Agalsidase alfa

Intravenous
Fabry disease

Prior to infusion, dilute the required total volume in 100 mL 0.9% NaCl solution for infusion. Gently mix the solution. Do not shake.

Hypersensitivity.

Patient with compromised cardiac function due to Fabry disease. Renal impairment (eGFR <60 mL/min). Children. Pregnancy and lactation.

Significant: Idiosyncratic infusion-related reactions (e.g. headache, nausea, rigors, pyrexia, flushing, fatigue), hypersensitivity reactions (including anaphylactic reactions), IgG antibody development.
Cardiac disorders: Palpitations, atrial fibrillation, tachycardia, chest pain or tightness.
Ear and labyrinth disorders: New-onset or aggravated tinnitus.
Eye disorders: Lacrimation increased, corneal reflex decreased.
Gastrointestinal disorders: Vomiting, abdominal pain or discomfort, diarrhoea, dysgeusia.
General disorders and administration site conditions: Peripheral oedema, asthenia, pain or discomfort, aggravated fatigue, feeling hot or cold, influenza-like illness, malaise, inj site rash.
Musculoskeletal and connective tissue disorders: Arthralgia, myalgia, back pain, pain in limb, joint swelling, musculoskeletal discomfort, peripheral swelling.
Nervous system disorders: Dizziness, neuropathic pain, tremor, paraesthesia, hypoaesthesia.
Psychiatric disorders: Hypersomnia.
Respiratory, thoracic and mediastinal disorders: Cough, dyspnoea, nasopharyngitis, pharyngitis, throat tightness, rhinorrhoea, hoarseness.
Skin and subcutaneous tissue disorders: Rash, acne, urticaria, erythema, pruritus, hyperhidrosis, livedo reticularis.
Vascular disorders: Hypertension, hypotension.

Amiodarone, monobenzone, chloroquine, or gentamicin may potentially inhibit intra-cellular α-galactosidase activity; avoid concomitant use.

Description:
Mechanism of Action: Agalsidase alfa is a recombinant form of α-galactosidase-A. It catalyses the hydrolysis of globotriaosylceramide (Gb3), the glycosphingolipid substrate that accumulates within the tissues of patients with Fabry disease, thereby cleaving the terminal galactose residue from the molecule. This action reduces the accumulation of Gb3 in many cell types including endothelial and parenchymal cells, resulting in stabilisation of or improvement in renal function and structure, reduction in pain, and decrease in cardiac mass with an associated improvement in cardiac function.
Pharmacokinetics:
Distribution: Volume of distribution: Male: 203 mL/kg (range: 89-6,778 mL/kg).
Metabolism: Metabolised in the plasma via peptide hydrolysis.
Excretion: Elimination half-life: Male: 54.7 minutes (range: 28.5-654.2 minutes).

Store between 2-8°C. Diluted solutions must be administered immediately; if not used immediately, diluted solutions are stable for 24 hours between 2-8°C.

Other Agents Affecting Metabolism

A16AB03 - agalsidase alfa ; Belongs to the class of enzymes. Used in the treatment of alimentary tract and metabolism problems.

Anon. Agalsidase Alfa. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 09/08/2021.

Buckingham R (ed). Alpha Galactosidase A. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 09/08/2021.

Joint Formulary Committee. Agalsidase Alfa. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 09/08/2021.

Replagal 1 mg/mL Concentrate for Solution for Infusion (Shire Human Genetic Therapies AB). MHRA. https://products.mhra.gov.uk. Accessed 09/08/2021.

Replagal Concentrate for Solution for Infusion 3.5 mg/3.5 mL (Takeda Pharmaceuticals [Hong Kong] Ltd). MIMS Hong Kong. http://www.mims.com/hongkong. Accessed 09/08/2021.

Takeda New Zealand Limited. Replagal 3.5 mg/3.5 mL Concentrate for Infusion Vial data sheet 28 September 2020. Medsafe. http://www.medsafe.govt.nz. Accessed 09/08/2021.