Flebogamma DIF Special Precautions

Certain severe adverse drug reactions may be related to the rate of infusion. The recommended infusion rate given under "Dosage & Administration" must be closely followed. Patients must be closely monitored and carefully observed for any symptoms throughout the infusion period.
Certain adverse reactions may occur more frequently: in case of high rate of infusion; in patients with hypo- 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.
True hypersensitivity reactions are rare. They can occur in the very seldom cases of IgA deficiency with anti-IgA antibodies.
Rarely, human normal immunoglobulin can induce a fall in blood pressure with anaphylactic reaction, even in patients who had tolerated previous treatment with human normal immunoglobulin.
Potential complications can often be avoided by ensuring: that patients are not sensitive to human normal immunoglobulin by first injecting the product slowly at an initial rate of 0.01 - 0.02 ml/kg/min; that patients are carefully monitored for any symptoms throughout the infusion period. In particular, patients naive to human normal immunoglobulin, patients 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.
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 through the high influx of immunoglobulin in at-risk patients. 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 and a history of vascular disease or thrombotic episodes, patients with acquired or inherited thrombophilic disorders, patients with prolonged periods of immobilisation, severely hypovolemic patients, and patients with diseases which increase blood viscosity).
Cases of acute renal failure have been reported in patients receiving IVIg therapy. In most cases, risk factors have been identified, such as pre-existing renal insufficiency, diabetes mellitus, hypovolemia, 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, 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 may be considered.
In patients at risk for acute renal failure or thromboembolic adverse reactions, IVIg products should be administered at the minimum rate of infusion and dose practicable.
In all patients, IVIg administration requires: adequate hydration prior to the initiation of the infusion of IVIg; monitoring of urine output; monitoring of serum creatinine levels; avoidance of concomitant use of loop diuretics.
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 side effect.
In case of shock, standard medical treatment for shock should be implemented.
Non-cardiogenic pulmonary edema may occur in patients following IGIV treatment. This Transfusion-Related Acute Lung Injury (TRALI) is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever. Symptoms typically appear within 1 to 6 hours after transfusion.
Monitor patients for pulmonary adverse reactions. If TRALI is suspected, perform appropriate tests for the presence of antineutrophil antibodies in both the product and patient serum.
Patients with TRALI may be managed by using oxygen therapy with adequate ventilatory support. 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. 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 HIV, HBV and HCV, and for the non-enveloped viruses 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 viral safety.
It is strongly recommended that every time Flebogamma 5% DIF 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.
Special warnings about excipients: This medicinal product contains 50 mg of sorbitol per ml as excipient. Patients with rare hereditary problems of fructose intolerance should not take this medicine. In babies and young children hereditary fructose intolerance may not yet be diagnosed and may be fatal, thus, they should not receive sorbitol-containing solutions. In other patients in case of inadvertent application and suspicion of fructose intolerance the infusion has to be stopped immediately, normal glycemia has to be re-established and organ function has to be stabilized by means of intensive care.
Interferences with determination of blood glucose levels are not expected.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed.
Since Flebogamma 5% DIF might induce dizziness, patients should be cautioned when driving or operating machines.