Thai doctors have been using a cocktail of flu and HIV drugs to treat coronavirus cases

Oseltamivir was discovered by scientists at Gilead Sciences using shikimic acid as a starting point for synthesis; shikimic acid was originally available only as an extract of Chinese star anise:

Shikimic acid, more commonly known as its anionic form shikimate, is a cyclohexene, a cyclitol and a cyclohexanecarboxylic acid. It is an important biochemical metabolite in plants and microorganisms.
Its name comes from the Japanese flower shikimi (シキミ, the Japanese star anise, Illicium anisatum),
from which it was first isolated in 1885 by Johan Fredrik Eykman.^[1]

Thai doctors have been using a cocktail of flu and HIV drugs to treat coronavirus cases

A man wears a mask to prevent the spread of the new coronavirus
as he walks near the Grand Palace at Bangkok, 

Soe Zeya Tun/Reuters | Thailand February 2, 2020

• A combination of flu and HIV medications are helping treat severe cases of the new coronavirus, Thai doctors said.
• Chinese health officials have already been administering the HIV and flu drugs to fight the coronavirus, but the combination of the three together in a cocktail seemed to improve the treatment.
• Thailand currently has recorded 19 cases of coronavirus, eight have recovered while 11 are still under treatment in hospitals.

BANGKOK (Reuters) - Thai doctors have seen success in treating severe cases of the new coronavirus with a combination of medications for flu and HIV, with initial results showing vast improvement 48 hours after applying the treatment, they said on Sunday.

The doctors from Rajavithi Hospital in Bangkok said a new approach in coronavirus treatment had improved the condition of several patients under their care, including one 70-year-old Chinese woman from Wuhan who tested positive for the coronavirus for 10 days.

The drug treatment includes a mixture of anti-HIV drugs lopinavir and ritonavir, in combination with flu drug oseltamivir in large doses.

"This is not the cure, but the patient's condition has vastly improved. From testing positive for 10 days under our care, after applying this combination of medicine the test result became negative within 48 hours," Dr. Kriangska Atipornwanich, a lung specialist at Rajavithi, told reporters.
"The outlook is good but we still have to do more study to determine that this can be a standard treatment."
Chinese health officials have already been administering the HIV and flu drugs to fight the coronavirus. The use of the three together in a cocktail seemed to improve the treatment, the Thai doctors said.

Another doctor said that a similar approach in two other patients resulted in one displaying some allergic reaction but the other showed improvement.
"We have been following international practices, but the doctor increased the dosage of one of the drugs," said Somsak Akkslim, director-general of the Medical Services Department, referring to the flu medicine Oseltamivir.
Thailand has recorded 19 cases of coronavirus. Of the Thai patients, eight have recovered and gone home while 11 are still under treatment in hospitals.

Somsak said the health ministry will meet on Monday to discuss the successful treatment in the case of the 70-year-old but said it is still too soon to say that this approach can be applied to all cases.
"Initially we will apply this approach only to severe cases," he said.

 

Read the original article on Reuters. Copyright 2020. Follow Reuters on Twitter.

 

Panu Wongcha-um,

Reuters | 4 hours ago

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More:

Cocktail of flu, HIV drugs appears to help fight coronavirus: Thai doctors
https://www.channelnewsasia.com/news/asia/wuhan-coronavirus-hiv-flu-drugs-remedy-thailand-12383016

Cocktail of flu, HIV drugs appears to help fight coronavirus: Thai doctors
https://headtopics.com/sg/cocktail-of-flu-hiv-drugs-appears-to-help-fight-coronavirus-thai-doctors-11052126

Thailand doctors sees success in treating Coronavirus with HIV and cocktail flu drugs
https://www.youtube.com/watch?v=9gdvi4IkkcY

Cocktail of flu, HIV drugs appears to help fight coronavirus: Thai doctors
https://twnews.us/us-news/cocktail-of-flu-hiv-drugs-appears-to-help-fight-coronavirus-thai-doctors

Flu, HIV Drugs Appear to Help Fight Coronavirus: Thai Doctors
https://www.theepochtimes.com/flu-hiv-drugs-appear-to-help-fight-coronavirus-thai-doctors_3224690.html

Thai doctors say cocktail of flu, HIV drugs appears to help fight coronavirus
https://www.wionews.com/world/thai-doctors-say-cocktail-of-flu-hiv-drugs-appears-to-help-fight-coronavirus-278168

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The Ebola virus can be destroyed naturally – despite what you’ve been told

To date, not a single virus has been tested that is not inactivated (killed) by a large enough dose of vitamin C (ascorbic acid).

Many other antioxidants have similar virucidal effects, but vitamin C appears uniquely to be of greatest potency and clinical efficacy, as its simple chemical structure allows for it to be disseminated throughout the body with little restriction. 
As such, it is able to effectively address viral populations present in both the intracellular and extracellular spaces.

Other antioxidants have been found to have higher ORAC (Oxygen Radical Absorbance Capacity) values – measurements which are used to quantify the antioxidant capacity of supplements (or foods). However, a virus can never be incapacitated by a potent antioxidant if the chemical structure of that antioxidant does not permit direct contact between the virus and the antioxidant.

Why is vitamin C so effective in killing viruses?

A primary way in which vitamin C destroys viruses, or sets them up for destruction by the immune system, is by activating the ‘Fenton reaction’. In a nutshell, this reaction can proceed inside the virus, inside cells in which viruses are replicating, and on the surfaces of the viruses themselves. The result of this reaction that is stimulated by the presence of vitamin C, one or more transition metal cations, and the local presence of peroxide is the immediate production of hydroxyl radicals.
These radicals are the most reactive oxidizing agents ever identified.
As such, they radically upregulate oxidative stress and end up destroying whatever is in their immediate environment.

The effects of vitamin C in “mopping up” after it inflicts its viral damage are further supported by its potent and multifaceted support of the immune system.

There is no other substance that singularly does as much to promote increased and strong immune function as vitamin C. Among many other effects, vitamin C directly stimulates interferon and antibody production, while effectively supercharging the functions of the white blood cells by becoming very concentrated inside those cells. To be balanced, it is also important to note that the effects of vitamin C on chronic viral infections, such as chronic hepatitis, AIDS, or HIV-positive states are less profound, as the virus works its way into physical locations much less accessible by vitamin C than when the viral infections are acute. Nevertheless, long-term, highly-dosed protocols of vitamin C often completely control and even occasionally cure these diseases.

Ebola NYC 2014: Nothing Fazes New Yorkers, Not Even Doctor's Diagnosis

O.K. – let’s talk about the clinical results

The actual evidence showing what vitamin C has done and can continue to do if properly utilized is there for anyone to see and review. The ‘multi-C protocol’ will reverse and cure any viral syndrome if secondary organ damage has not already advanced too far. Even then, many cases that would seem hopeless can still show dramatic clinical responses. Review for yourself the incredible clinical results of Frederick Klenner, MD, – who is truly the father of the clinical applications of vitamin C.
 Also, check out the H1N1 patient in New Zealand who was going to be taken off of life support when vitamin C finally came to the rescue.

The Use of Vitamin C as an Antibiotic.  Clinical Guide to the Use of Vitamin C 

More: http://graviolateam.blogspot.com/2014/10/the-ebola-virus-can-be-destroyed_27.html

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Oseltamivir, sold under the brand name Tamiflu, is an antiviral medication used to treat and prevent influenza A and influenza B (flu).^[3] 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.^[4] They recommend it to prevent infection in those at high risk, but not the general population.^[4] The Centers for Disease Control and Prevention (CDC) recommends that clinicians use their discretion to treat those at lower risk who present within 48 hours of first symptoms of infection.^[4][5][6] It is taken by mouth, either as a pill or liquid.^[3]

Recommendations regarding oseltamivir are controversial as are criticisms of the recommendations.^[4][7][8][9] A 2014 Cochrane Review concluded that oseltamivir does not reduce hospitalizations, and that there is no evidence of reduction in complications of influenza.^[9] Two meta-analyses have concluded that benefits in those who are otherwise healthy do not outweigh its risks.^[10][11] They also found little evidence regarding whether treatment changes the risk of hospitalization or death in high risk populations.^[10][11] However, another meta-analysis found that oseltamivir was effective for prevention of influenza at the individual and household levels.^[12]

Common side effects include vomiting, diarrhea, headache, and trouble sleeping.^[3] Other side effects may include psychiatric symptoms and seizures.^[3][13][14] In the United States it is recommended for influenza infection during pregnancy.^[1] It has been taken by a small number of pregnant women without signs of problems.^[1] Dose adjustment may be needed in those with kidney problems.^[3]

Oseltamivir was approved for medical use in the US in 1999.^[3] It was the first neuraminidase inhibitor available by mouth.^[15] It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.^[16] A generic version was approved in the US in 2016.^[17][18] As of 2014, the wholesale cost in the developing world was about US$4.27 per day.^[19] The wholesale cost for a course of treatment in the United States is about US$54.00 as of 2019.^[20] In 2016, it was the 249th most prescribed medication in the United States with more than a million prescriptions.^[21]

Contents

• 1Medical use
  • 1.1High-risk people
  • 1.2Otherwise healthy people
  • 1.3Prevention
• 2Side effects
• 3Mechanism of action
• 4Resistance
  • 4.1H1N1 flu or "Swine flu"
  • 4.2Seasonal flu
  • 4.3H3N2
  • 4.4Influenza B
  • 4.5H5N1 Avian influenza "Bird flu"
  • 4.6H7N9 Avian influenza
• 5Pharmacokinetics
• 6History
• 7Veterinary use
• 8See also
• 9References
• 10Further reading
• 11External links

Medical use[edit]

A oseltamivir capsule

Oseltamivir is used for the prevention and treatment of influenza caused by influenza A and B viruses.^[3][22] It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.^[16] The WHO supports its use for severe illness due to confirmed or suspected influenza virus infection in critically ill people who have been hospitalized.^[16] Oseltamivir's risk-benefit ratio is controversial.^[8][9] In 2017, it was moved from the core to the complementary list based on its lower cost-effectiveness.^[23]

High-risk people[edit]

The US Centers for Disease Control and Prevention (CDC), European Centre for Disease Prevention and Control (ECDC), Public Health England and the American Academy of Pediatrics (AAP) recommend the use of oseltamivir for people who have complications or are at high risk for complications.^{[4][5][24][25][26]} 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.^[24] The Infectious Disease Society of America takes the same position as the CDC.^[7]

A systematic review of systematic reviews in PLoS One 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",^[10] as did a 2014 Cochrane Review.^[27] 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 (NIs) for individuals with influenza."^[27] 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."^[27]

The CDC, ECDC, Public Health England, Infectious Disease Society of America, the AAP, and Roche (the originator) 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.^{[4][5][7][25][26]} The EMA did not change its labeling of the drug in response to the Cochrane study.^[28]

A 2014 review in the New England Journal of Medicine 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 PCR testing.^[29]

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.^[30] 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, [and] psychiatric events in adults and vomiting in children."^[31] The decrease in duration of sickness was about 18 hours.^[32]

Otherwise healthy people[edit]

In those who are otherwise healthy the CDC states that antivirals may be considered within the first 48 hours.^[24] A German clinical practice guideline recommends against its use.^[33]

Two 2013 meta-analyses have concluded that benefits in those who are otherwise healthy do not outweigh its risks.^[10][11] When the analysis was restricted to people with confirmed infection, a Cochrane Review found unclear evidence of change in the risk of complications such as pneumonia,^[27] while three other reviews found a decreased risk.^[11][34][35] Together, published studies suggest that oseltamivir reduces the duration of symptoms by 0.5–1.0 day.^[36] Any benefit of treatment must be balanced against side effects, which include psychiatric symptoms and increased rates of vomiting.^[14]

A 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 (such as pneumonia) 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.^[27][37]

The US Centers for Disease Control and Prevention (CDC), the European Centre for Disease Prevention and Control (ECDC), the Public Health England (PHE), the Infectious Disease Society of America (IDSA), the American Academy of Pediatrics (AAP), and Roche (the originator) rejected the recommendations of the 2014 Cochrane Review to urgently change treatment guidelines and drug labels.^{[4][5][7][25][26][28]}

Prevention[edit]

As of 2017, the CDC does not recommend to use oseltamivir generally for prevention due to concerns that widespread use will encourage resistance development.^[24] 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.^[24] They recommended it during outbreaks in long term care facilities and in those who are significantly immunosuppressed.^[24]

As of 2011, reviews concluded that when oseltamivir is used preventatively it decreases the risk of exposed people developing symptomatic disease.^[27][38] A systematic review of systematic reviews found low to moderate evidence that it decreases the risk of getting symptomatic influenza by 1 to 12% (a relative decrease of 64 to 92%).^[10] 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.^[10]

Side effects[edit]

A package of capsules

Common adverse drug reactions (ADRs) associated with oseltamivir therapy (occurring in over 1 percent of people) include 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. So, for every 22 adult people on oseltamivir one experienced vomiting. In the treatment of children, oseltamivir also induced vomiting. The number needed to harm was 19. So, for every 19 children on oseltamivir one experienced vomiting. In prevention 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.^[27]

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.^[39][40]

The US and EU package inserts for oseltamivir contain a warning of psychiatric effects observed in post-marketing surveillance.^[41][42] The frequency of these appears to be low and a causative role for oseltamivir has not been established.^[42][43] 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.^[27] Neither of the two most cited published treatment trials of oseltamivir reported any drug-attributable serious adverse events.^[41]

It is pregnancy category C in the United States and 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.^[22][44] Dose adjustment may be needed in those with kidney problems.^[3]

Mechanism of action[edit]

Oseltamivir is a neuraminidase inhibitor, a competitive inhibitor of influenza's neuraminidase enzyme. The enzyme cleaves the sialic acid which is found on glycoproteins on the surface of human cells that helps new virions to exit the cell. Thus oseltamivir prevents new viral particles from being released.^[22]

Resistance[edit]

Influenza (Flu)
Types
Avian  A/H5N1 subtype Canine Equine Swine  A/H1N1 subtype
Vaccines
2009 pandemic  Pandemrix Live attenuated Seasonal flu vaccine brands
Treatment
Amantadine Laninamivir Oseltamivir Peramivir Rimantadine Umifenovir Vitamin D Zanamivir
Pandemics
1918 Spanish flu 1957 Asian flu 1968–1969 Hong Kong 2009 swine
Outbreaks
1976 swine flu 2006 H5N1 India 2007 Australian equine 2007 Bernard Matthews H5N1 2008 West Bengal 2015 United States H5N2 outbreak
See also
Flu season Influenza evolution Influenza research Influenza-like illness Vaccine reformulations
v t e

The vast majority of mutations conferring resistance are single amino acid residue substitutions (His274Tyr in N1) in the neuraminidase enzyme.^[45] A 2011 meta-analysis of 15 studies found a pooled incidence rate for oseltamivir resistance of 2.6%. Subgroup analyses detected higher rates among influenza A patients, especially the H1N1 subtype. It was found that a substantial number of patients might become oseltamivir-resistant as a result of oseltamivir use, and that oseltamivir resistance might be significantly associated with pneumonia.^[45] In severely immunocompromised patients there were reports of prolonged shedding of oseltamivir- (or zanamivir)-resistant virus, even after oseltamivir treatment was stopped.^[4]

H1N1 flu or "Swine flu"[edit]

As of December 15, 2010, the World Health Organization (WHO) reported 314 samples of the prevalent 2009 pandemic H1N1 flu tested worldwide showed resistance to oseltamivir.^[46]

The CDC found sporadic oseltamivir-resistant 2009 H1N1 virus infections had been identified, including with rare episodes of limited transmission, but the public health impact had been limited. Those sporadic cases of resistance were found in immunosuppressed patients during oseltamivir treatment and persons who developed illness while receiving oseltamivir chemoprophylaxis.^[47]

During 2011, a new influenza A(H1N1)2009 variant with mildly reduced oseltamivir (and zanamivir) sensitivity was detected in more than 10% of community specimens in Singapore and more than 30% of samples from northern Australia.^[48]

While there is concern that antiviral resistance may develop in people with haematologic malignancies due to their inability to reduce viral loads and several surveillance studies found oseltamivir-resistant pH1N1 after administration of oseltamivir in those people, as of November 2013, widespread transmission of oseltamivir-resistant pH1N1 has not occurred.^[49]

During the 2007–08 flu season, the US CDC found 10.9% of H1N1 samples (n=1,020) to be resistant.^[50] In the 2008–09 season, the proportion of resistant H1N1 increased to 99.4%, while no other seasonal strains (H3N2, B) showed resistance.^[51]

Seasonal flu[edit]

From 2009 to 2014, oseltamivir resistance was very low in seasonal flu. In the 2010–11 flu season, 99.1% of H1N1, 99.8% of H3N, and 100% of Influenza B remained oseltamivir susceptible in the US.^[52] In January 2012, the US and European CDCs reported all seasonal flu samples tested since October 2011 to be oseltamivir susceptible.^[53][54] In the 2013–14 season only 1% of 2009 H1N1 viruses showed oseltamivir resistance. No other influenza viruses were resistant to oseltamivir.^[55]

H3N2[edit]

Three studies have found resistance in 0%, 3.3%, and 18% of subjects.^[45] In the study with the 18% resistance rate, the subjects were children, many of whom had not been previously exposed to influenza and therefore had a weakened immune response; the results suggest that higher and earlier dosing may be necessary in such populations.^[56]

Influenza B[edit]

In 2007, Japanese investigators detected neuraminidase-resistant influenza B virus strains in individuals not treated with these drugs. The prevalence was 1.7%.^[57] According to the CDC, As of 2019, transmission of oseltamivir-resistant influenza B virus strains -- from persons treated with the drug -- is rare. ^[58]

H5N1 Avian influenza "Bird flu"[edit]

As of 2013, H274Y and N294S mutations that confer resistance to oseltamivir have been identified in a few H5N1 isolates from infected patients treated with oseltamivir, and have emerged spontaneously in Egypt.^[59]

H7N9 Avian influenza[edit]

As of 2013, two of 14 adults infected with A(H7N9) and treated with oseltamivir developed oseltamivir-resistant virus with the Arg292Lys mutation.^[60]

Pharmacokinetics[edit]

Its oral bioavailability is over 80% and is extensively metabolised to its active form upon first-pass through the liver.^[2] It has a volume of distribution of 23–26 litres.^[2] Its half-life is about 1–3 hours and its active carboxylate metabolite has a half-life of 6–10 hours.^[2] More than 90% of the oral dose is eliminated in the urine as the active metabolite.^[2]

History[edit]

Plate from François-Pierre Chaumeton's 1833 "Flore Medicale"

Oseltamivir was discovered by scientists at Gilead Sciences using shikimic acid as a starting point for synthesis; shikimic acid was originally available only as an extract of Chinese star anise; but by 2006, 30% of the supply was manufactured recombinantly in E. coli.^[61][62] Gilead exclusively licensed their relevant patents to Roche in 1996.^[63] The drug's patent has not been protected in Thailand, the Philippines, Indonesia, and several other countries.^[63]

In 1999, the FDA approved oseltamivir phosphate for the treatment of influenza in adults^[64] based on two double-blinded, randomized, placebo-controlled clinical trials.^[65] In June 2002, the European Medicines Agency (EMA) approved oseltamivir phosphate for prophylaxis and treatment of influenza. In 2003, a pooled analysis of ten randomised clinical trials concluded that oseltamivir reduced the risk of lower respiratory tract infections resulting in antibiotic use and hospital admissions in adults.^[66]

Oseltamivir (as Tamiflu) was widely used during the H5N1 avian influenza epidemic in Southeast Asia in 2005.^{[medical citation needed]} In response to the epidemic, various governments – including those of the United Kingdom, Canada, Israel, United States, and Australia – stockpiled quantities of oseltamivir in preparation for a possible pandemic^[67] and there were worldwide shortages of the drug, driven by the high demand for stockpiling.^[61] In November 2005, US President George W. Bush requested that Congress fund US$1 billion for the production and stockpile of oseltamivir, after Congress had already approved $1.8 billion for military use of the drug. Defense Secretary Donald Rumsfeld, who was a past chairman of Gilead Sciences, recused himself from all government decisions regarding the drug.^[68]

In 2006, a Cochrane Review (since withdrawn) raised controversy by concluding that oseltamivir should not be used during routine seasonal influenza because of its low effectiveness.^[69]

In December 2008, the Indian drug company Cipla won a case in India's court system allowing it to manufacture a cheaper generic version of Tamiflu, called Antiflu. In May 2009, Cipla won approval from the World Health Organization (WHO) certifying that its drug Antiflu was as effective as Tamiflu, and Antiflu is included in the WHO list of prequalified medicinal products.^[70]

Marketing display used at festivals features a person living in a hermetically sealed environment

In 2009, a new A/H1N1 influenza virus was discovered to be spreading in North America. In June 2009, the WHO declared the A/H1N1 influenza a pandemic.^[71] The National Institute for Health and Care Excellence (NICE), the CDC, the WHO, and the ECDC maintained their recommendation to use oseltamivir.^[6][72]

From 2010 to 2012, Cochrane requested Roche's full clinical study reports of their trials, which they did not provide.^[73] In 2011, a freedom of information request to the European Medicines Agency (EMA) provided Cochrane with reports from 16 Roche oseltamivir trials. In 2012, the Cochrane team published an interim review based on those reports. In 2013, Roche released 74 full clinical study reports of oseltamivir trials after GSK released the data on zanamivir studies.^[74] In 2014, Cochrane published an updated review based solely on full clinical study reports and regulatory documents.^[27][73] In 2016, Roche's oseltamivir patents began to expire.^[63]

Veterinary use[edit]

There have been^[when?] reports of oseltamivir reducing disease severity and hospitalization time in canine parvovirus infection.^[75] The drug may limit the ability of the virus to invade the crypt cells of the small intestine and decrease gastrointestinal bacterial colonization and toxin production.^[76]

See also[edit]

• Amantadine and rimantadine – M2 inhibitors, for influenza treatment
• Baloxavir marboxil, an endonuclease inhibitor, for influenza treatment

References[edit]

1. ^ Jump up to:^a b c d "Oseltamivir (Tamiflu) Use During Pregnancy". Drugs.com. Archived from the original on 9 September 2017. Retrieved 16 January 2017.
2. ^ Jump up to:^{a b c d e f g h i} Davies BE (April 2010). "Pharmacokinetics of oseltamivir: an oral antiviral for the treatment and prophylaxis of influenza in diverse populations". The Journal of Antimicrobial Chemotherapy. 65 Suppl 2: ii5–ii10. doi:10.1093/jac/dkq015. PMC 2835511. PMID 20215135.
3. ^ Jump up to:^{a b c d e f g h} "Oseltamivir Phosphate Monograph for Professionals". The American Society of Health-System Pharmacists. Archived from the original on 13 May 2016. Retrieved 8 January 2017.
4. ^ Jump up to:^{a b c d e f g h} "CDC Recommendations for Influenza Antiviral Medications Remain Unchanged". U.S. Centers for Disease Control and Prevention (CDC). 10 April 2014. Archived from the original on 18 January 2017. Retrieved 16 January 2017.
5. ^ Jump up to:^a b c d European Centre for Disease Prevention and Control (2 June 2014). "New and updated evaluations of neuraminidase inhibitors for preventing and treating influenza published". Archived from the original on 2014-11-02.
6. ^ Jump up to:^a b "Amantadine, oseltamivir and zanamivir for the treatment of influenza". National Institute for Health and Care Excellence (NICE). 25 February 2009. Archived from the original on 18 January 2017. Retrieved 16 January 2017.
7. ^ Jump up to:^a b c d "IDSA Continues to Recommend Antivirals for Influenza". Archived from the original on 24 April 2014. Retrieved 24 April 2014.
8. ^ Jump up to:^a b Brownlee S (19 February 2013). "Tamiflu: Myth and Misconception". The Atlantic. Archived from the original on 29 December 2014. Retrieved 7 December 2014.
9. ^ Jump up to:^a b c Butler D (April 2014). "Tamiflu report comes under fire". Nature. 508 (7497): 439–40. Bibcode:2014Natur.508..439B. doi:10.1038/508439a. PMID 24759392.
10. ^ Jump up to:^{a b c d e f} Michiels B, Van Puyenbroeck K, Verhoeven V, Vermeire E, Coenen S (2013). Jefferson T (ed.). "The value of neuraminidase inhibitors for the prevention and treatment of seasonal influenza: a systematic review of systematic reviews". PLOS ONE. 8 (4): e60348. Bibcode:2013PLoSO...860348M. doi:10.1371/journal.pone.0060348. PMC 3614893. PMID 23565231.
11. ^ Jump up to:^a b c d Ebell MH, Call M, Shinholser J (April 2013). "Effectiveness of oseltamivir in adults: a meta-analysis of published and unpublished clinical trials". Family Practice. 30 (2): 125–33. doi:10.1093/fampra/cms059. PMID 22997224.
12. ^ Okoli GN, Otete HE, Beck CR, Nguyen-Van-Tam JS (9 December 2014). "Use of neuraminidase inhibitors for rapid containment of influenza: a systematic review and meta-analysis of individual and household transmission studies". PLOS ONE. 9 (12): e113633. Bibcode:2014PLoSO...9k3633O. doi:10.1371/journal.pone.0113633. PMC 4260958. PMID 25490762.
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Further reading[edit]

• Pollack A (5 November 2005). "Is Bird Flu Drug Really So Vexing? Debating the Difficulty of Tamiflu". The New York Times.
• Wong SS, Yuen KY (January 2006). "Avian influenza virus infections in humans". Chest. 129 (1): 156–68. doi:10.1378/chest.129.1.156. PMID 16424427.
• Rohloff JC, Kent KM, Postich MJ, Becker MW, Chapman HH, Kelly DE, et al. (1998). "Practical Total Synthesis of the Anti-Influenza Drug GS-4104". The Journal of Organic Chemistry. 63 (13): 4545–4550. Bibcode:2007JOCh...72.1134P. doi:10.1021/jo980330q.
• Karpf M, Trussardi R (March 2001). "New, azide-free transformation of epoxides into 1,2-diamino compounds: synthesis of the anti-influenza neuraminidase inhibitor oseltamivir phosphate (Tamiflu)". The Journal of Organic Chemistry. 66 (6): 2044–51. doi:10.1021/jo005702l. PMID 11300898.
• Abrecht S, Harrington P, Iding H, Karpf M, Trussardi R, Wirz B, Zutter U (2004). "The Synthetic Development of the Anti-Influenza Neuraminidase Inhibitor Oseltamivir Phosphate (Tamiflu^®): A Challenge for Synthesis & Process Research". CHIMIA International Journal for Chemistry. 58 (9): 621–629. doi:10.2533/000942904777677605.
• Yeung YY, Hong S, Corey EJ (May 2006). "A short enantioselective pathway for the synthesis of the anti-influenza neuramidase inhibitor oseltamivir from 1,3-butadiene and acrylic acid". Journal of the American Chemical Society. 128 (19): 6310–1. doi:10.1021/ja0616433. PMID 16683783.
• Tse N, Cederbaum S, Glaspy JA (October 1991). "Hyperammonemia following allogeneic bone marrow transplantation". American Journal of Hematology. 38 (2): 140–1. doi:10.1002/ajh.2830380213. PMID 1951305.
• Schneider RU (April 2001). "The race to develop GS4104". NZZ Folio (in German).
• "FDA Drug Safety Communication: Important safety changes to the influenza drug Tamiflu (oseltamivir phosphate) for oral suspension". U.S. Food and Drug Administration (FDA). 31 August 2011.

External links[edit]

Wikimedia Commons has media related to: Oseltamivir (category)

• "Oseltamivir". Drug Information Portal. U.S. National Library of Medicine.
• "Tamiflu (oseltamivir phosphate) Information". U.S. Food and Drug Administration (FDA). 11 September 2018.

https://en.wikipedia.org/wiki/Oseltamivir
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