Idursulfase

Registered South African indications:

• Hunter syndrome (Mucopolysaccharidosis II, MPS II)

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Preganancy
• Breastfeeding
• Elderly
• Severe underlying airway disease
• Acute febrile respiratory illness
• History of anaphylactoid/anaphylactic reactions
• Complete deletion/large rearrangement genotype
• Patients on a controlled sodium diet

See additional prescribing points

Forms avail. in SA and covered in this monograph: inj

Hunter syndrome (Mucopolysaccharidosis II, MPS II)

• IV: 0.5mg/kg, as an infusion over 3 hours, administered every week

The infusion period may be gradually reduced to 1 hour if no infusion-associated reactions are observed

Infusion of idursulfase at home may be considered for patients who are tolerating their infusions well

Idursulfase treatment should be supervised by a medical practitioner or other healthcare professional experienced in the management of patients with Hunter syndrome (MPS II disease) or other inherited metabolic disorders

Paed. forms avail. in SA and covered in this monograph: inj

Hunter syndrome (Mucopolysaccharidosis II, MPS II)

Younger than 16 months

• Not established for use

Older than 16 months 

• See adult dosage

In patients 16 months to 5 years of age, no data is available to demonstrate improvement in disease-related symptoms or long term clinical outcome; however, treatment with idursulfase has reduced spleen volume similarly to that of adults and children 5 years of age and older

Pregnancy

• Caution
• There are no data or limited amount of data from the use of idursulfase in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of idursulfase during pregnancy

Breastfeeding

• Caution; not recommended
• It is not known whether idursulfase is excreted in human breast milk. Available data in animals have shown excretion of idursulfase in milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from idursulfase therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman

Renal impairment

• No dose adjustment recommended

Hepatic impairment

• No dose adjustment recommended

Elderly

• Caution; no information available

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Dizziness
• Tremor

Cardiovascular Disorders

• Arrhythmia
• Tachycardia
• Hypertension
• Hypotension
• Face oedema
• Peripheral oedema

Respiratory Disorders

• Wheezing
• Dyspnoea
• Hypoxia
• Bronchospasm
• Cough
• Tachypnoea

Gastrointestinal Disorders

• Abdominal pain
• Nausea and vomiting
• Diarrhoea
• Swollen tongue
• Dyspepsia

Musculoskeletal Disorders

• Arthralgia
• Chest pain

Skin and Subcutaneous Tissue Disorders

• Urticaria
• Rash
• Pruritus
• Erythema

Immune, Blood and Lymphatic System Disorders

• Anaphylactoid/ anaphylactic reaction
• Cyanosis
• Flushing
• Pyrexia

Others

• Infusion site swelling
• Infusion-related reaction

No information available

• Infusion-related reactions
• Hypersensitivity reactions
• Pulmonary function
• Oxygen saturation
• Blood pressure

Anaphylactoid/anaphylactic reactions

• Anaphylactoid/anaphylactic reactions, which have the potential to be life threatening, have been observed in some patients treated with idursulfase up to several years after initiating treatment. Late emergent symptoms and signs of anaphylactoid/anaphylactic reactions have been observed as long as 24 hours after an initial reaction. If an anaphylactoid/anaphylactic reaction occurs the infusion should be immediately suspended and appropriate treatment and observation initiated

Patients with the complete deletion/large rearrangement genotype

• Paediatric patients with the complete deletion/large rearrangement genotype have a high probability of developing antibodies, including neutralizing antibodies, in response to exposure to idursulfase. Patients with this genotype have a higher probability of developing infusion-related adverse events and tend to show a muted response as assessed by decrease in urinary output of glycosaminoglycans, liver size and spleen volume compared to patients with the missense genotype. Management of patients must be decided on an individual basis

Administration directions

• Idursulfase is for intravenous infusion and must be diluted in sodium chloride 9 mg/ml (0.9%) solution for infusion prior to use
• Determine the number of vials to be diluted based on the individual patient’s weight and the recommended dose of 0.5mg/kg
• Withdraw the calculated volume of idursulfase from the appropriate number of vials
• Dilute the total volume required of idursulfase in 100ml of 9 mg/ml (0.9%) sodium chloride solution for infusion
• Care must be taken to ensure the sterility of the prepared solutions since idursulfase does not contain any preservative or bacteriostatic agent; aseptic technique must be observed
• Once diluted, the solution should be mixed gently, but not shaken

Idursulfase is a purified form of the lysosomal enzyme iduronate-2-sulfatase, produced in a human cell line providing a human glycosylation profile, which is analogous to the naturally occurring enzyme. Idursulfase is secreted as a 525 amino acid glycoprotein and contains 8 N-linked glycosylation sites that are occupied by complex, hybrid, and high-mannose type oligosaccharide chains. Intravenous idursulfase provides exogenous enzyme for uptake into cellular lysosomes. Mannose-6-phosphate (M6P) residues on the oligosaccharide chains allow specific binding of the enzyme to the M6P receptors on the cell surface, leading to cellular internalization of the enzyme, targeting to intracellular lysosomes and subsequent catabolism of accumulated glycosaminoglycans.

Injection (per ml) 2mg

• Elaprase (Sanofi) Originator