Zilbrysq · 4.1 Therapeutic indications · 1

HOS-099677 · has-adverse-reaction-information · PDF-Seite 18

Summary of the safety profile 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%)). Tabulated list of adverse reactions 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 Skin and subcutaneous tissue Common Morphoea*a disorders General disorders and Very common Injection site reactions* administration site conditions Investigations Common Lipase increased* 18  Common Amylase increased* Uncommon Blood eosinophils increased* * 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. Description of selected adverse reactions Injection site reactions 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. Upper respiratory tract infections The most common infections were nasopharyngitis, upper respiratory tract infection and sinusitis. More than 95% of the cases were mild or mod

Auszug; vollständigen Abschnitt im Original lesen.

HOS-099671 · has-adverse-reaction-information · PDF-Seite 5

Summary of the safety profile 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%)). Tabulated list of adverse reactions 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 Skin and subcutaneous tissue Common Morphoea*a disorders 5  General disorders and Very common Injection site reactions* administration site conditions Investigations Common Lipase increased* Common Amylase increased* Uncommon Blood eosinophils increased* * 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. Description of selected adverse reactions Injection site reactions 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. Upper respiratory tract infections The most common infections were nasopharyngitis, upper respiratory tract infection and sinusitis. More than 95% of the cases were mild or

Auszug; vollständigen Abschnitt im Original lesen.

HOS-099667 · has-contraindication-information · PDF-Seite 3

3 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.

HOS-099673 · has-contraindication-information · PDF-Seite 16

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 16 Patients who are not currently vaccinated against Neisseria meningitidis (see section 4.4). Patients with unresolved Neisseria meningitidis infection.

HOS-099666 · has-indication-information · PDF-Seite 2

Zilbrysq is indicated as an add-on to standard therapy for the treatment of generalised myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.

HOS-099672 · has-indication-information · PDF-Seite 15

Zilbrysq is indicated as an add-on to standard therapy for the treatment of generalised myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.

HOS-099675 · has-interaction-information · PDF-Seite 17

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.

HOS-099669 · has-interaction-information · PDF-Seite 4

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. 4

HOS-099676 · has-pregnancy-information · PDF-Seite 17

17 Pregnancy 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. Breast-feeding 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. Fertility 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).

HOS-099670 · has-pregnancy-information · PDF-Seite 5

Pregnancy 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. Breast-feeding 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. Fertility 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).

HOS-099668 · has-warning-information · PDF-Seite 4

Neisseria infections Meningococcal 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 card and patient/carer guide to patients treated with zilucoplan. Other Neisseria infections 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. Immunization Prior to initiating zilucoplan therapy, it is recommended that patients initiate immunizations according to current immunization guidelines. Sodium content This medicinal product contains less than 1 mmol sodium (23 mg) per pre-filled syringe, that is to say essentially ‘sodium-free’.

HOS-099674 · has-warning-information · PDF-Seite 17

Neisseria infections Meningococcal 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 card and patient/carer guide to patients treated with zilucoplan. Other Neisseria infections 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. Immunization Prior to initiating zilucoplan therapy, it is recommended that patients initiate immunizations according to current immunization guidelines. Sodium content This medicinal product contains less than 1 mmol sodium (23 mg) per pre-filled pen, that is to say essentially ‘sodium-free’.