Avalglucosidase alfa

Intravenous
Pompe disease

Allow vials to reach room temperature before reconstitution (approx 30 minutes). Reconstitute each vial with 10 mL of sterile water for inj by injecting the sterile water for inj slowly down the inside wall of each vial. Do not inject directly or forcefully onto the powder to avoid foaming. Gently tilt and roll each vial; do not invert, swirl or shake. Further dilute the reconstituted solution by withdrawing the required dose from the vials, then add it slowly and directly to a correct volume of dextrose 5% in water solution to make a final concentration of 0.5-4 mg/mL. Gently invert or massage the infusion bag to mix the solution. Do not shake. Recommendations for total infusion volume are based on patient's body weight (refer to specific product guidelines).

Hypersensitivity.

Patient with acute underlying illness, advanced Pompe disease; predisposition for fluid volume overload; acute underlying respiratory illness or compromised cardiac and/or respiratory function. Pregnancy and lactation.

Significant: Infusion-associated reactions (IARs), acute cardiorespiratory failure.
Cardiac disorders: Tachycardia, ventricular extrasystoles.
Eye disorders: Ocular hyperaemia, conjunctival hyperaemia, eyelid oedema, eye pruritus, conjunctivitis, increased lacrimation.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, swollen lip, swollen tongue, abdominal pain, upper abdominal pain, dyspepsia, oral hypoaesthesia, oral paraesthesia, dysphagia.
General disorders and administration site conditions: Chills, fatigue, chest discomfort, pain, infusion site pain, influenza-like illness, pyrexia, asthenia, facial oedema, feeling cold, feeling hot, sluggishness.
Investigations: Decreased oxygen saturation, increased body temperature, increased blood pressure.
Musculoskeletal and connective tissue disorders: Muscle spasms, myalgia, flank pain, pain in the extremity.
Nervous system disorders: Headache, dizziness, somnolence, burning sensation, tremor, paraesthesia.
Respiratory, thoracic and mediastinal disorders: Cough, dyspnoea, throat irritation, oropharyngeal pain, respiratory distress, tachypnoea, laryngeal oedema.
Skin and subcutaneous tissue disorders: Rash, pruritus, erythema, palmer erythema, urticaria, hyperhidrosis, skin plaque, angioedema, skin discolouration.
Vascular disorders: Hypertension, hypotension, flushing, cyanosis, pallor, hot flush.
Potentially Fatal: Hypersensitivity reactions (e.g. anaphylaxis).

This drug may cause dizziness, hypotension and somnolence; if affected, do not drive or operate machinery.

Monitor vital signs during (particularly before each infusion rate increase) and after infusion. Assess for hypersensitivity and infusion-associated reactions.

Description:
Mechanism of Action: Avalglucosidase alfa is a hydrolytic lysosomal glycogen-specific recombinant human acid α-glucosidase (GAA) enzyme that is conjugated with multiple synthetic bis-mannose-6-phosphate (bis-M6P)-tetra mannose glycans. The mannose-6-phosphate (M6P) on avalglucosidase alfa mediates binding to M6P receptors on the cell surface with high affinity. Subsequently, it is internalised and transported into lysosomes where it is activated for increased enzymatic glycogen cleavage.
Pharmacokinetics:
Distribution: Volume of distribution: 3.4 L.
Metabolism: Metabolised via catabolic pathways into small peptides and amino acids.
Excretion: Elimination half-life: 1.6 hours.

Intact vial: Store between 2-8°C. Reconstituted solution: Store between 2-8°C for up to 24 hours. Diluted solution: Store between 2-8°C for up to 24 hours or store at room temperature (up to 25°C) for up to 9 hours (including infusion time). Do not freeze.

Other Agents Affecting Metabolism

A16AB22 - avalglucosidase alfa ; Belongs to the class of enzymes. Used in the treatment of alimentary tract and metabolism problems.

Anon. Avalglucosidase Alfa-ngpt. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 04/11/2024.

Avalglucosidase Alfa. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 04/11/2024.

Joint Formulary Committee. Avalglucosidase Alfa. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/11/2024.

Nexviadyme 100 mg Powder for Concentrate for Solution for Infusion (Aventis Pharma Limited). MHRA. https://products.mhra.gov.uk. Accessed 04/11/2024.

Nexviazyme 100 mg Powder for Concentrate for Solution for Infusion (Sanofi-Aventis [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 04/11/2024.

Nexviazyme NGPT Injection, Powder, Lyophilized, for Solution (Genzyme Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 04/11/2024.

Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics. Nexviazyme 100 mg Powder for Concentrate for Solution for Infusion data sheet 18 October 2024. Medsafe. http://www.medsafe.govt.nz. Accessed 12/11/2024.