XEMBIFY

What it is

Xembify is a normal immunoglobulin (human) 20% solution for subcutaneous injection. One millilitre contains 200 mg of normal immunoglobulin with a purity of at least 98% human immunoglobulin G (IgG), produced from the plasma of human donors. Normal immunoglobulin contains mainly immunoglobulin G with a broad spectrum of antibodies against infectious agents. Xembify is subject to additional monitoring in Australia to allow quick identification of new safety information.

Approved indications

Xembify is indicated as replacement therapy in adult and paediatric patients for: — Primary immunodeficiency diseases (PID). — Symptomatic hypogammaglobulinaemia secondary to underlying disease or treatment.

Dosing overview

The dose and dose regimen are dependent on the indication, and the product should be administered via the subcutaneous route with doses individualised for each patient dependent on pharmacokinetic and clinical response. The dose regimen should achieve a trough level of IgG (measured before the next infusion) of at least 5 to 6 g/l and aim to be within the reference interval of serum IgG for age. 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 with a maximal daily dose of 0.1 to 0.15 g/kg. After steady state IgG levels have been attained, maintenance doses are administered at repeated intervals (approximately once per week) to reach a cumulative monthly dose of the order of 0.4 to 0.8 g/kg. The dosage in children and adolescents (0 to 18 years) is not different to that of adults as the dosage for each indication is given by body weight and adjusted to the clinical outcome in replacement therapy indications.

Key safety warnings

If Xembify is accidentally administered into a blood vessel, patients could develop shock. The recommended infusion rate must be closely followed and patients must be closely monitored and carefully observed for any symptoms throughout the infusion period. Arterial and venous thromboembolic events including myocardial infarction, stroke, deep venous thrombosis and pulmonary embolism have been associated with the use of immunoglobulins. Patients should be sufficiently hydrated before use of immunoglobulins, and caution should be exercised in patients with preexisting risk factors for thrombotic events including advanced age, hypertension, diabetes mellitus, history of vascular disease or thrombotic episodes, acquired or inherited thrombophilic disorders, prolonged periods of immobilisation, severe hypovolaemia, and diseases which increase blood viscosity. Aseptic meningitis syndrome has been reported to occur in association with subcutaneous immunoglobulin treatment with symptoms usually beginning within several hours to 2 days following treatment, and discontinuation of immunoglobulin treatment may result in remission within several days without sequelae. Normal immunoglobulin products, including Xembify, can contain blood group antibodies that may act as haemolysins and induce in vivo coating of red blood cells with immunoglobulin, which may cause a positive direct antiglobulin reaction and, rarely, haemolysis.

Contraindications

Xembify is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients. Xembify must not be given intravascularly or intramuscularly. Xembify is contraindicated in patients who have had an anaphylactic or severe systemic reaction to the administration of normal immunoglobulin. Xembify is contraindicated in IgA deficient patients with antibodies against IgA and history of hypersensitivity to normal immunoglobulin treatment.

Regulatory history

Xembify was first approved on 30 June 2022. Four strengths were registered on the ARTG on 2022-06-30: 1 g/5 mL, 2 g/10 mL, 4 g/20 mL, and 10 g/50 mL (all 20% solution for subcutaneous injection). An AusPAR (Australian Public Assessment Report) was published on 2022-07-08.