Oseltamivir Phosphate Granules for the prevention of influenza A and B in adults and children. Linsuan Aositawei Keli. (10 sachets*5 boxes/lot).
Names
磷酸奥司他韦颗粒
Oseltamivir Phosphate Granules
Linsuan Aositawei Keli
Lin Suan Ao Si Ta Wei Ke Li
Linsuan Aositawei Granules
Lin Suan Ao Si Ta Wei Granules
FUNCTION and INDICATIONS
1.For the treatment of influenza A and B in children and adults aged 1 and over (Oseltamivir phosphate can effectively treat influenza A and B, but clinical data on influenza B are not yet available).
2. For the prevention of influenza A and B in adults and adolescents 13 and over.
INGREDIENTS
Oseltamivir Phosphate.
DESCPRIPTION
This product is white or off-white particles.
SPECIFICATION AND PACKAGE
15mg*10 sachets/box.
USAGE AND DOSAGE
This product is completely dissolved with warm boiling water and taken orally. Oseltamivir phosphate can be taken with or without food. However, for some patients, taking medication at the same time can increase the tolerance of the drug. Treatment of influenza should begin on the first or second day of the onset of influenza symptoms (ideally within 36 hours). Dose Guidance The recommended oral dose of oseltamivir phosphate for adults and adolescents in adults and adolescents over 13 years is 75 mg twice daily for 5 days. For children over 1 year old, it is recommended to take the following weight-dose table for the recommended weight (taken for 5 days) ≤ 15 kg 30 mg, twice daily 15-23 kg 45 mg, twice daily 23-40 kg 60 mg 40 kg 75 mg twice daily for flu prevention twice daily The recommended oral dose of oseltamivir phosphate for flu prevention after close contact with flu patients is 75 mg once daily for at least 7 days . It should also be started within 2 days after close contact. The recommended dose of oseltamivir phosphate for the prevention of influenza during the flu season is 75 mg once daily. Data show that the drug is safe and effective for 6 weeks. It has been preventive during the medication. Medications for special populations guide flu treatment in patients with renal insufficiency: No dose adjustment is necessary for patients with creatinine clearance greater than 30 ml / min. For patients with creatinine clearance of 10-30 ml / min, the recommended dose reduction is 75 mg once daily. 5 days in total. Oseltamivir phosphate is not recommended for patients with a creatinine clearance of less than 10 ml / min and patients with severe renal failure who require regular hemodialysis or continuous peritoneal dialysis. Dosage information for children without renal failure (see [Pharmacokinetics] and [Precautions]). Influenza prevention: No dose adjustment is necessary for patients with creatinine clearance greater than 30 ml / min. For patients with creatinine clearance of 10-30 ml / min, the recommended dose is reduced to 75 mg of oseltamivir phosphate once every other day or 30 mg daily. Not recommended for patients with end-stage renal failure, including patients with chronic periodic hemodialysis, continuous peritoneal dialysis, or a creatinine clearance of less than 10 ml / min (see [Pharmacokinetics]). Patients with liver dysfunction: Do not need to adjust the dose when treating and preventing influenza for patients with mild to moderate liver dysfunction (Child-Pugh score ≤ 9).
ADVERSE REACTION
Clinical Research Experience Adult Treatment Trial In the Phase III clinical trial of adult influenza treatment, a total of 1887 patients participated in the trial, receiving placebo, 75 mg oseltamivir phosphate, and 150 mg oseltamivir phosphate. Adverse events reported The highest rates were nausea and vomiting. Symptoms are transient and often occur on the first dose. The vast majority of cases did not result in patients discontinuing the study drug. At the recommended dose of 75 mg twice daily, 3 patients withdrew from the trial due to nausea and 3 patients withdrew from the trial due to vomiting. In adult phase III clinical trials, the incidence of some adverse events was higher in the oseltamivir phosphate group than in the placebo group. Adverse events with an incidence rate of ≥1% are shown in Table 1. The data summarizes Jiankang's young and high-risk patients (referring to people at high risk of flu complications, such as elderly patients, patients with chronic heart disease or respiratory diseases). Whether or not related to the drug, adverse events that occurred more frequently in the oseltamivir phosphate group than in the placebo group included nausea, vomiting, bronchitis, insomnia, and dizziness. Table 1. Oseltamivir 75 mg twice daily for natural acquired flu elbow incidence ≥1% Adverse events Summary Adverse event treatment flu prevention flu placebo N = 716 Osvita 75 mg twice daily N = 724 Placebo N = 1434 Oseltamivir 75 mg twice daily N = 1480 Nausea (without vomiting) 48 (6.7%) 97 (13.4%) 56 (3.9%) 104 (7.0%) Vomiting 21 (2.9%) 68 (9.4%) 15 (1.0%) 31 (2.1%) Diarrhea 70 (9.8%) 48 (6.6%) 38 (2.6%) 48 (3.2%) Bronchitis 15 (2.1%) 17 (2.3 %) 17 (1.2%) 11 (0.7%) abdominal pain 16 (2.2%) 16 (2.2%) 23 (1.6%) 30 (2.0%) dizziness 25 (3.5%) 15 (2.1%) 21 (1.5%) 24 (1.6%) headache 14 (2.0%) 13 (1.8%) 251 (17.5%) 298 (20.1%) cough 12 (1.7%) 9 (1.2%) 86 (6.0%) 83 (5.6%) insomnia 6 (0.8 %) 8 (1.1%) 14 (1.0%) 18 (1.2%) Dizziness 3 (0.4%) 7 (1.0%) 3 (0.2%) 4 (0.3%) Weakness 7 (1.0%) 7 (1.0%) 107 (7.5%) 117 (7.9%) * Includes all adverse events ≥1% in patients taking oseltamivir 75 mg twice daily in an influenza treatment trial. Overall, the incidence of adverse reactions in high-risk patients was similar to that in healthy adults. Influenza prevention trials A total of 3,434 people participated in the phase III influenza prevention trials, including young people, adults, and the elderly. Among them, 1480 people took the recommended dose of 75 mg of oseltamivir once per mesh for 6 weeks. Although the medication has been taken for a long time, the incidence of adverse events was similar to that of the flu-treated trials (see Table 1). The incidence of the following adverse events in the influenza prevention trial was higher in the oseltamivir group than in the placebo group, and higher than the corresponding adverse events in the influenza treatment trial: pain, runny nose, indigestion, and upper respiratory tract infection. However, these adverse events differed by less than 1% in the oseltamivir phosphate group and the placebo group. There are no clinically significant differences in the safety of oseltamivir phosphate and placebo among older people compared with younger people. Treatment trials in children In a Phase III clinical trial of oseltamivir for influenza, a total of 1,032 children aged 1-12 years participated in the trial, including 698 children aged 1-12 years without basic disease and 334 with a history of asthma Children 6-12 years old. A total of 515 children received oseltamivir oral suspension. Adverse events with a incidence of ≥1% in children are shown in Table 2. The highest reported adverse event was vomiting, and other more common adverse events were abdominal pain, epistaxis, ear pain, and conjunctivitis. These adverse events usually only occur once and can be alleviated by continued medication. In most cases, this will not result in stopping treatment. Table 2. Phase III clinical trial of oseltamivir in children with naturally acquired influenza. Adverse events with an incidence of ≥1%. Adverse events. Placebo N = 517 oseltamivir, 2 mg / kg N-515 vomiting 9.3% 15.0% Diarrhea 10.6% 9.5% Abdominal pain 3.9% 4.7% Nausea 4.3% 3.3% Otitis media 11.2% 8.7% Pneumonia 3.3% 1.9% Sinusitis 2.5% 1.7% Bronchitis 2.1% 1.6% Asthma (including asthma exacerbation) 3.7% 3.5% Nasal crest 2.5 % 3.1% ear symptoms 1.2% 1.7% tympanic membrane abnormality 1.2% 1.0% dermatitis 1.9% 1.0% lymphadenopathy 1.5% 1.0% conjunctivitis 0.4% 1.0% post-marketing experience skin and subcutaneous tissue changes: very few cases report allergies Reactions, toxic epidermal necrosis, Stevens-Johnson syndrome, erythema polymorpha, redness (rash), dermatitis, and herpes. Liver and biliary tract: Few cases have been reported in patients with influenza-like illnesses with hepatitis and elevated liver enzymes. Cases have been reported of pancreatitis, angioedema, laryngeal edema, bronchospasm, facial edema, elevated eosinophils, decreased white blood cells, and hematuria. If the patient has a similar response. Oseltamivir should be discontinued and promptly seek medical attention.
Medication for children
For the dosage, see [Usage and Dosage]. The safety and effectiveness of oseltamivir phosphate in children under 1 year have not been determined.
Medication for elderly patients
Do not need to adjust the dose for the treatment and prevention of elderly patients (see [Pharmacokinetics]).
CONTRAINDICATIONS
Those who are allergic to any component of this product are prohibited.
Warning
1.Avoid alcohol and tobacco and spicy,cold, greasy food during taking this product.
2.It’s not appropriate to take nourishing chinese medicine wihle taking medicine.
2.Patients with diabetes,high blood pressure, heart diseases, liver disease, kidney disease and other severe chronic diseases shall take medicine under guidance of physician.
3.In accordance with the usage and dosage, children, elderly ,feeble and weak patients should be taken under the guidance of physician.
5.Two weeks without any remission,or symptems aggravated,appeared new serious symptems, should go to hospital.
6.Hypersensitivity to this product should stop using，allergic constitution with caution.
7.Do not use this product if the property changed.
8.Children should take under the supervision of adult.
9.Keep out of reach of children.
10.If you are using other drugs, please consult your doctor before using this product.
DRUG INTERACTION
Interaction with Influenza Vaccines: No systematic review of the interaction of oseltamivir phosphate with attenuated live influenza vaccines has been performed. However, due to the possible interaction between the two, unless clinically required, oseltamivir phosphate should not be taken within two weeks of using live attenuated influenza vaccine, and attenuated should not be used within 48 hours after taking oseltamivir phosphate. Live flu vaccine. Because oseltamivir as an antiviral drug may inhibit the replication of live vaccine viruses. Trivalent inactivated influenza vaccine can be used at any time before or after taking oseltamivir phosphate. Pharmacological and pharmacokinetic data show that there is essentially no significant clinically significant interaction between oseltamivir phosphate and other drugs. Oseltamivir phosphate is rapidly converted into an active metabolite (oseltamivir carboxylate) by an esterase mainly distributed in the liver. Drug interactions related to competing esterases are rarely reported in the literature. The low protein binding rate of oseltamivir and its active metabolites suggests that drug interactions related to protein binding are unlikely to occur. In vitro studies have shown that neither oseltamivir phosphate nor its active metabolite is a good substrate for P450 mixed function oxidase or glucuronyl transferase (see [Pharmacokinetics]). No mechanism of drug interaction with oral contraceptives. Cimetidine is a non-specific inhibitor of the cytochrome P450 isoenzyme, and can compete with renal tubular secretion with alkaline or cationic substances, but has no effect on the plasma concentration of oseltamivir or its active metabolites. Therefore, clinically, drug interactions related to changes in gastric pH (antacids) and to competitive clearance of the renal tubular secretion pathway are unlikely to occur. However, there is no in vivo study of the interaction of oseltamivir phosphate with antacids. Drug interactions related to tubule competition and secretion are unlikely to have important clinical significance because most drugs have a wide safety range. Excretion of active metabolites of oseltamivir phosphate includes glomerular filtration and tubule secretion. Pathway, and the clearance capacity of these two pathways is great. However, caution should be exercised in combination with drugs that are also secreted by the kidney and have a narrow safety range (such as chlorosulfuramide, methotrexate, and butazone). Combined with probenecid, due to the decline in the renal tubular secretion capacity, the body's availability of active metabolites is increased by a factor of two. But because of the wide range of safety of active metabolites. There is no need to adjust the drug dose when used with probenecid. The combination with amoxicillin does not change the plasma concentrations of the two drugs, indicating that the competitive effect of anion pathway elimination is not significant. Post-marketing surveillance has reported individual cases of interactions with ganciclovir, which is also secreted through the renal tubules. In combination with paracetamol (acetaminophen), the plasma concentrations of oseltamivir and its active metabolites or paracetamol did not change. Taking oseltamivir (75 mg twice daily for 4 days) and aspirin (900 mg single dose) at the same time did not find oseltamivir, its active metabolite (oseltamivir carboxylate) or aspirin Changes in pharmacokinetic parameters. Taking oseltamivir (single dose of 150 mg) and a single dose of an antacid containing aluminum hydroxide and magnesium hydroxide or a single dose of an antacid containing calcium carbonate did not find oseltamivir and its active metabolite (Austriavir The pharmacokinetic parameters of staveway carboxylate were changed. In the phase III clinical study of influenza treatment and influenza prevention, oseltamivir phosphate has been used in combination with some commonly used drugs, such as ACE inhibitors (enalapril, captopril), thiazide diuretics (benzyl fluthizone) Azine), antibiotics (penicillin, cephalosporin, azithromycin, erythromycin, doxycycline), H2 blockers (ranitidine, cimetidine), beta blockers (propranolol) , Baicalin (theophylline), sympathomimetic (pseudoephedrine), opioid (codeine), steroid hormones. Inhaled bronchiectasis and analgesics (aspirin, ibuprofen and paracetamol). No adverse events were observed or altered in the incidence of oseltamivir phosphate in combination with these drugs.
DRUG OVERDOSE
No overdose has been reported. It is estimated that acute drug overdose is most likely to manifest as nausea with or without vomiting. Studies have shown that after taking up to 1000 mg of oseltamivir phosphate in a single dose to 6 healthy volunteers, one volunteer developed nausea. Another volunteer had vomiting for 2 consecutive days.
PHARMACOLOGIC and TOXICOLOGY
Oseltamivir phosphate is a prodrug of its active metabolite, and its active lake product (oseltamivir carboxylate) is a selective inhibitor of influenza virus neuraminidase. Neuraminidase is a glycoprotein on the surface of the virus. Its activity is essential for the release of newly formed virus particles from infected cells and the further spread of infectious virus in the human body. The active generation product of oseltamivir phosphate can inhibit neuraminidase activity of influenza A and B viruses. The concentration of half inhibition of viral neuraminidase activity in vitro is as low as nanogram levels. Active metabolites were observed to inhibit the growth of influenza virus in vitro, and they were also observed to inhibit the replication and pathogenicity of influenza virus in vivo. This product reduces the spread of influenza A or B virus by inhibiting the release of virus from infected cells. Studies of naturally acquired and laboratory influenza have shown that the use of oseltamivir phosphate does not affect the body's normal humoral immune response to infection. The antibody response to the inactivated vaccine was not affected by oseltamivir treatment.
PHARMACOKINETICS
After oral administration, oseltamivir phosphate is rapidly absorbed in the gastrointestinal tract, and is rapidly converted into the active metabolite (oseltamivir carboxylate) by the liver or intestinal wall esterase. At least 75% of the oral dose enters the circulation in the form of active metabolites. Relative to the active metabolite, less than 5% of the drug exists as a prodrug. The plasma concentration of active metabolites is proportional to the dose taken and is not affected by eating (see [Dosage and Administration]). The average distribution volume (Vss) of active metabolites (oseltamivir carboxylate) in humans is about 23 liters. Studies on ferrets, rats and rabbits have shown that active metabolites of the drug can reach all sites of influenza virus infection. Studies have shown that active metabolites of oseltamivir phosphate can achieve effective antiviral levels in the lungs, bronchus, alveolar lavage fluid, nasal mucosa, middle ear and trachea. The binding of active metabolites to human plasma proteins is negligible (about 3%). The metabolism of oseltamivir phosphate is almost completely converted into active metabolites (oseltamivir carboxylate) from vinegar enzymes mainly located in the liver and intestinal wall. Neither oseltamivir phosphate nor its active metabolites are substrates or inhibitors of the major cytochrome P450 isoenzymes, so they will not trigger drug-drug interactions due to competition for these enzymes. Elimination of absorbed oseltamivir is mainly achieved by conversion to active metabolites (> 90%). Active metabolites are no longer metabolized, but are excreted by the urine. After the active metabolites reach the peak concentration, the plasma concentration drop half-life is 6 to 10 hours. Over 99% of active metabolites are excreted by the kidneys. The renal clearance rate (18.8 liters / hour) exceeds the glomerular filtration rate (7.5 liters / hour), indicating that in addition to glomerular filtration, there is also a pathway of renal tubular secretion. Oral radiolabeled drug studies have shown that less than 20% of the dose is excreted in feces. Pharmacokinetics in special populations: Influenza treatment in patients with renal insufficiency: 100 mg oseltamivir phosphate is administered to patients with varying degrees of renal insufficiency twice daily for 5 days. The results show active metabolites (oseltamivir Carboxylate) is inversely proportional to the degree of decrease in renal function. For patients with creatinine clearance greater than 30 ml / min, no dose adjustment is required. For patients with creatinine clearance of 10-30 ml / min, the recommended dose is reduced to 75 mg oseltamivir phosphate once daily for 5 days. Oseltamivir phosphate is not recommended for patients with a creatinine clearance of less than 10 ml / min and patients with severe renal failure who require regular hemodialysis or continuous peritoneal dialysis (see [Dosage and Administration]). Flu prevention: For patients with creatinine clearance of 10-30 ml / min, the recommended dose is reduced to 75 mg of oseltamivir phosphate. Take medicine every other day or 30 mg daily. Not recommended for patients with end-stage renal failure, including patients with long-term hemodialysis, continuous peritoneal dialysis, or a creatinine clearance of less than 10 ml / min (see [Notes] and [Dosage and Administration] Special Dose Guidelines). In vitro studies of patients with liver dysfunction have shown that patients with liver dysfunction do not show a significant increase in oseltamivir levels or a significant decrease in active metabolite levels as expected (see [Dosage and Administration]). The elderly were given the same dose of oseltamivir phosphate, and the availability of the steady-state active metabolites of the elderly (same as 65-78 years old) was 25 to 35% higher than that of young people. Drug half-life is similar in young people. Taking into account the availability and tolerance of the body, the elderly do not need to adjust the dose (see [Dosage and Administration]). Children performed small sample single-dose oseltamivir pharmacokinetics in children 5-16 years and 3-12 years of age, and the results showed that young patients were susceptible to oseltamivir and its active metabolites (oseltamivir Carboxylate) is cleared faster than adults, so it is calculated by weight. Children's availability is low at the same dose. The 2 mg / kg dose for children is comparable to the 75 mg capsule (approximately 1 mg / kg) dose for adults. The pharmacokinetics of oseltamivir in children over 12 years is similar to that in adults. Data on drug metabolism in children without renal failure.
STORAGE
Hermetically sealed,keep in cool and dry places.
PERIOD OF VALIDITY
24 months.
CERTIFICATE NO
Stage Food and Drug Administration Approval number:H20080763.
Manufactured
YICHANGDONG YANGGUANG CHANGJIANG PHARMACEUTICAL CO.,LTD
Tips: Please read the directions for use in retail or directed by physician.
Part of the goods frequent replacement of packaging, such as goods and pictures are not exactly the same, please refer to the goods you receive.
General Cautions
Keep away from animals and children.This product has not been evaluated by the FDA. It is not intended to diagnose, treat, cure, or prevent any disease.We highly recommend that you consult with a Traditional Chinese Medical practitioner or physician before taking any products or if you have any questions regarding your health.