Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: UCB Pharma S.A., Allée de la Recherche 60, B-1070 Bruxelles, Belgium
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Patients who are not currently vaccinated against Neisseria meningitidis (see section 4.4).
Patients with unresolved Neisseria meningitidis infection.
Due to its mechanism of action, the use of zilucoplan may increase the patient’s susceptibility to infections with Neisseria meningitidis. As a precautionary measure, all patients must be vaccinated against meningococcal infections, at least 2 weeks prior to the start of treatment.
If treatment needs to start less than 2 weeks after vaccination against meningococcal infections, the patient must receive appropriate prophylactic antibiotic treatment until 2 weeks after the first vaccination dose. Meningococcal vaccines reduce but do not completely eliminate the risk of meningococcal infections.
Vaccines against serogroups A, C, Y, W, and where available, serogroup B, are recommended for preventing the commonly pathogenic meningococcal serogroups. Vaccination and prophylactic antibiotic treatment should occur according to most current relevant guidelines.
During treatment, patients should be monitored for signs and symptoms of meningococcal infection and evaluated immediately if infection is suspected. In case of a suspected meningococcal infection, appropriate measures such as treatment with antibiotics and discontinuation of treatment, should be taken until the meningococcal infection can be ruled out. Patients should be instructed to seek immediate medical advice if signs or symptoms of meningococcal infections occur.
Prescribers should be familiar with the educational materials for the management of meningococcal infections and provide a patient alert card and patient/carer guide to patients treated with zilucoplan.
In addition to Neisseria meningitidis, patients treated with zilucoplan may also be susceptible to infections with other Neisseria species, such as gonococcal infections. Patients should be informed on the importance of gonorrhea prevention and treatment.
Prior to initiating zilucoplan therapy, it is recommended that patients initiate immunizations according to current immunization guidelines.
This medicinal product contains less than 1 mmol sodium (23 mg) per pre-filled syringe, that is to say essentially ‘sodium-free’.
No interaction studies have been performed. Based on results from in vitro testing, zilucoplan will not inhibit or induce drug metabolising enzymes (CYPs and UGTs) and common transporters in a clinically relevant manner.
Based on the potential inhibitory effect of zilucoplan on complement-dependent cytotoxicity of rituximab, zilucoplan may reduce the expected pharmacodynamic effects of rituximab.
There are no data from the use of zilucoplan in pregnant women.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).
Treatment of pregnant women with Zilbrysq should only be considered if the clinical benefit outweighs the risks.
It is unknown whether zilucoplan is excreted in human milk or absorbed systemically after oral ingestion by the newborns/infants. A risk to the newborns/infants cannot be excluded.
A decision must be made whether to discontinue breast-feeding or to discontinue zilucoplan therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
The effect of zilucoplan on human fertility has not been evaluated. In some non-human primate fertility and repeat-dose toxicity studies, findings of uncertain clinical relevance were observed in male and female reproductive organs (see section 5.3).
Zilbrysq has no or negligible influence on the ability to drive and use machines.
The most frequently reported adverse reactions were injection site reactions (injection site bruising (13.9%) and injection site pain (7.0%)) and upper respiratory tract infections (nasopharyngitis (5.2%), upper respiratory tract infection (3.5%) and sinusitis (3.5%)).
Table 2 presents the adverse reactions from the pooled placebo-controlled (n=115) and open-label extension (n=213) studies in gMG together with a classification of the frequency in the zilucoplan treated patients, 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), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
Table 2. Adverse reactions:
| System organ class | Frequency | Adverse reaction |
|---|---|---|
| Infections and infestations | Very common | Upper respiratory tract infections* |
| Gastrointestinal disorders | Common | Diarrhoea |
| General disorders and administration site conditions | Very common | Injection site reactions* |
| Investigations | Common | Lipase increased* |
| Common | Amylase increased* | |
| Uncommon | Blood eosinophils increased* | |
| Skin and subcutaneous tissue disorders | Common | Morphoeaa* |
* See paragraph Description of selected adverse reactions.
a Morphoea was reported only in long-term open-label clinical studies. The maximum duration of exposure to ZLP during the long-term clinical studies was more than 4 years.
The most common reactions were injection site bruising, pain, nodule, pruritus and haematoma. All cases were mild or moderate in severity, and less than 3% of reactions led to treatment discontinuation.
The most common infections were nasopharyngitis, upper respiratory tract infection and sinusitis. More than 95% of the cases were mild or moderate in severity and did not lead to treatment discontinuation. In pooled placebo-controlled studies, upper respiratory tract infections were reported in 13.0% of patients treated with zilucoplan and in 7.8% of patients treated with placebo.
Cases of lipase increase (5.2%) and/or amylase increase (6.1%) were observed. These elevations were transient and rarely led to treatment discontinuation. The majority occurred within 2 months of starting zilucoplan and normalized within 2 months.
Elevations of blood eosinophils were observed. These were transient and not leading to treatment discontinuation. The majority occurred within 2 months of starting zilucoplan and normalized within 1 month.
Cases of morphoea were observed after long-term treatment during the open-label extension study. The majority of the cases had a time to onset longer than one year after start of treatment, were mild or moderate in severity and did not lead to treatment discontinuation.
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.
Not applicable.
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