Dupixent · 4.8 Undesirable effects · 2

HOS-098193 · has-adverse-reaction-information · PDF-Seite 10

Summary of the safety profile The most common adverse reactions in atopic dermatitis, asthma, and CRSwNP are injection site reactions (includes erythema, oedema, pruritus, pain, and swelling), conjunctivitis, conjunctivitis allergic, arthralgia, oral herpes, and eosinophilia. An additional adverse reaction of injection site bruising or haematoma was reported in EoE,COPD and CSU. Additional adverse reactions of injection site induration and injection site dermatitis were reported in COPD and CSU. Additional adverse reactions of injection site rash were reported in COPD. Rare cases of serum sickness, serum sickness- like reaction, anaphylactic reaction, and ulcerative keratitis have been reported (see section 4.4). Tabulated list of adverse reactions The dupilumab safety data presented in Table 8 were predominantly derived from 12 randomised, placebo-controlled trials, including atopic dermatitis, asthma, and CRSwNP patients. These studies involved 4,206 patients receiving dupilumab and 2,326 patients receiving placebo during the controlled period are representative of the overall safety profile for dupilumab. 10 Listed in Table 8 are adverse reactions observed in clinical trials and/or postmarketing setting presented by system organ class and frequency, using the following categories: 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 order of decreasing seriousness. Table 8: List of adverse reactions MedDRA System Frequency Adverse Reaction Organ Class Infections and Common Conjunctivitis* infestations Oral herpes* Blood and lymphatic Common Eosinophilia system disorders Immune system Uncommon Angioedema# disorders Rare Anaphylactic reaction Serum sickness reaction Serum sickness-like reaction Eye disorders Common Conjunctivitis allergic* Uncommon Keratitis*# Blepharitis*† Eye pruritus*†

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HOS-098199 · has-adverse-reaction-information · PDF-Seite 72

Summary of the safety profile The most common adverse reactions in atopic dermatitis, asthma, and CRSwNP are injection site reactions (includes erythema, oedema, pruritus, pain and swelling), conjunctivitis, conjunctivitis allergic, arthralgia, oral herpes, and eosinophilia. An additional adverse reaction of injection site bruising or haematoma was reported in EoE, COPD and CSU. Additional adverse reactions of injection site induration and injection site dermatitis were reported in COPD and CSU. Additional adverse reactions of injection site rash were reported in COPD.Rare cases of serum sickness, serum sickness-like reaction, anaphylactic reaction, and ulcerative keratitis have been reported (see section 4.4). Tabulated list of adverse reactions The dupilumab safety data presented in Table 8 were predominantly derived from 12 randomised, placebo-controlled trials, including atopic dermatitis, asthma, and CRSwNP patients. These studies involved 4,206 patients receiving dupilumab and 2,326 patients receiving placebo during the controlled period are representative of the overall safety profile for dupilumab. Listed in Table 8 are adverse reactions observed in clinical trials and/or postmarketing setting presented by system organ class and frequency, using the following categories: 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 72 rare (< 1/10 000); not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Table 8: List of adverse reactions MedDRA System Frequency Adverse Reaction Organ Class Infections and Common Conjunctivitis* infestations Oral herpes* Blood and lymphatic Common Eosinophilia system disorders Immune system Uncommon Angioedema# disorders Rare Anaphylactic reaction Serum sickness reaction Serum sickness-like reaction Eye disorders Common Conjunctivitis allergic* Uncommon Keratitis*# Blepharitis*† Eye pruritus*†

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HOS-098195 · has-contraindication-information · PDF-Seite 70

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-098189 · has-contraindication-information · PDF-Seite 8

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-098194 · has-indication-information · PDF-Seite 65

Atopic dermatitis Adults and adolescents Dupixent is indicated for the treatment of moderate-to-severe atopic dermatitis in adults and adolescents 12 years and older who are candidates for systemic therapy. Children 6 months to 11 years of age Dupixent is indicated for the treatment of severe atopic dermatitis in children 6 months to 11 years old who are candidates for systemic therapy. Asthma Adults and adolescents Dupixent is indicated in adults and adolescents 12 years and older as add-on maintenance treatment for severe asthma with type 2 inflammation characterised by raised blood eosinophils and/or raised fraction of exhaled nitric oxide (FeNO), see section 5.1, who are inadequately controlled with high dose inhaled corticosteroids (ICS) plus another medicinal product for maintenance treatment. Children 6 to 11 years of age 65 Dupixent is indicated in children 6 to 11 years old as add-on maintenance treatment for severe asthma with type 2 inflammation characterised by raised blood eosinophils and/or raised fraction of exhaled nitric oxide (FeNO), see section 5.1, who are inadequately controlled with medium to high dose inhaled corticosteroids (ICS) plus another medicinal product for maintenance treatment. Eosinophilic esophagitis (EoE) Dupixent is indicated for the treatment of eosinophilic esophagitis in adults, adolescents and children aged 1 year and older, weighing at least 15 kg, who are inadequately controlled by, are intolerant to, or who are not candidates for conventional medicinal therapy (see section 5.1).Error! No document variable supplied. Chronic Spontaneous Urticaria (CSU) Dupixent is indicated for the treatment of moderate to severe chronic spontaneous urticaria in adults, adolescents, and children (2 years and above) with inadequate response to H1 antihistamines and who are naive to anti-IgE therapy for CSU.

HOS-098188 · has-indication-information · PDF-Seite 2

Atopic dermatitis Adults and adolescents Dupixent is indicated for the treatment of moderate-to-severe atopic dermatitis in adults and adolescents 12 years and older who are candidates for systemic therapy. Children 6 months to 11 years of age Dupixent is indicated for the treatment of severe atopic dermatitis in children 6 months to 11 years old who are candidates for systemic therapy. Asthma Adults and adolescents Dupixent is indicated in adults and adolescents 12 years and older as add-on maintenance treatment for severe asthma with type 2 inflammation characterised by raised blood eosinophils and/or raised fraction of exhaled nitric oxide (FeNO), see section 5.1, who are inadequately controlled with high dose inhaled corticosteroids (ICS) plus another medicinal product for maintenance treatment. 2 Children 6 to 11 years of age Dupixent is indicated in children 6 to 11 years old as add-on maintenance treatment for severe asthma with type 2 inflammation characterised by raised blood eosinophils and/or raised fraction of exhaled nitric oxide (FeNO), see section 5.1, who are inadequately controlled with medium to high dose inhaled corticosteroids (ICS) plus another medicinal product for maintenance treatment. Chronic rhinosinusitis with nasal polyposis (CRSwNP) Dupixent is indicated as an add-on therapy with intranasal corticosteroids for the treatment of adults with severe CRSwNP for whom therapy with systemic corticosteroids and/or surgery do not provide adequate disease control. Prurigo Nodularis (PN) Dupixent is indicated for the treatment of adults with moderate-to-severe prurigo nodularis (PN) who are candidates for systemic therapy. Eosinophilic esophagitis (EoE) Dupixent is indicated for the treatment of eosinophilic esophagitis in adults, adolescents and children aged 1 year and older, weighing at least 15 kg, who are inadequately controlled by, are intolerant to, or who are not candidates for conventional medicinal therapy (see section 5.1). Chronic obstructive pulmonary disease (COPD) Dupixent is indicated in adults as add-on maintenance treatment for uncontrolled chronic obstructive pulmonary disease (COPD) characterised by raised blood eosinophils on a combination of an inhaled corticosteroid (ICS), a long-acting beta2-agonist (LABA), and a long-acting muscarinic antagonist (LAMA), or on a combination of a LABA and a LAMA if ICS is not appropriate (see Section 5.1). Chronic Sp

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HOS-098197 · has-interaction-information · PDF-Seite 71

Immune responses to vaccination were assessed in a study in which patients with atopic dermatitis were treated once weekly for 16 weeks with 300 mg of dupilumab. After 12 weeks of dupilumab administration, patients were vaccinated with a Tdap vaccine (T cell-dependent), and a meningococcal polysaccharide vaccine (T cell-independent) and immune responses were assessed 4 weeks later. Antibody responses to both tetanus vaccine and meningococcal polysaccharide vaccine were similar in dupilumab-treated and placebo-treated patients. No adverse interactions between either of the non-live vaccines and dupilumab were noted in the study. 71 Therefore, patients receiving dupilumab may receive concurrent inactivated or non-live vaccinations. For information on live vaccines see section 4.4. In a clinical study of atopic dermatitis patients, the effects of dupilumab on the pharmacokinetics (PK) of CYP substrates were evaluated. The data gathered from this study did not indicate clinically relevant effects of dupilumab on CYP1A2, CYP3A, CYP2C19, CYP2D6, or CYP2C9 activity. An effect of dupilumab on the PK of co-administered medicinal products is not expected. Based on the population analysis, commonly co-administered medicinal products had no effect on dupilumab pharmacokinetics on patients with moderate to severe asthma.

HOS-098191 · has-interaction-information · PDF-Seite 9

Immune responses to vaccination were assessed in a study in which patients with atopic dermatitis were treated once weekly for 16 weeks with 300 mg of dupilumab. After 12 weeks of dupilumab administration, patients were vaccinated with a Tdap vaccine (T cell-dependent), and a meningococcal polysaccharide vaccine (T cell-independent) and immune responses were assessed 4 weeks later. Antibody responses to both tetanus vaccine and meningococcal polysaccharide vaccine were similar in 9 dupilumab-treated and placebo-treated patients. No adverse interactions between either of the non-live vaccines and dupilumab were noted in the study. Therefore, patients receiving dupilumab may receive concurrent inactivated or non-live vaccinations. For information on live vaccines see section 4.4. In a clinical study of atopic dermatitis patients, the effects of dupilumab on the pharmacokinetics (PK) of CYP substrates were evaluated. The data gathered from this study did not indicate clinically relevant effects of dupilumab on CYP1A2, CYP3A, CYP2C19, CYP2D6, or CYP2C9 activity. An effect of dupilumab on the PK of co-administered medicinal products is not expected. Based on the population analysis, commonly co-administered medicinal products had no effect on dupilumab pharmacokinetics on patients with moderate to severe asthma.

HOS-098198 · has-pregnancy-information · PDF-Seite 72

Pregnancy There is a limited amount of data from the use of dupilumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). Dupilumab should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. Breast-feeding It is unknown whether dupilumab is excreted in human milk or absorbed systemically after ingestion. A decision must be made whether to discontinue breast-feeding or to discontinue dupilumab therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. Fertility Animal studies showed no impairment of fertility (see section 5.3).

HOS-098192 · has-pregnancy-information · PDF-Seite 10

Pregnancy There is a limited amount of data from the use of dupilumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). Dupilumab should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. Breast-feeding It is unknown whether dupilumab is excreted in human milk or absorbed systemically after ingestion. A decision must be made whether to discontinue breast-feeding or to discontinue dupilumab therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. Fertility Animal studies showed no impairment of fertility (see section 5.3).

HOS-098196 · has-warning-information · PDF-Seite 70

Traceability 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 exacerbations of Asthma or COPD Dupilumab must not be used to treat acute symptoms or acute exacerbations of asthma or COPD. Dupilumab must not be used to treat acute bronchospasm or status asthmaticus. Corticosteroids It is recommended that systemic, topical, or inhaled corticosteroids not be discontinued abruptly upon initiation of therapy with dupilumab. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy. Biomarkers of type 2 inflammation may be suppressed by systemic corticosteroid use. This should be taken into consideration to determine type 2 status in patients taking oral corticosteroids (see section 5.1). Hypersensitivity If a systemic hypersensitivity reaction (immediate or delayed) occurs, discontinue administration of dupilumab immediately and initiate appropriate therapy. Cases of anaphylactic reaction, angioedema, and serum sickness/serum sickness-like reaction have been reported. Anaphylactic reactions and angioedema have occurred from minutes to up to seven days after the dupilumab injection (see section 4.8). Eosinophilic conditions Cases of eosinophilic pneumonia and cases of vasculitis consistent with eosinophilic granulomatosis with polyangiitis (EGPA) have been reported with dupilumab in adult patients who participated in the asthma development program. Cases of vasculitis consistent with EGPA have been reported with dupilumab and placebo in adult patients with co-morbid asthma in the CRSwNP development program. Physicians should be alert to vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients with eosinophilia. Patients being treated for asthma may present with serious systemic eosinophilia sometimes presenting with clinical features of eosinophilic pneumonia or vasculitis consistent with eosinophilic granulomatosis with polyangiitis, conditions which are often treated with systemic corticosteroid therapy. These events usually, but not always, may be associated with the reduction of oral corticosteroid therapy.

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HOS-098190 · has-warning-information · PDF-Seite 8

Traceability 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 exacerbations of Asthma or COPD Dupilumab must not be used to treat acute symptoms or acute exacerbations of asthma or COPD. Dupilumab must not be used to treat acute bronchospasm or status asthmaticus. Corticosteroids It is recommended that systemic, topical, or inhaled corticosteroids not be discontinued abruptly upon initiation of therapy with dupilumab. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy. Biomarkers of type 2 inflammation may be suppressed by systemic corticosteroid use. This should be taken into consideration to determine type 2 status in patients taking oral corticosteroids (see section 5.1). Hypersensitivity If a systemic hypersensitivity reaction (immediate or delayed) occurs, discontinue administration of dupilumab immediately and initiate appropriate therapy. Cases of anaphylactic reaction, angioedema, and serum sickness/serum sickness-like reaction have been reported. Anaphylactic reactions and angioedema have occurred from minutes to up to seven days after the dupilumab injection (see section 4.8). Eosinophilic conditions Cases of eosinophilic pneumonia and cases of vasculitis consistent with eosinophilic granulomatosis with polyangiitis (EGPA) have been reported with dupilumab in adult patients who participated in the asthma development program. Cases of vasculitis consistent with EGPA have been reported with dupilumab and placebo in adult patients with co-morbid asthma in the CRSwNP development program. Physicians should be alert to vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients with eosinophilia. Patients being treated for asthma may present with serious systemic eosinophilia sometimes presenting with clinical features of eosinophilic pneumonia or vasculitis consistent with eosinophilic granulomatosis with polyangiitis, 8 conditions which are often treated with systemic corticosteroid therapy. These events usually, but not always, may be associated with the reduction of oral cortico

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