One of three articles in the 2016 Flu Review:
Predicting the Flu: The New Vaccines by Evan Schwarz, MD
How Accurate Are Rapid Flu Tests? by Bill Sullivan, DO, JD
We may not be seeing a spike in influenza yet this season, but we still need to keep up on the facts. Here are four thoughts to consider as more flu-like symptoms start to reach the ED.
Economics
A search of goodrx.com [1], the website we often use to find drug coupons for our patients, gives the current US price of Tamiflu at $138.34-$156.00 for a 10-pill, 5 day course (without coupon).
In April 2014, Andrew Jack, BMJ deputy analysis editor, called Tamiflu ‘a nice little earner’ for Roche pharmaceuticals. The company reportedly earned > $18 bn since 1999, with half of the total expenditure for pandemic preparation stockpiles [2].
Chicken Soup
Several critiques suggest that Tamiflu® should have been compared to other treatments for ILI (influenza-like illness) or influenza, not just placebo. For instance, remedies such as echinacea and zinc reportedly have some benefit. One European study caught my eye: 473 patients with ILI, but unfortunately only 47% with viral cultures obtained, were given either Tamiflu or an OTC preparation called Echinaforce Hotdrink. In this randomized, double-blind, double-dummy multi-center trial in Prague, Echinaforce Hotdrink® was determined to be non-inferior to Tamiflu® One of the tables showed more symptom improvement in the first 24 hours with Tamiflu® compared to the echinacea preparation, but in overall efficacy, both drugs were similar [5]. My dad, who was raised in Eastern Europe, always laughed at US ‘modern’ medicine, saying that none of us fancy doctors ever looked back to see what worked in the old country. Maybe he was on to something.
Treatment in Healthy, Low-Risk Non-Hospitalized Patients
There are three neuraminidase inhibitors available, all with comparable efficacy. Oseltamivir/Tamiflu® (oral), zanamivir (inhaled) and peramivir (intravenous). This discussion focuses on Tamiflu® as it is the most studied. The 2014 Cochrane review so far remains the most robust analysis of Tamiflu® effectiveness [6,7].
The populations studied were basically healthy (asthma, diabetes, and hypertension were included) non-hospitalized children and adults. The only outcome studied was the duration of symptoms.
Absent a pandemic of virulent influenza virus, ambulatory healthy patients are the least likely to develop severe disease or require hospitalization. In the non-hospitalized, Tamiflu® ameliorates symptoms for about half a day in adults (from about 7 to about 6 and a half days), and a bit over a day in children [6]. Tamiflu® is not effective against non-influenza viral illnesses. In healthy outpatients, viral shedding occurs in the first 2-3 days and is correlated with symptoms, so this is the reason for the timing of administration of the drug. All these facts make the prescription for Tamiflu a real toss-up for healthy, low-risk non-hospitalized patients (the side effects are also real, however – mostly vomiting but also some psychiatric effects and renal events in certain populations).
Tamiflu is often cited for its ability to prevent pneumonia, but the Cochrane review makes clear that when pneumonia was clearly defined, the drug had no effect on prevention in healthy adults and children [7].
Treatment in High-risk ambulatory patients and severely ill (hospitalized) patients
Recommendations for treatment of ill patients are extrapolated from outpatient studies, and it is unlikely that we will see RCT’s assessing affecting treatment for hospitalized severely ill patients. But still, following society guidelines, it’s important to base treatment decisions on your individual patients—those at risk for severe influenza. In children and the immunosuppressed, viral shedding can continue beyond 2-3 days. In ill hospitalized patients, viral shedding can continue for weeks. Therefore, in high-risk patients, treatment can be given even if symptoms have persisted beyond 2-3 days.
The April 2014 Infectious Disease Society of America (IDSA) recommendations state: start antiviral treatment with oral oseltamivir as soon as possible for any hospitalized patient with suspected or confirmed influenza, and for any patient with suspected or confirmed influenza who has severe or progressive illness, and for those at higher risk for influenza complications: children < 2 yrs old, elderly, pregnant women, chronic conditions including neuromuscular conditions, immunosuppression, those with BMI +/> 40, nursing home residents, American Indians, and Alaska natives [8].
REFERENCES
- http://goodrx.com, accessed dec 6, 2015
- BMJ 2014; 348 doi http://dx.doi.org/10.1136/bmj.g2524 (April 9, 2014)
- http://www. CDC. .gov (Table. Influenza vaccines – United States, 2015-2016 Influenza season/seasonal influenza/Flu/CDC , accessed Dec 6, 2015 )
- Welch et al ‘High-dose versus standard dose oseltamivir for treatment of severe influenza in adult intensive care unit patients’ Intensive Care Med (May 2015 41:1365-1366)
- Raus K, et al ‘Effect of an Echinacea-Based Hot Drink Versus Oseltamivir in Influenza Treatment: A Randomized, Double-Blind, Double-Dummy, Multicenter, Noninferiority Clinical Trial’ Curr Ther Res 77 (2015); 66-72.
- Jefferson T et al ‘Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children’ The Cochrane database of systematic reviews 2014; 4 CD008965.
- Jefferson T, et al ‘Oseltamivir for Influenza in Adults and Children: systematic rview of clinical study reports and regulatory coments; BMJ 2014 Apr 9;348g2545 PMID 24811411
- Statement by the Infectious Disease Society of America on the recent publication on ‘Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children, April 2014, http://idsociety.org, accessed 12/6/15.
- http:www.cdc. gov/flu/Rapid Diagnostic Testing for Influenza: page updated October 13, 2015, accessed Dec 9, 2015.
- Louie JK and Lampiris H Treatment Influenza with Neuraminidase Inhibitors. What is the Evidence? JAMA Intern Med 2015:175 (12) 1899-1900.
