Relenza, 5 mcg/dose 4 doses

Pharmgroup:

An antiviral drug.

Pharmacological action:

Relenza is an antiviral drug, a highly selective inhibitor of neuraminidase (surface enzyme of influenza virus). Viral neuraminidase ensures release of viral particles from the infected cell and may accelerate penetration of the virus through the mucosal barrier to the surface of epithelial cells, thus ensuring infection of other cells of the respiratory tract. The inhibitory activity of zanamivir has been shown both in vitro and in vivo and includes all 9 subtypes of influenza virus neuraminidases, including circulating and virulent for different species. The half inhibitory concentration (IC50) for virus A and B strains, ranges from 0.09 to 95.2 pM.

The replication of influenza virus is restricted to the cells of the surface epithelium of the respiratory tract. Zanamivir acts in the extracellular space to reduce replication of both types of influenza A and B virus by preventing the release of viral particles from the cells of the surface epithelium of the airways.

The efficacy of zanamavir when administered by inhalation has been confirmed in controlled clinical studies. Use of zanamavir as therapy of acute infections caused by influenza virus resulted in reduction of virus release (compared to placebo). No development of resistance to zanamivir has been reported.

Clinical efficacy and safety

Zanamivir used in doses used in the treatment of influenza in healthy, at-risk subjects (usually those who were in contact with those who were ill) relieves symptoms and reduces the duration of the disease. Combined analysis of the results of 3 studies showed that the median time to symptom relief was reduced to 1.5 days in patients in the zanamivir group compared to patients in the placebo group (pIt was shown that zanamivir was also effective in preventing influenza in children over 5 years and in adults. The percentage of effective protection is 67-79% compared with placebo and 56-61% compared with active controls.

Pharmacokinetics:

Intake

In inhalation the absolute bioavailability of the drug is low (on average 2%). Systemic absorption is approximately 10-20%. After a single dose of 10 mg, Cmax is 97 ng/ml and is reached after 1.25 hours. Due to low absorption, plasma concentrations of the active substance are low (low absorption persists with repeated inhalations).

Distribution
After inhalation zanamivir is distributed in the tissues of the respiratory tract, reaching high concentrations. When used in a single dose of 10 mg, zanamivir is determined in the epithelial layer of the respiratory tract, which is the primary site of influenza virus replication.

The concentration of zanamivir at 12 h and 24 h after inhalation is approximately 340 and 52 times the average IC50 value for viral neuraminidase, respectively. The high concentration of zanamivir in the respiratory tract provides rapid inhibition of viral neuraminidase.

Zanamivir accumulates predominantly in the tissues of the oropharynx and lungs (77.6% and 13.2% on average, respectively).

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

The T1/2 of zanamivir after inhalation ranges from 2.6 to 5.05 h. Total clearance is 2.5 to 10.9 L/h.

Pharmacokinetics in special clinical cases

In elderly patients at a therapeutic dose of 20 mg/day the bioavailability is low (10-20%), therefore there is no systemic effect of zanamivir. Age-related changes in pharmacokinetics are unlikely (no dose adjustment is required).

In children, the pharmacokinetics of zanamivir were evaluated in a controlled study in 24 patients aged 3 months to 12 years using nebulizer (10 mg) and powder inhaler (10 mg). Pharmacokinetic parameters in children were not different from those in adults.

In patients with impaired renal function at therapeutic doses of 20 mg the bioavailability is low and is 10-20%; therefore, systemic concentrations of zanamivir are insignificant. Given the wide range of safety of the drug, the possible increase in systemic concentrations in patients with severe renal impairment remains clinically insignificant and does not require dosing adjustments.

Because zanamivir is not metabolized, no dosing regimen adjustment is necessary in patients with impaired hepatic function.

Indications

– treatment and prevention of infection caused by influenza virus type A and B in children over 5 years and adults.

Active ingredient

Composition

1 dose contains zanamivir 5 mg, plus lactose as a filler.

How to take, the dosage

Inhaled, using a special device “Relenza Dischaler”.

Treatment: 2 inhalations (5 mg x 2) 2 times daily for 5 days (maximum daily dose 20 mg); treatment is recommended to start within the first two days of illness.

Prophylaxis: 2 inhalations (5 mg x 2) once daily for 10 days (maximum daily dose is 10 mg).

Interaction

Do not combine with other inhaled drugs (including bronchodilators).

Special Instructions

If bronchospasm develops, stop inhalation immediately and consult a physician.

If there is a history of respiratory problems accompanied by bronchospasm, bronchodilators (e.g., salbutamol) should be available for the duration of treatment.

Contraindications

Hypersensitivity to the ingredients of the drug.

Side effects

Very rarely – bronchospasm, shortness of breath, allergic reactions (including rash, urticaria, swelling of the face and oropharyngeal mucosa).

Overdose

Accidental overdose is unlikely due to the dosing, route of administration and low bioavailability of the drug.

No adverse effects have been reported with inhaled administration of 64 mg/day (more than 3 times the recommended daily dose). No side effects have been reported with parenteral administration of Relenza at a dose of 1.2 g/day for 5 days.

Pregnancy use

It is contraindicated in I trimester of pregnancy, in II and III trimesters it is possible if the expected effect of therapy exceeds the potential risk to the fetus. Breastfeeding should be stopped during treatment.