Tamiflu - Influenzaand Avian Flu Vaccination

View The Complete Range Of Prescription Medications Available At Discount Online Prices

Worldwide Shipping On All Pharmacy Medications

Spanish Flu
La Grippe
Global Epidemic
Today’s Parallels
Bird Flu Like 1918
1918 Bird Flu
Great Flu Pandemic

1918 Flu Pandemic

Click Here For Natural Supplements To Boost The Immune System At Discount Prices From Plaza Discounts

CLICK HERE TO ORDER TAMIFLI BIRD FLU VACCINE

Avian & Bird Flu Facts

Tamiflu For Avian Flu
How Tamiflu Works
Tamiflu Vaccine FAQ
Tamiflu Safety
Influenza FAQ
Influenza Prevention
What Tamiflu Does

ORDER TAMIFLU VACCINATION FOR INFLUENZA AND AVIAN FLU ONLINE
Everything You Need To Know About Tamiflu Influenza And Avian Flu Vaccine
Tamiflu Flu Vaccine Facts - Tamiflu Flu Vaccine Information
Your Questions About Tamiflu Influenza And Avian Flu Vaccine Answered

Tamiflu Avian Flu Vaccine

ORDER TAMIFLU VACCINE NOW
FOR INFLUENZA - FOR FLU VIRUS
FOR AVIAN FLU - FOR BIRD FLU

Tamiflu - Influenza and Avian Flu Vaccination - Oseltamivir

Ramiflu - Oseltamivir - is an antiviral drug that is used in the treatment and prophylaxis of both Influenzavirus A and Influenzavirus B. Like zanamivir, Tamiflu is a neuraminidase inhibitor. It acts as a transition-state analogue inhibitor of influenza neuraminidase, preventing new viruses from emerging from infected cells. Oseltamivir was the first orally active neuraminidase inhibitor commercially developed. It is a prodrug, which is hydrolysed hepatically to the active metabolite, the free carboxylate of Tamiflu. It was developed by Gilead Sciences and is currently marketed by Hoffmann-La Roche (Roche) under the trade name Tamiflu. It is generally available by prescription only. With increasing fears about the potential for a new influenza pandemic, Tamiflu has received substantial media attention. Production capacity is limited, and governments (and even some private individuals) are stockpiling the drug.

Tamiflu Indications and dosage

Tamiflu is indicated for the treatment of infections due to influenza A and B virus in people at least one year of age, and prevention of influenza in people at least 1 year or older. 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. Tamiflu 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.

Tamiflu Use in Avian Influenza, Also Known as Bird Flu

Tamiflu has also been found that the standard recommended dose incompletely suppresses viral replication in at least some patients with H5N1 influenza, rendering therapy ineffective and increasing the risk of viral resistance (de Jong et al. 2005). Accordingly, it has been suggested that higher doses and longer durations of therapy should be used for treatment of patients with the H5N1 virus (de Jong et al. 2005, Ward et al. 2005). See Resistance section, below.

Chokephaibulkit et al recommend the use of Tamiflu in pediatric patients, based on experience with one patient.

Sir Liam Donaldson, UK chief medical officer states in the British Medical Journal that Oseltamivir has "lack of convincing evidence" of benefit in treating avian influenza. After following WHO protocols in treating 41 victims of the H5N1 bird flu virus (19% of the world-wide cases of bird flu reported to date), Nguyen Tuong Van, MD, who runs the intensive care unit of the Center for Tropical Diseases in Hanoi, Vietnam concluded that Tamiflu, the drug most widely stockpiled around the world to combat a potential bird flu pandemic, is "useless." According to this article, the WHO confirmed Van's experience stating that Tamiflu has not been "widely successful in human patients", but speculated the drug has not been administered until late in the disease in many Asian countries.

Tamiflu Co-administration with probenecid

It has been suggested that co-administration of Tamiflu with probenecid could extend the limited supply of Tamiflu. Probenecid reduces renal excretion of the active metabolite of Tamiflu. One study showed that 500 mg of probenicid given every six hours doubled both the peak plasma concentration and the half-life of Tamiflu, increasing overall systemic exposure (AUC) by 2.5-fold. (Hill et al., 2002) Although the evidence for this interaction comes from a study by Roche, it was publicised only in October 2005 by a doctor who had reviewed the data (Butler, 2005). Probenecid was used in similar fashion during World War II to extend limited supplies of penicillin, and is still currently used to increase penicillin concentrations in serious infections.

Tamiflu Dosage forms

Oseltamivir is marketed by Roche under the trade name Tamiflu, as capsules (containing Tamiflu phosphate 98.5 mg equivalent to Tamiflu 75 mg) and as a powder for oral suspension (Tamiflu phosphate equivalent to Tamiflu 12 mg/mL).

Tamiflu Adverse effects

Common adverse drug reactions (ADRs) associated with Tamiflu therapy include: nausea, vomiting, diarrhoea, abdominal pain, and headache. Rare ADRs include: hepatitis and elevated liver enzymes, rash, allergic reactions including anaphylaxis, and Stevens-Johnson syndrome. (Rossi, 2006)

Various other ADRs have been reported in postmarketing surveillance including: toxic epidermal necrolysis, cardiac arrhythmia, seizure, confusion, aggravation of diabetes, and haemorrhagic colitis.

Tamiflu Neurological effects

In May 2004, the safety division of Japan's health ministry ordered changes to the literature accompanying Tamiflu to add neurological and psychological disorders as possible adverse effects, including: impaired consciousness, abnormal behavior, and hallucinations. Various cases of psychological disorders were associated with Tamiflu therapy between 2000–2004, including several deaths.

On 2005-11-18 the United States Food and Drug Administration (FDA) issued a report regarding the paediatric safety of Tamiflu, which stated that there was insufficient evidence to claim a causal link between Tamiflu use and the deaths of 12 Japanese children (only two from neurological problems). However, it was recommended that a warning was added to the Product Information regarding rashes associated with Tamiflu therapy (Pediatric Advisory Committee, 2005).

Tamiflu Mode of action

Tamiflu is a neuraminidase inhibitor. By blocking the activity of the neuraminidase, Tamiflu prevents new viral particles from being released by infected cells.

Tamiflu Resistance

As with other antivirals, resistance to the agent was expected with widespread use of Tamiflu, though the emergence of resistant viruses was expected to be less frequent than with amantadine or rimantadine. The resistance rate reported during clinical trials up to July 2004 was 0.33% in adults, 4.0% in children, and 1.26% overall. Mutations conferring resistance are single amino acid residue substitutions in the neuraminidase enzyme (Ward et al., 2005).

Mutant H3N2 influenza A virus isolates resistant to Tamiflu were found in 18% of a group of 50 Japanese children treated with Tamiflu (Kiso et al., 2004). This rate was similar to another study where resistant isolates of H1N1 influenza virus were found in 16.3% of another cohort of Japanese children (Ward et al., 2005). Several explanations were proposed by the authors of the studies for the higher-than-expected resistance rate detected. First, children typically have a longer infection period, giving a longer time for resistance to develop. Second, Kiso et al. (2004) claim to have used more rigorous detection techniques than previous studies. Third, the dosage regimen in Japan is different from that of other nations, and some children may have been given a suboptimal dosage of Tamiflu.

High-level resistance has been detected in one girl suffering from H5N1 avian influenza in Vietnam. She was being treated with Tamiflu at time of detection (Le et al., 2005; World Health Organization, 2005).

de Jong et al. (2005) describe resistance development in two more Vietnamese patients suffering from H5N1, and compare their cases with six others. They suggest that the emergence of a resistant strain may be associated with a patient's clinical deterioration. They also note that the recommended dosage of Tamiflu does not always completely suppress viral replication, a situation that could favor the emergence of resistant strains. Moscona (2005) gives a good overview of the resistance issue, and says that personal stockpiles of Tamiflu could lead to under-dosage and thus the emergence of resistant strains of H5N1.

Resistance is of concern in the scenario of an influenza pandemic (Wong and Yuen 2005), and may be more likely to develop in avian influenza than seasonal influenza due to the potentially longer duration of infection by novel viruses. Kiso et al. (2004) suggest that "a higher prevalence of resistant viruses should be expected" during a pandemic.

The genetic sequence for the neuraminidase enzyme is highly conserved across virus strains. This means that there are relatively few variations, and there is also evidence that variations that do occur tend to be less "fit." Thus, mutations that convey resistance to Tamiflu may also tend to cripple the virus by giving it an otherwise less-functional enzyme. The lack of variation in neuraminidase gives two advantages to Tamiflu and zanamivir, the drugs that target that enzyme. First, these drugs work on a broader spectrum of influenza strains. Second, the development of a robust, resistant virus strain appears to be less likely (Ward et al., 2005). It is worth noting that the Tamiflu-resistant strains detected by Kiso et al. (2004) all appeared within individual children after treatment with Tamiflu – the children did not catch the resistant strains in human-to-human or bird-to-human transmission.

Pandemic fears

Tamiflu - Oseltamivir - was widely used during the H5N1 avian influenza epidemic in Southeast Asia in 2005. In response to the avian flu epidemic, various governments - including those of the United Kingdom, Canada, United States and Australia - stockpiled quantities of Tamiflu in preparation for a possible pandemic. Though large, the quantities stockpiled would not have been sufficient to protect the entire population of these countries.

Taiwan to violate Tamiflu patent in order to compensate for vaccine shortage

In October 2005, the Indian drug company Cipla announced their plan to begin manufacture of generic Tamiflu without license from Roche. Most patent laws allow governments to authorise supply from generic companies, subject to remuneration to patent owners to address public health problems, including emergencies, although Roche has announced its intention to remain the sole supplier of the drug. Cipla argues that it can legally sell Tamiflu to India and 49 other developing countries, possibly as early as January 2006. Also in October, it was announced that Roche was in discussions with four generic drug manufacturers about the possibility of issuing sublicenses to increase production.

In late October 2005, Roche announced that it was suspending shipments to pharmacies in the United States and Canada until the North American seasonal flu outbreak began, to address concerns about private stockpiling and to preserve supplies for seasonal influenza. It said that, when distribution resumes in Canada, the remaining available drug will be saved for use in high-risk settings like long-term care facilities and hospitals. Sales were suspended in Hong Kong as well, and on November 8, also in China. Roche said it would instead send all supplies to China's health ministry.

On November 9, 2005, Vietnam became the first country to be granted permission by Roche to produce a generic version of Tamiflu. The week before, Thai authorities said they would begin producing generic Tamiflu, claiming that Roche had not patented Tamiflu in Thailand. The first Thai generic Tamiflu was produced in February 2006 and are to be available to the public in July 2006.

In December 2005, Roche also signed a sublicense for complete Tamiflu production with China's Shanghai Pharmaceuticals, and by March 2006 a sublicense had also been granted to India's Hetero. In June 2006, the Chinese government gave Shanghai Pharmaceuticals permission to proceed, based upon tests of the domestic production. The company said it planned to market the drug by the end of the month

In late May 2006, the World Health Organization asked Roche to be ready to ship an emergency stockpile of Tamiflu to Indonesia if needed. The alert was in response to suspected human-to-human transmission within a family and was planned to last for two weeks.

U.S. Government policy and Tamiflu

In November, 2005, U.S. president George W. Bush requested that Congress fund $7.1 billion in emergency spending for flu pandemic prepardness (the Senate had already passed an $8.1 billion bill). Bush's plan included $1.4 billion for government purchases of antiviral drugs. Some commentators (e.g. question the motives of the U.S. government's endorsement and planned purchase of Tamiflu, noting Secretary of Defense Donald Rumsfeld's close ties to Gilead Sciences, rightsholder to the Tamiflu patent. Rumsfeld is a former chairman of Gilead, and federal disclosure forms indicate that he owns between USD$5 million and USD$25 million in Gilead stock (Schwartz 2005. The rise in Gilead's share prices from USD$35 to USD$57 per share will have added between USD$2.5 million to USD$15.5 million to Rumsfeld's net worth.

On the other hand, at least one Democratic Senator has criticized Bush for not planning to buy enough antiviral drugs.

Personal stockpiling of Tamiflu

The short supply of Tamiflu has prompted some individuals to stockpile the drug. Several American states, including Massachusetts and Colorado, have issued advisories strongly discouraging this practice. One argument against individual stockpiling is that limited drugs should be kept for more strategic or ethical deployment, that is, to hard-hit areas, to people in critical roles (e.g., healthcare and government workers), to people vulnerable to seasonal flu, or to people who actually have come down with avian influenza. Ethical arguments are sometimes made: Why should affluent people (or nations) have preferred access to antiviral medications? Illegal importation may divert the drug from poorer countries where the risk of avian influenza is actually higher.

In the New England Journal of Medicine, Moscona (2005) argues that the use of personal stockpiles of Tamiflu could result in the administration of low dosages, allowing for the development of drug-resistant virus strains. Many stockpilers will only have ten 75 mg pills (the current recommended dosage for Tamiflu), but this may be insufficient for the treatment of H5N1.

Another argument is that it would be difficult for home users to determine whether illegally-imported Tamiflu is counterfeit. This is genuinely a potential problem, but, in the face of a shortage, some individuals may be willing to face such a risk. In December 2005, 53 packages of counterfeit Tamiflu tablets were intercepted by the US Customs Service in South San Francisco. The packages were labeled "Generic Tamiflu". Roche officials know of only one instance of counterfeit Tamiflu appearing outside of the United States: incorrectly-labelled tablets found in Holland, which contained only Vitamin C and lactose. However, sophisticated criminals could produce convincing fake packaging in the future.

A fourth purported problem is that the H5N1 virus can be reliably diagnosed only in a small number of labs around the world; therefore, there is no way for home users to know whether flu-like symptoms are the result of avian flu or a more benign ailment. This argument lacks face validity, since treatment must begin before such tests results would be available anyway.

Tamiflu Production shortage

In early 2005, Roche announced a production shortage. According to Roche, the major bottleneck in Tamiflu production is the availability of shikimic acid, which cannot be synthesised economically and is only effectively isolated from Chinese star anise, an ancient cooking spice. Although most autotrophic organisms produce shikimic acid, the isolation yield is low. A shortage of star anise is one of the key reasons why there is a worldwide shortage of Tamiflu. Star anise is grown in four provinces in China and harvested between March and May. It is also produced in Lang Son province, Vietnam. The shikimic acid is extracted from the seeds in a ten-stage manufacturing process. Thirteen grams of star anise make 1.3 grams of shikimic acid, which can be made into 10 Tamiflu 75 mg capsules. Ninety percent of the harvest is already used by Roche in making Tamiflu.

Some academic experts and other drug companies are disputing the difficulty of producing shikimic acid by means other than star anise extraction. An alternative method for production of the acid involves fermentation of genetically-modified bacteria. Other potential sources of shikimic acid include the ginkgo tree. In addition, quinic acid, derived from the bark of the cinchona tree of the Democratic Republic of the Congo, is a potential alternative base material for the production of Tamiflu.

However, as is clear by the multistep synthesis shown above, although the major bottleneck for Roche may be the availability of shikimic acid, production of Tamiflu is very involved. Increasing production volume (by Roche or others) would require construction of extensive new facilities (which may not be amenable to scaleup and, even if identical on paper, may not necessarily produce acceptable yields), and even if current facilities could handle a larger feedstock quantity, there would be a delay in production as the material makes it down the pipeline - 6 months or so.

In March 2006, Roche announced that it was making utilizing the resources of 15 external contractors in 9 countries, allowing production to expand to "as much as 400 million doses annually by the end of this year".

Canadian generic drug company Apotex is attempting to modify Oseletamivir to use a synthetic alternative to shikimic acid.

Tamiflu Vaccine For Influenza, Avian Flu And Bird Flu

There is evidence that the deadly H5N1 influenza virus strain - known as Avian Flu or Bird Flu - are susceptible to antiviral drugs such as Tamiflu. Governments are building Tamiflu stockpiles against the contingency of an Avian Flu pandemic. With the increased demand for Tamiflu, we are offering Tamiflu Vaccine for purchase online with free prescriptions to cope with possible World shortages. Tamiflu can be prescribed without a physical examination. Consultations can now be done online for free. Online consultations are an innovation in health care that utilizes the Internet to improve patient access to the physician.

“There is evidence that the H5N1 influenza virus strain - Avian Flu or Bird Flue - is susceptible to the Tamiflu antiviral drug. World governments are expanding stockpiles of Tamiflu against the contingency of a flu pandemic. With the increased demand for Tamiflu, we are offering Tamiflu for purchase online with free prescriptions to cope with shortages. Tamiflu can be prescribed without a physical examination. Consultations can now be done online for free. Protect your family against Avian or Bird Flue by ordering Tamiflu Influenza Vaccine online now. “