Satralizumab interacts in the following cases:
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.
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.
The safety and efficacy of satralizumab have not been studied in patients with hepatic impairment. No data are available. Elevations of liver enzymes have been observed during treatment with satralizumab.
The safety and efficacy of satralizumab have not been formally studied in patients with renal impairment. No dose adjustment is recommended for patients with mild renal impairment.
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.
Administration of satralizumab should be delayed in patients with an active infection until the infection is controlled.
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.
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. As a precautionary measure, it is preferable to avoid the use of satralizumab 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 satralizumab could be considered during breast-feeding only if clinically needed.
Carcinogenicity studies of satralizumab-mwge were not conducted.
Genetic toxicology studies of satralizumab-mwge were not conducted. As an antibody, satralizumab-mwge is not expected to interact directly with DNA.
No clinical data are available on the effect of satralizumab on human fertility. Animal studies showed no impairment of male or female fertility.
Satralizumab 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%).
The following table 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 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).
| 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.
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.
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