Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Management of compromised airways
Caution must be exercised in the management and treatment of patients with compromised airways by limitation or careful monitoring of antihistamine and other sedative medicinal product use. Institution of positive–airway pressure during sleep as well as potential tracheostomy in clinically appropriate situations should also be considered.

Patients who present with an acute febrile or respiratory illness may need to have their Naglazyme infusions delayed.


Management of infusion-associated reactions
Patients treated with Naglazyme have developed infusion-associated reactions (IARs), defined as any adverse reactions occurring during the infusion or until the end of the infusion day (see section 4.8).

Based on data obtained during Naglazyme clinical trials, the majority of patients are expected to develop IgG antibodies to galsulfase within 4-8 weeks of treatment initiation.

In the Naglazyme clinical trials, IARs were usually manageable by interrupting or slowing the rate of infusion and by (pre-) treating the patient with antihistamines and/or antipyretics (paracetamol), thus enabling the patient to continue treatment.

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

With administration of Naglazyme it is recommended that patients be administered pre-treatment medicinal products (antihistamines with or without antipyretics) approximately 30-60 minutes prior to the start of the infusion, to minimise the potential occurrence of IARs.

In case of a mild or moderate IAR, treatment with antihistamines and paracetamol should be considered and/or a reduction in the infusion rate to half the 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 should be considered. The infusion can be restarted with a reduction of the infusion rate to 50% – 25% of the rate 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 and/or corticosteroids) and a reduction of the infusion rate to 50% – 25% of the rate at which the previous reaction occurred.

As with any intravenous protein medicinal product, severe allergic-type hypersensitivity reactions are possible. If these reactions occur, immediate discontinuation of Naglazyme is recommended and appropriate medical treatment should be initiated. The current medical standards for emergency treatment are to be observed. In patients who have experienced allergic reactions during infusion with Naglazyme, caution should be exercised upon rechallenge; appropriately trained personnel and equipment for emergency resuscitation (including epinephrine) should be available during infusions.
Severe, or potentially life-threatening hypersensitivity is a contraindication to rechallenge, if hypersensitivity is not controllable. See also section 4.3.

Spinal or cervical cord compression
Spinal/cervical cord compression (SCC) with resultant myelopathy is a known and serious complication that can be due to MPS VI. There have been post-marketing reports of patients treated with Naglazyme who experienced the onset or worsening of SCC requiring decompression surgery.
Patients should be monitored for signs and symptoms of spinal/cervical cord compression (including back pain, paralysis of limbs below the level of compression, urinary and faecal incontinence) and given appropriate clinical care.

Risk of Acute Cardio-respiratory Failure

Caution should be exercised when administering Naglazyme to patients susceptible to fluid volume overload; such as in patients weighing 20 kg or less, patients with acute underlying respiratory illness, or patients with compromised cardiac and/or respiratory function, because congestive heart failure may occur. Appropriate medical support and monitoring measures should be readily available during Naglazyme infusion, and some patients may require prolonged observation times that should be based on the individual needs of the patient (see section 4.2).

Immune-mediated Reactions
Type III immune complex-mediated reactions including membranous glomerulonephritis have been observed with Naglazyme. If immune-mediated reactions occur, discontinuation of the administration of Naglazyme should be considered, and appropriate medical treatment initiated. The risks and benefits of re-administering Naglazyme following an immune-mediated reaction should be considered (see section 4.2).

Sodium restricted diet

This medicinal product contains 0.8 mmol (18.4 mg) sodium per vial and is administered in sodium chloride 9 mg/ml solution for injection (see section 6.6). To be taken into consideration by patients on a controlled sodium diet.

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.