Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: GlaxoSmithKline Trading Services Limited, Currabinny, Carrigaline, County Cork, Ireland
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded in the patient file.
Nucala should not be used to treat acute asthma exacerbations.
Asthma-related adverse 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.
Abrupt discontinuation of corticosteroids after initiation of Nucala therapy is not recommended. Reduction in corticosteroid doses, if required, should be gradual and performed under the supervision of a physician.
Acute and delayed systemic reactions, including hypersensitivity reactions (e.g. anaphylaxis, urticaria, angioedema, rash, bronchospasm, hypotension), have occurred following administration of Nucala. These reactions generally occur within hours of administration, but in some instances have a delayed onset (i.e. typically within several days). These reactions may occur for the first time after a long duration of treatment (see section 4.8).
Eosinophils may be involved in the immunological response to some helminth infections. Patients with pre-existing helminth infections should be treated before starting therapy. If patients become infected whilst receiving treatment with Nucala and do not respond to anti-helminth treatment, temporary discontinuation of therapy should be considered.
This medicinal product contains less than 1 mmol sodium (23 mg) per 100 mg dose, i.e. essentially “sodium-free”.
No interaction studies have been performed.
Cytochrome P450 enzymes, efflux pumps and protein-binding mechanisms are not involved in the clearance of mepolizumab. Increased levels of pro-inflammatory cytokines (e.g. IL-6), via interaction with their cognate receptors on hepatocytes, have been shown to suppress the formation of CYP450 enzymes and drug transporters, however, elevation of systemic pro-inflammatory markers in severe refractory eosinophilic asthma is minimal and there is no evidence of IL-5 receptor alpha expression on hepatocytes. The potential for interactions with mepolizumab is therefore considered low.
There is a limited amount of data (less than 300 pregnancy outcomes) from the use of mepolizumab in pregnant women.
Mepolizumab crosses the placental barrier in monkeys. Animal studies do not indicate reproductive toxicity (see section 5.3). The potential for harm to a human fetus is unknown.
As a precautionary measure, it is preferable to avoid the use of Nucala during pregnancy. Administration of Nucala to pregnant women should only be considered if the expected benefit to the mother is greater than any possible risk to the fetus.
There are no data regarding the excretion of mepolizumab in human milk. However, mepolizumab was excreted into the milk of cynomolgous monkeys at concentrations of less than 0.5% of those detected in plasma.
A decision must be made whether to discontinue breast-feeding or to discontinue Nucala therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
There are no fertility data in humans. Animal studies showed no adverse effects of anti-IL5 treatment on fertility (see section 5.3).
Nucala has no or negligible influence on the ability to drive and use machines.
In clinical studies in subjects with severe refractory eosinophilic asthma, the most commonly reported adverse reactions during treatment were headache, injection site reactions and back pain.
A total of 896 adults and 19 adolescent subjects with severe refractory eosinophilic asthma received either a subcutaneous or an intravenous dose of mepolizumab during three placebo-controlled clinical studies of 24 to 52 weeks duration. The table below presents the adverse reactions from the two placebo-controlled studies in patients receiving mepolizumab 100 mg subcutaneously (n=263).
The safety profile of mepolizumab in severe refractory eosinophilic asthma patients (n=998) treated for a median of 2.8 years (range 4 weeks to 4.5 years) in open-label extension studies was similar to that observed in the placebo-controlled studies.
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.
Common: Lower respiratory tract infection, Urinary tract infection, Pharyngitis,
Common: Hypersensitivity reactions (systemic allergic)*
Rare: Anaphylaxis**
Very common: Headache
Common: Nasal congestion
Common: Abdominal pain upper
Common: Eczema
Common: Back pain
Common: Administration-related reactions (systemic non allergic)***, Local injection site reactions, Pyrexia
* Systemic reactions including hypersensitivity have been reported at an overall incidence comparable to that of placebo. For examples of the associated manifestations reported and a description of the time to onset, see section 4.4.
** From spontaneous post marketing reporting.
*** The most common manifestations associated with reports of systemic non-allergic administration-related reactions were rash, flushing and myalgia; these manifestations were reported infrequently and in <1% of subjects receiving mepolizumab 100 mg subcutaneously.
In 2 placebo-controlled studies the incidence of local injection site reactions with mepolizumab 100 mg subcutaneous and placebo was 8% and 3%, respectively. These events were all non-serious, mild to moderate in intensity and the majority resolved within a few days. Local injection site reactions occurred mainly at the start of treatment and within the first 3 injections with fewer reports on subsequent injections. The most common manifestations reported with these events included pain, erythema, swelling, itching, and burning sensation.
Thirty-seven adolescents (aged 12-17) were enrolled in four placebo-controlled studies (25 mepolizumab treated intravenously or subcutaneously) of 24 to 52 weeks duration. Thirty-six paediatric patients (aged 6-11) received mepolizumab subcutaneously in an open-label study for 12 weeks. After a treatment interruption of 8 weeks, 30 of these patients, received mepolizumab for a further 52 weeks. The safety profile was similar to that seen in adults. No additional adverse reactions were identified.
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.
This medicinal product must not be mixed with other medicinal products.
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