With the outbreak of seasonal influenza this year, many people began to snap up oseltamivir, the "flu specific drug".
The question is, is oseltamivir really a flu drug?
Oseltamivir is widely recommended for influenza treatment and prevention
Almost all medical institutions in the world recommend oseltamivir for the treatment of influenza in children and adults; It is also recommended for influenza prophylaxis in children and adults who have been in close contact with influenza patients.
The WHO also recommends that member countries stockpile oseltamivir in response to seasonal influenza or influenza pandemics.
The mechanism of action of oseltamivir against influenza is mainly that, as a neuraminidase inhibitor, it can hinder sialidase activity and virus release from cells by competitively binding to the neuraminidase active site of influenza virus.
The reason oseltamivir is recommended for influenza treatment and prevention is that clinical trials have shown that oseltamivir can shorten the time to relief of influenza symptoms by about 1 day; It can reduce the risk of complications such as pneumonia, bronchitis, otitis media and sinusitis to varying degrees.
Therefore, it seems that oseltamivir, although not a flu specific drug, can at least be said to be an effective treatment and prevention drug.
Cochrane's ingenious roundup: few effects, many side effects
A unique review conducted by the Cochrane Acute Respiratory Infections Unit came to mixed conclusions.
The Cochrane group believes that the popular mainstream rhetoric about oseltamivir comes from published clinical trial data, these are promotional videos between finely decorated samples, I don't watch these things; I want to see the original documents of the rough room quality inspection report submitted by the developer to the regulatory authorities, that is, the original clinical research report submitted by the oseltamivir manufacturer to the drug regulatory agency.
Typically, these reports are large documents of tens or hundreds of pages, are not published publicly, and are confidential.
Given the Cochrane Collaborative's pre-eminent position in evidence-based medicine, they had access to the documents.
The Cochrane team analysed dozens of studies on oseltamivir clinical trials obtained from the US Food Administration (FDA), the European Medicines Agency (EMA) and Japanese regulatory agencies and found that:
Oseltamivir, used in the treatment of influenza in adults, can shorten the time to symptom relief by 16.8 hours. This means that the time to first relief of symptoms is reduced from 7 days to 6.3 days; for flu treatment in healthy children, the time to symptom relief can be shortened by an average of 29 hours, but there is no effect on children with asthma.
Oseltamivir did not significantly reduce the risk of hospitalization, i.e., it did not reduce the risk of severe influenza disease in either children or adults.
Unlike published trials, oseltamivir did not significantly reduce serious complications of influenza in either adult or pediatric influenza treatment trials.
Among them, although oseltamivir significantly reduced the risk of self-reported, undiagnosed pneumonia in adults; However, there was no effect on the risk of more clearly diagnosed pneumonia. In children, even undiagnosed pneumonia has no significant effect.
Although zanamivir, another neuraminidase inhibitor, significantly reduced the risk of bronchitis in adult treatment trials, oseltamivir did not show this efficacy. Neither oseltamivir nor zanamivir significantly reduced the risk of otitis media and sinusitis in adults and children.
That said, unlike published clinical trial data that one can see, clinical studies submitted by manufacturers to regulatory agencies did not show the effect of oseltamivir in reducing serious flu-related complications.
In this regard, the US FDA and the European EMA have adopted different regulatory attitudes.
Since the FDA approved the oseltamivir label in 2000, it has consistently stated: "Severe bacterial infections may begin with flu-like symptoms or may coexist with or occur as a complication of influenza." Tamiflu (oseltamivir from Roche) has not been shown to prevent these complications. ”
In response to Roche's statement that "Tamiflu can reduce the complication rate of secondary bacterial infections by 45%", the FDA sent a regulatory letter, calling Roche's above statement a "misleading efficacy statement." In the information in the promotional materials of the subsequent product, the claims regarding oseltamivir have been consistent with FDA requirements.
Unlike the FDA, the EMA has long supported the claim that oseltamivir can prevent complications of influenza, and its published oseltamivir "Product Characteristics Overview" states that oseltamivir significantly reduces the incidence of "specific lower respiratory tract complications (mainly bronchitis) treated with antibiotics" in individuals 13 years of age and older.
The Cochrane review supports the FDA's regulatory view.
In terms of prevention, trial evidence suggests that oseltamivir does reduce the risk of symptomatic influenza in close contacts.
However, we know that seasonal influenza epidemics span several months, and people can't take oseltamivir for a long time throughout the flu season to prevent the flu, right?
Therefore, saying oseltamivir does not have much value in preventing influenza.
Compared with the relatively few therapeutic and prophylactic effects, the side effects associated with oseltamivir use are not aging.
Side effects of oseltamivir are mainly manifested in nausea, vomiting, and the risk of altered mental status.
It is not a special medicine, or a "miracle medicine"
The Cochrane review also has evidence that questions the mechanism of action of oseltamivir in the treatment of influenza.
Evidence showed a significant but slightly reduced proportion of serum influenza virus antibody titers increased by 4 times or more in participants treated with oseltamivir; Moreover, studies have also shown that oseltamivir reduces serum antibody titers while also reducing the level of secretory IgA antibodies in the nasal cavity and bronchoalveoli by a larger extent (80%).
At the same time, oseltamivir significantly inhibits levels of major inflammatory factors including interleukin-6, tumor necrosis factor α, and interferon γ.
There is also conclusive evidence that oseltamivir treatment in animals attacked by respiratory syncytial viruses lacking the neuraminidase gene has also shown symptomatic relief. That is, although oseltamivir has little effect in treating influenza, it also appears to be effective against respiratory syncytial virus infection.
Based on the above evidence, the authors suggest that the mechanism of action by oseltamivir to relieve influenza symptoms through immunosuppression may be more certain, regardless of whether influenza virus replication is inhibited.
In addition, oseltamivir has potential cooling or defervescing effects as a central nervous system depressant, and may also help relieve influenza symptoms.
That is, whether or not it really has an anti-influenza effect, oseltamivir will relieve flu symptoms through hormonal or ibuprofen-type anti-inflammatory drug mechanisms.
Given the extremely limited effect of symptomatic relief, antiviral or anti-inflammatory, which is the real effect of oseltamivir "anti-influenza"?
In summary, oseltamivir can shorten the time of influenza symptoms by half a day to 1 day, and cannot reduce the risk of complications such as pneumonia; The limited effect is uncertain whether it is achieved by antiviral mechanisms or may be "credited" to immunosuppressive and anti-inflammatory effects.
It seems that oseltamivir is not an anti-flu specific drug, but more like an over-touted "miracle drug".