TAMIFLU
The first case of swine flu resistant to the antiviral drug Tamiflu has been found in Denmark, according to Danish health officials. The United States has about 52 million courses of antiviral drugs in its stockpiles. Argentina, Brazil, Chile and other countries are experiencing rapid increases in serious cases and deaths as the winter flu season sets in. The United States will donate 420,000 packets of the antiviral drug Tamiflu to the Pan-American Health Organization to help fight the swine flu pandemic in Latin America and the Caribbean, federal health officials said Thursday. Tamiflu and hand sanitizer are added to the usual routines of swimming and crafts. Sales of the drug Tamiflu have skyrocketed since the outbreak of swine flu in April with people buyin and taking Tamiflu as a precaution. , bolstering the profits of the drugs maker, Roche. The government is grappling with competing and sometimes conflicting goals: preventing widespread panic, but preparing for the worst. The outbreak has caused panic in much of the country, with schools, theaters and shopping malls closing in many places. India is struggling to cope with the spread of swine flu, with at least 17 deaths confirmed from the virus and nearly 1,200 diagnosed cases. Here are the reactions that showed up more frequently in patients taking the drug.
Most problems noted during tests of Tamiflu were indistinguishable from the symptoms of flu. What side effects may occur? It should be refrigerated, but do not freeze. Use the liquid suspension within 10 days. Keep the blister package dry. Shake the liquid suspension before each use. If Tamiflu upsets your stomach, try taking it with food. Protection lasts as long as you take the drug.
How should you take Tamiflu? Should you take Tamiflu as a precaution? For older adults, those in high-risk situations such as health-care work, and people with an immune deficiency or respiratory disease, vaccination remains a must. Tamiflu can prevent the flu as long as you continue taking this medication, but getting a yearly flu shot is still the best way of avoiding the disease entirely. Tamiflu is taken in liquid or capsule form.
Neuraminidase inhibitors fight the virus by preventing the release of new copies from infected cells. Tamiflu belongs to a class of antiviral drugs called neuraminidase inhibitors. It also can prevent the flu if treatment is started within 2 days after exposure to a flu victim. Tamiflu speeds recovery from the flu.
This site also offers information on the flu viruses, symptoms, and how to prepare for the threat of a flu pandemic. Learn more about human and avian flu viruses, and how Tamiflu can protect you and your family from possible death. It was again cited Tamiflu should be prescribed to a pregnant woman only if the case justifies the potential benefit of the foetus. Anyway the conclusion drawn is also the same as that drawn for the pregnancy test. A similar human study could not be conducted due to the lack of lactating mothers infected by the flu who are willing to contribute towards experimentation.
It was observed that Oseltamivir and Oseltamivir carboxylate are given out in the milk. A similar study was conducted on rats and rabbits for the effects of Tamiflu in lactating mothers. The studies came to the conclusion as such, Tamiflu should be prescribed to a pregnant woman only if the case justifies the potential benefit of the fetus. However the abnormality remained in the background. Skeletal abnormalities were observed in the cases where the doses were increased. The rabbit showed slight maternal toxicities. In the case of the rats, the maternal toxicity was minimal that too in the one thousand five hundred milligram per kilogram per day group. Pharmacokinetic study showed that fetal exposure was there in both the cases. The relative exposure rates were accounted for. Both these animals were given the medication by the oral route. The rabbits were given fifty, one hundred and fifty and five hundred milligrams for every kilogram per day.
They were administered dosages of fifty, two hundred and fifty and one thousand five hundred milligrams for per kilogram per day. The pregnant rats were given Tamiflu in different proportions. Then in a later stage we switched over to rabbits. As there was no human specimens in the tests initial tests were conducted on rats. The data collected is insufficient to give a clear picture on the effects of Tamiflu on pregnant women and her developing fetus. The FDA has categorized this drug under the medical category C. Now I will be discussing the studies conducted on the medication for pregnancy.
So this is the approximate dosage of what a pregnant lady will have if she is faced with the consequences of taking Tamiflu. In the earlier case the person is prescribed this medicine for a period of five days and in the second case for a period of seven days. For people who have been exposed to the influenza virus and they who are taking this medicine as a preventive measure against the flu should take only one seventy five grams capsule in a day. For persons afflicted by the flu, they re supposed to take two capsules orally; one capsule in the morning and one in the evening. The capsule is a grey and light yellow capsule. Each capsule of the medication contains seventy five grams of the active drug. For knowing its effects on pregnancy one should know the dosage of the capsule. So you can simply say that Tamiflu treats the flu at the source of the infection. Most other medications for flu go for the symptoms and try to cure the symptoms or mask them. You will feel the symptoms reducing within a span of two days.
The medicine acts in this way; it attacks the influenza virus in the body and stops it from spreading inside the body. This medicine belongs among a group of medications which is called the neuraminidase inhibitors. The main ingredient of the Tamiflu medicine is the Oseltamivir phosphate. Now that I have covered what Tamiflu is briefly I will go into the details and then give you a study on the effects of Tamiflu when you are pregnant and lactating because this too is an important part of pregnancy. Tamiflu is a medicine that is to be taken when you are infected by the influenza virus.
It is possible to buy tamiflu online by using our consultation service which if successful can allow you to obtain tamiflu 75mg from the comfort of your own home. Tamiflu is an influenza treatment manufactured by Roche and is the only treatment which is effective at treating avian bird flu.
You should not purchase Tamiflu for people under the age of 1 year and people who complain of uncomplicated acute illness due to influenza infection and show symptoms for no more than 2 days. By preventing the spread of the virus from cell to cell, the symptoms and duration of an influenza infection are significantly reduced. Tamiflu Influenza treatment acts a transition-state analogue inhibitor of the influenza neuraminidase, preventing the growth of new viruses in contaminated cells. Tamiflu capsule works by interfering with the flu viral reproductive, inhibiting an enzyme called neuraminidase, preventing the virus from spreading. Common symptoms of the flu include fever, runny nose, muscle pains and a feeling of weakness. When the virus enters the body, it thrives and multiplies by using living cells and its host. Influenza, commonly known as the flu, is a highly contagious influenza virus which affects the respiratory system. Before buying Tamiflu, it is important to understand how the medication and the Influenza virus works. If you feel any of these side effects, it is important to seek medical attention urgently.
There have been some very rare cases of self-injury and delirium due to the use of Tamiflu in patients with the flu. Taking Tamiflu with food may help to reduce the probability of nausea. The most common side effects of Tamiflu are nausea, diarrhea, bronchitis, abdominal pain, headache, dizziness and vomiting. The probability of experiencing side effects with Tamiflu is very slim.
What are the side effects of Tamiflu? Many people use Tamiflu as a precaution too. Complete the entire treatment of 10 doses. Tamiflu should be taken within 48 hours of witnessing flu symptoms or after being exposed to a person suffering from flu. You may take Tamiflu with food or milk to minimize stomach upset. Do not leave your Tamiflu dosage incomplete if you want to prevent relapse. Tamiflu dosage normally lasts for five days and two tablets a day are to be taken. It contains the key ingredient called oseltamivir. Tamiflu comes in 75mg capsule form and is taken orally.
What is the recommended dosage of Tamiflu? It can help to minimize the bird flu symptoms to the point where a patient may survive the virus, whereas without Tamiflu, the attack would be fatal. Tamiflu can also reduce the effects of bird flu and help speed up recovery time. You can also buy Tamilfu to prevent influenza from starting, if you believe you have been exposed to the virus but not yet received any symptoms. Tamiflu reduces the duration of influenza symptoms by one and a half days if treatment is started within forty-eight hours after symptoms occur.
When will I see results with Tamiflu? The World Health Organization has indicated there is a serious risk of swine flu developing into a global pandemic. First reported in Mexico in April 2009, it has now spread around the world with thousands of reported cases. Swine flu has evolved into a strain that has never been seen before and is more easily transmissible between humans. Flu viruses are constantly changing and evolving, resulting in new strains of the same virus being produced. Swine flu is a disease usually affecting pigs. Tamiflu works against both the influenza type A and type B viruses and can also give effective fortification against the attack of H1N1 swine flu virus, prior to the illness occurring. Tamiflu is manufactured by the Swiss pharmaceutical company Hoffmann-La Roche.
This illness, more commonly known as the flu, is extremely contagious and is known to cause a ranging severity of sickness in children and adults of all ages. Tamiflu is an antiviral prescription medication designed to treat the influenza virus, including the H1N1 swine flu virus. It is has been so easy to become totally confused by the different reports on Tamiflu and Relenza. Content on this page requires a newer version of Adobe Flash Player. If you are not sure if your medicine belongs to one of these categories, talk to your prescriber of pharmacist.
Talk to your prescriber, pharmacist or nurse at once and check that they still want you to have Tamiflu. Some hospital workers may be taking tamiflu for longer periods of time and those with undiagnosed liver, kidney or other undiagnosed problems might be in danger of organ failure. Remember the amount of these things are going to accumulate as you dose. These are some ingredients in Tamiflu. Your prescriber may decide to change the dose or stop you from having this medicine again. If you feel unwell or are worried, contact your prescriber, pharmacist or nurse at once. If you did not get a Patient Information Leaflet with your medicine, ask your pharmacist for one. Read the Patient Information Leaflet that comes with your medicine for more information. This is the list of side-effects that Tamiflu can cause. The dosing device dispensed with the commercially available Tamiflu for Oral Suspension should NOT be used with the compounded suspension since they have different concentrations. Note: This compounding procedure results in a 15 mg/mL suspension, which is different from the commercially available Tamiflu for Oral Suspension, which has a concentration of 12 mg/mL.
Carefully separate the capsule body and cap and transfer the contents of the required number of Tamiflu 75 mg Capsules into a clean mortar. This compounded suspension should not be used for convenience or when the FDA-approved Tamiflu for Oral Suspension is commercially available. In the event that Tamiflu for Oral Suspension is not available, the pharmacist may compound a suspension from Tamiflu Capsules 75 mg using either of two vehicles: Cherry Syrup or Ora-Sweet SF. Commercially manufactured Tamiflu for Oral Suspension is the preferred product for pediatric and adult patients who have difficulty swallowing capsules or where lower doses are needed. These directions are not intended to be used if the FDA-approved, commercially manufactured Tamiflu for Oral Suspension is readily available from wholesalers or the manufacturer.
The constituted Tamiflu for Oral Suspension should be used within 10 days of preparation; the pharmacist should write the date of expiration of the constituted suspension on a pharmacy label. For the prophylaxis of influenza, dose adjustment is recommended for patients with creatinine clearance between 10 and 30 mL/min receiving Tamiflu. Dose adjustment is recommended for patients with creatinine clearance between 10 and 30 mL/min receiving Tamiflu for the treatment of influenza. The recommended oral dose of Tamiflu for pediatric patients 1 year and older following close contact with an infected individual is shown in Table 6. The safety and efficacy of Tamiflu for prophylaxis of influenza in pediatric patients younger than 1 year of age have not been established. The recommended oral dose of Tamiflu for prophylaxis of influenza in adults and adolescents 13 years and older following close contact with an infected individual is 75 mg once daily for at least 10 days. If the for Oral Suspension product is not available, Tamiflu Capsules may be opened and mixed with sweetened liquids such as regular or sugar-free chocolate syrup.
For pediatric patients who cannot swallow capsules, Tamiflu for Oral Suspension is the preferred formulation. Tamiflu for Oral Suspension may also be used by patients who cannot swallow a capsule. The recommended oral dose of Tamiflu for pediatric patients 1 year and older is shown in Table 5. Tamiflu is not indicated for treatment of influenza in pediatric patients younger than 1 year. Treatment should begin within 2 days of onset of symptoms of influenza.
The recommended oral dose of Tamiflu for treatment of influenza in adults and adolescents 13 years and older is 75 mg twice daily for 5 days. However, when taken with food, tolerability may be enhanced in some patients. Tamiflu may be taken with or without food. Single doses of up to 1000 mg of Tamiflu have been associated with nausea and/or vomiting. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to Tamiflu exposure. The following adverse reactions have been identified during postmarketing use of Tamiflu. Pooled data from Phase III trials of Tamiflu treatment of naturally acquired influenza. Other events reported more frequently by pediatric patients treated with Tamiflu included abdominal pain, epistaxis, ear disorder, and conjunctivitis. Adverse events occurring in 1% of pediatric patients receiving Tamiflu treatment are listed in Table 4. A total of 515 pediatric patients received treatment with Tamiflu for Oral Suspension. A total of 1032 pediatric patients aged 1 to 12 years participated in phase III studies of Tamiflu given for the treatment of influenza. There were no clinically relevant differences in the safety profile of the 942 elderly subjects who received Tamiflu or placebo, compared with the younger population.
However, the difference in incidence between Tamiflu and placebo for these events was less than 1%. Tamiflu is available as capsules containing 30 mg, 45 mg, or 75 mg oseltamivir for oral use, in the form of oseltamivir phosphate, and as a powder for oral suspension, which when constituted with water as directed contains 12 mg/mL oseltamivir base. Tamiflu Official FDA information, side effects and uses. Swine Flu SymptomsHeight Predictor - How tall will your kids be? Several shipments of fake or counterfeit Tamiflu pills have been seized recently, so if ordering Tamiflu on the internet, only buy Tamiflu from a reputable online pharmacy. Tamiflu is being investigated under the Best Pharmaceuticals for Children Act, because in a safety review, 'unusual neurologic or psychiatric events such as delirium, hallucinations, confusion, abnormal behavior, convulsions, and encephalitis' were reported. The most common side effects in pediatric patients taking Tamiflu for the treatment of the flu include vomiting, abdominal pain, epistaxis , ear disorders, and conjunctivitis.
It is also indicated as prophylaxis, or a preventative, against the flu for adults and children over age 12 months. Tamiflu is approved to treat the flu in adults and children over age 12 months. Tamiflu is a prescription antiviral medication that can be used to treat influenza infections in children and adults, if their symptoms have started within the last day or two before starting to take Tamiflu. These documents are available to you in Adobe Acrobat's.PDF format. Where can I get more information? Do not start using a new medication without telling your doctor. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Tell your doctor about all the prescription and over-the-counter medications you use. There may be other that can interact with Tamiflu. What other drugs will affect Tamiflu? Call your doctor for medical advice about side effects.
This is not a complete list of side effects and others may occur. Some people using oseltamivir have had rare side effects of sudden confusion, delirium, hallucinations, unusual behavior, or self-injury. Stop using Tamiflu and get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat; a red and blistering or peeling skin rash. This medicine may interfere with the drug action of FluMist, making the vaccine less effective. Do not use a nasal flu vaccine within 48 hours after taking Tamiflu. What should I avoid while taking Tamiflu?
Overdose symptoms may include nausea and vomiting. Seek emergency medical attention if you think you have used too much of this medicine. What happens if I overdose? If your next dose is less than 2 hours away, skip the missed dose and take the medicine at the next regularly scheduled time.
Take the missed dose as soon as you remember. Throw away any unused liquid after 10 days. Store Tamiflu liquid in the refrigerator but do not freeze. Store the capsules at room temperature away from moisture and heat.
Your symptoms may get better before the infection is completely treated. Use this medication for the entire length of time prescribed by your doctor. You may take Tamiflu with or without food. If you do not have the syringe or another medicine dose-measuring device, ask your pharmacist for one. Do not measure the medicine with a regular table spoon. To be sure you get the correct dose, measure the liquid with the syringe provided with the medicine. Shake the oral suspension well just before you measure a dose. Do not take Tamiflu for longer than your doctor has prescribed. Do not take more of the medication than recommended. Take Tamiflu exactly as your doctor has prescribed it for you.
Do not take this medication without telling your doctor if you are breast-feeding a baby. It is not known whether oseltamivir passes into breast milk or if it could harm a nursing baby. Your doctor will decide whether you should receive this vaccine, especially if you have a high risk of infection with H1N1 influenza. However, not vaccinating the mother could be more harmful to the baby if the mother becomes infected with a disease that this vaccine could prevent. Vaccines may be harmful to an unborn baby and generally should not be given to a pregnant woman. You should not use Tamiflu if you are allergic to oseltamivir. Tamiflu should not be used in place of getting a yearly flu shot. The Centers for Disease Control recommends an annual flu shot to help protect you each year from new strains of influenza virus. Oseltamivir should not be used in place of getting a yearly flu shot. However, anyone using this medicine should be watched closely for signs of confusion or unusual behavior.
It is not known whether Tamiflu was the exact cause of these symptoms. These symptoms have occurred most often in children. Some people using this medicine have had rare side effects of sudden confusion, delirium, hallucinations, unusual behavior, or self-injury. Your symptoms may start to improve before the infection is completely treated. Treatment with Tamiflu should start as soon as possible when flu symptoms appear, such as fever, chills, muscle aches, sore throat, and runny or stuffy nose. Also tell your doctor if you have any condition causing swelling or disorder of the brain.
Before taking Tamiflu, tell your doctor if you have received a nasal flu vaccine within the past 2 weeks, or if you have kidney disease, heart disease, lung disease, or any other serious disease or health problem. Oseltamivir will not treat the common cold. Tamiflu may also be used for other purposes not listed in this medication guide. Tamiflu may also be given to prevent influenza in people who may be exposed but do not yet have symptoms.
Tamiflu is used to treat flu symptoms caused by influenza virus in patients who have had symptoms for less than 2 days. Tamiflu is an antiviral medication that blocks the actions of influenza virus types A and B in your body. This medication is not a substitute for the flu vaccine. Canadian residents should call their local poison control center directly. OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. This document does not contain all possible interactions. Wait at least 2 days after ending treatment with this medication before receiving flu vaccine given in the nose.
This medication may lower your protection from flu vaccine given in the nose. Tell your doctor if you have received flu vaccine in the nose within 2 weeks before treatment with this medication. Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use especially of: clopidogrel. Consult your doctor before breast-feeding.
Discuss the risks and benefits with your doctor. This medication should be used only when clearly needed during pregnancy. This drug may make you dizzy; use caution engaging in activities requiring alertness such as driving or using machinery. Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease. PRECAUTIONS: Before taking oseltamivir, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration at 1-800-FDA-1088. Contact your doctor for medical advice about side effects. If you notice other effects not listed above, contact your doctor or pharmacist. This is not a complete list of possible side effects. A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Seek immediate medical attention if this rare but very serious side effect occurs: chest pain.
Tell your doctor immediately of any signs of unusual behavior including confusion, agitation, self-injury. This may be more likely in children. The flu itself or oseltamivir may rarely cause serious mental/mood changes. Many people using this medication do not have serious side effects. Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. If any of these effects persist or worsen, notify your doctor or pharmacist promptly. Inform your doctor if your condition persists or worsens or if new symptoms appear. Stopping the medication too early may allow the virus to continue to grow, which may result in a relapse of the infection or failure to protect you from the flu.
Continue to take it for the full time prescribed. Therefore, take this drug at evenly spaced intervals at the same time every day. This medication works best when the amount of medicine in your body is kept at a constant level. Follow your doctor s instructions for how long to take this medicine.
Oseltamivir works best if you start taking it within 2 days of either of these events. Take this medication as soon as flu symptoms appear or as soon as possible after you have been exposed to the flu. You may take it with food or milk to minimize stomach upset. Take this medication by mouth as directed by your doctor. If you have any questions, consult your doctor or pharmacist. Consult your doctor or pharmacist for more details.
Oseltamivir should not be used in infants younger than 1 year of age. This medication works by stopping the flu virus from growing. This medication is also used to prevent the flu if you have been exposed to someone who already has the flu. It helps make the symptoms less severe and shortens the recovery time by 1-2 days. USES: Oseltamivir is used to treat symptoms caused by the flu virus.
This information does not contain any assurances that this product is safe, effective, or appropriate for you. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. For complete information about this product or your specific health needs, ask your health care professional. Stir the mixture and give the entire dose to the child. Add a small amount of a sweetened liquid such as chocolate syrup that the child will consume completely. Holding one capsule over a small bowl, carefully pull the capsule open and pour the complete contents of the capsule into the bowl.
Please follow instructions carefully to ensure proper dosing. Disassemble oral dispenser, rinse under running tap water and air dry prior to next use. Close bottle with child-resistant cap after each use. Do not mix with any liquid prior to dispensing. Turn the entire unit right side up and remove the oral dispenser slowly from the bottle. Pull the plunger out slowly until the desired amount of medication is withdrawn into the oral dispenser.
Turn the entire unit upside down. Insert tip firmly into opening of the bottle adapter. Before inserting the tip of the oral dispenser into bottle adapter, push the plunger completely down toward the tip of the oral dispenser. Shake closed bottle well for about 5 seconds before each use. Please follow instructions carefully to ensure proper dosing of the oral suspension. You can ask your pharmacist or healthcare professional for information about TAMIFLU that is written for health professionals. If you would like more information, talk with your healthcare professional. Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Keep this medication out of reach of children. If you notice any side effects not mentioned in this leaflet, or if you have any concerns about the side effects you get, tell your healthcare professional. Before taking TAMIFLU, please let your healthcare provider know if you have received nasally administered influenza virus vaccine during the past two weeks. Therefore, patients should be observed for signs of unusual behavior and a healthcare professional should be contacted immediately if the patient shows any signs of unusual behavior.
These events are uncommon but may result in accidental injury to the patient. These events may occur shortly after beginning TAMIFLU or may occur when flu is not treated. People with the flu, particularly children and adolescents, may be at an increased risk of seizures, confusion, or abnormal behavior early during their illness. If you develop an allergic reaction or severe rash, stop taking TAMIFLU and contact your healthcare professional. They usually happen in the first 2 days of treatment. These are usually mild to moderate.
If you miss several doses, tell your healthcare professional and follow the advice given to you. Please follow the dosing instructions below. If TAMIFLU for Oral Suspension is not available, your healthcare provider may instruct you to open TAMIFLU Capsules and mix the contents with sweetened liquids such as regular or sugar-free chocolate syrup. If you lose or damage the dispenser and cannot use it, contact your healthcare professional or pharmacist for advice on the proper dose.
Review the instructions below on how to use the dispenser and ask your pharmacist if you have any questions. In order to be sure you receive the proper dose, it is important that you use the dispenser provided. Follow your healthcare professional's instructions on which dose to take or how to combine them for the proper dose for you. If you are taking TAMIFLU for Oral Suspension, your pharmacist will give you a dosing dispenser marked with three possible doses. TAMIFLU has not been studied in children 1 to 12 years of age for preventing flu during an outbreak in your community or for use for more than 10 days. If you feel worse or develop new symptoms during treatment with TAMIFLU, or if your flu symptoms do not start to get better, you should contact your healthcare professional.
It is important that you begin your treatment with TAMIFLU as soon as possible from the first appearance of your flu symptoms or soon after you are exposed to the flu. Sorbitol may cause upset stomach and diarrhea in patients with a family history of fructose intolerance. Tell your healthcare professional if you have any type of kidney disease, heart disease, respiratory disease, or any serious health condition. TAMIFLU is not recommended for use in children younger than 1 year of age. TAMIFLU is normally not recommended for use during pregnancy or nursing, as the effects on the unborn child or nursing infant are unknown. Before starting treatment, make sure your healthcare professional knows if you take any other medicines, or are pregnant, planning to become pregnant, or breastfeeding. You should continue to get a flu vaccination every year, according to your healthcare professional's advice. Outside of those outbreaks, only a very tiny number of respiratory infections are caused by the influenza virus. Flu outbreaks happen about once a year, usually in the winter, when the influenza virus spreads widely in the community.
Flu symptoms include fever and problems such as cough, sore throat, runny or stuffy nose, headaches, muscle aches, fever, and extreme tiredness. TAMIFLU can also reduce the chance of getting the flu if there is a flu outbreak in the community. TAMIFLU can also reduce the chance of getting the flu in people age 1 and older who have a higher chance of getting the flu because they spend time with someone who has the flu. TAMIFLU is for treating adults and children age 1 and older with the flu whose flu symptoms started within the last day or two. TAMIFLU treats flu at its source, by attacking the virus that causes the flu, rather than simply masking symptoms. TAMIFLU attacks the influenza virus and stops it from spreading inside your body. This information does not take the place of talking with your healthcare professional about your medical condition or your treatment. Read it well before you begin treatment. At this dosage, the exposure to prodrug was approximately 800-fold the exposure expected in a 1-year-old child. These observations suggest that the levels of oseltamivir in the brains of rats decrease with increasing age and most likely reflect the maturation stage of the blood-brain barrier.
Plasma levels of the prodrug were 10-fold higher in 7-dayold rats as compared with adult rats. Further follow-up investigations of the unexpected deaths of 7-day-old rats at 1000 mg/kg revealed that the concentrations of the prodrug in the brains were approximately 1500-fold those of the brains of adult rats administered the same oral dose of 1000 mg/kg, and those of the active metabolite were approximately 3-fold higher. In a 2-week study in unweaned rats, administration of a single dose of 1000 mg/kg oseltamivir phosphate to 7-day-old rats resulted in deaths associated with unusually high exposure to the prodrug. Laboratory-confirmed clinical influenza was defined as oral temperature 100F/37.8C plus cough and/or coryza recorded within 48 hours, plus either a positive virus isolation or a fourfold or greater increase in virus antibody titers from baseline or at illness visits. The efficacy of TAMIFLU in preventing naturally occurring influenza illness has been demonstrated in a randomized, open-label, postexposure prophylaxis study in households that included children aged 1 to 12 years, both as index cases and as family contacts. In a study of postexposure prophylaxis in household contacts of an index case, TAMIFLU 75 mg once daily administered within 2 days of onset of symptoms in the index case and continued for 7 days reduced the incidence of laboratoryconfirmed clinical influenza from 12% in the placebo group to 1% for the TAMIFLU group. About 80% of this elderly population were vaccinated, 14% of subjects had chronic airway obstructive disorders, and 43% had cardiac disorders. In a seasonal prophylaxis study in elderly residents of skilled nursing homes, TAMIFLU 75 mg once daily taken for 42 days reduced the incidence of laboratory-confirmed clinical influenza from 4.4% for the placebo group to 0.4% for the TAMIFLU group. In a pooled analysis of two seasonal prophylaxis studies in healthy unvaccinated adults , TAMIFLU 75 mg once daily taken for 42 days during a community outbreak reduced the incidence of laboratory-confirmed clinical influenza from 4.8% for the placebo group to 1.2% for the TAMIFLU group. Laboratory-confirmed clinical influenza was defined as oral temperature 99.0F/37.2C plus at least one respiratory symptom and at least one constitutional symptom , all recorded within 24 hours, plus either a positive virus isolation or a fourfold increase in virus antibody titers from baseline.
The primary efficacy parameter for all these studies was the incidence of laboratory-confirmed clinical influenza. The efficacy of TAMIFLU in preventing naturally occurring influenza illness has been demonstrated in three seasonal prophylaxis studies and a postexposure prophylaxis study in households. Subgroup analyses of this study by gender showed no differences in the treatment effect of TAMIFLU in males and females. TAMIFLU is not indicated for either treatment or prophylaxis of influenza in pediatric patients younger than 1 year of age because of uncertainties regarding the rate of development of the human blood-brain barrier and the unknown clinical significance of non-clinical animal toxicology data for human infants. The safety and efficacy of TAMIFLU in pediatric patients younger than 1 year of age have not been studied. Many of these individuals had cardiac and/or respiratory disease, and most had received vaccine that season. Safety and efficacy have been demonstrated in elderly residents of nursing homes who took TAMIFLU for up to 42 days for the prevention of influenza. Some seasonal variability was noted in the clinical efficacy outcomes. The safety of TAMIFLU has been established in clinical studies which enrolled 741 subjects. TAMIFLU should, therefore, be used only if the potential benefit for the lactating mother justifies the potential risk to the breast-fed infant. It is not known whether oseltamivir or oseltamivir carboxylate is excreted in human milk.
In lactating rats, oseltamivir and oseltamivir carboxylate are excreted in the milk. Because animal reproductive studies may not be predictive of human response and there are no adequate and well-controlled studies in pregnant women, TAMIFLU should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. However, the individual incidence rate of each skeletal abnormality or variant remained within the background rates of occurrence in the species studied. There was a dosedependent increase in the incidence rates of a variety of minor skeletal abnormalities and variants in the exposed offspring in these studies. In the rabbit study, slight and marked maternal toxicities were observed, respectively, in the 150 and 500 mg/kg/day groups. In the rat study, minimal maternal toxicity was reported in the 1500 mg/kg/day group. Pharmacokinetic studies indicated that fetal exposure was seen in both species.
Studies for effects on embryo-fetal development were conducted in rats and rabbits by the oral route. There are insufficient human data upon which to base an evaluation of risk of TAMIFLU to the pregnant woman or developing fetus. There were no effects on fertility, mating performance or early embryonic development at any dose level. Males were dosed for 4 weeks before mating, during and for 2 weeks after mating. In a fertility and early embryonic development study in rats, doses of oseltamivir at 50, 250, and 1500 mg/kg/day were administered to females for 2 weeks before mating, during mating and until day 6 of pregnancy. Oseltamivir carboxylate was non-mutagenic in the Ames test and the L5178Y mouse lymphoma assay with and without enzymatic activation and negative in the SHE cell transformation test. It was found to be positive in a Syrian Hamster Embryo cell transformation test.
Oseltamivir was found to be non-mutagenic in the Ames test and the human lymphocyte chromosome assay with and without enzymatic activation and negative in the mouse micronucleus test. The respective safety margins of the exposures to the active oseltamivir carboxylate were 15 and 50-fold. The mean maximum daily exposures to the prodrug in mice and rats were approximately 130- and 320-fold, respectively, greater than those in humans at the proposed clinical dose based on AUC comparisons. In 2-year carcinogenicity studies in mice and rats given daily oral doses of the pro-drug oseltamivir phosphate up to 400 mg/kg and 500 mg/kg, respectively, the pro-drug oseltamivir phosphate and the active form oseltamivir carboxylate induced no statistically significant increases in tumors over controls. For patients with hereditary fructose intolerance, this is above the daily maximum limit of sorbitol and may cause dyspepsia and diarrhea. Patients should continue receiving an annual flu vaccination according to guidelines on immunization practices. Patients should be instructed to take any missed doses as soon as they remember, except if it is near the next scheduled dose , and then continue to take TAMIFLU at the usual times. These events may occur in the setting of encephalitis or encephalopathy but can occur without obvious severe disease. Influenza can be associated with a variety of neurologic and behavioral symptoms which can include events such as hallucinations, delirium, and abnormal behavior, in some cases resulting in fatal outcomes. TAMIFLU should be stopped and appropriate treatment instituted if an allergic-like reaction occurs or is suspected. Rare cases of anaphylaxis and serious skin reactions including toxic epidermal necrolysis, Stevens-Johnson Syndrome, and erythema multiforme have been reported in postmarketing experience with TAMIFLU.
The safety and pharmacokinetics in patients with severe hepatic impairment have not been evaluated. Serious bacterial infections may begin with influenza-like symptoms or may coexist with or occur as complications during the course of influenza. Efficacy of TAMIFLU for treatment or prophylaxis has not been established in immunocompromised patients. Safety and efficacy of repeated treatment or prophylaxis courses have not been studied. No information is available regarding treatment of influenza in patients with any medical condition sufficiently severe or unstable to be considered at imminent risk of requiring hospitalization. No difference in the incidence of complications was observed between the treatment and placebo groups in this population. Efficacy of TAMIFLU in the treatment of subjects with chronic cardiac disease and/or respiratory disease has not been established. Efficacy of TAMIFLU in patients who begin treatment after 40 hours of symptoms has not been established. Use of Tamiflu should not affect the evaluation of individuals for annual influenza vaccination in accordance with guidelines of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices. There is no evidence for efficacy of Tamiflu in any illness caused by agents other than influenza viruses Types A and B.
Tamiflu is contraindicated in patients with known hypersensitivity to any of the components of the product. Among household contacts 1 to 12 years of age not already shedding virus at baseline, TAMIFLU for Oral Suspension 30 mg to 60 mg taken once daily for 10 days reduced the incidence of laboratory-confirmed clinical influenza from 17% in the group not receiving prophylaxis to 3% in the group receiving prophylaxis. Laboratory-confirmed clinical influenza was defined as oral temperature 100 F/37.8 C plus cough and/or coryza recorded within 48 hours, plus either a positive virus isolation or a fourfold or greater increase in virus antibody titers from baseline or at illness visits. The primary efficacy parameter for this study was the incidence of laboratory-confirmed clinical influenza in the household. All index cases in this study received treatment. The efficacy of Tamiflu in preventing naturally occurring influenza illness has been demonstrated in a randomized, open-label, postexposure prophylaxis study in households that included children aged 1 to 12 years, both as index cases and as family contacts. Index cases did not receive Tamiflu in the study.
In a study of postexposure prophylaxis in household contacts of an index case, Tamiflu 75 mg once daily administered within 2 days of onset of symptoms in the index case and continued for 7 days reduced the incidence of laboratory-confirmed clinical influenza from 12% in the placebo group to 1% for the Tamiflu group. In a seasonal prophylaxis study in elderly residents of skilled nursing homes, Tamiflu 75 mg once daily taken for 42 days reduced the incidence of laboratory-confirmed clinical influenza from 4.4% for the placebo group to 0.4% for the Tamiflu group. In a pooled analysis of two seasonal prophylaxis studies in healthy unvaccinated adults , Tamiflu 75 mg once daily taken for 42 days during a community outbreak reduced the incidence of laboratory-confirmed clinical influenza from 4.8% for the placebo group to 1.2% for the Tamiflu group. The efficacy of Tamiflu in preventing naturally occurring influenza illness has been demonstrated in three seasonal prophylaxis studies and a postexposure prophylaxis study in households.
Subgroup analyses of this study by gender showed no differences in the treatment effect of Tamiflu in males and females. TAMIFLU treatment of 2 mg/kg twice daily, started within 48 hours of onset of symptoms, significantly reduced the total composite time to freedom from illness by 1.5 days compared to placebo. These were: alleviation of cough, alleviation of coryza, resolution of fever, and parental opinion of a return to normal health and activity. The primary endpoint in this study was the time to freedom from illness, a composite endpoint which required 4 individual conditions to be met. Of the 452 influenza-infected patients, 67% were infected with influenza A and 33% with influenza B. Of 698 patients enrolled in this trial, 452 were influenza-infected. One double-blind placebo-controlled treatment trial was conducted in pediatric patients aged 1 to 12 years , who had fever plus one respiratory symptom when influenza virus was known to be circulating in the community. However, the magnitude of treatment effect varied between studies. In the pooled analysis, at the recommended dose of TAMIFLU 75 mg twice daily for 5 days, there was a 1 day reduction in the median time to improvement in influenzainfected subjects receiving TAMIFLU compared to those receiving placebo. Of the 476 influenza-infected patients, 95% were infected with influenza type A and 5% with influenza type B. Of 741 patients enrolled, 476 patients were influenza-infected.
The enrollment criteria were similar to that of adult trials with the exception of fever being defined as >97.5 F. Three double-blind placebo-controlled treatment trials were conducted in patients 65 years of age in three consecutive seasons. In the treatment of influenza, no increased efficacy was demonstrated in subjects receiving treatment of 150 mg TAMIFLU twice daily for 5 days. Subgroup analyses of these studies by gender showed no differences in the treatment effect of TAMIFLU in men and women. In both studies, at the recommended dose of TAMIFLU 75 mg twice daily for 5 days, there was a 1.3 day reduction in the median time to improvement in influenza-infected subjects receiving TAMIFLU compared to subjects receiving placebo. Time to improvement was calculated from the time of treatment initiation to the time when all symptoms were assessed as "none" or "mild".
Of 1355 patients enrolled in these two trials, 849 patients were influenza-infected. In addition, all patients enrolled in the trials were allowed to take fever-reducing medications. Patients were eligible for these trials if they had fever >100F, accompanied by at least one respiratory symptom and at least one systemic symptom and influenza virus was known to be circulating in the community. Two phase III placebo-controlled and double-blind clinical trials were conducted: one in the USA and one outside the USA. Based on drug exposure and tolerability, dose adjustments are not required for geriatric patients for either treatment or prophylaxis. Half-lives observed in the geriatric patients were similar to those seen in young adults. Exposure to oseltamivir carboxylate at steady-state was 25% to 35% higher in geriatric patients compared to young adults given comparable doses of oseltamivir. The pharmacokinetics of oseltamivir in pediatric patients over 12 years of age are similar to those in adult patients. For oseltamivir carboxylate, apparent total clearance decreases linearly with increasing age. Younger pediatric patients cleared both the prodrug and the active metabolite faster than adult patients resulting in a lower exposure for a given mg/kg dose.
The pharmacokinetics of oseltamivir and oseltamivir carboxylate have been evaluated in a single dose pharmacokinetic study in pediatric patients aged 5 to 16 years and in a small number of pediatric patients aged 3 to 12 years enrolled in a clinical trial. In clinical studies oseltamivir carboxylate exposure was not altered in patients with mild or moderate hepatic impairment. Oseltamivir carboxylate exposures in patients with normal and abnormal renal function administered various dose regimens of oseltamivir are described in Table 2. Administration of 100 mg of oseltamivir phosphate twice daily for 5 days to patients with various degrees of renal impairment showed that exposure to oseltamivir carboxylate is inversely proportional to declining renal function.
Less than 20% of an oral radiolabeled dose is eliminated in feces. Renal clearance exceeds glomerular filtration rate indicating that tubular secretion occurs, in addition to glomerular filtration. Oseltamivir carboxylate is eliminated entirely by renal excretion. Plasma concentrations of oseltamivir carboxylate declined with a half-life of 6 to 10 hours in most subjects after oral administration. Oseltamivir carboxylate is not further metabolized and is eliminated in the urine. Plasma concentrations of oseltamivir declined with a half-life of 1 to 3 hours in most subjects after oral administration. Absorbed oseltamivir is primarily eliminated by conversion to oseltamivir carboxylate. Neither oseltamivir nor oseltamivir carboxylate is a substrate for, or inhibitor of, cytochrome P450 isoforms. Oseltamivir is extensively converted to oseltamivir carboxylate by esterases located predominantly in the liver.
The binding of oseltamivir to human plasma protein is 42%, which is insufficient to cause significant displacement-based drug interactions. The binding of oseltamivir carboxylate to human plasma protein is low. Coadministration with food has no significant effect on the peak plasma concentration and the area under the plasma concentration time curve of oseltamivir carboxylate. Plasma concentrations of oseltamivir carboxylate are proportional to doses up to 500 mg given twice daily. Exposure to oseltamivir is less than 5% of the total exposure after oral dosing. At least 75% of an oral dose reaches the systemic circulation as oseltamivir carboxylate. Oseltamivir is readily absorbed from the gastrointestinal tract after oral administration of oseltamivir phosphate and is extensively converted predominantly by hepatic esterases to oseltamivir carboxylate.
In studies of naturally acquired and experimental influenza, treatment with TAMIFLU did not impair normal humoral antibody response to infection. No influenza vaccine interaction study has been conducted. However, two of the three oseltamivir-induced substitutions in the viral neuraminidase from clinical isolates occur at the same amino acid residues as two of the three substitutions observed in zanamivir-resistant virus. Due to limitations in the assays available to detect drug-induced shifts in virus susceptibility, an estimate of the incidence of oseltamivir resistance and possible cross-resistance to zanamivir in clinical isolates cannot be made. Cross-resistance between zanamivir-resistant influenza mutants and oseltamivir-resistant influenza mutants has been observed in cell culture. In clinical studies of postexposure and seasonal prophylaxis, determination of resistance by population nucleotide sequence analysis was limited by the low overall incidence rate of influenza infection and prophylactic effect of TAMIFLU. Insufficient information is available to fully characterize the risk of emergence of TAMIFLU resistance in clinical use. Substitutions in influenza A neuraminidase resulting in decreased susceptibility were H274Y in neuraminidase N1 and E119V and R292K in neuraminidase N2.
In clinical studies in the treatment of naturally acquired infection with influenza virus, 1.3% of posttreatment isolates in adult patients and adolescents, and 8.6% in pediatric patients aged 1 to 12 years showed emergence of influenza variants with decreased neuraminidase susceptibility in cell culture to oseltamivir carboxylate. Substitutions A28T and R124M have been selected in the hemagglutinin of influenza A H3N2 and substitution H154Q in the hemagglutinin of a reassortant human/avian virus H1N9. Resistance substitutions selected in cell culture in neuraminidase are I222T and H274Y in influenza A N1 and I222T and R292K in influenza A N2. Genetic analysis of these isolates showed that reduced susceptibility to oseltamivir carboxylate is associated with mutations that result in amino acid changes in the viral neuraminidase or viral hemagglutinin or both. Influenza A virus isolates with reduced susceptibility to oseltamivir carboxylate have been recovered by serial passage of virus in cell culture in the presence of increasing concentrations of oseltamivir carboxylate. The relationship between the antiviral activity in cell culture and the inhibition of influenza virus replication in humans has not been established. The concentrations of oseltamivir carboxylate required for inhibition of influenza virus were highly variable depending on the assay method used and the virus tested. The antiviral activity of oseltamivir carboxylate against laboratory strains and clinical isolates of influenza virus was determined in cell culture assays.