Diskhaler Relenza 5 mg. 20 doses
Diskhaler Relenza 5 mg. 20 doses
Qualitative and quantitative sastavVsyaka available dose inhalation powder (per card) contains 5 mg zanamivir (zanamivir). Each dose released [amount that passes through the mouthpiece of the inhalation device Diskhaler (Diskhaler)] contains 4 rag zanamivir.
Inhalation Powder pre-metered
Relenza is indicated for the treatment of influenza A and B in adults and adolescents over 12 years who exhibit typical symptoms of the disease in a season of widespread influenza infection.
Dosage and method of administration
Treatment should be started as soon as possible - within 48 hours of onset of simptomite.Relenza applies only inhaled by mouth, inhaled through a device Diskhaler. For each inhalation use only one blister.
The recommended dosage is twice daily for two inhalations (2x5 mg) for 5 days. The total daily dose is 20 mg Relenza day.
Inhaled drugs, eg. asthma medications should be taken before Relenza (see 4.4.).
In patients with renal or hepatic impairment: no dose adjustments are required (see 5.2.).
Elderly: no dosage adjustments are required (see 5.2.).
Relenza is contraindicated in patients with hypersensitivity to any component of the product (see 6.1. Excipients).
Special warnings and precautions for use
Due to the limited number of treated patients with severe asthma and other chronic respiratory diseases, patients with unstable place hrrnichni immunocompromised patients (see 5.1), it is possible to demonstrate the efficacy and safety of Relenza in these groups. Efficacy of zanamivir in patients over 65 years have not been established (see section 5.1)..
In very rare cases of bronchospasm and / or deterioration of respiratory function, which may be acute or serious after using Relenza in patients. Some of these patients had no history of respiratory disease. Patients who exhibit such reactions, you should immediately stop taking Relenza and seek medical pomosht.Poradi limited experience in patients with severe asthma should carefully weigh the risk against the expected benefit. Relenza should not be used without a location close medical supervision and in the presence of suitable hospital in case of bronchospasm. During treatment with Relenza in patients with persistent asthma or severe chronic obstructive pulmonary disease (COPD) is necessary to optimize the treatment of the disease.
If the doctor deems it appropriate to use Relenza in patients with asthma or chronic obstructive pulmonary disease, they should be informed of the potential risk of bronchospasm after taking Relenza and have quick bronchodilator. Patients maintained on bronchodilator therapy should be advised to take bronchodilators before taking Relenza (see section 4.2)..
Zanamivir is not bound to plasma proteins and is not metabolized or modified in the liver. Therefore, clinically significant drug interactions. Administered for 28 days, zanamivir does not deteriorate the immune response to influenza vaccine.
Pregnancy and lactation
The safety of Relenza during pregnancy has not been dokazana.Provedeni in rats and rabbits. It was found that zanamivir crosses the placenta. High doses of zanamivir were not associated with malformations in rats or rabbits, but reported only minor deviations. The potential risk for humans is unknown. Not recommended intake of Relenza during pregnancy unless it is considered that the therapeutic benefits to the patient outweigh the possible risks to the fetus.
In rats zanamivir in breast milk. No evidence of drug transfer into human milk.
Not recommended for use by nursing mothers zanamivir.
Effects on ability to drive and use machines
Not been established.
Reports of acute bronchospasm and / or serious deterioration of respiratory function after using Relenza in patients with a history of respiratory diseases (asthma, COPD) are rare (see 4.4.).
Side effects that may be related to treatment are listed below by body system, organ class and frequency of occurrence.
Frequencies are defined as: very common (> 1/10), common (> 1100, <1/10), uncommon (> 1/1000, <1/100), rare (> 1/10, 000 to <1 / 1000), very rare (<1/10, 000)
Very rare: allergic-type reactions including swelling of the face and oropharynx.
Respiratory, thoracic and mediastinal disorders:
Very rare: bronchospasm, dyspnea, tightness in the throat.
Skin and subcutaneous tissue disorders:
Very rare: rash, urticaria.
Accidental overdose is unlikely for several reasons: inhalation device that limits the intake of too large doses, route of administration and low (2 to 3%) oral bioavailability of zanamivir. Inhaled through the mouth (by spray) at a dose up to 64 mg/24h, ie 3 times the maximum daily dose not lead to adverse drug reactions. When intravenous doses up to 1200 mg/24 h for 5 days also did not induce adverse reactions.
ATC code: J05AH01
Mechanism of action:
Zanamivir is a selective inhibitor of neuraminidase - an enzyme on the surface of the influenza virus. In in vitro and inhibition of this enzyme takes place at very low concentrations of zanamivir (50% inhibition at 0.64 nm - 7.9 nm) against influenza virus type A and type B). Viral neuraminidase support the release of newly formed virus from infected cells. The enzyme may facilitate the passage of the virus through the mucus to the surface of epithelial cells, and viral infection of other cells. In in vitro and in vivo inhibition of this enzyme is expressed in antiviral activity against influenza virus type A and type B, but also covers all known subtypes of influenza virus neuraminidase type A.
Zanamivir shows its extracellular activity. Limits the spread of influenza viruses type A and type B phase by inhibiting release of influenza virions from the epithelial cells of the respiratory tract. Replication of influenza virus occurs in the surface epithelium of the respiratory tract. The efficacy of topical administration of zanamivir has been shown in clinical trials. In studies limited number of samples were not detected viruses with reduced susceptibility to zanamivir.
Relenza relieve the symptoms of flu and reduces the average duration of 1.5 days (between 0.25 and 2.5 days), as shown in the table below. The efficacy of Relenza has been demonstrated in patients without other diseases, treatment is started no later than 48 hours after onset of symptoms. There is no documented therapeutic benefit in patients with fever jobless disease (<37,8 ° C).
There were five randomized, placebo-controlled, parallel-group multicenter phase III clinical trials with zanamivir (NAIB3001, NAIA3002, NAIB3002, NAI30008 and NAI30012) for the treatment of naturally acquired influenza A and type B Testing NAI30008 enrolled patients with asthma (n = 399), COPD (n = 87) or asthma and COPD (n = 32), NAI aizpitvane covers only 30,012 patients over 65 years of age (n = 358). Provided for inclusion in the patient treatment phase of the five trials were 2,471, of which 1,266 take 10 mg zanamivir twice daily by oral inhalation. The primary outcome (time to alleviation of clinically significant symptoms of influenza) is identical in five Phase Y. Mitigation is defined as the absence of high temperature ie temperature below 37,8 ° C and the temperature evaluation "no" ("normal / no" when NAI30012) and evaluation "no" ("normal / no" when NAI30012) or "mild" for headache, myalgia, cough and sore throat and does not change over the course of 24 hours.
There was no significant reduction in mean time to relief of symptoms of influenza in the elderly (> 65 years).
As provided for inclusion in the patient treatment phase difference in time to alleviation of symptoms was 1.0 days (95% CI: 0,5 to 1.5) in the combined analysis na NAIB3001, NAIA3002 and NAIB3002, 1,0 day (95% CI : 0 to 2) in study NAI30008 and 1.0 days (95% CI-1, 0 to 3.0) in the combined analysis NA130012.V trial in patients suffering from influenza type B (n = 163), including 79 patients treated with zanamivir, the observed benefit of treatment was 2 days (95% CI: 0.50 to 3.50).
In the combined analysis of three phase III trials for flu mostly positive healthy adults, the incidence of complications was 152/558 (27%) in placebo and 119/609 (20%) patients who received zanamivir (relative risk 0.73, 95% CI 0,59 to 0.90, p = 0.004). The study NAI30008, including patients with asthma and COPD incidence of complications was 56/153 (37%) in the placebo influenza-positive patients and 52/160 (33%) in influenza-positive patients receiving zanamivir (relative risk 0.89; 95% CI: 0.65 to 1.21, p = 0.520). The study NAI30012, including elderly incidence of complications was 46/114 (40%) in the placebo influenza-positive patients and 39/120 (33%) in influenza positive patients receiving zanamivir (0,80,95% relative risk CI: 0,57 to 1.13, p = 0.256). placebo-controlled study in patients with predominantly mild / moderate asthma and / or chronic obstructive pulmonary disease (COPD), no clinically significant difference between zanamivir and placebo in forced expiratory volume in one second (FEV) or level of peak expiratory flow (PEF), measured during treatment or after treatment.
Studies of the pharmacokinetics of the product in humans have shown that the absolute oral bioavailability is low [average of 2% (minimum 1%, maximum 5%)]. Similar studies have shown that orally inhaled zanamivir is absorbed systemically in 10 to 20% of the dose. Peak plasma concentrations are reached within 1 to 2 hours. The weak absorption of the product results in low serum concentrations. This reduces the probability of systemic effects of inhaled received zanamivir. No evidence of a change in the pharmacokinetics repeated inhaled doses.
After orally inhaled zanamivir is deposited in high concentrations in the airways. Thus, the drug reaches the site of influenza infection. After a single dose of 10 mg zanamivir concentrations measured in saliva. Zanamivir concentrations of 337 (range 58-1593) and 52 (range 17-286) times the average viral neuraminidase IC50 were measured at 12 hours and 24 hours respectively. High concentrations of zanamivir in the respiratory tract leads to rapid onset of inhibition of viral neuraminidase. The drug is deposited in the oropharynx largely (average 78% of the dose), where zanamivir is cleared rapidly from the gastrointestinal tract. Initial deposition throughout the lungs varies between 8 and 21 percent.
Zanamivir is excreted unchanged by the kidneys and without metabolism. In vitro studies suggest that zanamivir does not affect the number of isoenzymes of cytochrome P450 (CYP1A / 2, A6, 2C9, 2S18, 2D6, 2E1, ZA4) in liver microsomes of man, neither induces expression of cytochrome P450 in rats, suggesting that metabolic interactions between zanamivir and other drugs are unlikely in vivo.
The serum half-life of zanamivir following oral inhalation is between 2.6 and 5.05 hours. Excreted in the urine completely intact. Calculated as the clearance of urinary total clearance is between 2.5 and 10,91 / h. Excreted entirely by the kidneys within 24 hours.
Patients with renal impairment:
Absorption of inhaled zanamivir in oral approximately 10-20% of the inhaled dose. Patients with severe renal impairment who received single doses of intravenous zanamivir, were tested after a dose of 2 mg, which is 2 to 4 times higher dose than expected during inhalation. In the usual regimen (10 mg twice daily) potential exposure of the fifth day was 40 times lower than that tolerated by healthy subjects after repeated intravenous administration. Because of the importance of local concentrations, low systemic exposure and tolerability established at much higher exposure is not necessary to change the dosage.
Patients with hepatic impairment:
Zanamivir is not metabolised. No need dose adjustment in patients with hepatic impairment.
At therapeutic doses of 20 mg zanamivir daily bioavailability is low (10-20%) and do not expect significant systemic effects. Changes in the pharmacokinetics of zanamivir, age-related, are not clinically significant and no dose adjustments are required.
Preclinical safety data
In general toxicity studies no significant toxicity of zanamivir. Zanamivir was not genotoxic and no clinically relevant data in carcinogenicity studies for a long period of time in rats and mice.
List of excipients and their amounts
Excipient CONTENTS dozaLactose (monohydrate) 20 mg lactose
Special precautions for storage
Do not store above 30 ° C.