Anti-Influenza Agents

Background:

Influenza A is the predominant virus type, accounting for 99.5% of influenza cases. The incidence of influenza peaks in the last week of December. The optimal time to vaccinate is during October and November.

Oseltamivir (Tamiflu) and zanamivir (Relenza) block the neuraminidase surface protein on both influenza A and influenza B.

Amantadine and rimantadine prevent early viral replication of influenza A only.

Recommendations - CDC Health Advisory:
The recommendations were prompted by preliminary data in a limited number of states indicating a high prevalence of the oseltamivir-resistant influenza A (H1N1) strain. Influenza activity remains low at the present time, but of the 50 H1N1 isolates from 12 states tested between October 1 and December 19, 2008, 49 (98%) were resistant to oseltamivir. The CDC is unable to make any accurate predictions of which influenza virus types (A or B) or subtypes of influenza A (H1N1 or H3N2) will predominate during the 2008-09 season, but based on the current findings, the following recommendations have been made:

* Patients testing positive for influenza type B: If treatment is indicated, patients may receive either oseltamivir or zanamivir (no preference).

* Patients testing positive for influenza type A (or patients testing negative for influenza, but likelihood of influenza infection is high): If treatment is indicated, patient may receive zanamivir. If zanamivir therapy is inappropriate (eg, patients with chronic respiratory disease, patients <7 years of age) or zanamivir is unavailable, combination treatment with oseltamivir and rimantadine is acceptable (if rimantadine is unavailable, amantadine may be substituted). Oseltamivir monotherapy should only be used if local surveillance indicates that influenza A (H3N2) or influenza type B viruses are likely.

* If confirmatory diagnostic testing to distinguish between subtypes of influenza A (H1N1 or H3N2) is available, and treatment is indicated:

Patients testing positive for influenza A (H3N2): Use oseltamivir or zanamivir (no preference)
Patients testing positive for influenza A (H1N1): Use zanamivir (or combination treatment with oseltamivir and rimantadine as an alternative)

Patients requiring chemoprophylaxis due to potential exposure with laboratory-confirmed influenza A (H3N2) or influenza B should receive oseltamivir or zanamivir. Patients requiring chemoprophylaxis due to influenza A (H1N1) virus should receive zanamivir (or rimantadine, if zanamivir use contraindicated).

The CDC is reminding clinicians to continue to vaccinate patients using the influenza vaccine, which is expected to be effective against all circulating influenza vaccines, including the oseltamivir-resistant strain.

For additional information, including the CDC Health Advisory, please refer to http://www2a.cdc.gov/HAN/ArchiveSys/ ViewMsgV.asp?AlertNum=00279
amantadine (Symmetrel ®): oseltamivir phosphate (Tamiflu®):
rimantadine (Flumadine ®): zanamivir (Relenza ®):

amantadine (Symmetrel ®):  top of page icon

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 ®):  top of page icon

INDICATIONS
Treatment of Influenza: TAMIFLU is indicated for the treatment of uncomplicated acute illness due to influenza infection in patients 1 year and older who have been symptomatic for no more than 2 days.
Prophylaxis of Influenza: TAMIFLU is indicated for the prophylaxis of influenza in patients 1 year and older.
TAMIFLU is not a substitute for early vaccination on an annual basis as recommended by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices.

Dosage (Adults):  -----------------------
 Influenza prophylaxis: Oral: 75 mg once daily; initiate treatment within 2 days of contact with an infected individual; duration of treatment: 10 days. During community outbreaks, dosing is 75 mg once daily. May be used for up to 6 weeks; duration of protection lasts for length of dosing period.

 Influenza treatment: Oral: 75 mg twice daily initiated within 2 days of onset of symptoms; duration of treatment: 5 days

Dosage (Pediatric):   ---------------------------
 Influenza prophylaxis: Oral: Initiate treatment within 2 days of contact with an infected individual; duration of treatment: 10 days:
Children: 1-12 years:
<=15 kg: 30 mg once daily
>15 kg to =23 kg: 45 mg once daily
>23 kg to =40 kg: 60 mg once daily
>40 kg: 75 mg once daily

 Influenza treatment: Oral: Initiate treatment within 2 days of onset of symptoms; duration of treatment: 5 days:
Children: 1-12 years:
<=15 kg: 30 mg twice daily
>15 kg - =23 kg: 45 mg twice daily
>23 kg - =40 kg: 60 mg twice daily
>40 kg: 75 mg twice daily

Adolescents >=13 years: Refer to adult dosing.
Renal Dosing: 
CRCL 10-30 mL/minute:
Treatment: Reduce dose to 75 mg once daily for 5 days.
Prophylaxis: Administer 75 mg every other day or 30 mg once daily.

Supplied
:
Capsule:
Tamiflu®: 30 mg, 45 mg, 75 mg

Powder for oral suspension:
Tamiflu®: 12 mg/mL

rimantadine (Flumadine ®):  top of page icon

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 ®):  top of page icon

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.
 

Disclaimer

Listed dosages are for - Adult patients ONLY. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER. GlobalRPH does not directly or indirectly practice medicine or provide medical services and therefore assumes no liability whatsoever of any kind for the information and data accessed through the Service or for any diagnosis or treatment made in reliance thereon.

David F. McAuley, Pharm.D., R.Ph.  GlobalRPh Inc.