Relenza powder for inhalation. + inhaler 5mg / d, No. 1

• Treatment of infection caused by influenza A and B viruses in children over 5 years of age and in adults;

• prevention of infection caused by influenza A and B viruses in children over 5 years of age and adults.

Relenza is used only by oral inhalation using the supplied Diskhaler device.

Patients who are prescribed other inhaled drugs (for example, fast-acting bronchodilators) in conjunction with Relenza should be advised to use these drugs before using Relenza.

Treatment

Adults

The recommended dose of Relenza is two inhalations (2Ц5 mg) 2 times / day for 5 days. The total daily dose is 20 mg. To achieve the optimal effect, treatment should be started as early as possible (preferably within 2 days) when the first symptoms of the disease appear.

Correction of the dosage regimen in children is not required.

Correction of the dosage regimen in elderly patients is not required.

In patients with impaired renal and hepatic function, dosage adjustment is not required.

Prophylaxis

Adults

The recommended dose of Relenza is two inhalations (2Ц5 mg) once a day for 10 days. The total daily dose is 10 mg. The period of preventive therapy can be increased to one month if the period of risk of contact with the infectious agent exceeds 10 days.

The full course of preventive therapy should be completed as prescribed.

Correction of the dosage regimen in children is not required.

In elderly patients, no dosage adjustment is required.

In patients with impaired renal and hepatic function, dosage adjustment is not required.

Instructions for using Diskhaler with Rotadisks

The Diskhaler device is used to inhale zanamivir from Rotadisk.

The dischaler consists of the following parts:

• case with a lid and a plastic needle for piercing the Rotadisk cell;

• pull-out tray with a mouthpiece and a rotating wheel on which the Rotadisk is placed.

• case for the mouthpiece.

The rotadisk is placed on the wheel.

Do not use alone until you have read step by step instructions.

Rotadisk is a 4-cell blister, each containing 5 mg of zanamivir. The recommended dose of Relenza is two cells (10 mg).

Important! Do not pierce the Rotadisk before inserting it into the Diskhaler inhalation device. Rotadisk can be stored in Diskhaler, but the blister should be pierced immediately before inhalation of the drug. Diskhaler should be kept clean. After use, wipe the mouthpiece with a clean cloth and cover with a blue cover.

Uploading Rotadisk to Dischaler

1. Remove the blue case from the mouthpiece. Make sure the mouthpiece is clean inside and out.

2. Gently pull out the white drawer until the plastic clips come out by grasping the corners of the drawer. The tray should be pulled out as far as it will go so that the notches on the side of the clips are visible.

3. Pull out the white tray completely by squeezing the notches on the side of the clips with your thumb and forefinger.

4. Place the new Rotadisk on the wheel with the label facing up and cells facing down. The cells should line up with the holes in the wheel.

5. Insert the tray back into the housing. If inhalation is not carried out immediately after the Rotadisk is installed, put the blue cover on the mouthpiece again.

Preparing for inhalation

Rotadisk should be pierced only immediately before inhalation.

6. Holding the Dischaler horizontally, lift its lid up until it stops to pierce the top and bottom Rotadisk foil. The cover must be fully upright. Close the lid. The dischaler is ready to use.

The dischaler with a punctured Rotadisk should be held horizontally until inhalation.

Inhalation

7. Take a comfortable sitting position. Without bringing Diskhaler to your mouth, exhale completely. You can not breathe out into the inhaler. Otherwise, you can blow the powder out of the blister.

After exhaling completely, place the mouthpiece between your teeth and squeeze tightly with your lips. Do not grip the mouthpiece with your teeth or block the air holes on either side of the mouthpiece. Take one quick, deep breath through your mouth.

Important! Breathe in through your mouth, not through your nose.

Remove the mouthpiece from your mouth. Hold your breath as much as possible, then exhale slowly.

Preparing the next cell (second part of the dose)

8. Pull out the drawer as far as it will go (do not press on the clips or pull out the drawer completely) and insert it back. In this case, Rotadisk will turn one cell and will be ready for the next inhalation. Repeat as needed until the cell is under the needle.

For inhalation, repeat steps 6 and 7.

9. After completion of inhalation (usually using two cells), wipe the mouthpiece and close with a blue cover.

It is important to keep Diskhaler clean.

Rotadisk replacement

10. Each Rotadisk contains 4 cells. After four inhalations, remove the empty Rotadisk from the Diskhaler and replace it with a new one (steps 1-5).

Important! Children should use the inhalation device under the supervision of an adult.

Powder for inhalation, dosed from white to almost white.

1 dose zanamivir (micronized) 5 mg

Excipients: lactose monohydrate - up to 25 mg.

Hypersensitivity to the components of the drug.

With care: diseases of the respiratory tract, accompanied by bronchospasm (including a history); lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

pharmachologic effect

Zanamivir is a highly active and highly selective inhibitor of neuraminidase (a surface enzyme of the influenza virus). Viral neuraminidase provides the release of newly formed viral particles from infected cells and can accelerate the penetration of the virus through the mucosal barrier to the surface of epithelial cells, thereby providing infection of other cells. The inhibitory activity of zanamivir against the replication of influenza A and B viruses has been shown both in vitro and in vivo, and includes all known subtypes of influenza A neuraminidase.

Influenza virus replication is limited to cells of the surface epithelium of the respiratory tract. Zanamivir acts in the extracellular space and reduces the reproduction of both types of influenza virus (A and B), preventing the release of infectious viral particles from the epithelial cells of the respiratory tract. The effectiveness of zanamivir for inhalation use has been confirmed by clinical studies.

Clinical data show that the use of zanamivir for the treatment of acute infections caused by the influenza virus leads to a decrease in virus shedding from the respiratory tract compared with the placebo group, while the emergence of strains with reduced susceptibility to zanamivir has not been identified.

Pharmacokinetics

Suction

Pharmacokinetic studies in humans have shown that the absolute bioavailability of zanamivir after oral administration is low and averages 2%. Similar studies of zanamivir after oral inhalation indicate that approximately 10% to 20% of the administered dose undergoes systemic absorption, and plasma Cmax is usually reached within 1 to 2 hours after administration. The low degree of absorption of the drug leads to low systemic concentrations, i.e. zanamivir after oral inhalation has no significant systemic effects. There is no evidence of a change in the pharmacokinetics of the drug after repeated oral inhalation.

Distribution

Plasma protein binding of zanamivir is very low (<10%). The Vd of zanamivir in adults is about 16 liters, which roughly corresponds to the volume of extracellular fluid.

After oral inhalation, zanamivir is deposited throughout the respiratory tract in high concentrations, ensuring the delivery of the drug to the site of infection. After a single inhalation of 10 mg zanamivir, the concentration of the drug in the epithelial layer of the respiratory tract - the main zone of replication of the influenza virus - exceeded the average IC50 value for viral neuraminidase by about 340 times 12 hours after inhalation and approximately 52 times after 24 hours after inhalation, providing rapid inhibition viral neuraminidase. Zanamivir is deposited mainly in the mouth of the pharynx and lungs (average 77.6% and 13.2%, respectively).

Metabolism

Zanamivir is not metabolized and is excreted unchanged by the kidneys.

Withdrawal

In adult patients with normal renal function, T1 / 2 of zanamivir is approximately 2-3 hours.

Pharmacokinetics in special patient groups

Children. The pharmacokinetics of zanamivir was evaluated in an open-label, single-dose study using a nebulizer (10 mg) and a powder inhaler (10 mg) in 24 patients aged 3 months to 12 years. Systemic concentrations in children did not differ from those in adults when using 10 mg zanamivir in the form of a powder for inhalation.

Elderly patients. With daily use of zanamivir in the form of inhalation in a therapeutic dose of 20 mg, the bioavailability of the drug is low and amounts to 10-20%, therefore, systemic concentrations of zanamivir are insignificant. Correction of the dosage regimen is not required, since it is unlikely that any changes in the pharmacokinetic profile associated with age will have clinically significant consequences.

Patients with impaired renal function. With daily use of zanamivir in the form of inhalation in a therapeutic dose of 20 mg, the bioavailability of the drug is low and amounts to 10-20%, therefore, systemic concentrations of zanamivir are insignificant. Given the wide range of safety of zanamivir, a possible increase in systemic concentrations in patients with severe renal insufficiency is not considered clinically significant and does not require dosage adjustment when used as inhalation. In patients with severe renal impairment (CC <30 ml / min), T1 / 2 from the blood serum increases to about 12-20 hours. In patients with end-stage chronic renal failure, the elimination of zanamivir has not been studied.

Patients with impaired liver function. Since zanamivir is not metabolized, no dosage adjustment is required in patients with hepatic impairment.

Side effect

Frequency categories were formed on the basis of clinical studies of the drug and post-marketing follow-up.

From the immune system: very rarely - allergic reactions, including anaphylactic and anaphylactoid reactions, edema of the face and oropharynx.

From the nervous system: very rarely - vasovagal reactions (were recorded in patients with symptoms of the influenza virus, such as fever, dehydration, observed immediately after the Relenza drug).

From the side of the psyche: the frequency is unknown - convulsions, confusion, behavioral disturbances, hallucinations, agitation, anxiety, delirium were recorded when using the drug Relenza in patients with influenza, mainly among children and adolescents. Seizures and neuropsychiatric symptoms have also been reported in patients with influenza who did not take Relenza.

From the side of the cardiovascular system: arrhythmia, fainting.

From the respiratory system: very rarely - bronchospasm, shortness of breath.

Skin and subcutaneous tissue disorders: very rarely - rash, urticaria, severe skin reactions, including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Application during pregnancy and lactation

Pregnancy

The safety of using zanamivir during pregnancy has not been established.

Reproductive studies in rats and rabbits have shown that zanamivir crosses the placental barrier. In studies on rats, no signs of teratogenic effects, effects on fertility, or clinically significant disturbances in the peri- or postnatal development of offspring were found after using zanamivir. However, there are no data on the penetration of zanamivir through the placental barrier in humans.

Zanamivir should not be taken by women during pregnancy, especially in the first trimester, unless the expected benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding period

It has been shown that in rats, zanamivir passes into breast milk. However, there is no information on the penetration of zanamivir into breast milk in humans.

Due to limited experience, zanamivir should only be used during breastfeeding when the expected benefit to the mother outweighs the potential risk to the baby.

Application for violations of liver function

No dose adjustment is required in patients with impaired liver function.

Application for impaired renal function

No dose adjustment is required in patients with impaired renal function.

Application in children

The drug is prescribed for children over 5 years old.

Use in elderly patients

Elderly patients do not need dose adjustment.

special instructions

Influenza virus infection may be accompanied by increased airway hyperresponsiveness. There have been very rare reports of bronchospasm and / or deterioration in respiratory function after inhalation of zanamivir in patients during influenza treatment; some of these patients had no history of respiratory tract disease. In such cases, it is necessary to stop treatment with zanamivir and consult a specialist for a medical examination. Patients with comorbid airways who are taking inhaled zanamivir should carry a fast-acting bronchodilator.

In patients with severe bronchial asthma, it is necessary to assess the intended benefits and possible risks when using the drug. Relenza should not be prescribed unless proper medical supervision is exercised. In patients with bronchial asthma and severe chronic obstructive pulmonary disease (COPD), the treatment of the underlying disease should be optimized during therapy with Relenza. The patient should be informed about the potential risk of bronchospasm.

The drug Relenza, a dosed powder for inhalation, should not be used to prepare a solution and should not be used through a nebulizer or a ventilator. There have been reports of hospitalizations for patients with influenza who were prescribed a solution made from powder for inhalation of zanamivir and administered via a nebulizer or ventilator. In addition, a fatal case was described in which it was reported that the lactose, which is part of the drug, provoked obstruction of the equipment. Therefore, Relenza should only be used with the supplied Diskhaler device.

Influenza can be accompanied by a variety of neurological and behavioral symptoms. Post-marketing reports (mostly seen in children in Japan) have reported seizures, delirium, hallucinations, and deviant behavior in influenza patients taking neuraminidase inhibitors, including zanamivir. These phenomena were observed mainly in the early stages of the disease, often characterized by sudden onset and rapid resolution. A causal relationship between taking zanamivir and the above adverse events has not been established. If any neuropsychiatric symptoms occur, it is necessary to assess the risk / benefit ratio of further treatment with zanamivir for each individual patient.

Influence on the ability to drive vehicles and mechanisms

No data available.

Overdose

Symptoms: accidental overdose is unlikely due to the characteristics of the form of release itself, the route of administration and the low bioavailability (10-20%) of zanamivir. When studying the use of an aqueous solution of zanamivir without lactose, inhalation (through a nebulizer) at a dose of 64 mg / day (more than 3 times the recommended daily dose), side effects were not registered. In addition, side effects have not been reported with IV use of zanamivir for 5 days up to 1200 mg / day in clinical trials.

Treatment: t. zanamivir is characterized by low molecular weight, negligible binding to blood plasma proteins and low Vd, the possibility of excretion of the drug by hemodialysis is expected. Thus, hemodialysis can be considered as a treatment option for Relenza overdose.

Drug interactions

Zanamivir does not bind to proteins, nor is it metabolized or altered in the liver. Clinically significant drug interactions are unlikely.