RELENZA

Active material: Zanamivir
When ATH: J05AH01
CCF: Viricide
ICD-10 codes (testimony): J10
When CSF: 09.01.03
Manufacturer: GlaxoSmithKline Trading Company (Russia)

DOSAGE FORM, COMPOSITION AND PACKAGING

The powder for inhalation dose white or nearly white.

Excipients: lactose monohydrate.

Rotadisk (5) – plastic boxes (1) complete with diskhalerom (1 PC.) – packs cardboard.

Pharmacological action

Viricide, highly selective inhibitor of neuraminidase (influenza virus surface enzyme). Viral neuraminidase provides release of virus particles from infected cells and can accelerate penetration of virus across the mucosal barrier to the epithelial cell surface, thereby providing airway infection with other cells. Inhibitory activity is shown as zanamivir in vitro and in vivo and includes all 9 neuraminidase subtypes of influenza viruses, incl. circulating virulent and for different types of. Half inhibitory concentration (IC₅₀)virus strains A and B, It is between 0.09 to 95.2 pM.

Replication of influenza virus limited surface epithelial cells of the respiratory tract. Zanamivir is active in the extracellular space, reducing the reproduction of both types of influenza A and B, preventing release of virus particles from the surface epithelial cells of the respiratory tract.

zanamivir Efficiency confirmed by inhalation use in controlled clinical studies. Using zanamavira as the treatment of acute infections, caused by influenza virus, It led to a reduction in the release of the virus (compared to placebo). the development of resistance to zanamivir is not registered.

Clinical effectiveness and safety

Zanamivir, applied doses, used in the treatment of influenza, healthy, at risk (usually, have been in contact with sick), It eases symptoms and reduces the duration of illness. A combined analysis of the results 3 research has shown, that the median time to alleviation of symptoms of the disease is reduced to 1.5 days in patients zanamivir group compared with patients in the placebo group (p<0.001). The number of complications was reduced in the zanamivir group 171/769 (22%) compared to placebo 208/711 (29%) and the relative risk: 0.77; (95% CI: 0.65-0.92; p = 0.004). The use of antibiotics to treat complications after suffering flu was also reduced 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). Optimum efficiency of zanamivir has been shown in the case of the start of treatment as soon as possible after the first symptoms of the disease.

It has been shown, that zanamivir is also effective as a means of prevention of influenza in children older 5 years and in adults. Percent protection is effective 67-79% compared to placebo and 56-61% compared to the active control.

Pharmacokinetics

Absorption

When inhalation use low absolute bioavailability (average 2%). Systemic absorption is approximately 10-20%. After receiving a single dose 10 mg C_max is 97 ng / ml achieved after 1.25 no. Due to the low absorption of the active substance concentration in the blood plasma of low (low degree of absorption stored in repeated inhalation).

Distribution

After inhalation, zanamivir is distributed in the tissues of the respiratory tract, attaining high concentrations. When used as a single dose 10 mg zanamivir defined in airway epithelial layer, which is the main influenza virus replication site.

Concentration through zanamivir 12 and h 24 h after inhalation approximately 340 and 52 times, respectively, higher than the average IC₅₀ for viral neuraminidase. High concentration of zanamivir in the respiratory tract provides rapid inhibition of viral neuraminidase.

Zanamivir is accumulated mainly in the oropharynx and pulmonary tissues (average 77.6% and 13.2% respectively).

Metabolism and excretion

Zanamivir is excreted by the kidneys in unchanged form and is metabolized.

T_1/2 zanamivir after inhalation ranges from 2.6 to 5.05 no. Total clearance – from 2.5 to 10.9 l /.

Pharmacokinetics in special clinical situations

Elderly patients with a therapeutic dose 20 mg / day low bioavailability (10-20%), therefore systemic exposure to zanamivir offline. changes in pharmacokinetics, age-related, unlikely (dose adjustment is not required).

Pediatric pharmacokinetics of zanamivir was evaluated in a controlled trial 24 patients aged 3 Months before 12 years using a nebulizer (10 mg) and a dry powder inhaler (10 mg). The pharmacokinetic parameters in children are not different from those in adults.

Patients with impaired renal function when using therapeutic doses 20 mg bioavailability is low and 10-20%, Consequently, negligible systemic concentrations of zanamivir. Given the wide range of drug safety, possible increase in systemic concentrations in patients with severe renal insufficiency patients remained clinically insignificant and does not require correction dosing regimen.

Because zanamivir is not metabolized, with abnormal liver function does not require a correction mode.

Testimony

- treatment and prevention of infection, caused by influenza virus types A and B, in children older 5 years and adults.

Dosage regimen

It is intended only for inhalation into the respiratory tract using the supplied inhaler Diskhaler. Other inhalants, eg, fast-acting bronchodilators, It should be taken prior to inhalation drug Relenza.

At the treatment of influenza A and B adults and children over 5 years It is encouraged to nominate for 2 inhalation (2× 5 mg) 2 times / day for 5 days. Daily dose – 20 mg.

Elderly patients and patients with impaired renal and hepatic function dose adjustment is required.

For optimal effect, treatment should be initiated as early as possible.

FROM the purpose of the prevention of influenza A and B adults and children over 5 years It is encouraged to nominate for 2 inhalation (2× 5 mg) 1 times / day for 10 days. Daily dose – 10 mg. prevention of course can be extended to 1 Months, if the risk of the disease persists for more than 10 days.

Elderly patients and patients with impaired renal and hepatic function dose adjustment is not required.

Rules applying Diskhalera

Diskhaler device is used for inhalation rotadiska (Relenza release form). Diskhaler consists of the following components:

- housing with lid and a plastic needle to puncture the cell rotadiska;

- Case for the mouthpiece;

- a sliding tray with the mouthpiece and a rotary wheel, on which it is placed Rotadisk;

Rotadisk consists of 4 blisterov, each of which contains a defined dose.

Rotadisk may be stored in a device for inhalation Diskhaler, Nonetheless, blister should be pierced immediately prior to inhalation of the drug. Otherwise, it could disrupt and Diskhalera, respectively, reduce the effectiveness of the drug.

Important: should not pierce rotadisk before, he will be placed in the Diskhaler.

Loading rotadiska in Diskhaler

1. Remove the cover from the mouthpiece, make sure, that the mouthpiece clean inside and out.

2. Carefully pull the drawer before the plastic clips, holding tray corners. The tray should be pulled up to the stop, were visible incisions on the side clamps.

3. Pull out the tray completely, curled finger and thumb notches on the side clamps.

4. Put rotadisk wheel mesh downward and insert the tray back into Diskhaler.

Inhalation

1. To lift the cover up until it stops Diskhalera, to pierce the upper and lower foil Rotadiska. Close the lid.

Important: do not lift the lid before, as the drawer is completely installed.

2. After complete exhalation mouthpiece placed between the teeth, firmly grasp the mouthpiece lips, without closing the air holes on either side of die. Make a slow deep breath (necessarily through the mouth, rather than through the nose). Remove the mouthpiece mouth. Hold your breath as much as possible. slowly exhale. You can not breathe out into the inhaler.

3. Gently push the drawer once the stop, without pressing jaws, and push. Thus rotadisk rotated by one cell and is ready for the next inhalation.

Important: pierce cell should only immediately before inhalation.

For repeated inhalation of claim 1 and claim 2 repeat.

Replacing empty rotadiska

Each rotadisk comprises 4 cells. After four inhalations empty rotadisk should be replaced by a new (p.2-4).

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

Side effect

In controlled clinical trials, the incidence of adverse events similar to zanamivir group and the placebo group. Spontaneous reports contained information on adverse reactions to the use of zanamivir and were classified as follows:: Often (≥1/10), often (≥1/100, <1/10) sometimes (≥1/1000, <1/100), rarely (≥1/10 000, <1/1000), rarely (<1/10 000), including individual cases.

Allergic reactions: rarely – allergic reactions, including swelling of the face and throat.

The respiratory system: rarely – bronchospasm, difficulty breathing.

Dermatological reactions: rarely – rash, hives.

Contraindications

- Hypersensitivity to the drug.

FROM caution drug should be used for diseases of the respiratory tract, accompanied by bronchospasm (incl. history).

Pregnancy and lactation

Efficacy and safety of zanamivir during pregnancy and lactation (breast-feeding) I have not been studied.

IN experimental studies on animals have shown, that zanamivir crosses the placenta and is excreted in breast milk, Nonetheless, not observed a teratogenic effect or impaired fertility or clinical manifestations of any disturbance in pre- and postnatal periods. Information about the penetration of the placenta or into breast milk in humans is not.

Nonetheless, Zanamivir should not be used during pregnancy and breast-feeding, especially in the I trimester, except, when the expected use of the benefit to the mother outweighs the potential risk to the fetus.

Cautions

Recorded very rare isolated reports of bronchospasm development and / or deterioration of respiratory function after use zanamavira, incl. no prior history of diseases. In the case of one of the above events should discontinue zanamivir and seek medical advice.

Patients with respiratory problems should have as a means of emergency short-bronchodilators for the treatment of zanamivir.

Infection, caused by the influenza virus, may be, It is associated with various neurological and behavioral disorders. reports, obtained post-marketing period (mainly registered among children in Japan), observed seizures, delirium, hallucinations and deviant behavior in patients, infected with influenza virus and host neuraminidase inhibitors, including zanamivir. These effects were observed at the early stages of the disease, often have a sudden onset and rapid onset of outcome. The causal relationship between the intake of zanamivir and the above-mentioned adverse events has not been proven. If you experience any neuropsychiatric symptoms soootnoshenie necessary to evaluate the risk / benefit of further treatment with zanamivir for the individual patient.

Effects on ability to drive vehicles and management mechanisms

It does not affect.

Overdose

Accidental overdose is unlikely due to dosing, the method of application and the low bioavailability of the drug.

When inhalation use 64 mg / day (more than 3 times the recommended daily dose) registered side effects. Also, they are not registered and parenteral administration of the drug at a dose of 1.2 g / day for 5 days.

Drug Interactions

Data on drug interactions Relenza drug is not provided.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at or above 30 ° C. Shelf life – 5 years.