Oseltamivir (INN) (pronounced /ɒsəlˈtæmɨvɪər/) is an antiviral drug that slows the spread of influenza (flu) virus between cells in the body by stopping the virus from chemically cutting ties with its host cell—median time to symptom alleviation is reduced by 0.5–1 day[1]. The drug is sold under the trade name Tamiflu and is taken orally in capsules or as a suspension. It has been used to treat and prevent Influenzavirus A and Influenzavirus B infection in over 50 million people since 1999.[citation needed]
Oseltamivir is a prodrug, a (relatively) inactive chemical which is converted into its active form by metabolic process after it is taken into the body. It was the first orally active neuraminidase inhibitor commercially developed.[citation needed] It was developed by C.U. Kim, W. Lew and X. Chen of US based Gilead Sciences and is currently marketed by Hoffmann–La Roche (Roche). In Japan, it is marketed by Chugai Pharmaceutical Co., which is more than 50% owned by Roche.[2][3]
As of May 2010[update], the World Health Organization (WHO) reported 285 out of over 15,000 samples of the prevalent 2009 pandemic H1N1 (swine) flu tested worldwide have shown resistance to oseltamivir,[4] contrasting sharply with the 99.6% of the seasonal H1N1 flu strains tested which have resistance to oseltamivir.[5]

Indications and dosage:
Oseltamivir is marketed by Roche under the trade name Tamiflu, as capsules (containing oseltamivir phosphate 98.5 mg equivalent to oseltamivir 75 mg) and as a powder for oral suspension (oseltamivir phosphate equivalent to oseltamivir 12 mg/ml).
Oseltamivir is indicated for the treatment and prevention of infections due to influenza A and B virus.
Oseltamivir is approved for use in persons age 1 and over. There is also currently an FDA Emergency Use authorization temporarily allowing the use of Tamiflu in children less than one year old.[7] The usual adult dosage for treatment of influenza is 75 mg twice daily for 5 days, beginning within 2 days of the appearance of symptoms and with decreased doses for children and patients with renal impairment. Oseltamivir may be given as a preventive measure either during a community outbreak or following close contact with an infected individual. Standard prophylactic dosage is 75 mg once daily for patients aged 13 and older, which has been shown to be safe and effective for up to six weeks. The importance of early treatment is that the NA protein inhibition is more effective within the first 48 hours. If the virus has replicated and infected many cells the effectiveness of this medication will be severely diminished, especially over time.[6][8]
The Centers for Disease Control and Prevention (CDC) recommends physicians prioritize which patients they prescribe oseltamivir to. Specifically, people hospitalized with more severe illness, children younger than 2 years old, adults over 65, pregnant women, people with certain chronic medical or immunosuppressive conditions and adults under 19 on long-term aspirin therapy. However, they also advise that children and adults presenting with suspected flu that have symptoms of lower respiratory tract illness or clinical deterioration should also receive prompt empiric antiviral therapy, regardless of previous health or age.[9]
The standard recommended dose incompletely suppresses viral replication in at least some patients with H5N1 avian influenza, increasing the risk of viral resistance and rendering therapy less effective.[10] Accordingly, it has been suggested that higher doses and longer durations of therapy should be used for treatment of patients with the H5N1 virus.[10][11]
Clinical trials for an increased dosage began in May 2007. All avian influenza cases in Indonesia, Thailand, and Vietnam were inducted into the trial. The trial also included 100 cases of severe seasonal influenza from each of those countries and the United States. Half received the current standard dose, and half received a double dose, but for the standard length of time.[12]

Possible side effects:Common adverse drug reactions (ADRs) associated with oseltamivir therapy (occurring in over 1% of clinical trial participants) include: nausea, vomiting, diarrhea, abdominal pain, and headache. Rare ADRs include: hepatitis and elevated liver enzymes, rash, allergic reactions including anaphylaxis, and Stevens-Johnson syndrome.[6][8]
Various other ADRs have been reported in postmarketing surveillance including: toxic epidermal necrolysis, cardiac arrhythmia, seizure, confusion, aggravation of diabetes, and haemorrhagic colitis.[6]
There are concerns that oseltamivir may cause dangerous psychological, neuropsychiatric side effects including self harm in some users. These dangerous side effects occur more commonly in children than in adults.[18] This stems from cases in Japan, where the drug is most heavily prescribed, consuming 60% of the world’s production.[19] Concern has focused on teenagers, but problems have also been reported in children and adults.
In March 2007, Japan’s Health Ministry warned that oseltamivir should not be given to those aged 10 to 19. The Ministry had previously decided, in May 2004, to change the literature accompanying oseltamivir to include neurological and psychological disorders as possible adverse effects, including: impaired consciousness, abnormal behavior, and hallucinations.[19]
According to Japan’s Health Ministry, between 2004 and March 2007, fifteen people aged 10 to 19 have been injured or killed by jumps or falls from buildings after taking oseltamivir, and one 17-year-old died after he jumped in front of a truck.[20] A renewed investigation of the Japanese data was completed in April 2007. It found that 128 patients had been reported to behave abnormally after taking oseltamivir since 2001. Forty-three of them were under 10 years old, 57 patients were aged 10 to 19, and 28 patients were aged 20 or over. Eight people, including five teens and three adults, had died from these actions.[21][22][20]
In October 2006, Shumpei Yokota, a professor of pediatrics at Yokahama City University, released the results of research involving around 2,800 children which found no difference in the behavior between those who took oseltamivir and those who did not. Chugai Pharmaceutical Co. (which produces oseltamivir in Japan) gave Yokota’s department 10 million yen (about US$105,000) over five years.[23]
To determine whether to lift the 2007 ban, a research team from the Japanese Health, Labour and Welfare Ministry studied 10,000 children under the age of 18 who had been diagnosed with influenza since 2006. The study was finalised in April 2009. Taking into account all degrees of abnormal behaviour, including minor behavioural problems such as incoherent speech, the study found that children who took oseltamivir were 54 percent more likely to exhibit abnormal behaviour than those who did not take the drug. When the team limited its analysis to children who had displayed serious abnormal behaviour that led to injury or death, it found those who had taken oseltamivir were 25 per cent more likely to behave unusually.[24]
In November 2006, the United States Food and Drug Administration (FDA) amended the warning label to include the possible side effects of delirium, hallucinations, or other related behavior.[25] This went further than the FDA’s previous pronouncement, from a year before, that there was insufficient evidence to claim a causal link between oseltamivir use and the deaths of 12 Japanese children (only two were from neurological problems, although more have died since then).[26] The change to a more cautionary stance was attributed to 103 new reports that the FDA received of delirium, hallucinations and other unusual psychiatric behavior, mostly involving Japanese patients, received between August 29, 2005 and July 6, 2006. This was an increase from the 126 similar cases logged between the drug’s approval in 1999 and August 2005.[27]
Roche points out that oseltamivir has been used to treat over 50 million people since 1999, and states that influenza may itself cause psychological problems.
In March 2007, the European Medicines Agency said that the benefits of oseltamivir outweighed the costs, but that it would closely monitor reports from Japan.
In April 2007, South Korea issued a safety warning against prescribing oseltamivir to teenagers except in special cases.[28]
A joint investigation by the British Medical Journal (BMJ) and British TV Channel 4 published in the BMJ on December 8, 2009 [29][30] concluded that in otherwise healthy adults they “have no confidence in claims that oseltamivir reduces the risk of complications and hospital admission in people with influenza” and believe it should not be used in routine control of seasonal influenza. There was also concern about under-reporting of side effects of the drug. In contrast, according to the BMJ, Roche has stated in media briefings that oseltamivir reduced hospital admissions by 61%; secondary complications (including bronchitis, pneumonia, and sinusitis) by 67% in otherwise healthy individuals and lower respiratory tract infections requiring antibiotics by 55%.
BMJ editor Dr. Fiona Godlee, said “claims that oseltamivir reduces complications have been a key justification for promoting the drug’s widespread use. Governments around the world have spent billions of pounds on a drug that the scientific community has found itself unable to judge.”
There is evidence that oseltamivir has a modest effect in reducing some minor flu symptoms and contagiousness in otherwise healthy adults by about one day, but this is probably not the main reason most doctors are prescribing the drug for their patients. This less important benefit may well be offset by the risks of the drug.

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