Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Infusion-associated reactions
Patients treated with Aldurazyme may develop infusion-associated reactions (IARs), defined as any related adverse event occurring during the infusion or until the end of the infusion day (see section 4.8). Some of these IARs may be severe (see below).

Patients treated with Aldurazyme should be closely monitored and all cases of infusion-associated reactions, delayed reactions and possible immunological reactions reported. Antibody status should be regularly monitored and reported.

Severe IAR have been reported in patients with pre-existent severe underlying upper airway involvement and therefore specifically these patients should continue to be closely monitored and only be infused with Aldurazyme in an appropriate clinical setting where resuscitation equipment to manage medical emergencies would be readily available.

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.

Based on the Phase 3 clinical trial, almost all patients are expected to develop IgG antibodies to laronidase, mostly within 3 months of initiation of treatment.
Patients who have developed antibodies or symptoms of IARs should be treated with caution when administering Aldurazyme (see sections 4.3 and 4.8).
In clinical studies IARs were usually manageable by slowing the rate of infusion and by (pre-) treating the patient with antihistamines and/or antipyretics (paracetamol or ibuprofen), thus enabling the patient to continue treatment.

As there is little experience on resumption of treatment following prolonged interruption, use caution due to the theoretical increased risk of hypersensitivity reaction after treatment interruption.

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.



In case of a mild or moderate IAR, treatment with antihistamines and paracetamol/ibuprofen should be considered and/or a reduction in the infusion rate to half the infusion rate at which the reaction occurred.
In case of a single severe IAR, the infusion should be stopped until the symptoms are resolved and treatment with antihistamines and paracetamol/ibuprofen should be considered. The infusion can be restarted with a reduction of the infusion rate to 1/2 – 1/4 the rate of the infusion at which the reaction occurred.
In case of a recurrent moderate IAR or re-challenge after a single severe IAR, pre-treatment should be considered (antihistamines and paracetamol/ibuprofen and/or corticosteroids) and a reduction of the infusion rate to 1/2 – 1/4 the rate of the infusion at which the previous reaction occurred.

As with any intravenous protein product, severe allergic-type hypersensitivity reactions are possible.
If these reactions occur, immediate discontinuation of Aldurazyme is recommended and appropriate medical treatment should be initiated. The current medical standards for emergency treatment are to be observed.

Excipients
This medicinal product contains 30 mg sodium per vial, equivalent to 1.5% of the WHO recommended maximum daily intake of 2 g sodium for an adult, and is administered in 0.9% sodium chloride intravenous solution (see section 6.6).

Traceability
In order to improve the traceability of biological medicinal products, the name of the administered product should be clearly recorded. It is recommended to record the batch number as well.

Effects on Driving

4.7   Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.