Composition, form of production and packaging
The powder for inhalation is dosed from white to almost white.
1 dose
zanamivir (micronized) 5 mg
[PRING] lactose monohydrate - up to 25 mg.
4 doses - rotadiski (5) - plastic bottles (1) complete with Dischaler (1 pc.) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2017.
PHARMACHOLOGIC EFFECT
Antiviral drug, a strong and highly selective inhibitor of neuraminidase (a 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, incl. circulating and virulent for different species. Half the inhibitory concentration (IC 50 ) for strains of virus A and B, is from 0.09 to 95.2 pM.
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 A and B virus 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 zanamavir 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.
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 for the treatment of 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: 0.60-0.95; 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 has been 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.
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, 10 mg of C max is 97 ng / ml after 1.25 hours. A low degree of absorption leads to low systemic concentrations and a small area under
pharmacokinetic curve "concentration - time". Due to low absorption, the concentration of active substance in the blood plasma is low (a low degree of absorption persists with repeated inhalations).
Distribution
The binding of zanamivir to plasma proteins is very low (<10%). V d 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 "gateway" of the infection. After 10 mg zanamivir inhalation in the epithelial layer of the respiratory tract, zanamivir concentrations exceeded the mean IC 50 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 score is 77.6% and 13.2%, respectively).
Metabolism and excretion
Zanamivir is not metabolized, excreted by the kidneys unchanged.
T 1/2 from blood plasma after oral inhalation ranges from 2.6 to 5.05 hours. The total clearance is from 2.5 to 10.9 l / h.
Special patient groups
Patients of advanced age. 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. The pharmacokinetics of zanamivir was evaluated in a controlled trial 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 of 20 mg, 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 liver function . Since zanamivir is not metabolized, no dosage adjustment is required.
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 virus type A and B, in children older than 5 years and adults.
DOSING MODE
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 (2-5 mg) 2 times / 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 hepatic function
Correction of the dosing regimen is not required.
Prevention
Adults
The recommended dose of Relenza is two inhalations (2-5 mg) 1 time / 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 pathogen of the 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.
Instructions for using the Dischaler with rotadiscs
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;
- case for the mouthpiece;
- A sliding tray with a mouthpiece and a rotating wheel on which a rotadisk is placed.
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 the rotadisk before it is placed in the dischaler.
Loading the rotadisk in Diskhaler
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 top and bottom foil 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. Thus the rotadisk will turn on one cell and will be ready for the next inhalation
Important! Puncture the cell only immediately before inhalation.
For repeated inhalations, repeat steps 5 and 6
Replacing an 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.
SIDE EFFECT
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, <1/10), infrequently (? 1/1000, <1/100), rarely (? 1/10 000, < 1/1000), 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.
From the side of the immune system: very rarely - allergic reactions, including anaphylactic and anaphylactoid reactions, edema of the face and oropharynx.
From the side of the nervous system: very rarely - vasovagal reactions (were recorded in patients with symptoms of the influenza virus, such as fever, dehydration, observed immediately after zanamivir inhalation).
From the side of the psyche: the frequency is unknown - convulsions, confusion, behavioral disorders, hallucinations, agitation, anxiety, delirium, 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 Relensa.
From the heart: arrhythmia, fainting.
From the respiratory system, chest and mediastinum: very rarely - bronchospasm, dyspnea.
From the skin and subcutaneous tissues: very rarely - rash, hives, severe skin reactions, including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
CONTRAINDICATIONS
- Hypersensitivity to the components of the drug.
With caution should prescribe the drug for 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 is excreted in breast milk. However, there is no information on the isolation of zanamivir with human milk.
Since experience is limited, in the period of breastfeeding, zanamivir should be used only if the expected benefit to the mother exceeds the potential risk for the child.
APPLICATION FOR FUNCTIONS OF THE LIVER
Patients with impaired renal function are not required to adjust the dose.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Patients of the liver do not need dose adjustment.
APPLICATION FOR CHILDREN
The drug is prescribed for children older than 5 years.
APPLICATION IN ELDERLY PATIENTS
Older patients are not required to adjust the dose.
SPECIAL INSTRUCTIONS
Influenza may be accompanied by increased airway hyperreactivity Very rare reports have been received
on attacks of bronchospasm and / or impairment of pulmonary function after zanamivir inhalation to 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 the Relensa drug. 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 an IVL apparatus.
There were reports of hospitalization of patients with influenza, including one death, while
a solution prepared from the Relensa preparation, 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. Thus, 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, t. the medicinal product contains lactose.
Impact on the ability to drive vehicles and manage mechanisms
Not noted.
OVERDOSE
Symptoms: a random overdose is unlikely because of the particular form of the release, route of administration and low bioavailability (10-20%) of zanamivir. When studying the use of an aqueous solution of zanamivir without lactose, no side effects were reported by inhalation (through the nebulizer) at a dose of 64 mg / day (more than 3 times the recommended daily dose). Also they are not registered and with intravenous administration for .5 days to 1200 mg / day in clinical trials.
Treatment: zanamivir has a low molecular weight, a low bond with plasma proteins and a small V d , and is expected to be excreted by hemodialysis. Thus, hemodialysis can be considered as a treatment option for overdose of zanamivir.
DRUG INTERACTION
Zanamivir does not bind to proteins, nor is it metabolized and does not undergo changes in the liver. Clinically significant drug interaction is unlikely.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of no higher than 30 В° C. Shelf life - 7 years.
