4.1. Therapeutic indications

Asthma

Tezspire is indicated as an add-on maintenance treatment in adults and adolescents 12 years and older with severe asthma who are inadequately controlled despite high dose inhaled corticosteroids plus another medicinal product for maintenance treatment.

Chronic rhinosinusitis with nasal polyps (CRSwNP)

Tezspire is indicated as an add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP for whom therapy with systemic corticosteroids, and/or surgery do not provide adequate disease control.

4.2. Posology and method of administration

Treatment should be initiated by physicians experienced in the diagnosis and treatment of conditions for which Tezspire is indicated (see section 4.1).

Posology

Tezspire is intended for long-term treatment. A decision to continue the therapy should be made at least annually based on the patient's level of disease control.

Asthma

Adults and adolescents (aged 12 years and older)

The recommended dose is 210 mg of tezepelumab by subcutaneous injection every 4 weeks.

CRSwNP

The recommended dose for adult patients is 210 mg of tezepelumab by subcutaneous injection every 4 weeks.

Missed dose

If a dose is missed, the dose should be administered as soon as possible. Thereafter, the patient can resume dosing on the scheduled day of administration. If the next dose is already due, then administer as planned. A double dose must not be administered.

Special populations

Elderly (≥65 years of age)

No dose adjustment is required for elderly patients (see section 5.2).

Renal and hepatic impairment

No dose adjustment is required for patients with renal or hepatic impairment (see section 5.2).

Paediatric population

The safety and efficacy of Tezspire in children under 12 years of age for the treatment of asthma have not been established. No data are available.

The safety and efficacy of Tezspire in children under 18 years of age for the treatment of CRSwNP have not been established. No data are available.

Method of administration

Tezspire is administered as a subcutaneous injection.

A patient may self-inject or the patient's caregiver may administer this medicinal product after training in subcutaneous injection technique. Proper training should be provided to patients and/or caregivers on the preparation and administration of Tezspire prior to use according to the “Instructions for Use”.

Tezspire should be injected into the thigh or abdomen, except for the 5 cm around the navel. If a healthcare professional or caregiver administers the injection, the upper arm can also be used. A patient should not self-inject in the arm. It should not be injected into areas where the skin is tender, bruised, erythematous, or hardened. It is recommended to rotate the injection site with each injection.

Comprehensive instructions for administration using the pre-filled pen is provided in the “Instructions for Use”.

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4. Special warnings and precautions for use

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 anti-helminth treatment, therapy with tezepelumab should be discontinued until infection resolves.

Excipients with known effect

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

This medicinal product contains 48 mg of L-proline in each 210 mg dose (1.91 mL). L-proline may be harmful for patients with hyperprolinaemia.

This medicinal product contains 0.19 mg of polysorbate 80 in each 210 mg dose (1.91 mL). Polysorbates may cause allergic reactions.

4.5. Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

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

In a randomised, double blind, parallel group study of 70 patients aged between 12 and 21 years with moderate to severe asthma, tezepelumab treatment did not appear to affect the humoral antibody responses induced by seasonal quadrivalent influenza vaccination.

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.

4.6. Fertility, pregnancy and lactation

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).

4.7. Effects on ability to drive and use machines

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

4.8. Undesirable effects

Summary of the safety profile

The most commonly reported adverse reactions during treatment for asthma are arthralgia (3.8%) and pharyngitis (4.1%) and during treatment for CRSwNP is pharyngitis (5.4%).

Tabulated list of adverse reactions

Table 1 presents the adverse reactions from clinical studies in patients with severe asthma and CRSwNP who received at least one dose of Tezspire in trials of 52 weeks duration, and from post-marketing experience.

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

System organ class

Adverse reactions

Frequency

Infections and infestations

Pharyngitisa

Common

Immune system disorders

Hypersensitivity (including anaphylactic reaction)

Not known

Skin and subcutaneous tissue disorders

Rashb

Common

Musculoskeletal and connective tissue disorders

Arthralgia

Common

General disorders and administration site conditions

Injection site reactionc

Common

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:

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

In clinical trials, doses of up to 280 mg were administered subcutaneously every 2 weeks (Q2W) and doses of up to 700 mg were administered intravenously every 4 weeks (Q4W) to patients with asthma without evidence of dose-related toxicities.

There is no specific treatment for an overdose with tezepelumab. If overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary.