Oseltamivir (Tamiflu) for Children, Maybe Not a Magic Pill
Making a patient feel better is empowering and rejuvenates our professional spirits. This is why we all love taking care of the patient with a Patellar Dislocation, Shoulder Dislocation, or a Nursemaid’s elbow. Obviously, administering Adenosine for SVT can make you feel like a magician also! Unfortunately, the availability of Magic Medicine is limited. Even more unfortunate, our patients are often preconditioned to look for a magic pill. This flu season has been challenging, on multiple fronts, because patients have been told of the importance of Oseltamivir (Tamiflu). I, personally, however, have not seen a magic pill in our clinical environments. When something seems to be incongruent, I look to see what the Cochrane Library has to say. Let us review what is known about oseltamivir today (and actually since 2014):
Influenza
- Influenza is highly contagious.
- Influenza can may cause mild disease, but can also lead to severe illness and complications. [CDC, Disease Burden]
- Remember — never say “It’s just a virus” as a means to convey reassurance…
- Numerous viral infections can lead to horrific outcomes.
- There are special populations who are at greater risk from the disease:
- >65 years of age
- Pregnant (and up to 2 weeks post partum)
- Residents of long-term care facilities
- Children <5 years of age (particularly <2 years of age)
- Patient with chronic medical problems, like asthma (see CDC list)
- Influenza Vaccination has proven to be an effective means to reduce influenza-related morbidity.
- Unfortunately, influenza vaccination is still underused among at risk patients. [CDC, Flu Vaccination Rates]
Influenza: Therapies(?)
- The Center for Disease Control (CDC) currently states:
- “Prescription medications called ‘antiviral drugs’ … can be used to treat flu illness.” (CDC.gov)
- “It’s very important that flu antiviral drugs are started as soon as possible to treat: (CDC.gov)
- hospitalized flu patients,
- people who are very sick with the flu but who do not need to be hospitalized,
- and people who are at high risk of serious flu complications.”
- “…most people who are otherwise healthy and get the flu do not need to be treated with antiviral drugs.” (CDC.gov)
- The available “therapies” for children:
- Peramivir – for patients 2 years and older (only in IV form)
- Zanamivir – for patients 7 years and older (not for pts with asthma)
- Oseltamivir – for patients 14 days and older
- Oseltamivir is on the World Health Organizations List of Essential Medicines
- Governments now stockpile Oseltamivir to be prepared for pandemics.
Oseltamivir and Neuraminidase Inhibitors: The Problem
- Much of the the justification for recommendations and stockpiling are based on pharmaceutical company-based research. [Gupta, 2015]
- Not that industry-sponsored research is unable to generate important information and be valuable… but…
- These particular studies, when re-reviewed, had issues: [Jefferson, 2014]
- The original detailed data was not made easily available.
- Definitions of disease and complications were vague.
- Placebo interventions (when used) may have had active substances.
- In order to address developing concerns about zanamivir and oseltamivir, Jefferson et al.: [Jefferson, 2014]
- Did not use the journal publications (as there was publication bias and discrepancies).
- Instead, obtained the manufacturers’ reports to regulators and the regulators’ comments.
- These are unpublished, extensive documents with great detail on the trials that formed the basis for market approval.
- They include the protocols, methods and results.
- They are typically confidential – seen only by the manufacturers and regulators.
- After review of this information, found “substantial problems with the design, conduct, reporting, and availability of information from many trials.”
- Based on this re-review, several areas of potential bias were found:
- Performance Bias – from differences in care provided to participants.
- Selection Bias – there was inadequate reporting to understand how groups were assigned to therapies
- Attrition Bias – participants who drop out (possible due to side-effects) not being included in the results.
Oseltamivir: What is Concluded
- For adults, Oseltamivir (Tamiflu): [Jefferson, 2014]
- Reduced time to alleviation of symptoms by 16.8 HOURS.
- Prophylactic use can reduce the risk of developing symptomatic influenza.
- Had no significant effect on hospitalizations.
- Did not reduce complications classified as serious.
- Did not reduce the otitis media or sinusitis.
- May have reduced self-reported, unverified pneumonia (lack of definition)
- Side-effects seen:
- Nausea with Number Needed to Harm (NNTH) = 28
- Vomiting with NNTH = 22
- Dose-response effect on psychiatric events.
- Headache, renal and psychiatric events seen during prophylaxis therapy.
- In children, Oseltamivir (Tamiflu): [Jefferson, 2014]
- Reduced time to alleviation of symptoms by 29 HOURS in healthy children.
- Had NO SIGNIFICANT effect in children with asthma (one of the high risk groups).
- Had NO SIGNIFICANT effect in hospitalizations.
- Had NO SIGNIFICANT effect in prophylaxis.
- Did not reduce complications classified as serious.
- Did not reduce the otitis media or sinusitis.
- Did not have an effect on unverified pneumonia.
- Nausea is seen frequently as side-effect with NNTH = 19
Moral of the Morsel
- Don’t be Biased! Regardless of where research originates from, its conclusions may be substantially influenced by numerous biases… good study design aims to help reduce this risk.
- Don’t be Bullied! Understand the recommendations… but also their limitations. Asthma may place a patient in the high risk category, but there is no evidence that a child with asthma benefits from oseltamivir.
- Weigh Risk and Benefit! We do this with all conditions, evaluations, and therapies… hopefully this Morsel will help you with the true weight of the items in this specific equation.
- Educate Your Patients and Their Families! This goes without saying… but is the most important.
Sean Fox, thanks a lot for the article post.Much thanks again. Fantastic.
You are welcome!
Sean,
AWESOME job on this week’s morsel. This provides clarity on what has been a very confusing flu season in regards to CDC recs. I continue to read your morsels every single week and appreciate them so much. Keep up the great work!
Seth
Niswonger Children’s ED – Johnson City, TN
Excellent