Aldurazyme

HOS-093586 · has-adverse-reaction-information · PDF-Seite 6

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. 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. 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, re

Auszug; vollständigen Abschnitt im Original lesen.

HOS-093582 · has-contraindication-information · PDF-Seite 3

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).

HOS-093581 · has-indication-information · PDF-Seite 2

Aldurazyme is indicated for long-term enzyme replacement therapy in patients with a confirmed diagnosis of Mucopolysaccharidosis I (MPS I; α-L-iduronidase deficiency) to treat the non- neurological manifestations of the disease (see section 5.1).

HOS-093584 · has-interaction-information · PDF-Seite 5

No interaction studies have been performed. Based on its metabolism, laronidase is an unlikely candidate for Cytochrome P450 mediated interactions. Aldurazyme should not be administered simultaneously with chloroquine or procaine due to a potential risk of interference with the intracellular uptake of laronidase.

HOS-093585 · has-pregnancy-information · PDF-Seite 5

Pregnancy There are inadequate data on the use of Aldurazyme in pregnant women. Animal studies do not indicate direct or indirect harmful effects on pregnancy, embryonal/foetal development, parturition and postnatal development (see section 5.3). The potential risk for humans is unknown. Therefore Aldurazyme should not be used during pregnancy unless clearly necessary. Breast-feeding Laronidase may be excreted in milk. Because there are no data available in neonates exposed to laronidase via breast milk, it is recommended to stop breast-feeding during Aldurazyme treatment. Fertility There are no clinical data on the effects of laronidase on fertility. Preclinical data did not reveal any significant adverse finding (see section 5.3).

HOS-093583 · has-warning-information · PDF-Seite 3

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. 3 Hypersensitivity reactions (including anaphylaxis) Hypersensitivity reactions, including anaphylaxis have been reported in patients treated with Aldurazyme (see section 4.8). Some of these reactions were life threatening and included respiratory failure/distress, stridor, obstructive airways disorder, hypoxia, hypotension, bradycardia, and urticaria. Appropriate medical support measures, including cardiopulmonary resuscitation equipment should be readily available when Aldurazyme is administered. If anaphylaxis or other severe hypersensitivity reactions occur, the infusion of Aldurazyme should be discontinued immediately. Caution should be exercised if epinephrine is being considered for use in patients with MPS I due to the increased prevalence of coronary artery disease in these patients. In patients with severe hypersensitivity, desensitization procedure to Aldurazyme may be considered. If the decision is made to re-administer the product, extreme care should be exercised, with appropriate resuscitation measures available. If mild or moderate hypersensitivity reactions occur, the infusion rate may be slowed or temporarily stopped. Once a patient tolerates the infusion, the dose may be increased to reach the approved dose. Infusion-associated reactions (IARs) IARs, defined as any related adverse event occurring during the infusion or until the end of the infusion day were reported in patients treated with Aldurazyme (see section 4.8). Patients with an acute underlying illness at the time of Aldurazyme infusion appear to be at greater risk for IARs. Careful consideration should be given to the patient’s clinical status prior to administration of Aldurazyme. With initial administration of Aldurazyme or upon re-administration following interruption of treatment, it is recommended that patients be administered pre-treatment medicines (antihistamines and/or antipyretics) approximately 60 minutes prior to the start of the infusion, to minimise the potential occurrence of IARs. If clinically indicated, administration of pre-treatment medications with subsequent infusions of Aldurazyme should be considered. As there is little experience on resumption of treatment following prolonged interruption, use caution due to the theoretical

Auszug; vollständigen Abschnitt im Original lesen.