detailed in Table 2 below.

  • Adults and adolescents (13 years and older): 75 mg twice daily for 5 days
  • Pediatric patients 1 to 12 years of age: Based on weight twice daily for 5 days
  • Pediatric patients 2 weeks to less than 1 year of age: 3mg/kg twice daily for 5 days.
  • Renally impaired adult patients (creatinine clearance >30-60 mL/min): Reduce to 30 mg twice daily for 5 days
  • Renally impaired adult patients (creatinine clearance >10-30 mL/min): Reduce to 30 mg once daily for 5 days
  • ESRD patients on hemodialysis: Reduce to 30 mg after every hemodialysis cycle. Treatment duration not to exceed 5 days
  • ESRD patients on CAPD: Reduce to a single 30 mg dose administered immediately after a dialysis exchange

Table 2 Recommended Dose Adjustments for Treatment of Influenza in Adult Patients with Renal Impairment or End Stage Renal Disease (ESRD) on Dialysis

Renal Impairment/Creatinine Clearance Recommended Treatment Regimen*
Mild
Creatinine Clearance >60-90 mL/min
75 mg twice daily for 5 days
Moderate
Creatinine Clearance >30-60 mL/min
30 mg twice daily for 5 days
Severe
Creatinine Clearance >10-30 mL/min
30 mg once daily for 5 days
ESRD Patients on Hemodialysis
Creatinine Clearance ≤10 mL/min
30 mg after every hemodialysis cycle. Treatment duration not to exceed 5 days†
ESRD Patients on Continuous Ambulatory Peritoneal Dialysis‡
Creatinine Clearance ≤10 mL/min
A single 30 mg dose administered immediately after a dialysis exchange
*Capsules or suspension can be used for 30 mg dosing.

Assuming three hemodialysis sessions are performed in the 5-day period. Treatment can be initiated immediately if influenza symptoms develop during the 48 hours between hemodialysis sessions; however, the post-hemodialysis dose should still be administered independently of time of administration of the initial dose.

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

Prophylaxis of Influenza
For the prophylaxis of influenza, dose adjustment is recommended for adult patients with creatinine clearance between 10 and 60 mL/min and patients with end-stage renal disease (ESRD) undergoing hemodialysis or continuous peritoneal dialysis receiving TAMIFLU [see Clinical Pharmacology (12.3)]. The duration of prophylaxis is the same as recommended for patients with normal renal function. TAMIFLU is not recommended for patients with ESRD not undergoing dialysis. The recommended doses are detailed in Table 3 below.

  • Adults and adolescents (13 years and older): 75 mg once daily for at least 10 days
    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
    Community outbreak: Based on weight once daily for up to 6 weeks
  • Renally impaired adult patients (creatinine clearance >30-60 mL/min): Reduce to 30 mg once daily
  • Renally impaired adult patients (creatinine clearance >10-30 mL/min): Reduce to 30 mg once every other day
  • ESRD patients on hemodialysis: Reduce to 30 mg after alternate hemodialysis cycles for the recommended duration of prophylaxis
  • ESRD patients on CAPD: Reduce to 30 mg once weekly immediately after dialysis exchange for the recommended duration of prophylaxis

Table 3 Recommended Dose Adjustments for Prophylaxis of Influenza in Adult Patients with Renal Impairment or End Stage Renal Disease (ESRD) on Dialysis

Renal Impairment/Creatinine Clearance Recommended Prophylaxis Regimen*
Mild
Creatinine Clearance >60-90 mL/min
75 mg once daily
Moderate
Creatinine Clearance >30-60 mL/min
30 mg once daily
Severe
Creatinine Clearance >10-30 mL/min
30 mg every other day
ESRD Patients on Hemodialysis
Creatinine Clearance ≤10 mL/min
30 mg after alternate hemodialysis cycles†
ESRD Patients on Continuous Ambulatory Peritoneal Dialysis‡
Creatinine Clearance ≤10 mL/min
30 mg once weekly immediately after dialysis exchange
*Capsules or suspension can be used for 30 mg dosing.
†An initial dose can be administered prior to the start of dialysis.
‡Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients.

Supplied:
Capsules: 30 mg, 45 mg, 75 mg
Powder for oral suspension: 360 mg oseltamivir base (constituted to a final concentration of 6 mg/mL)

 peramivir injection - rapivab™ 

Drug UPDATES:  RAPIVAB™ (peramivir injection), for intravenous use
[Drug information  /  PDF]  
Dosing:  Click (+) next to Dosage and Administration section (drug info link)

Initial U.S. Approval:  2014

Mechanism of Action: Peramivir is an antiviral drug with activity against influenza virus

INDICATIONS AND USAGE:
RAPIVAB is indicated for the treatment of acute uncomplicated influenza in patients 18 years and older who have been symptomatic for no more than 2 days.

Limitations of Use:
Efficacy of RAPIVAB is based on clinical trials of naturally occurring influenza in which the predominant influenza infections were influenza A virus; a limited number of subjects infected with influenza B virus were enrolled.
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 RAPIVAB [see Microbiology (12.4)].
The efficacy of RAPIVAB could not be established in patients with serious influenza requiring hospitalization [see Clinical Studies (14.2)].

HOW SUPPLIED:: Each vial of RAPIVAB injection contains 200 mg per 20 mL (10 mg per mL) as a clear, colorless solution

Rimantadine (flumadine ®) 

INDICATIONS: Rimantadine HCl is indicated for the prophylaxis and treatment of illness caused by various strains of influenza A virus in adults.

Dosing (Adults): The recommended adult dose of rimantadine HCl is 100 mg twice a day. In patients with severe hepatic dysfunction, renal failure (CrCl ≤ 10 ml/min) and elderly nursing home patients, a dose reduction to 100 mg daily is recommended. There are currently no data available regarding the safety of rimantadine during multiple dosing in subjects with renal or hepatic impairment. Because of the potential for accumulation of rimantadine metabolites during multiple dosing, patients with any degree of renal insufficiency should be monitored for adverse effect, with dosage adjustments being made as necessary. Rimantadine HCl therapy should be initiated as soon as possible, preferably within 48 hours after onset of signs and symptoms of influenza A infection. Therapy should be continued for approximately seven days from the initial onset of symptoms.

Zanamivir (relenza ®) 

INDICATIONS
Treatment of Influenza: RELENZA is indicated for treatment of uncomplicated acute illness due to influenza A and B virus in adults and pediatric patients 7 years of age and older who have been symptomatic for no more than 2 days.

Prophylaxis of Influenza: RELENZA is indicated in adults and pediatric patients 5 years of age and older for prophylaxis of influenza.

Dosing (Adults):
Treatment
The recommended dose of RELENZA for treatment of influenza in adults and pediatric patients ages 7 years of age and older is 2 inhalations (one 5-mg blister per inhalation for a total dose of 10 mg) twice daily (approximately 12 hours apart) for 5 days. Two doses should be taken on the first day of treatment whenever possible provided there is at least 2 hours between doses. On subsequent days, doses should be about 12 hours apart (e.g., morning and evening) at approximately the same time each day. There are no data on the effectiveness of treatment with RELENZA when initiated more than 2 days after the onset of signs or symptoms.

Prophylaxis
Household Setting:  The recommended dose of RELENZA for prophylaxis of influenza in adults and pediatric patients 5 years of age and older in a household setting is 10 mg once daily for 10 days. The 10-mg dose is provided by 2 inhalations (one 5-mg blister per inhalation). The dose should be administered at approximately the same time each day. There are no data on the effectiveness of prophylaxis with RELENZA in a household setting when initiated more than 1.5 days after the onset of signs or symptoms in the index case.

Community Outbreaks:  The recommended dose of RELENZA for prophylaxis of influenza in adults and adolescents in a community setting is 10 mg once daily for 28 days. The 10-mg dose is provided by 2 inhalations (one 5-mg blister per inhalation). The dose should be administered at approximately the same time each day. There are no data on the effectiveness of prophylaxis with RELENZA in a community outbreak when initiated more than 5 days after the outbreak was identified in the community. The safety and effectiveness of prophylaxis with RELENZA have not been evaluated for longer than 28 days duration.

Reference(s)

National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
Provides access to the latest drug monographs submitted to the Food and Drug Administration (FDA). Please review the latest applicable package insert for additional information and possible updates.  A local search option of this data can be found here.

Anti-Influenza Agents

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