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CME / ABIM MOC / CE

Influenza: Antiviral Treatments and Prophylaxis in Children and Adolescents

  • Authors: Leigh Montejo, DNP, FNP-BC; Tina Q. Tan, MD
  • CME / ABIM MOC / CE Released: 11/14/2022
  • Valid for credit through: 11/14/2023
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  • Credits Available

    Physicians - maximum of 0.50 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 0.50 ABIM MOC points

    Nurses - 0.50 ANCC Contact Hour(s) (0.25 contact hours are in the area of pharmacology)

    Pharmacists - 0.50 Knowledge-based ACPE (0.050 CEUs)

    IPCE - 0.50 Interprofessional Continuing Education (IPCE) credit

    You Are Eligible For

    • Letter of Completion
    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for pediatricians, primary care physicians, nurse practitioners, nurses, and other clinicians who treat pediatric patients with influenza.

The goal of this activity is for learners to be better able to improve their ability to recommend current treatments and prophylaxis for influenza in children and adolescents.

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • Influenza antiviral medications for prophylaxis or treatment of children and adolescents
  • Have greater competence related to
    • Selecting appropriate influenza antiviral prophylaxis or treatments in children and adolescents
  • Demonstrate greater confidence in their ability to
    • Manage influenza in children and adolescents in an interprofessional team environment
    • Treat children and adolescents for influenza and prevent its spread to household contacts


Disclosures

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All relevant financial relationships for anyone with the ability to control the content of this educational activity are listed below and have been mitigated. Others involved in the planning of this activity have no relevant financial relationships.


Faculty

  • Leigh Montejo, DNP, FNP-BC

    Assistant Professor
    Johns Hopkins - School of Nursing
    Baltimore, MD
    Family Nurse Practitioner
    Premise Health
    Tampa, Florida

    Disclosures

    Participation by Dr Montejo does not constitute or imply endorsement by the Johns Hopkins University or the Johns Hopkins Hospital and Health System.

    Leigh Montejo, DNP, FNP-BC, has no relevant financial relationships.

  • Tina Q. Tan, MD

    Professor, Pediatrics and Infectious Diseases
    Northwestern University Feinberg School of Medicine
    Pediatric Infectious Diseases Attending
    Ann and Robert H. Lurie Children's Hospital of Chicago
    Chicago, Illinois

    Disclosures

    Tina Q. Tan, MD, has the following relevant financial relationships:
    Consultant or advisor for: GlaxoSmithKline; Merck; Moderna; Pfizer; Sanofi Pasteur
    Research funding from: GlaxoSmithKline; Pfizer

Editors

  • Iwona Misiuta, PhD, MHA

    Medical Education Director, Medscape, LLC

    Disclosures

    Iwona Misiuta, PhD, MHA, has no relevant financial relationships.

  • Kalanethee Paul-Pletzer, PhD

    Medical Education Director, Medscape, LLC

    Disclosures

    Kalanethee Paul-Pletzer, PhD, has no relevant financial relationships.

Compliance Reviewer/Nurse Planner

  • Leigh Schmidt, MSN, RN, CNE, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Leigh Schmidt, MSN, RN, CNE, CHCP, has no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has no relevant financial relationships.


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This activity was planned by and for the healthcare team, and learners will receive 0.50 Interprofessional Continuing Education (IPCE) credit for learning and change.

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  • Medscape, LLC designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credit(s)™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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CME / ABIM MOC / CE

Influenza: Antiviral Treatments and Prophylaxis in Children and Adolescents

Authors: Leigh Montejo, DNP, FNP-BC; Tina Q. Tan, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 11/14/2022

Valid for credit through: 11/14/2023

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Activity Transcript

Leigh Montejo, DNP, FNP-BC: Hello, I'm Dr. Leigh Montejo, assistant professor at Johns Hopkins School of Nursing in Baltimore, Maryland, and a family nurse practitioner for Premise Health in Tampa, Florida. Welcome to this program titled, Influenza Antiviral Treatment and Prophylaxis in Children and Adolescents. I'm happy to have my colleague joining me today. Dr. Tina Tan, professor of Pediatrics and Infectious Disease at Northwestern University Feinberg School of Medicine in Chicago, Illinois. Welcome, Dr. Tan.

Tina Q. Tan, MD: Thank you.

Dr Montejo: An overview of what we will cover in this program: influenza antiviral medication for prophylaxis or treatment in children and adolescents; the selection of appropriate influenza antiviral medications for prophylaxis or treatment in children and adolescents; management of influenza in children and adolescents in an interprofessional team environment; and finally, treating children and adolescents for influenza and preventing its spread to household contacts.

Dr Tan will now start with burden of disease in the pediatric population.

Dr Tan: Well, thank you. So, I think the one thing that people need to remember is that each year influenza places a very large burden on the health and wellbeing of children and their families. And even though the last 2 years we've had mild influenza season, based upon what was seen in Australia and the Southern hemisphere, this particular influenza season is expected to be more severe.

In any given year, influenza causes disease in millions of children. And children commonly need medical care because of influenza, especially young children under 5 years of age. And for the 2019/2020 influenza season, there were over 6.6 million medical visits for influenza in the pediatric population. We also know that each year tens of thousands of children are hospitalized for flu and its complications. And even though deaths from flu are fairly rare, we know that for the 2019/2020 influenza season, there were over 500 children, between zero and 17 years of age, that died from influenza, with over 70% of the deaths occurring in the young child population, under 5 years of age. We also know that approximately 80% of the deaths occurred in children who were not fully vaccinated. And so, that is really a major reason why you should get your patients vaccinated, in order to protect them against serious influenza disease, hospitalization, and death.

Now, when you think about the signs and symptoms of influenza, one thing to remember is that the signs and symptoms do differ depending upon the age of the child. But one thing that is very common is that you get the abrupt onset of both constitutional as well as upper respiratory track signs and symptoms. These include things such as fever, chills, myalgia, headaches, nonproductive cough, sore throat, and rhinitis. But the symptoms in young children, especially those under 2 years of age, can be more nonspecific, and may include fever plus increased sleepiness, decreased activity, and fatigue, rhinorrhea. And one thing to remember in this young child population is that GI symptoms, such as vomiting and diarrhea, tend to be very, very common symptoms associated with an influenza infection.

Now, the best way to prevent influenza disease is to vaccinate your patients. But what do you do if someone comes down with influenza? Well, there are antiviral medications that are recommended for the treatment of influenza. The 2 different classes of antiviral medications that are available include neuraminidase inhibitors and the agents in that particular class, oseltamivir, zanamivir, and peramivir. And then you have the polymerase acidic endonuclease inhibitor, of which baloxavir is the agent in that particular class. For neuraminidase inhibitors, oseltamivir can be used for individuals 2 weeks of age and older. Zanamivir, because it is inhaled, an individual has to be able to use an inhaler. So normally, it's recommended for individuals 7 years of age and older. And peramivir, which is an IV medication, is recommended for individuals 6 months of age and older. For the polymerase acidic endonuclease inhibitor, baloxavir, it is recommended for healthy individuals 5 years of age and older, that have acute uncomplicated influenza, and for individuals 12 years of age and older, if they're at high risk for developing influenza related complications.

Basically, when you think about the priority groups, for whom should receive antiviral treatment for influenza, antiviral treatment is recommended as soon as possible, for any patient with suspected or confirmed influenza, who is in the hospital, who has severe, complicated, or progressive illness, or who was considered at higher risk for influenza complications. The important thing to remember is, there is no need to wait for laboratory confirmation of the influenza infection in order to start the antiviral treatment, for any of the patients that were just discussed with suspected influenza. If you strongly suspect that the patient has influenza and they're hospitalized, have severe, complicated, or progressive disease, or are considered at higher risk for influenza complications, you should just go ahead and start your antiviral therapy. Antiviral therapy should be started as soon as possible, in order to get the maximal benefits from using antiviral treatment.

Now, children at the greatest risk for serious influenza related complications include all children under 6 months of age, because these individuals are too young to be vaccinated. And once they get influenza, they can become seriously ill with it. Also, we know that during pregnancy, it is very strongly recommended, that a woman get vaccinated during her pregnancy, in order to protect her and her infant against getting influenza during influenza season. The father should also be vaccinated. And then after birth, all close contacts of that infant should receive an influenza vaccination. We also know that kids under 5 years of age, just by virtue of their age, if they're healthy, are considered at high risk for complications and serious influenza infection. And compared with healthy, older children, individuals 2 to 5 years of age, once they come down with influenza, are much more likely to visit a doctor, an urgent care center, or an emergency room, because of the symptoms that they are experiencing with influenza. We also know that all children, 6 months to 18 years of age, who have chronic underlying health problems, are considered at high risk for serious influenza related complications. And there are certain ethnic groups that are also considered at high risk, and this includes your American Indian, and Alaskan native children. They are much more likely to develop severe influenza infection that can result in hospitalization or death. So, just remember that children between 6 months to 18 years of age, that have chronic health problems, are at increased risk for serious influenza related complications.

What are those problems? These problems are the problems that are shown here on the slide. But keep in mind, that asthma is considered to be one of the chronic health problems, that places an otherwise normal healthy child at risk for severe influenza disease and the complications associated with it.

So, what are the antiviral treatment recommendations for your non-high-risk outpatients? Well, clinicians can consider early empiric antiviral treatment for non-high-risk outpatients with suspected influenza, based upon their clinical judgment, if the treatment can be initiated within 48 hours of illness onset. So, you don't have to wait for confirmation of the influenza infection. But if you suspect that your patient has influenza, you should start them on antiviral treatment as early as possible.

And basically, the influenza antiviral treatment recommendations do differ a little bit. Depending upon whether the patient has progressive disease, or suspected or confirmed influenza, in these individuals, you would use oral oseltamivir. For outpatients with suspected or confirmed uncomplicated influenza, there are a number of different options you can use, including oral oseltamivir, inhaled zanamivir, IV peramivir, or oral baloxavir. And all of this depends upon the approved age groups for the use of these drugs. In individuals that are at high risk of developing influenza-related complications, in which, baloxavir is the drug that is recommended. And then in hospitalized patients, you can use oral or enterically administer oseltamivir. You can also, in that situation, use IV peramivir.

If we look at the duration of the neuraminidase inhibitors, so again, these are going to be oseltamivir, zanamivir and peramivir. If you look at oseltamivir, which is an oral agent, and zanamivir, which is an inhaled agent, the duration of treatment is 5 days, and the dosing does differ depending upon the age of the patient. So, for oseltamivir, if you're under a year of age, down to 2 weeks of age, the dosing is 3 milligrams per kilogram per dose twice a day. If you're over a year of age, depending upon your weight, the dosing is going to differ. But just remember that for oseltamivir, the duration of treatment is 5 days. For zanamivir, it's an inhaled medication at 10 milligrams twice daily. And again, the duration of therapy is 5 days. And for peramivir, which is an intravenous medication, it is a single dose, and depending upon your age, will determine what dose you receive. So, if you're between 6 months and 12 years of age, you get 12 milligrams per kilo[gram] up to 600 milligrams. And if you're 13 years of age and older, you get a single dose of 600 milligrams. We look at baloxavir, which is your polymerase acidic endonuclease inhibitor, it's a single dose, and dosing does differ depending upon the weight of the patient. So, if someone is 5 years of age and older, and they're between 20 kilos and less than 80 kilos, the dose is 40 milligrams. And if they're 80 or over, the dose is 80 milligrams. One thing to recognize is that, for this particular influenza season, the oral suspension formulation of baloxavir will not be available here in the United States. So, if you want to place your patient that's 5, 6, 7 years of age on baloxavir and they're unable to swallow a tablet, you will have to ask the pharmacy to compound the agent into a form that these individuals will be able to take.

So, what is the reason that we place people on antiviral medications for the treatment of influenza? Well, if you look at the efficacy of the antiviral medications, what these medications do, is that they shorten the duration of fever and the illness symptoms, usually by a day or more. They reduce the risk of some influenza complications, especially otitis media in young children; pneumonia, whether it's just influenza pneumonia or bacterial pneumonia that complicates the influenza pneumonia; and it also reduces the risk for respiratory failure. It reduces death in hospitalized patients, and it does shorten the duration of hospitalization. And just remember that the sooner you're able to start the medication in someone that you suspect has influenza, the more efficacious the medication is going to be. Now, the clinical benefit, as I just mentioned, is greatest, when treatment is administered early, especially within 48 hours of influenza onset. However, treatment does continue to have benefit in patients with severe, complicated, or progressive illness, and in hospitalized patients, when it's started after 48 hours of illness onset. And usually, the benefits extend out to around 5 days after symptom onset. Sort of beyond 5 days, you really don't have too much of a benefit for treating individuals with antiviral medications.

Now, chemoprophylaxis is another way to use antiviral medications. And chemoprophylaxis is something that many people don't think very much about. If you think about chemoprophylaxis and the agents that you can use: for neuraminidase inhibitors, you can use oseltamivir, if an individual is 3 months of age and older; or zanamivir, if someone is 5 years of age and older. And for baloxavir, which is a polymerase acidic endonuclease inhibitor, you can use chemoprophylaxis if an individual is 5 years of age and older.

So, when do you chemoprophylax? Well, in general, whether it's pre-exposure or post-exposure prophylaxis, the widespread or routine use of antiviral medications for chemoprophylaxis is really not routinely recommended, except in the pre-exposure situation, if it can be used as one of multiple interventions to control large influenza outbreaks. And in the post-exposure situation, the one reason to really not use chemoprophylaxis is that, if an individual has influenza, and you put them on subtherapeutic treatment doses, and the person has the infection, you're not going to treat the infection, and you may predispose this individual to developing a resistant organism. So, in general, for most situations, pre-exposure and post-exposure chemoprophylaxis is not really recommended.

However, there are certain situations in the community setting where chemoprophylaxis can be considered for individuals 3 months of age and older. This includes individuals that are considered at very high risk of developing influenza associated complications, and influenza vaccination is contraindicated, unavailable, or they're expected to have low effectiveness. And the best example of this is very young infants, under 6 months of age, who cannot be vaccinated. Those individuals at the highest risk of influenza associated complications are individuals that are immune compromised, such as people that are recipients of stem cell transplants; in the first 6 to 12 months post-transplant, as well as other transplant recipients. Individuals that are not yet vaccinated and are at high risk of developing complications from influenza, when influenza is circulating in the community. And close contacts of persons at high risk of developing influenza complications, in whom influenza vaccination is contraindicated, who are unable to take antiviral chemoprophylaxis.

In the post-exposure chemoprophylaxis situations, there are certain situations in which you can consider chemoprophylaxis for asymptomatic individuals, after exposure to a person with influenza. And these again, include individuals at very high risk of influenza complications. So, very young infants; individuals that are severely immune compromised; and in those individuals in whom influenza vaccination is contraindicated, unavailable, or expected to have very low effectiveness. And you really should initiate the chemoprophylaxis within 48 hours of exposure. Also, the other group to consider post-exposure prophylaxis in are those individuals not yet vaccinated and are household contacts of a person at very high risk for complications from influenza. The most common example of this is someone who is severely immunocompromised.

How effective are these antiviral medications for chemoprophylaxis? Well, if we look at the neuraminidase inhibitors, they are anywhere from 70% to 90% effective in preventing influenza, in those individuals who are either pre-exposed or post-exposed. And if you look at the polymerase acidic endonuclease inhibitor baloxavir, it is 86% effective in preventing influenza in household contacts post-exposure. So, you can see, that these antiviral medications are very effective in preventing and protecting individuals from getting influenza.

We look at the adverse effects associated with the antiviral medications. For oral oseltamivir, the most common adverse events are GI upset. So, you have nausea, vomiting. And you can also have headache. And in some cases, people can develop more serious neurologic complications. For zanamivir, because it is inhaled, there is a risk of bronchospasm, especially in the setting of individuals that have underlying airway reactive disease; sinusitis; and dizziness. And so, with zanamivir, there is a precaution for not using zanamivir in those individuals that have asthma or other underlying reactive airway disease. And peramivir, which is given intravenously, the major adverse event associated with that particular medication is GI [gastrointestinal] upset and diarrhea. For baloxavir, which is an oral agent, the most common adverse events that are seen with this particular drug are GI upset. So, diarrhea and nausea, as well as headache.

Dr Montejo: Great. Dr. Tan shared a wealth of information on this topic. Now we'd like you to join us in an interprofessional discussion. Dr. Tan, I found it very beneficial to be able to discuss the risk and benefits of influenza treatment and prophylaxis with my patients. What recommendations do you have for how to effectively educate pediatric patients and their families about antiviral treatment and prophylaxis?

Dr Tan: I think, probably the most important thing is to really find out whether or not patients and their parents know about antiviral treatment and their use for prophylaxis. You can discuss that with them. You can basically discuss the risks and the benefits of not using antiviral treatment or chemoprophylaxis. And then, you can also identify barriers that they may have to access the drugs and help them determine whether or not they would like to use these medications. Now one thing about baloxavir is that, for individuals that have Medicaid, at this point in time, they are not able to access baloxavir. So, you will have to use neuraminidase inhibitors for treatment, as well as chemoprophylaxis, in these individuals.

Dr Montejo: That's a great clinical pearl, Doc, to be familiar with and understand what is covered and not covered for a patient-specific approach. We want to remember that using evidence-based approach to educating the patients is going to be your best bet and being able to explain and provide the evidence is helpful. So, if you're familiar with the evidence, you can explain it, and provide that evidence to your patients.

Dr. Tan mentioned identifying the barriers that prevent access. So, you want to make sure that there's not only an individualized or personalized plan, but also, what are those barriers? So, it's not covered by their insurance? Is it a matter of availability or timing? So, if vaccines can be available at a variety of times and different variety of settings, it increases access for those patients.

And then again, repetition of information, and providing information to your patients in a variety of communication modalities, is going to be very helpful. So, you can give in-person face to face information; or you can distribute information electronically, like via the patient portal or email. So, there's a lot of ways to inform the patient and they can make their informed decisions.

Speaking of communication, there are some strategies on communicating personalized influenza treatment plans for pediatric patients and their families that have been effective. Are there any that you have personally found to be effective?

Dr Tan: I have. Actually, for the patients that I care for, which is patients of all different ethnicities, very, very diverse, it really is face-to-face, one-on-one discussions with them, that they really feel like you are invested in them and their child. And they are definitely much more receptive to receiving information in that manner, because they have the ability to ask questions if they don't understand this. As opposed to, giving them information via email or via patient portal, they don't have the ability to actually ask questions about things that they don't understand.

Dr Montejo: I think you make a great point in that we want to be able to have a dialogue, a back-and-forth conversation with our patients about the benefits, the risk. So how do I identify those symptoms early? There are realistic time constraints in practice. So, I think one of the good interventions that has been helpful, is utilizing your support staff to start this conversation at check-in, and then we can continue the conversation as the provider. So, I think that's a great opportunity there, to be able to connect with the patient, and really give them that evidence-based rationale, and let them make their informed decisions.

So again, just making sure that you're utilizing community partners as well, so outpatient settings that can provide information and that can have the same conversation. So, some examples of that are, anybody in retail clinics or pharmacies, where they can disseminate that information and have that dialogue, conversation, and then the patient can follow up either, if it's available in that setting, or they can follow up with us as well. So yeah, I think that's really useful, is the dialogue back and forth, and having an informed conversation is really beneficial to uptake.

And finally, as we discussed, primary prevention of influenza is obtained through annual influenza immunization for all members of the household. So, what are some recommendations you have for those children and adolescents in their household, who may need treatment, if they either have not had the prevention, or the prevention was not as effective as we would've hoped?

Dr Tan: In these situations, I think when you present influenza vaccination, it's always important to say, no vaccination is 100%. The major reason that we vaccinate, and the major reason to be vaccinated, is to prevent serious disease, complications, hospitalizations, and death, which is what vaccines do. I think we also need to make our patients aware of the fact that if they come down with influenza, that there are medications that they can take that will help them get over this influenza infection more quickly. And these medications can be used for chemoprophylaxis, in the situation where they're living in multi-generational households, and there are people in the household that, if they got influenza, may become very, very seriously ill with it. So, I think again, it goes back to having a dialogue with the patient and providing them with the information about vaccination, about antivirals, and about how to recognize influenza, when to seek medical treatment, and basically, what is available.

Dr Montejo: Yes, perfect. Exactly. So, I think, one of the big things is making sure we provide education on those signs and symptoms. Right? Because if we need to intervene, what we've learned is, the earlier we can intervene with those antivirals for treatment is better. So yes. Excellent. Thank you so much for your knowledge and your expertise in this great discussion today.

So, I wanted to, in summary, just provide a couple of key takeaway points for everyone. There are 2 classes of antiviral medications for prophylaxis or treatment of influenza in children and adolescents. Those are going to be neuraminidase inhibitors or the polymerase acid endonuclease inhibitor. The use of each class is dependent on age, risk, availability, and any barriers to obtaining the medication. Routine use of chemoprophylaxis is generally not recommended pre- or post-exposure, but it can be considered in those very high-risk situations that we discussed.

Clinical benefit of antiviral treatment has the greatest treatment benefit when administered early, especially within 48 hours of influenza illness onset. Recognizing those signs and symptoms and seeking care is important. It is especially important to initialize treatment for any patient with suspected or confirmed influenza who is hospitalized; has severe, complicated, or progressive illness; or is at high risk of influenza complication. In these populations, there is still benefit in treatment, if initiated after the 48 hours.

Management of influenza in children and adolescents should include an interprofessional team approach, to ensure an individualized care plan that identifies and overcomes barriers. Annual influenza immunization is important in preventing the spread of influenza within households and the overall community.

Again, Dr. Tan, thank you so much for joining me in this program, and for the great discussion, and sharing of your expertise.

Dr Tan: My pleasure.

Dr Montejo: Thank you all for participating in this activity.

This transcript has not been copyedited.

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