Administering anti-influenza medications

How can influenza be managed with medications? In this lesson, we'll cover the mechanisms of action, spectrums, side effects, indications and contraindications of neuraminidase inhibitors, amantadine, and rimantadine.

John F. Fisher, MD MACP FIDSA
John F. Fisher, MD MACP FIDSA
5th Aug 2019 • 3m read

In this short video, Dr John Fisher–infectious disease specialist–will teach you the nuts and bolts of anti-influenza medications. You'll learn about the indications, contraindications, and best practices regarding these medications with a focus on neuraminidase inhibitors, amantadine, and rimantadine.

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Video Transcript

[00:00:00] During influenza epidemics, attack rates and unvaccinated populations are estimated to be 10% to 20%. The CDC reported that the burden of illness during the 2017-2018 season had an estimated 48.8 million people getting sick with influenza, 22.7 million people going to a health care provider,

[00:00:30] 959,000 hospitalizations, and 79,400 deaths from influenza in the United States alone. There are several classes of drugs that target influenza through different mechanisms. Let's start by looking at the neuraminidase inhibitors. After infecting and replicating in bronchial epithelial cells, influenza virus requires an enzyme called neuraminidase

[00:01:00] in order to allow it to freely leave the cell and infect nearby cells. As their name suggests, neuraminidase inhibitors inhibit this enzyme effectively, trapping the virus within the infected cell, and preventing spread to neighboring cells. Common neuraminidase inhibitors include zanamivir which is inhaled, oseltamivir which is orally active, and peramivir which is typically

[00:01:30] administered IV. The neuraminidase inhibitors are reasonably effective for preventing influenza among household contacts or in nursing home settings during an outbreak. However, the data show that they are not particularly effective for treating influenza especially if given after infection has been present for more than 48 hours and they are expensive. Oral administration of oseltamivir

[00:02:00] is associated with nausea, epigastric distress or emesis in 10% to 15% of adults. Other side effects are uncommon. Because inhaled zanamivir can cause bronchospasm, they should not be used in persons with serious underlying respiratory disease, for example, COPD. For completeness, amantadine and rimantadine should be discussed even though many current

[00:02:30] strains of influenza virus have developed resistance to these agents. The ion channel protein M2 on influenza viruses allows acids in respiratory epithelial cells to enter the virus. This triggers the virus to release genetic instructions and "replicate." Amantadine and rimantadine sterically interfere with the function of the M2 protein channel,

[00:03:00] thus, preventing viral replication. Once reasonably effective for prophylaxis but minimally effective for treatment, since the 2004-2005 outbreak of H3N1 influenza, there has been fairly widespread resistance to these agents. Moreover, the CNS side effects made them not ideal for prevention in nursing home settings. So these drugs are generally reserved for seriously ill patients

[00:03:30] with a hope that they may be of some help in eliminating the virus. Amantadine and rimantadine are commonly associated with CNS toxicity which may be mild, such as nervousness, anxiety, difficulty concentrating, lightheadedness are rarely serious, including confusion, delirium, or hallucinations. Influenza generally differs clinically from a typical respiratory infection due to other viruses

[00:04:00] in that it is much more aggressive and patients have to go to bed often with fever and chills, bad muscle aches, headache, and joint aches. Since the drugs are expensive, and the symptoms begin abruptly, rapid influenza testing and treatment would be reasonable for patients who present within the first 48 hours after disease onset. If the illness has been present for more than 48 hours, the literature suggests

[00:04:30] that the drugs are unlikely to be as effective. This does not mean that they are not at all effective. Indeed, there is evidence of decreased mortality in patients hospitalized with proven influenza if treated with neuraminidase inhibitors. This is the reason that the current guidelines recommend that persons of any age who are hospitalized with influenza regardless of illness duration prior to hospitalization be treated. Because

[00:05:00] the clinical benefit of treatment as great as the earlier the treatment is initiated, empirical antiviral treatment should be given as soon as possible without waiting for influenza testing results when patients with suspected influenza are being admitted to the hospital. Antiviral drugs should not be used for routine or widespread chemoprophylaxis outside of institutional outbreaks.