RELENZA Inhalation powder, pre-dispensed Ref.[8276] Active ingredients: Zanamivir

Due to the limited number of patients with severe asthma or with other chronic respiratory disease, patients with unstable chronic illnesses or immunocompromised patients (see Section 5.1) who have been treated, it has not been possible to demonstrate the efficacy and safety of Relenza in these groups. Due to limited and inconclusive data, the efficacy of Relenza in the prevention of influenza in the nursing home setting has not been demonstrated. The efficacy of zanamivir for the treatment of elderly patients ≥65 years has also not been established (see section 5.1).

There have been very rare reports of patients being treated with Relenza who have experienced bronchospasm and/or decline in respiratory function which may be acute and/or serious. Some of these patients did not have any previous history of respiratory disease. Any patients experiencing such reactions should discontinue Relenza and seek medical evaluation immediately.

Due to the limited experience, patients with severe asthma require a careful consideration of the risk in relation to the expected benefit, and Relenza should not be administered unless close medical monitoring and appropriate clinical facilities are available in case of bronchoconstriction. In patients with persistent asthma or severe COPD, management of the underlying disease should be optimised during therapy with Relenza.

Should zanamivir be considered appropriate for patients with asthma or chronic obstructive pulmonary disease, the patient should be informed of the potential risk of bronchospasm with Relenza and should have a fast acting bronchodilator available. Patients on maintenance inhaled bronchodilating therapy should be advised to use their bronchodilators before taking Relenza (see section 4.2).

Zanamivir inhalation powder must not be made into an extemporaneous solution for administration by nebulisation or mechanical ventilation. There have been reports of hospitalised patients with influenza who received a solution made with zanamivir inhalation powder administered by nebulisation or mechanical ventilation, including a fatal case where it was reported that the lactose in this formulation obstructed the proper functioning of the equipment. Zanamivir inhalation powder must only be administered using the device provided (see section 4.2).

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Relenza is not a substitute for influenza vaccination and the use of Relenza must not affect the evaluation of individuals for annual vaccination. The protection against influenza only lasts as long as Relenza is administered. Relenza should be used for the treatment and prevention of influenza only when reliable epidemiological data indicate that influenza is circulating in the community.

Relenza is effective only against illness caused by influenza viruses. There is no evidence for the efficacy of Relenza in any illness caused by agents other than influenza viruses.

Neuropsychiatric events have been reported during administration of Relenza in patients with influenza, especially in children and adolescents. Therefore, patients should be closely monitored for behavioural changes and the benefits and risks of continuing treatment should be carefully evaluated for each patient (see section 4.8).

Potential for other drugs to affect zanamivir

Zanamivir is eliminated through renal filtration. Clinically significant drug interactions are unlikely.

Potential for zanamivir to affect other drugs

Zanamivir does not inhibit the cytochrome P450 (CYP) enzymes CYP1A1/2, 2A6, 2C9, 2C19, 2D6, 2E1 and 3A4. Zanamivir does also not affect the renal transporters OAT1, 2, 3 and 4, OCT1 and 2, OCT2-A, OCT3 and the urate transporter hURAT1.

Zanamivir, when given for 28 days, did not impair the immune response to influenza vaccine.

Pregnancy

Systemic exposure to zanamivir is low following administration by inhalation; however, there is no information on placental transfer of zanamivir in humans. There is a limited amount of data (less than 300 pregnancy outcomes) from the use of zanamivir in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

As a precautionary measure, it is preferable to avoid the use of Relenza during pregnancy, unless the clinical condition of the woman is such that the potential benefit to the mother significantly outweighs the possible risk to the foetus.

Breastfeeding

Systemic exposure to zanamivir is low following administration by inhalation; however, there is no information on secretion of zanamivir into human breast milk. A risk to the breastfed child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Relenza therapy, taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Fertility

Animal studies indicate no clinically meaningful effects of zanamivir on male or female fertility (see section 5.3).

Zanamivir has no or negligible influence on ability to drive and use machines.

There have been rare reports of patients with previous history of respiratory disease (asthma, COPD) and very rare reports of patients without previous history of respiratory disease, who have experienced acute bronchospasm and/or serious decline in respiratory function after use of Relenza (see section 4.4).

The adverse events considered at least possibly related to the treatment are listed below by body system, organ class and absolute frequency. Frequencies are defined as very common (≥1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (≥1/10,000, <1/1000), very rare (<1/10,000), not known (cannot be estimated from the available data).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Immune system disorders

Uncommon: allergic-type reactions including oropharyngeal oedema

Rare: Anaphylactic/Anaphylactoid reactions, facial oedema

Nervous systems disorders

Uncommon: vasovagal-like reactions have been reported in patients with influenza symptoms, such as fever and dehydration, shortly following inhalation of zanamivir.

Respiratory, thoracic and mediastinal disorders

Uncommon: bronchospasm, dyspnea, throat tightness or constriction

Skin and subcutaneous tissue disorders

Common: rash

Uncommon: urticaria

Rare: Severe skin reactions including Erythema Multiforme, Stevens-Johnson syndrome and Toxic epidermal necrolysis

Psychiatric and nervous system disorders

Convulsions and psychiatric events such as depressed level of consciousness, abnormal behaviour, hallucinations and delirium have been reported during Relenza administration in patients with influenza. The symptoms were mainly reported in children and adolescents. Convulsions and psychiatric symptoms have also been reported in patients with influenza not taking Relenza.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Not applicable.