Oseltamivir
Oseltamivir, sold under the brand name Tamiflu among others, is an antiviral medication used to treat and prevent influenza A and influenza B, viruses that cause the flu. Many medical organizations recommend it in people who have complications or are at high risk of complications within 48 hours of first symptoms of infection. They recommend it to prevent infection in those at high risk, but not the general population. The Centers for Disease Control and Prevention recommends that clinicians use their discretion to treat those at lower risk who present within 48 hours of first symptoms of infection. It is taken by mouth, either as a pill or liquid.
Recommendations regarding oseltamivir are controversial as are criticisms of the recommendations. A 2014 Cochrane Review concluded that oseltamivir does not reduce hospitalizations, and that there is no evidence of reduction in complications of influenza. Two meta-analyses have concluded that benefits in those who are otherwise healthy do not outweigh its risks. They also found little evidence regarding whether treatment changes the risk of hospitalization or death in high risk populations. However, another meta-analysis found that oseltamivir was effective for prevention of influenza at the individual and household levels.
Common side effects include vomiting, diarrhea, headache, and trouble sleeping. Other side effects may include psychiatric symptoms and seizures. In the United States, it is recommended for influenza infections during pregnancy. It has been taken by a small number of pregnant women without signs of problems. Dose adjustment may be needed in those with kidney problems.
Oseltamivir was approved for medical use in the US in 1999. It was the first neuraminidase inhibitor available by mouth. It is on the World Health Organization's List of Essential Medicines but was downgraded to "complementary" status in 2017. A generic version was approved in the US in 2016. In 2023, it was the 250th most commonly prescribed medication in the United States, with more than 1million prescriptions.
Medical use
Oseltamivir is used for the prevention and treatment of influenza caused by influenza A and B viruses. It is on the World Health Organization's List of Essential Medicines. The World Health Organization supports its use for severe illness due to confirmed or suspected influenza virus infection in critically ill people who have been hospitalized. Oseltamivir's risk-benefit ratio is controversial. In 2017, it was moved from the core to the complementary list based on its lower cost-effectiveness. The Expert Committee did not recommend the deletion of oseltamivir from the EML and EMLc, recognizing that it is the only medicine included on the Model Lists for critically ill patients with influenza and for influenza pandemic preparedness. However, the Committee noted that, since the inclusion of oseltamivir on the Model List in 2009, new evidence in seasonal and pandemic influenza has lowered earlier estimates of the magnitude of effect of oseltamivir on relevant clinical outcomes. The Committee recommended that the listing of oseltamivir be amended, moving the medicine from the core to the Complementary List, and that its use be restricted to severe illness due to confirmed or suspected influenza virus infection in critically ill hospitalized patients. The Expert Committee noted that WHO guidelines for pharmacological management of pandemic and seasonal influenza would be updated in 2017: unless new information is provided to support the use of oseltamivir in seasonal and pandemic outbreaks, the next Expert Committee might consider oseltamivir for deletion.High-risk people
The US Centers for Disease Control and Prevention, European Centre for Disease Prevention and Control, Public Health England, and the American Academy of Pediatrics recommend the use of oseltamivir for people who have complications or are at high risk for complications. This includes those who are hospitalized, young children, those over the age of 65, people with other significant health problems, those who are pregnant, and Indigenous peoples of the Americas among others. The Infectious Disease Society of America takes the same position as the CDC.A systematic review of systematic reviews did not find evidence for benefits in people who are at risk, noting that "the trials were not designed or powered to give results regarding serious complications, hospitalization and mortality", as did a 2014 Cochrane Review. The Cochrane Review further recommended: "On the basis of the findings of this review, clinicians and healthcare policy-makers should urgently revise current recommendations for use of the neuraminidase inhibitors for individuals with influenza." That is not utilizing NIs for prevention or treatment "Based on these findings there appears to be no evidence for patients, clinicians or policy-makers to use these drugs to prevent serious outcomes, both in annual influenza and pandemic influenza outbreaks."
The CDC, ECDC, Public Health England, Infectious Disease Society of America, the AAP, and Roche reject the conclusions of the Cochrane Review, arguing in part that the analysis inappropriately forms conclusions about outcomes in people who are seriously ill based on results obtained primarily in healthy populations, and that the analysis inappropriately included results from people not infected with influenza. The EMA did not change its labeling of the drug in response to the Cochrane study.
A 2014 review recommended that all people admitted to intensive care units during influenza outbreaks with a diagnosis of community-acquired pneumonia receive oseltamivir until the absence of influenza infection is established by polymerase chain reaction testing.
A 2015 systematic review and meta-analysis found oseltamivir effective at treating the symptoms of influenza, reducing the length of hospitalization, and reducing the risk of otitis media. The same review found that oseltamivir did not significantly increase the risk of adverse events. A 2016 systematic review found that oseltamivir slightly reduced the time it takes for the symptoms of influenza to be alleviated, and that it also increased the risk of "nausea, vomiting, psychiatric events in adults and vomiting in children." The decrease in duration of sickness was about 18 hours.
Otherwise healthy people
In those who are otherwise healthy the US Centers for Disease Control and Prevention states that antivirals may be considered within the first 48 hours. A German clinical practice guideline recommends against its use.Two 2013 meta-analyses have concluded that benefits in those who are otherwise healthy do not outweigh its risks. When the analysis was restricted to people with confirmed infection, the same 2014 Cochrane Review found unclear evidence of change in the risk of complications such as pneumonia, while three other reviews found a decreased risk. Together, published studies suggest that oseltamivir reduces the duration of symptoms by 0.5–1.0 day. Any benefit of treatment must be balanced against side effects, which include psychiatric symptoms and increased rates of vomiting.
The 2014 Cochrane Collaboration review concluded that oseltamivir did not affect the need for hospitalizations, and that there is no proof of reduction of complications of influenza because of a lack of diagnostic definitions, or reduction of the spread of the virus. There was also evidence that suggested that oseltamivir prevented some people from producing sufficient numbers of their own antibodies to fight infection. The authors recommended that guidance should be revised to take account of the evidence of small benefit and increased risk of harms.
The US Centers for Disease Control and Prevention, the European Centre for Disease Prevention and Control, the Public Health England, the Infectious Disease Society of America, the American Academy of Pediatrics, and Roche rejected the recommendations of the 2014 Cochrane Review to urgently change treatment guidelines and drug labels.
Prevention
, the US Centers for Disease Control and Prevention does not recommend to use oseltamivir generally for prevention due to concerns that widespread use will encourage resistance development. They recommend that it be considered in those at high risk, who have been exposed to influenza within 48 hours and have not received or only recently been vaccinated. They recommended it during outbreaks in long term care facilities and in those who are significantly immunosuppressed., reviews concluded that when oseltamivir is used preventatively it decreases the risk of exposed people developing symptomatic disease. A systematic review of systematic reviews found low to moderate evidence that it decreases the risk of getting symptomatic influenza by 1 to 12%. It recommended against its use in healthy, low-risk persons due to cost, the risk of resistance development, and side effects and concluded it might be useful for prevention in unvaccinated high risk persons.
Side effects
According to the FDA, the two most common adverse drug reactions associated with oseltamivir therapy are nausea and vomiting. In adults, oseltamivir increased the risk of nausea for which the number needed to harm was 28 and for vomiting was 22. This means that for every 22 adult people on oseltamivir one experienced vomiting. In the treatment of children, oseltamivir also induced vomiting. The number needed to nausea was 19. So, for every 19 children on oseltamivir one experienced vomiting. When used as a prophylactic there were more headaches, kidney, and psychiatric events. Oseltamivir's effect on the heart is unclear: it may reduce cardiac symptoms, but may also induce serious arrhythmias.Postmarketing reports include liver inflammation and elevated liver enzymes, rash, allergic reactions including anaphylaxis, toxic epidermal necrolysis, abnormal heart rhythms, seizure, confusion, aggravation of diabetes, and haemorrhagic colitis and Stevens–Johnson syndrome. Neuropsychiatric symptoms and body pain, followed by skin problems, were identified as the side effects most significantly reducing patient satisfaction on a drug review platform.
The US and EU package inserts for oseltamivir contain a warning of psychiatric effects observed in post-marketing surveillance. The frequency of these appears to be low and a causative role for oseltamivir has not been established. The 2014 Cochrane Review found a dose-response effect on psychiatric events. In trials of prevention in adults one person was harmed for every 94 treated. Neither of the two most cited published treatment trials of oseltamivir reported any drug-attributable serious adverse events. Subsequent studies found that neuropsychiatric and psychiatric adverse events are associated with influenza itself rather than oseltamivir treatment. Oseltamivir treatment is associated with a reduced risk of neuropsychiatric events and oseltamivir prophylaxis is not associated with an increased risk of neuropsychiatric events compared to individuals without influenza infection.
It is pregnancy category B in Australia, meaning that it has been taken by a small number of women without signs of problems and in animal studies it looks safe. Dose adjustment may be needed in those with kidney problems.