Oseltamivir , sold under the trademark Tamiflu , is an antiviral drug used to treat and prevent influenza A and influenza B (flu). Many medical organizations recommend it to people who have complications or are at high risk of complications within 48 hours of the first infection symptoms. They recommend it to prevent infection in those at high risk, but not the general population. The CDC recommends that clinicians use their discretion to treat those at low risk who are present within 48 hours of the first symptoms of infection. It is taken, either as a pill or a liquid.
Recommendations on controversial oseltamivir such as criticism of recommendations. The Cochrane 2014 review concluded that oseltamivir did not reduce hospitalization, and that there was no evidence of reduced influenza complications. Two meta-analyzes concluded that the benefits to those who are healthy did not outweigh the risks. They also found little evidence as to whether treatment changed the risk of hospitalization or death in high-risk populations. However, another meta-analysis found that oseltamivir is effective for prevention of influenza at the individual and household level.
Common side effects include vomiting, diarrhea, headaches, and difficulty sleeping. Other side effects may include psychiatric symptoms and seizures. In the United States is recommended for influenza infection during pregnancy. It has been taken by a small number of pregnant women without any sign of trouble. Dose adjustments may be needed in those with kidney problems.
Oseltamivir was approved for medical use in the US in 1999. It was the first available neuraminidase inhibitor by mouth. This is a complementary list of the World Health Organization's Essential Medicines List, which shows a lower cost-benefit ratio. The generic version has been approved in the US in 2016. In 2014, wholesale costs in developing countries are approximately US $ 4.27 per day. Beginning in December 2016, a $ 139.70 course maintenance fee in the US.
Video Oseltamivir
Medical use
Oseltamivir is used for the prevention and treatment of influenza caused by influenza viruses A and B. This is a complementary list of the World Health Organization's Essential Medicines List, the most important drugs needed in basic health systems. The risk-benefit ratio of Oseltamivir is controversial. In 2017 moved from core to complementary list based on lower cost effectiveness.
High-risk people
The United States Centers for Disease Control and Prevention (CDC), the European Center for Disease Prevention and Control (ECDC), the British Public Health and American Academy of Pediatrics (AAP) recommend the use of oseltamivir for people with complications or at high risk for complications. These include those hospitalized, young children, those over the age of 65, people with other important health problems, those who are pregnant, and Native Americans among others. The Infectious Disease Society of America takes the same position as the CDC.
A systematic review of systematic reviews in PLoS One found no evidence to benefit people at risk, noting that "trials were not designed or supported to provide results regarding serious complications, hospitalization and death", as Cochrane 2014 reviewed. The Cochrane review further recommends: "On the basis of the findings of this review, clinicians and health policy makers should promptly revise the current recommendations for the use of neuraminidase inhibitors (NIs) for individuals with influenza." It does not use NI for prevention or treatment. "Based on these findings there seems to be no evidence for patients, clinicians or policymakers to use this drug to prevent serious outcomes, both in the annual influenza outbreak and pandemic influenza outbreaks."
The CDC, ECDC, Public Health England, Infectious Disease Society of America, the AAP, and Roche (the originator) dismiss the conclusions of the Cochrane review, arguing that the analysis is not accurately forming conclusions about outcomes in severely diseased people based on results obtained primarily on healthy populations, and improper analyzes including results from people not infected with influenza. The EMA did not alter its drug labels in response to Cochrane's research.
A 2014 review in the New England Journal of Medicine has recommended that all people treated in the intensive care unit during an influenza outbreak with a diagnosis of community acquired pneumonia receive oseltamivir until no influenza infection is established by PCR. testing.
The systematic review and meta-analysis 2015 found oseltamivir to be effective in treating influenza symptoms, reducing length of stay, and reducing the risk of otitis media. The same review found that oseltamivir did not significantly increase the risk of side effects. A systematic review of 2016 found that oseltamivir reduced the amount of time needed for influenza-related symptoms, and it also increased the risk of "nausea, vomiting, [and] psychiatric events in adults and vomiting in children." The decrease in the duration of the disease is about 18 hours.
Healthy person
In those who are healthy, the CDC states that antiviral drugs can be considered within the first 48 hours. German clinical practice guidelines recommend its use.
Two 2013 meta-analyzes concluded that the benefits to those who are healthy did not outweigh the risks. When the analysis was confined to people with confirmed infections, Cochrane's review found unclear evidence of a change in the risk of complications such as pneumonia, while three other reviews found a reduced risk. Together, published studies show that oseltamivir reduces the duration of symptoms by 0.5-1.0 days. Each treatment benefit should be offset by side effects, which include psychiatric symptoms and increased levels of vomiting.
Cochrane Collaboration 2014's review concluded that oseltamivir did not affect the need for hospitalization, and that there was no evidence of reduced influenza complications (such as pneumonia) due to lack of diagnostic definitions, or reduced viral spread. There is also evidence to suggest that oseltamivir prevents some people from producing their own antibodies in sufficient quantities to fight infection. The authors recommend that guidelines should be revised to consider evidence of small benefits and increased risk of harm.
The US and European Centers for Disease Control (CDC), British Public Health, Infectious Society of America Disease, and the American Academy of Pediatrics, and Roche (the originator) rejected Cochrane 2014's review recommendation to immediately change treatment guidelines and label drugs.
Prevention
By 2017, the CDC does not recommend to use oseltamivir in general for prevention because of 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 recently vaccinated. They recommend it during outbreaks in long-term care facilities and in those with significant immunosuppression.
In 2011, the review concluded that when oseltamivir is used preventatively, it reduces the risk of people affected by developing symptomatic disease. A systematic review of systematic reviews finds low to moderate evidence that it reduces the risk of symptomatic influenza by 1 to 12% (a relative decrease of 64-92%). It is recommended against its use in healthy people, low risk due to cost, the risk of developing resistance, and side effects and concludes it may be useful for prevention in unvaccinated high risk people.
Maps Oseltamivir
Side effects
Adverse general drug reactions (ADR) associated with oseltamivir therapy (occurring in more than 1 percent of people) include nausea and vomiting. In adults, oseltamivir increases the risk of nausea where the amount needed to be hurt is 28 and for vomiting is 22. So, for every 22 adults in oseltamivir, a person experiences vomiting. In the treatment of children, oseltamivir also triggers vomiting. The amount to be harmed is 19. So, for every 19 children in oseltamivir, a person experiences vomiting. In prevention there are more headaches, kidney, and psychiatric events. The effects of Oseltamivir on the heart are unclear: it can reduce heart symptoms, but it can also cause serious heart rhythm problems.
Postpartum reports include liver inflammation and elevated liver enzymes, rashes, allergic reactions including anaphylaxis, toxic epidermal necrolysis, abnormal heart rhythm, seizures, confusion, diabetes aggravation, and haemorrhagic colitis and Stevens-Johnson syndrome.
US and EU package insertion for oseltamivir contains psychiatric effects warning observed in post marketing surveillance. This frequency seems low and the causative role for oseltamivir has not been established. The Cochrane 2014 review found a dose-response effect on psychiatric events. In the prevention trial in adults one person is harmed for every 94 treated. None of the two most frequently cited treatment trials of oseltamivir reported any serious adverse effects caused by the drug.
This is the category of pregnancy C in the United States and category B in Australia, which means that it has been taken by a small number of women with no signs of trouble and in research on the animal it looks safe. Dose adjustments may be needed in those with kidney problems.
Action mechanism
Oseltamivir is a neuraminidase inhibitor, a competitive inhibitor of influenza neuraminidase enzymes. The enzyme cleaves the sialic acid found in glycoproteins on the surface of human cells that help the new virions to get out of the cell. So oseltamivir prevents new virus particles released.
Resistance
Most of the mutating mutations are the substitution of a single amino acid residue (His274Tyr in N1) in the neuraminidase enzyme. A 2011 meta-analysis of 15 studies found a combined incidence rate for oseltamivir resistance of 2.6%. Subgroup analyzes detect a higher rate among influenza A patients, especially the H1N1 subtype. It was found that large numbers of patients may become resistant to oseltamivir as a result of oseltamivir, and that oseltamivir resistance may be significantly associated with pneumonia. In patients with severe immune disorders there are reports of prolonged spread of the oseltamivir- (or zanamivir) virus, even after oseltamivir treatment is stopped.
H1N1 flu or" Swine flu "
On December 15, 2010, the World Health Organization (WHO) reported 314 samples of the 2009 H1N1 flu pandemic tested worldwide have shown resistance to oseltamivir.
The CDC found sporadic and identified H1N1 2009 virus infection, including with rare episodes of limited transmission, but limited public health impact. Sporadic cases of resistance are found in immunosuppressed patients during oseltamivir treatment and people who develop the disease when receiving oseltamivir chemoprophylaxis.
During 2011, a new 2009 influenza A (H1N1) variant with slightly reduced oseltamivir (and zanamivir) sensitivity was detected in more than 10% of community specimens in Singapore and over 30% of samples from northern Australia.
Although there are concerns that antiviral resistance may develop in people with haematological malignancies because of their inability to reduce viral load and some surveillance studies have found oseltamivir resistant to pH1N1 after oseltamivir administration in these individuals, in November 2013 the transmission spreading from oseltamivir-resistant pH1N1 has not happen.
During the 2007-08 flu season, the US CDC found 10.9% of the H1N1 sample (n = 1,020) to be resistant. In the 2008-09 season, the proportion of resistant H1N1 increased to 99.4%, while no other seasonal strains (H3N2, B) showed resistance.
Seasonal flu
From 2009 to 2014, oseltamivir resistance is very low in seasonal flu. In the 2010-11 flu season, 99.1% of H1N1, 99.8% of H3N, and 100% of Influenza B remain vulnerable to oseltamivir in the US. In January 2012, the US and European CDC reported that all seasonal flu samples tested since October 2011 were susceptible to oseltamivir. In the 2013-14 season only 1% of the 2009 H1N1 virus showed oseltamivir resistance. No other influenza virus is resistant to oseltamivir.
H3N2
Three studies have found resistance at 0%, 3.3%, and 18% of subjects. In studies with an 18% resistance level, the subjects were children, many of whom had never been exposed to influenza and therefore had weak immune responses; the results suggest that higher and earlier doses may be required in such populations.
Influenza B
In 2007, Japanese researchers detected strains of influenza B virus that were resistant to neuraminidase in individuals not treated with these drugs. The prevalence is 1.7%. According to the CDC, on October 3, no strains of influenza B tested showed resistance to oseltamivir.
H5N1 Avian influenza "Bird flu"
By 2013, mutations of H274Y and N294S that provide resistance to oseltamivir have been identified in some H5N1 isolates from infected patients treated with oseltamivir, and have emerged spontaneously in Egypt.
H7N9 Avian influenza
In 2013 two of 14 A (H7N9) infected adults and treated with oseltamivir developed a virus resistant to oseltamivir with Arg292Lys mutation.
Pharmacokinetics
Its mouth bioavailability is over 80% and is extensively metabolized into its active form when it first passes through the liver. It has a distribution volume of 23-26 liters. The half-life is about 1-3 hours and the active carboxylic metabolite has a half-life of 6-10 hours. More than 90% of the oral dose is removed in the urine as an active metabolite.
History
Oseltamivir was discovered by scientists in Gilead using shikimic acid as a starting point for synthesis; Shikimic acid was originally only available as an extract of Chinese star fennel; but in 2006, 30% of the supplies were produced recombinantly in E. coli. Gilead exclusively licensed their relevant patents to Roche in 1996. The drug patent is not yet protected in Thailand, the Philippines, Indonesia and other countries.
In 1999, the FDA approved oseltamivir phosphate for the treatment of influenza in adults based on two placebo-controlled, double-blinded, randomized controlled trials. In June 2002 the EMA approved oseltamivir phosphate for prophylaxis and influenza treatment. In 2003, a combined analysis of 10 randomized clinical trials concluded that oseltamivir reduced the risk of lower respiratory tract infections resulting in antibiotic use and hospital admissions in adults.
Oseltamivir (such as Tamiflu) was widely used during the H5N1 avian influenza epidemic in Southeast Asia in 2005. In response to the epidemic, governments - including those from Britain, Canada, Israel, the United States and Australia - stockpiled oseltamivir in preparation for a possible pandemic and there is a worldwide shortage of drugs, driven by high demand for stockpiling. In November 2005, US President George W. Bush requested that Congress finance US $ 1 billion for oseltamivir production and supplies, after Congress had approved $ 1.8 billion for military use of the drug. Defense Secretary Donald Rumsfeld, who is the former chairman of Gilead Sciences, resigned from all government decisions on the drug.
In 2006, the Cochrane review caused controversy by concluding that oseltamivir should not be used during routine seasonal influenza due to its low effectiveness.
In December 2008, Indian drug company Cipla won a case in the Indian court system that enabled it to produce a cheaper version of the generic Tamiflu, called Antiflu. In May 2009, Cipla won the approval of WHO stating that its Antiflunya drug is as effective as Tamiflu, and Antiflu is included in the WHO list of pre-qualified drug products.
In 2009, the newly discovered A/H1N1 influenza virus spread in North America. In June 2009 the WHO declared an A/H1N1 pandemic as a pandemic. The National Institute for Health and Nursing Excellence (NICE), CDC, WHO, and ECDC maintain their recommendations for using oseltamivir.
From 2010 to 2012, Cochrane requested a full Roche clinical study report for their trials, which they did not provide. In 2011, the demand for freedom of information to the European Medicines Agency provided Cochrane with reports of 16 trials of Roche oseltamivir. In 2012, the Cochrane team published a temporary review based on these reports. In 2013, Roche released 77 full clinical trial reports from oseltamivir trials after GSK released data on zanamivir studies. In 2014, Cochrane publishes the most recent reviews based solely on clinical study reports and regulatory documents. By 2016, Roche oseltamivir patent is beginning to expire.
Veterinary use
Source of the article : Wikipedia
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