Certain severe adverse reactions may be related to the rate of infusion. The recommended infusion rate given in "Dosage & Administration" must be closely followed. Patients must be closely monitored and carefully observed for any symptoms throughout the infusion period and thereafter.
Certain adverse reactions may occur more frequently: in case of high rate of infusion; in patients with hypogammaglobulinaemia or agammaglobulinaemia, with or without IgA deficiency; in patients who receive human normal immunoglobulin for the first time or, in rare cases, when the human normal immunoglobulin product is switched or when there has been a long interval since the previous infusion.
Potential complications can often be avoided by ensuring that patients: are not sensitive to human normal immunoglobulin by initially infusing the product slowly (0.3 ml/kg bw/hr); are carefully monitored for any symptoms throughout the infusion period. In particular, patients, naive to human normal immunoglobulin, switched from an alternative IVIg product or when there has been a long interval since the previous infusion, should be monitored during the first infusion and for the first hour after the first infusion, in order to detect potential adverse signs. All other patients should be observed for at least 20 minutes after administration.
In case of adverse reaction, either the rate of administration must be reduced or the infusion stopped. The treatment required depends on the nature and severity of the adverse reaction. In case of shock, standard medical treatment for shock should be implemented.
Higher doses may be associated with increased rates of adverse effects. Therefore, the lowest effective dose should be sought in individual patients and careful monitoring routine is to establish.
In all patients, IVIg administration requires adequate hydration prior to the initiation of the infusion.
Hypersensitivity: True hypersensitivity reactions are rare. They can occur in patients with anti-IgA antibodies.
IVIg is not indicated in patients with selective IgA deficiency where the IgA deficiency is the only abnormality of concern.
Rarely, human normal immunoglobulin can induce a fall in blood pressure with anaphylactoid reaction, even in patients who had tolerated previous treatment with human normal immunoglobulin.
Haemolytic anaemia: IVIg products can contain blood group antibodies which may act as haemolysins and induce in vivo coating of red blood cells (RBC) with immunoglobulin, causing a positive direct antiglobulin reaction (Coombs` test) and, rarely, haemolysis. Haemolytic anaemia can develop subsequent to IVIg therapy due to enhanced RBC sequestration.
Isolated cases of haemolysis-related renal dysfunction/renal failure or disseminated intravascular coagulation in some cases leading to death have occurred.
The following risk factors are associated with the development of haemolysis: high doses, whether given as a single administration or divided over several days; blood group A, B and AB (non-0 blood group) and underlying inflammatory state. As this event was commonly reported in patients with blood group A, B or AB (non-0 blood group) receiving high doses for non-PID indications, increased vigilance is recommended.
Haemolysis has rarely been reported in patients given replacement therapy for PID. IVIg recipients should be monitored for clinical signs and symptoms of haemolysis. If signs and/or symptoms of haemolysis develop during or after IVIg infusion, discontinuation of IVIg treatment should be considered by the treating physician (see Adverse Reactions).
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.
Thromboembolism: There is clinical evidence of an association between IVIg administration and thromboembolic events such as myocardial infarction, cerebral vascular accident (including stroke), pulmonary embolism and deep vein thromboses which is assumed to be related to a relative increase in blood viscosity through the high influx of immunoglobulins in at-risk patients. Therefore caution should be exercised in prescribing and infusing IVIg in obese patients and in patients with pre-existing risk factors for thrombotic events (such as advanced age, hypertension, diabetes mellitus, a history of vascular disease or thrombotic episodes, acquired or inherited thrombophilic disorders, prolonged periods of immobilisation, severe hypovolaemia, diseases which increase blood viscosity).
In patients at risk for thromboembolic reactions, IVIg products should be administered at the minimum rate of infusion and minimum dose practicable.
Acute renal failure: Cases of acute renal failure have been reported in patients receiving IVIg therapy. In most cases risk factors have been identified e.g. pre-existing renal insufficiency, diabetes mellitus, hypovolaemia, overweight, concomitant nephrotoxic medicinal products or age over 65.
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 stabiliser accounted for a disproportionate share of the total number. In patients at risk, the use of IVIg products that do not contain sucrose should therefore be considered. Privigen does not contain sucrose, maltose or glucose.
In patients at risk of acute renal failure, IVIg products should be administered at the minimum rate of infusion and minimum dose practicable.
Transfusion-related acute lung injury (TRALI): Noncardiogenic pulmonary edema may very rarely occur following treatment with IVIg products, including Privigen. TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever. Symptoms typically appear within 1 to 6 hours following treatment.
Monitor patients for pulmonary adverse reactions. TRALI may be managed using oxygen therapy with adequate ventilatory support.
Information on safety in regard to transmissible agents: Privigen is made from human plasma. Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses (see Pharmacology: Pharmacodynamics under Actions). Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.
The measures taken are considered effective for enveloped viruses such as human immunodeficiency (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), and for the non-enveloped viruses such as hepatitis A (HAV) and parvovirus B19.
There is reassuring clinical experience regarding the lack of hepatitis A or parvovirus B19 transmission with immunoglobulins, and it is also assumed that the antibody content makes an important contribution to the viral safety.
It is recommended that every time Privigen is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.
Sodium content: Privigen is essentially sodium-free (Privigen has a low sodium content of ≤ 1 mmol/l).
Influence on diagnostic tests: After infusion of immunoglobulins, the transient increase in the various passively transmitted antibodies in the patient's blood can lead to false-positive results in serological tests.
The passive transmission of antibodies to erythrocyte antigens, e.g. A, B and D, can lead to incorrect results in some serological tests for erythrocyte isoantibodies (e.g. Coombs’ test), determinations of the reticulocyte count, and the haptoglobin test.
For interactions with attenuated live vaccines, see Interactions.
Effect on driving and the operation of machines: The ability to drive and operate machines may be impaired by some adverse reactions associated with Privigen. Patients who experience adverse reactions during treatment should wait for these to resolve before driving or operating machines.
Fertility: Clinical experience with immunoglobulins suggests that no harmful effects on fertility are to be expected.
Use in Children: Although limited data is available, it is expected that the same warnings, precautions and risk factors apply to the paediatric population.