FLEBOGAMMA

What it is

Flebogamma 10% DIF is a sterile, liquid ready to use preparation of highly purified immunoglobulin (IgG) obtained from human plasma pools. It is a highly purified (≥97% IgG), unmodified, human IgG that contains the antibody specificities found in the donor population. In the final formulation, Flebogamma 10% DIF contains 10 g human normal immunoglobulin and 5 g sorbitol (as stabiliser) in 100 ml of water for injections. The purification process includes cold alcohol fractionation, polyethylene glycol precipitation, ion exchange chromatography, low pH treatment, pasteurisation, solvent detergent treatment and two sequential nanofiltrations through 35 nm and 20 nm pore size nanofilters connected in series.

Approved indications

— Primary Immunodeficiency (PI) Diseases — Symptomatic hypogammaglobulinaemia secondary to underlying disease or treatment — Idiopathic Thrombocytopaenic Purpura (ITP), in patients at high risk of bleeding or prior to surgery to correct the platelet count — Guillain Barré syndrome — Kawasaki disease

Dosing overview

Flebogamma 10% DIF should be infused intravenously at an initial rate of 0.01 ml/kg/min for the first thirty minutes, advanced to 0.02 ml/kg/min for the second 30 minutes, then to 0.04 ml/kg/min for the third 30 minutes, and further increments of 0.02 ml/kg/min may be made at 30-minute intervals up to a maximum of 0.08 ml/kg/min if tolerated.

Key safety warnings

There is clinical evidence of an association between IVIg administration and thromboembolic events such as myocardial infarction, stroke, pulmonary embolism and deep vein thromboses which is assumed to be related to a relative increase in blood viscosity, and caution should be exercised in prescribing and infusing IVIg in obese patients and in patients with pre-existing risk factors for thrombotic events including advanced age, hypertension, diabetes mellitus, a history of vascular disease or thrombotic episodes, acquired or inherited thrombophilic disorders, prolonged immobilisation, severe hypovolaemia, and diseases which increase blood viscosity. Cases of acute renal failure have been reported in patients receiving IVIg therapy, and in most cases risk factors have been identified such as pre-existing renal insufficiency, diabetes mellitus, hypovolaemia, overweight, concomitant nephrotoxic medicinal products or age over 65. Flebogamma DIF does not contain sucrose. Non-cardiogenic pulmonary oedema may occur in patients following Flebogamma 10% DIF treatment, characterised by severe respiratory distress, pulmonary oedema, hypoxaemia, normal left ventricular function, and fever, with symptoms typically appearing within 1 to 6 hours following treatment. IVIg products can contain blood group antibodies which may act as haemolysins and induce in vivo coating of red blood cells with immunoglobulin, and haemolytic anaemia can develop subsequent to IVIg therapy due to enhanced red blood cell sequestration.

Contraindications

Hypersensitivity to the active substance or to any of the excipients, and hypersensitivity to human immunoglobulins, especially in very rare cases of IgA deficiency when the patient has antibodies against IgA. Hereditary fructose intolerance, and in babies and young children hereditary fructose intolerance may not yet be diagnosed and may be fatal, thus they should not receive this medicinal product.

Regulatory history

Flebogamma 10% DIF was first approved on 10 January 2013. The product was registered on the ARTG on 2013-02-12 in three strength presentations: 5 g/50 ml, 10 g/100 ml and 20 g/200 ml vials. An AusPAR (Australian Public Assessment Report) recorded approval on 2013-01-11 for replacement therapy for Primary Immunodeficiency Diseases and symptomatic hypogammaglobulinaemia, and immunomodulation for Idiopathic Thrombocytopaenic Purpura, Guillain Barré syndrome and Kawasaki disease, with the TGA approving the registration as a major variation despite initial quality concerns from the Pharmaceutical Subcommittee.