⚠️ Warnings
Traceability
In order to improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly recorded.
Precautions for use
Potential complications can often be avoided by ensuring that patients:
are not hypersensitive to normal human immunoglobulin by initially infusing the product slowly (0.5 mL/kg body weight/hour);
are carefully monitored for any symptoms throughout the infusion. In particular, patients naïve to normal human immunoglobulin, patients switched from an alternative IVIg product, and patients in whom 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 a healthcare setting under supervision, in order to detect potential adverse signs and ensure immediate emergency care if required. All other patients should be observed for at least 20 minutes after administration.
IVIg administration in all patients requires:
adequate hydration prior to the initiation of the IVIg infusion;
monitoring of urine output;
monitoring of serum creatinine levels;
avoidance of concomitant use of loop diuretics (see section 4.5).
In the event of an adverse reaction, either the infusion rate must be reduced or the infusion must be stopped. Appropriate treatment depends on the nature and severity of the adverse reaction.
If Deqsiga needs to be diluted to a lower concentration in patients with diabetes mellitus, the use of a 5% glucose solution may need to be reconsidered.
Infusion reactions
Certain adverse reactions (e.g. headache, flushing, chills, myalgia, wheezing, tachycardia, low back pain, nausea and hypotension) may be related to the rate of infusion. The recommended infusion rate given in section 4.2 must be closely followed. Patients must be closely monitored and carefully observed for any symptoms throughout the infusion.
Adverse reactions may occur more frequently:
in patients receiving normal human immunoglobulin for the first time or, in rare cases, when the normal human immunoglobulin product is switched or when there has been a long interval since the last infusion;
in patients with an active infection or underlying chronic inflammation.
Hypersensitivity
Hypersensitivity reactions are rare.
Deqsiga has a very low IgA content (no more than 2 micrograms/mL). It has been shown that patients who reacted to IVIg products with higher IgA concentrations tolerated IgA-free products better. However, the threshold IgA concentration to which patients are sensitive is not known.
Anaphylaxis may develop in any patient treated with IVIg, including:
patients with undetectable IgA who have anti-IgA antibodies;
those who have tolerated previous treatment with normal human immunoglobulin.
In case of shock, standard medical management of shock should be implemented.
Thromboembolism
There is clinical evidence of an association between IVIg administration and thromboembolic events such as myocardial infarction, stroke (including cerebral infarction), pulmonary embolism and deep vein thrombosis. These events are presumed 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, a history of vascular disease or thrombotic episodes, acquired or inherited thrombophilic disorders, prolonged periods of immobilisation, severe hypovolaemia and diseases which increase blood viscosity).
In patients at risk of thromboembolic adverse reactions, IVIg products should be administered at the minimum dose and infusion rate 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, such as pre-existing renal insufficiency, diabetes mellitus, hypovolaemia, overweight, concomitant nephrotoxic medicinal products and age over 65.
Renal parameters should be assessed prior to IVIg infusion, particularly in patients judged to have a potential increased risk of developing acute renal failure, and reassessed at appropriate intervals. In patients at risk of acute renal failure, IVIg products should be administered at the minimum dose and infusion rate practicable. In case of renal impairment, IVIg discontinuation should be considered.
Renal dysfunction and acute renal failure have been reported in association with the use of many licensed IVIg products containing various excipients such as sucrose, glucose and maltose; however, those containing sucrose as a stabiliser accounted for a disproportionate share of the total number. In at-risk patients, the use of IVIg products that do not contain these excipients may be considered. Deqsiga contains neither sucrose, maltose nor glucose.
Aseptic meningitis syndrome (AMS)
Aseptic meningitis syndrome has been reported in association with IVIg treatment. The syndrome usually begins within several hours to two days following IVIg treatment. Cerebrospinal fluid (CSF) 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.
Patients exhibiting such signs and symptoms should undergo a thorough neurological examination, including CSF studies, to rule out other causes of meningitis.
Discontinuation of IVIg treatment has resulted in remission of AMS within several days without sequelae.
Haemolytic anaemia
IVIg products can contain blood group antibodies which may act as haemolysins and induce in vivo coating of red blood cells with immunoglobulin, causing a positive direct antiglobulin (Coombs) test reaction and, rarely, haemolysis. Haemolytic anaemia can develop following IVIg therapy due to enhanced red blood cell sequestration. IVIg recipients should be monitored for clinical signs and symptoms of haemolysis (see section 4.8).
Neutropenia/leukopenia
A transient decrease in the neutrophil count and/or episodes of neutropenia, sometimes severe, have been reported following IVIg treatment. This typically occurs within hours or days after IVIg administration and resolves spontaneously within 7 to 14 days.
Transfusion-related acute lung injury (TRALI)
Cases of acute non-cardiogenic pulmonary oedema (transfusion-related acute lung injury, TRALI) have been reported in patients receiving IVIg. TRALI is characterised by severe hypoxia, dyspnoea, tachypnoea, cyanosis, fever and hypotension. Symptoms of TRALI typically develop during or within 6 hours of a transfusion, often within 1–2 hours. Therefore, IVIg recipients must be monitored for, and IVIg infusion must be immediately stopped in case of, pulmonary adverse reactions. TRALI is a potentially life-threatening condition requiring immediate intensive care management.
Interference with serological testing
After administration of immunoglobulin, the transitory rise of passively transferred antibodies in the patient's blood may result in misleading positive results in serological testing.
Passive transmission of antibodies to erythrocyte antigens, such as A, B and D, may interfere with some serological tests for red blood cell antibodies, for example the direct antiglobulin test (DAT, direct Coombs test).
Administration of Deqsiga can lead to false-positive readings in assays for the diagnosis of fungal infections that rely on detection of beta-D-glucans. This may persist for weeks following infusion of the product.
Transmissible agents
Deqsiga 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. Despite these measures, the possibility of transmitting infective agents cannot be totally excluded when medicinal products prepared from human blood or plasma are administered. This also applies to any unknown or emerging viruses or other pathogens.
The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), and for the non-enveloped viruses hepatitis A virus and parvovirus B19.
Clinical experience confirms the absence 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 Deqsiga 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.
Paediatric population
There are no specific paediatric risks associated with the adverse events listed above. Paediatric patients may be more sensitive to volume overload (see section 4.9).
