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Influenza
Treatment

Treatment considerations in influenza

When treating patients with influenza, there are many factors to take into consideration. The guidelines from the Infectious Diseases Society of America (IDSA) are available to help guide the clinical decision-making process.

Infectious Diseases Society of America (IDSA) algorithm1

Influenza Treatmenta

a This diagram suggests an algorithm for antiviral use, but is not a substitute for clinical judgment. Decisions on whether to use antiviral medications should be made in the context of individual patient presentations.

 

Antiviral treatment is underutilized for influenza

Patients who could benefit from the treatment of influenza may not be getting treatment that could help.

A recent survey among adults diagnosed with influenza-like illness in the United States showed that the majority of patients reported not receiving treatment for influenza, despite CDC and IDSA recommendations.2


Studies show that antiviral influenza treatment can shorten disease duration and severity of symptoms in patients.3
  • Despite the availability

  • of antiviral therapies to

  • treat the flu, only

  • 56% of children

  • 5-11 years of age and

  • 46% of children

  • 12-17 years of age

  • with influenza-like illness

  • sought health care.2

A survey of more than 75,000 adults in the United States was conducted by Biggerstaff M et al. Results published in the Journal of Infectious Diseases in 2014.2

 

Food and Drug Administration (FDA)–approved neuraminidase inhibitors

Several types of therapies are approved for the treatment of influenza. The neuraminidase inhibitors offer different methods of administration and varying indications for use.4

Peramivir5
Single 15- to 30-minute
intravenous (IV) infusion

Oseltamivir phosphate6
5-day oral
capsule (twice daily)

Zanamivir7
5-day oral
inhalation (twice daily)

 

The neuraminidase inhibitors include oseltamivir, zanamivir, and peramivir, which are active against both influenza A and B.3,5

The optimal benefit of antiviral influenza treatments occurs when they are administered within the first 48 hours of symptoms.3

Each neuraminidase inhibitor has a different route of administration: IV, oral, or inhalation. They also have varying treatment times.4

Treatment with neuraminidase inhibitors has been shown to have clinical and public health benefits in reducing illness and severe outcomes of influenza.8

Using patient characteristics to guide treatment selection

When choosing an influenza treatment, there are some important patient characteristics to consider before deciding on a treatment approach.

Oral therapy may not be appropriate for patients who:

Present with flu-associated gastrointestinal (GI) issues such as nausea, vomiting, or diarrhea9,10

 

Have difficulty swallowing or tolerating oral medication (e.g., children or those with dysphagia)11

 

In the United States, dysphagia affects 300,000 to 600,000 persons yearly, and estimates suggest it affects 15% of the elderly population.12

Inhaled antiviral flu therapy is not recommended for certain populations7:

Patients with underlying airway disease (e.g., asthma or COPD) due to serious risk of brochospasm7

 

Patients with allergies to milk proteins7

 

Asthma and COPD may preclude more than
25 million and almost 16 million people,
respectively, from treatment with inhaled antiviral
influenza therapy.13,14

Lactose is used as a delivery agent in the inhaled
antiviral treatment delivery device.7

 

 

References: 1. Influenza in adults and children. eGuidelines website. http://eguideline.guidelinecentral.com/i/244261-influenza. Updated 2013. Accessed October 17, 2016. 2. Biggerstaff M, Jhung MA, Reed C, Fry AM, Balluz L, Finelli L. Influenza-like illness, the time to seek healthcare, and influenza antiviral receipt during the 2010-2011 influenza season—United States. J Infect Dis. 2014;210(4):535-544. 3. Clark NM, Lynch JP III. Influenza: epidemiology, clinical features, therapy, and prevention. Semin Respir Crit Care Med. 2011;32(4):373-392. 4. What you should know about influenza (flu) antiviral drugs. Centers for Disease Control and Prevention website. https://www.cdc.gov/flu/pdf/freeresources/updated/antiviral-factsheet-updated.pdf. Updated November 22, 2016. Accessed April 18, 2017. 5. Rapivab [package insert]. Summit, NJ: Seqirus USA Inc; 2017. 6. Tamiflu [package insert]. South San Francisco, CA: Genentech, Inc.; 2016. 7. Relenza [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2016. 8. CDC health update regarding treatment of patients with influenza with antiviral medications. http://emergency.cdc.gov/han/han00375.asp. Updated January 9, 2015. Accessed October 17, 2016. 9. Dawood FS, Jain S, Finnelli L, et al; Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med. 2009;360(25):2605-2615. 10. Hueston WJ, Casey BR. Respiratory problems. In: South-Paul JE, Matheny SC, Lewis EL, eds. CURRENT Diagnosis & Treatment in Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2011. http://accessmedicine.mhmedical.com/content.aspx?bookid=377&sectionid=40349419. Accessed January 28, 2017. 11. Wright D, Tomlin S. How to help if a patient can’t swallow. Pharm J. 2011;286:271-274. http://www.pharmaceutical-journal.com/files/rps-pjonline/pdf/PJ050311_271-274.pdf. Published March 5, 2011. Accessed December 12, 2016. 12. Sura L, Madhavan A, Carnaby G, Crary MA. Dysphagia in the elderly: management and nutritional considerations. Clin Interv Aging. 2012;7:287-298. 13. Asthma. Centers for Disease Control and Prevention website. https://www.cdc.gov/nchs/fastats/asthma.htm. Updated March 31, 2017. Accessed October 10, 2017. 14. Chronic obstructive pulmonary disease (COPD). Centers for Disease Control and Prevention website. https://www.cdc.gov/nchs/fastats/asthma.html. Updated August 4, 2017. Accessed October 10, 2017.
Important Safety Information  

RAPIVAB® (peramivir injection) Important Safety Information

Indication

RAPIVAB is indicated for the treatment of acute uncomplicated influenza in patients 2 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.

  • The efficacy of RAPIVAB could not be established in patients with serious influenza requiring hospitalization.

Contraindications

RAPIVAB is contraindicated in patients with known serious hypersensitivity or anaphylaxis to peramivir or any component of the product. Severe allergic reactions have included anaphylaxis, erythema multiforme and Stevens-Johnson Syndrome.

Limitations of Use
  • Rare cases of serious skin reactions, including erythema multiforme, have been reported with RAPIVAB in clinical studies and in postmarketing experience. Cases of anaphylaxis and Stevens-Johnson Syndrome have been reported in postmarketing experience with RAPIVAB. Discontinue RAPIVAB and institute appropriate treatment if anaphylaxis or a serious skin reaction occurs or is suspected. The use of RAPIVAB is contraindicated in patients with known serious hypersensitivity or anaphylaxis to RAPIVAB.

  • 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. There have been postmarketing reports (from Japan) of delirium and abnormal behavior leading to injury in patients with influenza who were receiving neuraminidase inhibitors, including Rapivab. Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made, but they appear to be uncommon. These events were reported primarily among pediatric patients. The contribution of Rapivab to these events has not been established. Patients with influenza should be closely monitored for signs of abnormal behavior.

  • Serious bacterial infections may begin with influenza-like symptoms or may coexist with or occur as complications during the course of influenza. Rapivab has not been shown to prevent such complications.

Adverse Reactions

The most common adverse reaction in adults (18 years of age and older) was diarrhea (8% Rapivab vs 7% placebo). Lab abnormalities (incidence ≥2%) occurring more commonly with Rapivab than placebo were elevated ALT 2.5 times the upper limit of normal (3% vs 2%), elevated serum glucose >160 mg/dL (5% vs 3%), elevated CPK at least 6 times the upper limit of normal (4% vs 2%), and neutrophils <1.0 x 109/L (8% vs 6%). In a subset of subjects with serious influenza requiring hospitalization treated with RAPIVAB 600 mg as monotherapy (N=101), the following adverse reactions were also reported more frequently with RAPIVAB as compared to placebo: constipation (4% versus 2%), insomnia (3% versus 0%), AST increased (3% versus 2%), and hypertension (2% versus 0%).

The safety profile of RAPIVAB in subjects 2 to 17 years of age was generally similar to that observed in adults. Specific adverse reactions reported in pediatric subjects treated with RAPIVAB (occurring in ≥2% of subjects) and not reported in adults included vomiting (3% versus 9% for oseltamivir), fever and tympanic membrane erythema (2% versus 0%, respectively, for each of these events). The only clinically significant laboratory abnormality (DAIDS Grade 2) occurring in ≥2% of pediatric subjects treated with RAPIVAB was proteinuria by dipstick analysis (3% versus 0% for oseltamivir).

Concurrent Use with Live Attenuated Influenza Vaccine

Antiviral drugs may inhibit viral replication of a live attenuated influenza vaccine (LAIV) and thus may reduce vaccine efficacy). The concurrent use of Rapivab with LAIV intranasal has not been evaluated. Because of the potential for interference between these two products, avoid use of Rapivab within 2 weeks after or 48 hours before administration of LAIV unless medically indicated.

Please see full prescribing information for Rapivab.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

RAPIVAB is a registered trademark of Seqirus UK Limited or its affiliates.