HIZENTRA

What it is

Hizentra is a 20% solution (20 g/100 mL) of normal immunoglobulin (Human) for subcutaneous injection. It contains 20 g/100 mL of total human plasma protein with a purity of at least 98% immunoglobulin G (IgG). The distribution of the IgG subclasses is similar to that of normal human plasma (approximate values: 69% IgG1, 26% IgG2, 3% IgG3, 2% IgG4). Hizentra AU is manufactured from human plasma collected in Australia by Australian Red Cross Lifeblood, while Hizentra is manufactured from human plasma collected outside Australia by CSL Plasma.

Approved indications

— Replacement therapy in adults and children in Primary Immunodeficiency Disease (PID) . — Replacement therapy in adults and children with symptomatic hypogammaglobulinaemia secondary to underlying disease or treatment . — Immunomodulatory therapy in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) as maintenance therapy after stabilisation with IVIg .

Dosing overview

The dose and dose regimen are dependent on the indication and may need to be individualised for each patient dependent on the clinical response and serum IgG trough levels. For replacement therapy in PID and symptomatic hypogammaglobulinaemia: A loading dose of at least 0.2 to 0.5 g/kg body weight may be required, which may need to be divided over several days. After steady state IgG levels have been attained, maintenance doses are administered at repeated intervals, from daily to once every two weeks, to reach a cumulative monthly dose of the order of 0.4 to 0.8 g/kg body weight. For CIDP: Therapy with Hizentra is initiated 1 week after the last IVIg infusion. The recommended subcutaneous dose is 0.2 to 0.4 g/kg body weight per week. For dosing every two weeks, double the weekly Hizentra dose.

Key safety warnings

Hizentra is for subcutaneous use only. If Hizentra is accidentally administered into a blood vessel, patients could develop shock. Hypersensitivity reactions may occur even in patients who had tolerated previous treatment with human normal immunoglobulin. Severe hypersensitivity or anaphylactic reactions up to shock can particularly occur in patients with known allergies to anti-IgA antibodies. Arterial and venous thromboembolic events have been associated with the use of immunoglobulins. Caution should be taken in patients with pre-existing risk factors for thromboembolic events, such as advanced age, estrogen use, in-dwelling vascular catheters, a history of vascular disease or thrombotic episodes, cardiovascular risk factors, patients with acquired or inherited hypercoagulable states, patients with prolonged periods of immobilisation, severely hypovolaemic patients, and patients with diseases which increase blood viscosity. Aseptic Meningitis Syndrome has been reported with use of IVIg or subcutaneous immunoglobulin. The syndrome usually begins within several hours to 2 days following IgG treatment and is characterised by severe headache, neck stiffness, drowsiness, fever, photophobia, nausea, and vomiting.

Contraindications

Hizentra is contraindicated in patients with a history of severe systemic hypersensitivity or anaphylactic reactions to the active substance of Hizentra or to any of its excipients. Hizentra is contraindicated in patients with hyperprolinaemia type I or II.

Regulatory history

Hizentra was first listed on the ARTG on 8 May 2014 in multiple vial and pre-filled syringe presentations. Hizentra AU, manufactured from Australian plasma, received its first ARTG listing on 7 July 2020 in 5 mL, 10 mL, 20 mL and 50 mL vial presentations.