Agalsidase beta parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Parenteral formulations of agalsidase beta.
Agalsidase beta is a recombinant form of alpha-galactosidase A and is produced by recombinant DNA technology using a mammalian Chinese Hamster Ovary (CHO) cell culture. The amino acid sequence of the recombinant enzyme and the nucleotide sequence that encoded it, are identical to the natural form.
Drugs List
Therapeutic Indications
Uses
Enzyme replacement therapy - Fabry disease
Dosage
Treatment should be directed by a physician experienced in the treatment of Fabry disease.
Infusion of agalsidase beta at home may be considered for patients who are tolerating their infusions well, after evaluation and recommendation by the treating physician.
Dose and infusion rate should remain constant while at home, and not being changed without supervision of a healthcare professional.
Patients experiencing adverse events during the home infusion need to immediately stop the infusion process and seek medical attention. Subsequent infusion may need to occur in a clinical setting.
Adults
The recommended dose is 1mg/kg body weight administered once every 2 weeks.
Elderly
Safety and efficacy in patients over 65 years of age have not been established. No dosage regimen can be recommended in these patients at present.
Children
Children aged 8 years and older
The recommended dose is 1mg/kg body weight administered once every 2 weeks.
Administration
For intravenous infusion after reconstitution and dilution.
The initial infusion rate should be not more than 0.25mg/min (15mg/hour). After patient tolerance is well established, the infusion rate may be increased gradually with subsequent infusions.
The manufacturer recommends that the diluted solution be administered through an in-line low protein-binding 0.2 micron filter to remove any protein particles which will not result in a loss of agalsidase beta activity.
Contraindications
Children under 8 years
Precautions and Warnings
Antibodies to agalsidase beta
Patients over 65 years
Breastfeeding
Pregnancy
Advise ability to drive/operate machinery may be affected by side effects
Consider pre-medication with antihistamines and/or antipyretics
Treatment to be initiated and supervised by a specialist
Dilute and use as an infusion
If adverse reactions occur, reduce rate or temporarily stop infusion
Record name and batch number of administered product
Monitor periodically for IgG antibody formation
Discontinue if serious allergic or anaphylactic reaction occurs
It is expected that the majority of patients will develop IgG antibodies to agalsidase beta, typically within three months of the first infusion. Patients with IgG antibodies have a higher risk of infusion-associated hypersensitivity reactions. Patients who have developed infusion-associated reactions should be treated with caution when re-administering the product.
Allergic-type hypersensitivity reactions are possible, as with all intra-venous protein products. Discontinue the infusion immediately in the event of a severe allergic or anaphylactic-type reaction and initiate appropriate treatment in accordance with the current medical standards for emergency treatment. Careful rechallenge of agalsidase beta can be performed at a low dose and low infusion rate. Once the patient tolerates infusion, the dose may be increased to reach therapeutic dose of 1mg/kg and the infusion rate may be increased by slowly titrating upwards as tolerated.
The effect of agalsidase beta treatment on the kidneys of patients with advanced renal disease may be limited.
Pregnancy and Lactation
Pregnancy
Use agalsidase beta with caution during pregnancy.
The manufacturer recommends that agalsidase beta should not be used unless clearly necessary. Reproduction studies in rats have not shown a relation to agalsidase beta and impaired fertility or foetal harm. It is unknown whether agalsidase beta crosses the human placenta, however it's large molecular weight and short elimination half-life suggest that the enzyme may not cross to the foetus. At the time of writing there is no data on the use of agalsidase beta during human pregnancy, however, there has been one case report on the use of agalsidase alfa during pregnancy, resulting in the birth of a healthy male foetus. Briggs (2015), concludes that the animal data on agalsidase beta suggests that it is low risk when used in pregnancy, but the lack of human data prevents a complete foetal risk assessment. Due to the nature of Fabry disease, Briggs (2015) advises that if a pregnant woman requires enzyme replacement therapy and gives consent, agalsidase beta should not be withheld.
Lactation
Use agalsidase beta with caution during breastfeeding.
The manufacturer recommends to stop breastfeeding when agalsidase beta is used as there are no data available on the effects in neonates exposed to agalsidase beta via breast milk. It is not known whether agalsidase beta is excreted in human milk, however, Briggs (2015) concludes that the large molecular weight and short half-life suggest that agalsidase beta may not be excreted into breast milk, and if excreted, may be digested by the nursing infant's gut.
Side Effects
Abdominal discomfort
Abdominal pain
Anaphylactic reaction
Angioneurotic oedema
Antibody formation
Arthralgia
Asthenia
Auricular swelling
Back pain
Bradycardia
Bronchospasm
Burning sensation
Chest discomfort
Chest pain
Chills
Cough
Diarrhoea
Dizziness
Dyspepsia
Dysphagia
Dyspnoea
Ear pain
Erythema
Erythematous rash
Extremity pain
Facial oedema
Facial swelling
Fatigue
Flushing
Headache
Hot flushes
Hyperaesthesia
Hypersensitivity reactions
Hypertension
Hyperthermia
Hypoaesthesia
Hypotension
Hypoxia
Increased lacrimation
Influenza-like symptoms
Infusion-related symptoms
Injection site reactions
Lethargy
Leukocytoclastic vasculitis
Livedo reticularis
Local pain (injection site)
Maculopapular rash
Malaise
Muscle spasm
Muscle tension
Musculoskeletal pain
Myalgia
Nasal congestion
Nasopharyngitis
Nausea
Ocular hyperaemia
Ocular pruritus
Oedema
Oral hypoaesthesia
Oxygen saturation decreased
Pallor
Palpitations
Paraesthesia
Peripheral coldness
Peripheral oedema
Pharyngolaryngeal pain
Pruritus
Pyrexia
Rash
Rhinitis
Rhinorrhoea
Sensation of cold
Sensation of heat
Sinus bradycardia
Skin discolouration
Skin discomfort
Somnolence
Stiffness
Syncope
Tachycardia
Tachypnoea
Throat tightness
Thrombosis (injection site)
Tinnitus
Tremor
Upper respiratory tract congestion
Urticaria
Vertigo
Vomiting
Wheezing
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: July 2021
Reference Sources
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Summary of Product Characteristics: Fabrazyme 5mg, powder for concentrate for solution for infusion. Sanofi Genzyme. Revised July 2021.
Summary of Product Characteristics: Fabrazyme 35mg, powder for concentrate for solution for infusion. Sanofi Genzyme. Revised July 2021.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 20 July 2021.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.