Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Aldurazyme

Aldurazyme 100 U/ml concentrate for solution for infusion · Abschnitt 4.3 · PDF-Seite 3

HOS-111682 · Präparat HOS-093579

Severe hypersensitivity (e.g. anaphylactic reaction) to the active substance or to any of the excipients listed in section 6.1 (see sections 4.4 and 4.8).

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Wechselwirkungen · Aldurazyme

Aldurazyme 100 U/ml concentrate for solution for infusion · Abschnitt 4.5 · PDF-Seite 5

HOS-111683 · Präparat HOS-093579

No interaction studies have been performed. Based on its metabolism, laronidase is an unlikely candidate for Cytochrome P450 mediated interactions.

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Wechselwirkungen · Aldurazyme

Aldurazyme 100 U/ml concentrate for solution for infusion · Abschnitt 4.5 · PDF-Seite 5

HOS-111684 · Präparat HOS-093579

Aldurazyme should not be administered simultaneously with chloroquine or procaine due to a potential risk of interference with the intracellular uptake of laronidase.

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): procaine (HOS-111685) chloroquine (HOS-109138)

Nebenwirkungen · Aldurazyme

Aldurazyme 100 U/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 6

HOS-111686 · Präparat HOS-093579

Summary of the safety profile The majority of the related adverse events in the clinical trials were classified as infusion-associated reactions (IARs), experienced by 53% of the patients in the Phase 3 study (treated for up to 4 years) and 35% of the patients in the under 5 study (up to 1 year of treatment). Some of the IARs were severe. Over time the number of these reactions decreased. The most frequent adverse drug reactions (ADRs) were: headache, nausea, abdominal pain, rash, arthralgia, backpain, pain at extremity, flushing, pyrexia, infusion site reactions, blood pressure increased, oxygen saturation decreased, tachycardia and chills. Post-marketing experience of infusion-associated reactions revealed reporting of cyanosis, hypoxia, tachypnoea, pyrexia, vomiting, chills and erythema, in which some of these reactions were severe.

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Nebenwirkungen · Aldurazyme

Aldurazyme 100 U/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 6

HOS-111687 · Präparat HOS-093579

Tabulated list of adverse reactions ADRs to Aldurazyme reported during the Phase 3 study and its extension in a total of 45 patients age 5 years and older and treated up to 4 years are listed below using the following categories of frequency: 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) and not known (cannot be estimated from the available data). Due to the small patient population, an ADR reported in a single patient is classified as common.

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Nebenwirkungen · Aldurazyme

Aldurazyme 100 U/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 6–7

HOS-111688 · Präparat HOS-093579

6  MedDRA Very common Common Not known System Organ Class Immune system Anaphylactic reaction Hypersensitivity disorders Psychiatric disorders Restlessness Nervous system Headache Paraesthesia, dizziness disorders Cardiac disorders Tachycardia Bradycardia Vascular disorders Flushing Hypotension, pallor, Hypertension peripheral coldness Respiratory, thoracic Respiratory distress, Cyanosis, hypoxia, and mediastinal dyspnoea, cough tachypnoea, disorders bronchospasm, respiratory arrest, laryngeal oedema, respiratory failure, pharyngeal swelling, stridor, obstructive airways disorder Gastrointestinal Nausea, abdominal pain Vomiting, diarrhoea Lip swelling, swollen disorders tongue Skin and subcutaneous Rash Angioedema, swelling Erythema, facial edema, tissue disorders face, urticaria, pruritus, cold sweat, alopecia, hyperhidrosis Musculoskeletal and Arthropathy, arthralgia, Musculoskeletal pain connective tissue back pain, pain in disorders extremity General disorders and Pyrexia, infusion site Chills, feeling hot, Extravasation, oedema administration site reaction* feeling cold, fatigue, peripheral conditions influenza like illness, injection site pain Investigations Body temperature Drug specific antibody, increased, oxygen neutralizing antibodies, saturation decreased blood pressure increased * During clinical trials and post-marketing experience, infusion/injection site reactions notably included: swelling, erythema, oedema, discomfort, urticaria, pallor, macule, and warmth.

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Nebenwirkungen · Aldurazyme

Aldurazyme 100 U/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 7

HOS-111689 · Präparat HOS-093579

A single patient with pre-existing airway compromise developed a severe reaction three hours from the start of the infusion (at week 62 of treatment) consisting of urticaria and airway obstruction, requiring tracheostomy. This patient tested positive for IgE.

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Nebenwirkungen · Aldurazyme

Aldurazyme 100 U/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 7

HOS-111690 · Präparat HOS-093579

Additionally, a few patients who had a prior history of severe MPS I- related upper airway and pulmonary involvement, experienced severe reactions including bronchospasm, respiratory arrest, and facial oedema (see section 4.4).

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Nebenwirkungen · Aldurazyme

Aldurazyme 100 U/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 7

HOS-111691 · Präparat HOS-093579

Paediatric population ADRs to Aldurazyme reported during a Phase 2 study in a total of 20 patients, under 5 years of age and mainly of the severe phenotype, treated up to 12 months are listed below. ADRs were all mild to moderate in severity.

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Nebenwirkungen · Aldurazyme

Aldurazyme 100 U/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 7–8

HOS-111692 · Präparat HOS-093579

7  MedDRA MedDRA Frequency System Organ Class Preferred term Cardiac disorders tachycardia Very common General disorders and administration site pyrexia Very common conditions chills Very common blood pressure increased Very common Investigations oxygen saturation Very common decreased

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Nebenwirkungen · Aldurazyme

Aldurazyme 100 U/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 8

HOS-111693 · Präparat HOS-093579

In a phase 4 study 33 MPS I patients received 1 of 4 dose regimens: 100 U/kg IV every week (recommended dose), 200 U/kg IV every week, 200 U/kg IV every 2 weeks or 300 U/kg IV every 2 weeks. The recommended dose group had the fewest number of patients who experienced ADRs and IARs. The type of IARs was similar to those seen in other clinical studies.

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Nebenwirkungen · Aldurazyme

Aldurazyme 100 U/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 8

HOS-111694 · Präparat HOS-093579

Description of selected adverse reactions Immunogenicity Almost all patients developed IgG antibodies to laronidase. Most patients seroconverted within 3 months of initiation of treatment; although seroconversion in patients under 5 years old with a more severe phenotype occurred mostly within 1 month (mean 26 days versus 45 days in patients 5 years and older). By the end of the Phase 3 study (or at time of early study withdrawal), 13/45 patients had no detectable antibodies by radioimmunoprecipitation (RIP) assay, including 3 patients that had never seroconverted. Patients with absent to low antibody levels showed a robust reduction in urinary GAG level, whereas patients with high antibody titres showed variable reduction in urinary GAG. In addition, higher ADA titres were also observed in MPS I Registry patients with severe disease. Patients with persistently high ADA titres tended to have less reduction in urinary GAG.

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Nebenwirkungen · Aldurazyme

Aldurazyme 100 U/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 8

HOS-111695 · Präparat HOS-093579

In the Phase 2 and 3 studies, 60 patients were tested for in-vitro neutralising effects. Four patients (three in the Phase 3 study and one in the Phase 2 study) showed marginal to low level in vitro inhibition of laronidase enzymatic activity, which did not appear to impact clinical efficacy and/or urinary GAG reduction.

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Nebenwirkungen · Aldurazyme

Aldurazyme 100 U/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 8

HOS-111696 · Präparat HOS-093579

In patients with clinical decline, assessing urinary GAGs, ADA and neutralising antibodies should be considered.

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Nebenwirkungen · Aldurazyme

Aldurazyme 100 U/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 8

HOS-111697 · Präparat HOS-093579

The presence of antibodies was not consistently related to the incidence of IARs, although the onset of IARs typically coincided with the formation of IgG antibodies. Clinical trials and observational studies show only a small number of patients have tested positive for IgE antibodies. The development of IgE antibodies may be associated with hypersensitivity or anaphylactic reactions.

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Nebenwirkungen · Aldurazyme

Aldurazyme 100 U/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 8

HOS-111698 · Präparat HOS-093579

Reporting of suspected adverse reactions 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.

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