Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Teva B.V., Swensweg 5, 2031 GA Haarlem, The Netherlands
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Reslizumab 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.
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 systemic reactions, including anaphylactic reactions, have been reported in association with reslizumab (see section 4.8). These adverse reactions were observed during or within 20 minutes after completion of the infusion. Patients should be monitored during and for an appropriate time after administration of reslizumab. If an anaphylactic reaction occurs, administration of reslizumab should be stopped immediately and appropriate medical treatment should be provided; reslizumab must be discontinued permanently (see section 4.3).
Eosinophils may be involved in the immunological response to some helminth infections. Patients with pre-existing helminth infections should be treated before starting reslizumab therapy. If patients become infected whilst receiving treatment with reslizumab 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 dose, i.e. essentially ‘sodium-free’.
No formal clinical drug interaction studies have been performed with reslizumab. In vitro data indicate that IL-5 and reslizumab are unlikely to affect CYP1A2, 3A4 or 2B6 activity. Based on the characteristics of reslizumab, drug-drug interactions are not expected. Results of population pharmacokinetic analysis confirm that concomitant use of either leukotriene antagonists or systemic corticosteroids does not affect the pharmacokinetics of reslizumab (see section 5.2).
Reslizumab has not been studied in patients concurrently taking immunosuppressant medicinal products other than oral corticosteroids (OCS); therefore, the safety and efficacy profile of reslizumab in these patients is unknown.
Reslizumab has not been studied in patients receiving live vaccines. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving reslizumab or the response to new immunisations in patients receiving reslizumab.
There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of reslizumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of CINQAERO during pregnancy. Reslizumab has a long half-life (see section 5.2). This should be taken into consideration.
It is unknown whether reslizumab is excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown excretion of reslizumab in milk. In humans, during the first few days after birth antibodies may be transferred to the newborns through milk. In this short period, a risk to the suckling child cannot be excluded. Afterwards, CINQAERO could be used during breast-feeding if appropriate.
There are no fertility data in humans. Available non-clinical data do not suggest an effect on fertility.
CINQAERO has no or negligible influence on the ability to drive and use machines.
The most frequently reported adverse reaction during treatment was increased blood creatine phosphokinase, which occurred in approximately 2% of patients. Anaphylactic reaction (see section 4.4) occurred in less than 1% of patients.
During controlled clinical studies, the proportion of patients who discontinued due to any adverse event was 5% for both the 3 mg/kg reslizumab and placebo groups.
Overall, 2,195 subjects received at least one dose of reslizumab. Of these subjects, 1,006 asthma patients were exposed for at least 6 months, 759 exposed for at least 1 year and 237 exposed for longer than 2 years (up to 3 years).The following adverse reactions have been reported with reslizumab during placebo-controlled asthma studies for up to 52 weeks of treatment with a 3 mg/kg dose given intravenously (1,028 patients). Adverse reactions are listed below in Table 2 by system organ class and frequency (frequencies are defined as: 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), not known (cannot be estimated from the available data).
Table 2. Adverse reactions:
Uncommon: Anaphylactic reaction*
Uncommon: Myalgia*
Common: Blood creatine phosphokinase increased*
* See subsection “Description of selected adverse reactions” below
The serious adverse reaction of anaphylactic reaction was reported and considered related to reslizumab in 3 patients (0.19%) during placebo-controlled and open-label asthma studies. These reactions were observed during or within 20 minutes after completion of the reslizumab infusion and were reported as early as the second dose of reslizumab. They were fully resolved with standard treatment with no residual effect. Manifestations included skin or mucosal involvement, dyspnoea, wheezing, gastrointestinal symptoms and chills. These cases resulted in the discontinuation of treatment. Due to an overlap in signs and symptoms, it was not possible to distinguish between an anaphylactic reaction, another hypersensitivity reaction and an infusion-related reaction in all cases (see section 4.4).
Myalgia was reported in 0.97% of patients (10 out of 1,028) in the 3 mg/kg reslizumab group of the placebo-controlled asthma studies compared with 0.55% of patients (4 out of 730) in the placebo group.
Blood creatine phosphokinase elevations were transient and asymptomatic, and did not lead to treatment discontinuation.
In placebo-controlled clinical studies, 6 out of 1,028 patients (0.6%) receiving 3 mg/kg reslizumab had at least one malignant neoplasm reported compared to 2 out of 730 patients (0.3%) in the placebo group. The malignancies observed in reslizumab-treated patients were diverse in nature and without clustering of any particular tissue type.
Experience in paediatric patients is limited (see section 5.1). The data did not indicate a difference in the safety profile of reslizumab in paediatric patients compared with that in adult patients.
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 except those mentioned in section 6.6.
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