TEZSPIRE Solution for injection Ref.[50203] Active ingredients: Tezepelumab

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Acute asthma exacerbations

Tezspire should not be used to treat acute asthma exacerbations.

Asthma-related symptoms or exacerbations may occur during treatment. Patients should be instructed to seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment.

Corticosteroids

Abrupt discontinuation of corticosteroids after initiation of therapy is not recommended. Reduction in corticosteroid doses, if appropriate, should be gradual and performed under the supervision of a physician.

Hypersensitivity reactions

Hypersensitivity reactions (e.g. anaphylaxis, rash) may occur following administration of tezepelumab (see section 4.8). These reactions may occur within hours of administration, but in some instances have a delayed onset (i.e. days).

A history of anaphylaxis unrelated to tezepelumab may be a risk factor for anaphylaxis following Tezspire administration. In line with clinical practice, patients should be monitored for an appropriate time after administration of Tezspire.

In the event of a serious hypersensitivity reaction (e.g. anaphylaxis), administration of tezepelumab should be discontinued immediately and appropriate treatment as clinically indicated should be initiated.

Serious infections

Blocking thymic stromal lymphopoietin (TSLP) may theoretically increase the risk of serious infections. In placebo-controlled studies, no increase in serious infections was observed with tezepelumab.

Patients with pre-existing serious infections should be treated before initiating therapy with tezepelumab. If patients develop a serious infection while receiving tezepelumab treatment, therapy with tezepelumab should be discontinued until the serious infection resolves.

Serious cardiac events

In a long-term clinical study, a numerical imbalance in serious cardiac adverse events was observed in patients treated with tezepelumab compared to placebo. No causal relationship between tezepelumab and these events has been established, nor has a patient population at risk of these events been identified.

Patients should be advised of signs or symptoms suggestive of a cardiac event (for example, chest pain, dyspnoea, malaise, feeling lightheaded or faint) and to seek immediate medical attention if such symptoms occur. If patients develop a serious cardiac event while receiving tezepelumab treatment, therapy with tezepelumab should be discontinued until the acute event stabilises.

There is currently no data on re-treatment of patients who develop a serious cardiac event or serious infection.

Parasitic (helminth) infection

TSLP may be involved in the immunological response to some helminth infections. Patients with known helminth infections were excluded from participation in clinical trials. It is unknown if tezepelumab may influence a patient’s response against helminth infections.

Patients with pre-existing helminth infections should be treated before initiating therapy with tezepelumab. If patients become infected while receiving treatment and do not respond to antihelminth treatment, therapy with tezepelumab should be discontinued until infection resolves.

Sodium content

This medicinal product contains less than 1 mmol sodium (23 mg) per 210 mg dose, that is to say essentially ‘sodium-free’.

No interaction studies have been performed.

The use of live attenuated vaccines should be avoided in patients receiving tezepelumab.

A clinically relevant effect of tezepelumab on the pharmacokinetics of co-administered asthma medicinal products is not expected. Based on the population pharmacokinetic analysis, commonly co-administered asthma medicinal products (including leukotriene receptor antagonists, theophylline/aminophylline and oral corticosteroids) had no effect on tezepelumab clearance.

Pregnancy

There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of tezepelumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

Human IgG antibodies, such as tezepelumab, are transported across the placenta barrier; therefore, Tezspire may be transmitted from the mother to the developing foetus.

As a precautionary measure, it is preferable to avoid the use of Tezspire during pregnancy unless the expected benefit to the pregnant mother is greater than any possible risk to the foetus.

Breast-feeding

It is unknown whether tezepelumab is excreted in human milk. Human IgGs are known to be excreted in breast milk during the first few days after birth, which decreases to low concentrations soon afterwards; consequently, a risk to the breast-fed child cannot be excluded during this short period.

For this specific period, a decision should be made whether to discontinue/abstain from tezepelumab therapy, taking into account the benefit of breast-feeding to the child and the benefit of therapy to the woman.

Afterwards, tezepelumab could be used during breast-feeding if clinically needed.

See section 5.3 for information on the excretion of tezepelumab in animal (cynomolgus monkey) milk.

Fertility

There are no fertility data in humans. Animal studies showed no adverse effects of tezepelumab treatment on fertility (see section 5.3).

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

Summary of the safety profile

The most commonly reported adverse reactions during treatment are arthralgia (3.8%) and pharyngitis (4.1%).

Tabulated list of adverse reactions

In clinical studies in patients with severe asthma, a total of 665 patients received at least one dose of Tezspire in trials of 52 weeks duration.

The frequency of adverse reactions is defined using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); and not known (cannot be estimated from available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1. List of adverse reactions:

^a Pharyngitis was defined by the following grouped preferred terms: pharyngitis, pharyngitis bacterial, pharyngitis streptococcal and viral pharyngitis.
^b Rash was defined by the following grouped preferred terms: rash, rash pruritic, rash erythematous, rash maculo-papular, rash macular.
^c See ‘Description of selected adverse reactions’.

Description of selected adverse reactions

Injection site reactions

In the pooled safety data from PATHWAY and NAVIGATOR, injection site reactions (e.g. injection site erythema, injection site swelling, injection site pain) occurred at a rate of 3.8% in patients treated with tezepelumab 210 mg subcutaneous every 4 weeks (Q4W).

Paediatric population

A total of 82 adolescents aged 12 to 17 with severe, uncontrolled asthma were enrolled in the 52 week Phase 3 NAVIGATOR study (see section 5.1). The safety profile in adolescents was generally similar to the overall study population.

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 national reporting system listed in Appendix V.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.