s, patients with acquired or inherited thrombophilic disorders, hypercoagulable disorders, patients with prolonged periods of immobilisation, severely hypovolemic patients, patients with diseases which increase blood viscosity, patients with indwelling vascular catheters and patients with high dose and rapid infusion).
Hyperproteinemia, increased serum viscosity and subsequent relative pseudohyponatremia may occur in patients receiving IVIg therapy. This should be taken into account by physicians, since initiation of treatment for true hyponatremia (i.e. decreasing serum free water) in these patients may lead to a further increase in serum viscosity and a possible predisposition to thromboembolic events.
In patients at risk for thromboembolic adverse reactions, IVIg products should be administered at the minimum rate of infusion and dose practicable.
Acute renal failure
Cases of acute renal failure have been reported in patients receiving IVIg therapy. These include acute renal failure, acute tubular necrosis, proximal tubular nephropathy and osmotic nephrosis. In most cases, risk factors have been identified, such as pre-existing renal insufficiency, diabetes mellitus, hypovolemia, overweight, concomitant nephrotoxic medicinal products, age over 65, sepsis, hyperviscosity or paraproteinemia.
In case of renal impairment, IVIg discontinuation should be considered. While these reports of renal dysfunction and acute renal failure have been associated with the use of many of the licensed IVIg products containing various excipients such as sucrose, glucose and maltose, those containing sucrose as a stabilizer accounted for a disproportionate share of the total number. In patients at risk, the use of IVIg products that do not contain these excipients may be considered. KIOVIG does not contain sucrose, maltose or glucose.
In patients at risk for acute renal failure, IVIg products should be administered at the minimum rate of infusion and dose practicable.
Transfusion Related Acute Lung Injury (TRALI)
There have been reports of noncardiogenic pulmonary edema (Transfusion Related Acute Lung Injury, TRALI) in patients administered IVIg (including KIOVIG).
Aseptic meningitis syndrome (AMS)
Aseptic meningitis syndrome has been reported to occur in association with IVIg treatment. Discontinuation of IVIg treatment has resulted in remission of AMS within several days without sequelae. The syndrome usually begins within several hours to 2 days following IVIg treatment. Cerebrospinal fluid studies are frequently positive with pleocytosis up to several thousand cells per mm3, predominantly from the granulocytic series, and elevated protein levels up to several hundred mg/dL. AMS may occur more frequently in association with high-dose (2 g/kg) IVIg treatment.
From post-marketing data with KIOVIG no clear correlation of AMS to higher doses was observed. Higher incidences of AMS were seen in women.
Haemolytic anaemia
IVIg products can contain blood group antibodies that may act as hemolysins and induce in vivo coating of red blood cells with immunoglobulin, causing a positive direct antiglobulin reaction (Coombs' test) and, rarely, hemolysis. Haemolytic anaemia can develop subsequent to IVIg therapy due to enhanced red blood cells (RBC) sequestration. IVIg recipients should be monitored for clinical signs and symptoms of haemolysis. (See section 4.8.)
Interference with serological testing
After infusion of immu |
