Relenza - instructions for use, doses, side effects, contraindications

Active substanceZanamivirZanamivir

Similar drugsTo uncover

powder d / inhal.

Dosage form: & nbspPowder for inhalation dosed.

Composition:On a single dose:
Active substance:
Zanamivir (micronized) 5.0 mg
Excipient:
Lactose monohydrate - up to 25.0 mg

Description:Powder from white to almost white.

Pharmacotherapeutic group:Antiviral agent

ATX: & nbsp

J.05.A.H.01 Zanamivir

Pharmacodynamics:Zanamivir - strong and highly selective inhibitor of neuraminidase (surface enzyme of the influenza virus). Viral neuraminidase provides the release of viral particles from the infected cell and can accelerate the penetration of the virus through the mucosal barrier to the surface of epithelial cells, thereby ensuring the infection of other cells in the airways. The inhibitory activity of zanamivir is shown both in vitro and in vivo and includes all 9 subtypes of neuraminidase of influenza viruses, including circulating and virulent for various species. Half the inhibitory concentration (IC₅₀) for strains of virus A and B is from 0.09 to 95.2 nM.
Replication of the influenza virus is limited to the cells of the superficial epithelium of the respiratory tract. Zanamivir acts in the extracellular space, reducing the reproduction of both types of influenza virus (A and B) and preventing the release of viral particles from the cells of the superficial epithelium of the respiratory tract.The efficacy of zanamivir for inhalation has been confirmed in controlled clinical trials. The use of zanamivir as a therapy for acute infections caused by the influenza virus led to a decrease in the release of the virus (compared to placebo). The development of resistance to zanamivir in individuals with normal immunity is not recorded.

Pharmacokinetics:Suction
Absolute bioavailability is low and averages 2% after oral administration. After oral inhalation, approximately 10% to 20% of the administered dose is absorbed. After a single dose of 10 mg, the maximum concentration in the blood plasma C_max was 97 ng / ml after 1.25 hours. A low degree of absorption leads to low systemic concentrations and an insignificant area under the "concentration-time" pharmacokinetic curve. A low degree of absorption persists with repeated inhalations.
Distribution
The binding of zanamivir to plasma proteins is very low (<10%). The volume of distribution in adults is about 16 liters, which is approximately equal to the volume of extracellular fluid.
After oral inhalation zanamivir is deposited in the airways at high concentrations, ensuring delivery of the drug to the "entrance gate" of the infection. After inhalation of 10 mg of zanamivir in the epithelial layer of the respiratory tract, zanamivir concentrations exceeded the mean IC₅₀ for neuraminidase 340 times 12 hours after inhalation and 52 times 24 hours after inhalation, providing rapid inhibition of the viral enzyme. The main places of sedimentation are the oral part of the pharynx and the lungs (the average index is 77.6% and 13.2%, respectively).
Metabolism and excretion
Zanamivir is not metabolized, excreted by the kidneys in an unchanged form. Half-life of blood plasma
after oral inhalation varies from 2.6 to 5.05 hours. The total ground clearance is from 2.5 to 10.9 l / h.
Special patient groups
Elderly
The bioavailability of zanamivir after administration of a therapeutic dose of 20 mg is 10-20%, as a result of which the concentrations of zanamivir in the systemic blood stream are insignificant. Correction of the dosing regimen is not required, since any age changes, usually leading to a change in pharmacokinetic profiles of different drugs, in this case do not affect the pharmacokinetics of zanamivir.
Children
Zanamivir pharmacokinetics was evaluated in a controlled pediatric study in 24 patients aged 3 months to 12 years using a nebulizer (10 mg) and a powder inhaler (10 mg). Pharmacokinetic parameters in children did not differ from those in adults with 10 mg of zanamivir, a powder for inhalation. Patients with impaired renal function When using therapeutic doses, 20 mg of bioavailability is low and is 10-20%, therefore, systemic concentrations of zanamivir are insignificant. Given the wide range of drug safety, a possible increase in systemic concentrations in patients with severe renal insufficiency remains clinically insignificant and does not require correction of the dosing regimen. Patients with impaired hepatic function zanamivir does not undergo metabolism, does not require correction of the dosing regimen.
Clinical efficacy and safety
The use of zanamivir, a powder for inhalation dosed, in healthy people at risk (usually in contact with the sick), in doses used in the treatment of influenza, facilitates symptomatology and shortens the duration of the disease.A combined analysis of the results of phase III studies showed that the median time to alleviate the symptoms of the disease was reduced to 1.5 days in patients in the zanamivir group compared to patients in the placebo group, (p <0.001). The number of complications decreased in the group of zanamivir 171/769 (22%) compared with placebo 208/711 (29%) and the relative risk was: 0.77; (95% CI: 0.65-0.92, p = 0.004). The use of antibiotics to treat complications after influenza also decreased from 136/711 (19%) in the placebo group to 110/769 (14%) in the zanamivir group (relative risk: 0.76, 95% CI: 0.60-0.0, 95; p = 0.021).
The optimal efficacy of zanamivir was shown in the case of starting treatment as soon as possible after the appearance of the first symptoms of the disease. It was shown that zanamivir is also effective as a means of preventing influenza in children older than 5 years and in adults. The percentage of effective protection is 67-79% compared with placebo and 56-61% compared to active control.

Indications:Treatment of infection caused by the influenza A and B virus in children older than 5 years and adults.
Prevention of infection caused by the influenza A and B virus in children older than 5 children and adults.

Contraindications:Hypersensitivity to any of the components of the drug.

Carefully:Diseases of the respiratory tract, accompanied by bronchospasm (including in the anamnesis).

Pregnancy and lactation:Pregnancy
The effectiveness and safety of zanamivir in pregnancy is not established. Reproductive toxicity studies conducted on rats and rabbits showed that zanamivir penetrates the placental barrier. In studies on rats, there were no signs of teratogenicity, effects on fertility, or clinically significant disturbances in peri- or postnatal development of offspring after zanamivir. However, there are no data on the penetration of zanamivir through the placental barrier in humans.
Zanamivir should not be used in women during pregnancy, especially in the first trimester, unless the expected benefit to the mother exceeds the potential risk to the fetus.
Breastfeeding period
In rats zanamivir excreted in breast milk. However, there is no information on the isolation of zanamivir with human milk. Since experience is limited, during breastfeeding zanamivir It should be used only if the expected benefit for the mother exceeds the potential risk for the child.

Dosing and Administration:The drug Relenza is used only by inhalation orally. To ensure proper use of the drug, use the accompanying Dischaler.
Patients who have been given other inhalation medications (for example, fast-acting bronchodilators) with Relensa are advised to use these drugs before applying Relenza.
Treatment
Adults
The recommended dose of Relenza is two inhalations (2x5 mg) 2 times a day for 5 days. The total daily dose is 20 mg. To achieve the optimal effect, you should begin treatment as early as possible (preferably within 2 days) with the appearance of the first symptoms of the disease.
Children
Correction of the dosing regimen is not required.
Elderly patients
Correction of the dosing regimen is not required.
Patients with impaired renal function
Correction of the dosing regimen is not required.
Patients with impaired liver function
Correction of the dosing regimen is not required.
Prevention
Adults
The recommended dose of Relenza is two inhalations (2x5 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 causative agent of infection exceeds 10 days. The full course of preventive therapy should be completed in accordance with the purpose.
Children
Correction of the dosing regimen is not required.
Elderly patients
Correction of the dosing regimen is not required.
Patients with impaired renal function
Correction of the dosing regimen is not required.
Patients with impaired hepatic function
Correction of the dosing regimen is not required.

Side effects:The drug Relenza is well tolerated when applied in the form of oral inhalations.
In controlled clinical trials involving high-risk patients (elderly patients, as well as patients with certain chronic diseases), the incidence of adverse reactions is similar in the zanamivir group and in the placebo group.
The undesirable reactions presented below are listed in accordance with the damage to organs and organ systems and frequency of occurrence.Frequency of occurrence is defined as follows: very often (≥ 1/10), often (≥1 / 100 and <1/10), infrequently (≥ 1/1 000 and <1/100), rarely (≥1 / 10,000 and <1/1 000), very rarely (<1/10 000, including individual cases).
Frequency categories were formed on the basis of clinical studies of the drug and post-registration surveillance.
Immune system disorders
Very rarely: allergic reactions, including anaphylactic and anaphylactoid reactions, face and pharyngeal edema.
Disturbances from the nervous system
Very rarely: vasovagal reactions (have been documented in patients with symptoms of the influenza virus, such as fever, dehydration, observed immediately after zanamivir inhalation).
Disorders of the psyche
Frequency is unknown: convulsions, confusion, behavioral disorders, hallucinations, agitation, anxiety, delirium were recorded with Relenza in patients with influenza, mainly among children and adolescents. Seizures and psychoneurological symptoms were also noted in patients with influenza who did not take Relenza.
Heart Disease
The frequency is unknown: arrhythmia, fainting.
Disturbances from the respiratory system, chest and mediastinal organs
Very rarely: bronchospasm, shortness of breath.
Disturbances from the skin and subcutaneous tissues
Very rarely: rashes, hives, severe skin reactions, including erythema polymorph, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Overdose:Accidental overdose is unlikely due to the particular form of release, route of administration and low bioavailability after oral administration of zanamivir. When inhaled 64 mg per day (more than 3 times the recommended daily), there are no side effects. Also, they are not registered, and when administered parenterally for 5 days, 1200 mg per day.

Interaction:Zanamivir does not bind to proteins, nor is it metabolized and not subject to changes in the liver. Clinically significant drug interactions are unlikely.

Special instructions:Influenza may be accompanied by increased airway hyperreactivity.
Very rare reports of bronchospasm attacks and / or impairment of pulmonary function after zanamivir inhalation were obtained for patients,who have been treated with influenza; some of these patients had no history of chronic airway disease. In this case, it is necessary to stop zanamivir treatment and contact a specialist for a medical examination. Patients with chronic respiratory diseases receiving zanamivir therapy should have a fast-acting bronchodilator.
In patients with severe bronchial asthma, it is necessary to assess the estimated benefit and possible risk when using the drug. Do not prescribe the Relenza drug if proper medical control is not exercised. In patients with bronchial asthma and severe severity of chronic obstructive pulmonary disease (COPD), treatment of the underlying disease should be optimized during therapy with Relensa. The patient should be informed of the potential danger of bronchospasm. The Relenza preparation, a powder for inhalation dosed, should not be used for the preparation of a solution for a nebulizer or for a ventilator (IVL).
There were reports of hospitalization of patients with influenza, including one fatal case, using a solution prepared from Relenza, a powder for inhalation dosed, through a nebulizer or an IVL apparatus. In the description of the fatal case, it was reported that lactose, which is part of the Relensa preparation, a powder for inhalation dosed, prevented the normal functioning of the device. Therefore, the Relensa preparation, a powder for inhalation dosed, should only be used with the attached device (Dischaler).
Infection caused by the influenza virus can be accompanied by various neurological and behavioral symptoms. Posts received in the postgrade period (predominantly registered in children in Japan) showed convulsive seizures, delirium, hallucinations and deviant behavior in patients infected with the influenza virus and taking neuraminidase inhibitors, including zanamivir. These phenomena were observed mainly in the early stages of the disease, often had a sudden onset and rapid resolution.
The causal relationship between the administration of zanamivir and the above-mentioned undesirable phenomena has not been established. If any psychoneurological symptoms occur, the risk / benefit ratio of further treatment with zanamivir should be assessed for each individual patient.
The drug Relenza is recommended to be used with caution in patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption, since the drug contains lactose.
Instyukiya on the use of Dischaler with the Rotadisk
Dischaler device is used for inhalation of zanamivir from Rotadisk (Packing of Relensa preparation). The dischaler consists of the following parts:

a body with a lid and a plastic needle for piercing the cell of the Rotadisk;
cover for the mouthpiece;
A pull-out tray with a mouthpiece and a rotating wheel on which is placed the Rotadisk.

Rotadisk is a blister with 4 cells, each containing 5 mg of zanamivir. The rotadisk can be stored in a device for inhalation of a dischaler, however, the blister should be pierced immediately before inhalation of the drug.Failure to comply with this recommendation may disrupt the work of Diskhaler and, accordingly, reduce the effectiveness of the drug.
IMPORTANT! Do not pierce Rotadisk before he is placed in the dischaler.
Loading Rotadisk in Deschhaler
1. Remove the cover from the mouthpiece, make sure that the mouthpiece is clean inside and out.

2. Gently pull out the drawer until the plastic clips come out, grasping the corners of the tray. The tray should be pushed all the way out so that the notches on the side of the clips are visible.

3. Pull out the tray completely, pressing the thumb and index finger on the notch on the side of the clips.

4. Place the Rotadisk on the wheel with the cells down and insert the tray back into the Dischaler.

Carrying out inhalations
5. Lift the Dischaler's cover up to the stop to pierce the upper and lower foils of the Rotadisk. Close the cover.

IMPORTANT! Do not lift the cover before the drawer is fully installed.
6. After a full exhalation, place the mouthpiece between the teeth and lips, without closing the air holes on both sides of the mouthpiece. Make a slow deep breath (always through the mouth, not through the nose). Remove the mouthpiece from the mouth. Hold your breath as far as possible. Slowly exhale.Do not breathe out into the inhaler.

7. Carefully pull out the drawer one time as far as it will go, without pressing the clamps, and push it in. In this case, the Rotadisk will rotate by one cell and will be ready for the next inhalation.
IMPORTANT! Puncture the cell only immediately before inhalation.
To repeat inhalations repeat steps 5 and 6.
Replacing the empty Rotadisk
Each Rotadisk contains 4 cells.
After four inhalations, replace the empty Rotadisk with a new one (steps 2-4).

IMPORTANT! Children should use an inhalation device under the supervision of adults.

Effect on the ability to drive transp. cf. and fur:Not noted.

Form release / dosage:Powder for inhalation dosed with 5 mg / dose.

Packaging:Laminated aluminum Rotadisk with 4 cells (a round-shaped blister with 4 symmetrically arranged cells), each of which contains 1 dose of the drug. To 5 Rotadiskov (20 doses) in a plastic bottle. For 1 plastic bottle with Dischaler and instructions for use in a cardboard bundle.

Storage conditions:Store at a temperature not exceeding 30 ° C.
Keep out of the reach of children.

Shelf life:7 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-000095

Date of registration:31.05.2007 / 22.09.2014

Expiration Date:Unlimited

The owner of the registration certificate:GlaxoSmithKline Trading, ZAO GlaxoSmithKline Trading, ZAO Russia

Manufacturer: & nbsp

GLAXO WELLCOME PRODUCTION France

Representation: & nbspGlaxoSmithKline Trading, ZAOGlaxoSmithKline Trading, ZAO

Information update date: & nbsp2016-10-20