Agalsidase Beta

Registered South African indications:

• Fabry disease

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
  - Life-threatening (anaphylactic reaction)

Cautions

• Pregnancy
• Breastfeeding
• Hepatic impairment
• Elderly
• Advanced renal disease
• Little or no residual enzyme activity
• Antibodies to r-hαGAL
• May impair ability to drive and operate machinery

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

Fabry disease (α-galactosidase A deficiency) 

• IV: 1mg/kg, as an infusion, administered once every 2 weeks

The initial infusion rate should be no more than 0.25mg/min (15mg/hr) to minimise the potential occurrence of infusion-associated reactions. After patient tolerance is established, the infusion rate may be increased gradually with subsequent infusions

Infusion of agalsidase beta at home may be considered for patients who are tolerating their infusions well. The decision to have a patient move to home infusion should be made after evaluation and recommendation by the treating physician

Patients experiencing adverse events during the home infusion need to immediately stop the infusion process and seek the attention of a healthcare professional. Subsequent infusions may need to occur in a clinical setting. Dose and infusion rate should remain constant while at home, and not be changed without supervision of a healthcare professional

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

Fabry disease (α-galactosidase A deficiency) 

Younger than 8 years

• Not established for use

Between 8-16 years

• See adult dosage

Pregnancy

• Caution; not recommended
• There are no adequate data from the use of agalsidase beta in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to embryonal/ foetal development
• Agalsidase beta should not be used during pregnancy unless clearly necessary

Breastfeeding

• Caution; not recommended
• Agalsidase beta may be excreted in milk. Because there are no data available on effects in neonates exposed to agalsidase beta via breast milk, it is recommended to stop breastfeeding when agalsidase beta is used

Fertility

• Studies have not been conducted to assess the potential effects of agalsidase beta on impairment of fertility

Renal Impairment

• No dose adjustment recommended
  The effect of agalsidase beta treatment on the kidneys may be limited in patients with advanced renal disease

Hepatic Impairment

• Caution; no information available

Elderly

• Caution; no information available
  The safety and efficacy of agalsidase beta in patients >65 years have not been established and no dosage regimen can presently be recommended in these patients

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Paraesthesia
• Dizziness
• Somnolence
• Hypoaesthesia
• Lethargy
• Syncope
• Hyperaesthesia
• Tremor
• Fatigue

Cardiovascular Disorders

• Tachycardia
• Palpitations
• Bradycardia
• Sinus bradycardia
• Flushing
• Hypertension
• Pallor
• Hypotension
• Hot flush
• Peripheral coldness
• Chest discomfort/ pain

Respiratory Disorders

• Hypoxia (decreased oxygen saturation)
• Nasopharyngitis
• Rhinitis
• Dyspnoea
• Nasal congestion
• Throat tightness
• Wheezing
• Cough
• Exacerbated dyspnoea
• Bronchospasm
• Pharyngolaryngeal pain
• Rhinorrhoea
• Tachypnoea
• Upper respiratory tract congestion

Gastrointestinal Disorders

• Nausea and vomiting
• Abdominal pain
  - Upper abdominal pain
• Abdominal discomfort
• Stomach discomfort
• Oral hypoaesthesia
• Diarrhoea
• Dyspepsia
• Dysphagia

Endocrine and Metabolic Disorders

• Chills
• Hyperthermia

Musculoskeletal Disorders

• Pain in extremity
• Myalgia
• Back pain
• Muscle spasms
• Arthralgia
• Muscle tightness
• Musculoskeletal stiffness
• Musculoskeletal pain

Skin and Subcutaneous Tissue Disorders

• Burning sensation
• Pruritus
• Urticaria
• Rash
• Erythema
• Generalised pruritus
• Swelling face
• Rash maculopapular
• Livedo reticularis
• Erythematous rash
• Pruritic rash
• Skin discolouration
• Skin discomfort
• Leukocytoclastic vasculitis
• Face oedema
• Infusion site
  - Pain
  - Reaction
  - Thrombosis

Immune, Blood and Lymphatic System Disorders

• Anaphylactoid reaction
• Fever
• Oedema
  - Peripheral oedema
• Angioneurotic oedema
• Influenza-like illness
• Immunogenicity
• Formation of IgG antibodies

Sensory Disorders

• Increased lacrimation
• Eye pruritus
• Ocular hyperaemia
• Tinnitus
• Vertigo
• Auricular swelling
• Ear pain

Others

• Feeling cold
• Feeling hot
• Pain

• Chloroquine
• Amiodarone
• Benoquin
• Gentamicin

• Antibody status

Additional observations

• Development of IgG or IgE antibodies in patients with suspected allergic reactions
• Infusion-related reactions

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

Infusion-associated reactions

• Patients with antibodies to r-hαGAL have a greater potential to experience infusion-associated reactions (IARs), which are defined as any related adverse event occurring on the infusion day. These patients should be treated with caution when re-administering agalsidase beta. Antibody status should be regularly monitored
• Patients experiencing mild or moderate infusion-associated reactions when treated with agalsidase beta during clinical trials have continued therapy after a reduction in the infusion rate (~0.15mg/min; 10mg/hr) and/or pre-treatment with antihistamines, paracetamol, ibuprofen and/or corticosteroids

Agalsidase beta is used in the treatment of Fabry disease. Fabry disease is an inherited heterogeneous and multisystemic progressive disease, that affects both males and females. It is characterised by the deficiency of α-galactosidase. Reduced or absent α-galactosidase activity results in the presence of elevated concentrations of GL-3 and its associated soluble form lyso-GL-3 in plasma and in accumulation of GL-3 in the lysosomes of many cell types including the endothelial and parenchymal cells, ultimately leading to life-threatening clinical deteriorations as a result of renal, cardiac and cerebrovascular complications.

The rationale for enzyme replacement therapy is to restore a level of enzymatic activity sufficient to clear the accumulating substrate in the organ tissues; thereby, preventing, stabilizing or reversing the progressive decline in function of these organs before irreversible damage has occurred. After intravenous infusion, agalsidase beta is rapidly removed from the circulation and taken up by vascular endothelial and parenchymal cells into lysosomes, likely through the mannose-6 phosphate, mannose and asialoglycoprotein receptors.

Injection (per vial) 5mg

• Fabrazyme 5mg (Sanofi) originator

Injection (per vial) 35mg

• Fabrazyme 35mg (Sanofi) originator