Source: European Medicines Agency (EU) Revision Year: 2021 Publisher: Roche Registration GmbH, Emil-Barell-Strasse 1, 79639 Grenzach-Wyhlen, Germany
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
In order to improve traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Administration of satralizumab should be delayed in patients with an active infection until the infection is controlled (see section 4.2).
Vigilance for the timely detection and diagnosis of infection is recommended for patients receiving treatment with satralizumab. Treatment should be delayed in case the patient develops any serious or opportunistic infection and appropriate therapy should be initiated under further monitoring. Patients should be instructed on seeking early medical attention in case of signs and symptoms of infections to facilitate timely diagnosis of infections. Patients should be provided with a patient alert card.
Live and live-attenuated vaccines should not be given concurrently with satralizumab as clinical safety has not been established. The interval between live vaccinations and initiation of satralizumab treatment should be in accordance with current vaccination guidelines regarding immunomodulatory or immunosuppressive agents.
No data are available on the effects of vaccination in patients receiving satralizumab. It is recommended that all patients be brought up to date with all immunisations in agreement with current immunisation guidelines prior to initiating satralizumab treatment.
Mild and moderate elevations of liver transaminases have been observed with satralizumab treatment, most elevations were below 5 x ULN (see section 4.8).
ALT and AST levels should be monitored every four weeks for the first three months of treatment, followed by every three months for one year, thereafter as clinically indicated.
Treatment with satralizumab should be discontinued in patients with ALT or AST >5 x ULN (see section 4.2).
Decreases in neutrophil counts have occurred following treatment with satralizumab (see section 4.8). Neutrophil counts should be monitored 4 to 8 weeks after start of treatment and thereafter as clinically indicated. For recommended dose interruption see section 4.2.
No interaction studies have been performed.
Population pharmacokinetic (PK) analyses did not detect any effect of azathioprine (AZA), oral corticosteroids (OCs) or mycophenolate mofetil (MMF) on the clearance of satralizumab.
Both in vitro and in vivo studies have shown that the expression of specific hepatic CYP450 enzymes (CYP1A2, CYP2C9, CYP2C19, and CYP3A4) is suppressed by cytokines such as IL-6.
Therefore caution should be exercised when starting or discontinuing satralizumab treatment in patients also receiving substrates of CYP450 3A4, 1A2, 2C9 or 2C19, particularly those with a narrow therapeutic index (such as warfarin, carbamazepine, phenytoin and theophylline), and doses adjusted if needed.
Given the prolonged terminal half-life of satralizumab, the effect of satralizumab may persist for several weeks after stopping treatment.
There are no data from the use of satralizumab in pregnant women. Studies in monkeys do not indicate harmful effects with respect to reproductive toxicity (see section 5.3).
As a precautionary measure, it is preferable to avoid the use of Enspryng during pregnancy.
It is unknown whether satralizumab is excreted in human breast milk. Human IgG is known to be excreted in breast milk during the first days after birth, which is decreasing to low concentrations soon afterwards; consequently, a risk to breast-fed infants cannot be excluded during this short period. Afterwards, use of Enspryng could be considered during breast-feeding only if clinically needed.
No clinical data are available on the effect of satralizumab on human fertility. Animal studies showed no impairment of male or female fertility (see section 5.3).
Enspryng has no or negligible influence on the ability to drive and use machines.
The most frequently reported adverse reactions observed were: headache (19.2%), arthralgia (13.5%), white blood cell count decreased (13.5%), hyperlipidaemia (13.5%), and injection-related reactions (12.5%).
Table 3 summarises the adverse reactions that have been reported in association with the use of satralizumab as a monotherapy or in combination with IST in clinical trials.
Adverse reactions from clinical trials (Table 3) are listed by MedDRA system organ class. Adverse reactions are presented using number of adverse events per 100 patient years and by frequency figures. The corresponding frequency category for each adverse reaction is based on frequency figures and 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).
Table 3. Adverse reactions:
| System Organ Class | Frequency | |
|---|---|---|
| Very common | Common | |
| Blood and lymphatic system disorders | Hypofibrinogenaemia | |
| Metabolism and nutrition disorders | Hyperlipidaemia | |
| Psychiatric disorders | Insomnia | |
| Nervous system disorders | Headache | Migraine |
| Cardiac disorders | Bradycardia | |
| Vascular disorders | Hypertension | |
| Respiratory, thoracic and mediastinal disorders | Allergic rhinitis | |
| Gastrointestinal disorders | Gastritis | |
| Skin and subcutaneous tissue disorders | Rash, pruritus | |
| Musculoskeletal and connective tissue disorders | Arthralgia | Musculoskeletal stiffness |
| General disorders and administration site conditions | Injection-related reactions | Peripheral oedema |
| Investigations | White blood cell count decreased | Neutrophil count decreased platelet count decreased, transaminases increased, blood bilirubin increased, weight increased |
IRRs reported in patients treated with satralizumab were predominantly mild to moderate, and most occurred within 24 hours after injections. The most commonly reported systemic symptoms were diarrhoea and headache. The most commonly reported local injection site reactions were flushing, erythema, pruritus, rash and pain.
In the double-blinded treatment period, body weight increase ≥15% from baseline were observed in 3.8% of patients treated with satralizumab (monotherapy or in combination with IST) as compared with 2.7% of patients receiving placebo (or plus IST).
In the double-blinded treatment period, decreased neutrophils were observed in 31.7% of patients treated with satralizumab (monotherapy or in combination with IST) as compared with 21.6% of patients receiving placebo (or placebo plus IST). The majority of neutrophil decreases were transient or intermittent. 9.6% of patients receiving satralizumab had neutrophils below 1 × 109/L, compared with 5.4% receiving placebo (or placebo plus IST).
In the double-blinded treatment period, decreases in platelet count (below 150 × 109/l) occurred in 24.0% of patients on satralizumab (monotherapy or in combination with IST) as compared with 9.5% of patients receiving placebo or placebo plus IST. The decreased platelet count was not associated with bleeding events. The majority of the decreased platelets were transient and not below 75 × 109/l.
In the double-blinded treatment period, elevations in ALT or AST occurred in 27.9% and 18.3% of patients treated with satralizumab (monotherapy or in combination with IST) respectively, compared with 12.2% and 13.5% of patients receiving placebo or placebo plus IST. The majority of the elevations were below 3 x ULN, were transient and resolved without interruption of satralizumab.
Elevations in ALT or AST >3 x ULN occurred in 2.9% and 1.9% of patients treated with satralizumab (monotherapy or in combination with IST) respectively. These elevations were not associated with increases in total bilirubin.
Elevations of ALT above 5 x ULN were observed 4 weeks after initiation of therapy in one (1%) patient receiving satralizumab in combination with IST; normalising after discontinuation of treatment, and satralizumab was not reintroduced in this patient (see sections 4.2 and 4.4).
In the double-blinded treatment period, 10.6% of patients receiving satralizumab (monotherapy or in combination with IST) experienced elevations in total cholesterol above 7.75 mmol/l as compared with 1.4% of patients receiving placebo (or placebo plus IST); 20.2% of patients receiving satralizumab experienced elevations in triglycerides above 3.42 mmol/l as compared with 10.8% of patients receiving placebo.
The safety and efficacy of satralizumab have been studied in 9 children ≥12 years of age. Frequency, type and severity of adverse reactions in children from 12 years of age are expected to be the same as in adults.
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.
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