Presentation and Status in Health Basket
1 x 10 ml, 25 ml, 50 ml, 100 ml, 200 ml
The dose and dose regimen is dependent on the indication.
In replacement therapy the dose may need to be individualized for each patient dependent on the pharmacokinetic and clinical response. The following dose regimens are given as a guideline.
Replacement therapy in primary immunodeficiency syndromes: The dose regimen should achieve a trough level of IgG (measured before the next infusion) of at least 5 to 6 g/l. Three to six months are required after the initiation of therapy for equilibration to occur. The recommended starting dose is 4-8 ml (0.4-0.8 g)/kg given once, followed by at least 2 ml (0.2 g)/kg given every three to four weeks.
The dose required to achieve a trough level of 5-6 g/l is of the order of 2-8 ml (0.2-0.8 g)/kg/month. The dosage interval when steady state has been reached varies from 3-4 weeks.
Trough levels should be measured and assessed in conjunction with the incidence of infection. To reduce the rate of infection, it may be necessary to increase the dosage and aim for higher trough levels.
Hypogammaglobulinaemia and recurrent bacterial infections in patients with chronic lymphocytic leukaemia, in whom prophylactic antibiotics have failed; hypogammaglobulinaemia and recurrent bacterial infections in plateau phase multiple myeloma patients who have failed to respond to pneumococcal immunisation; congenital AIDS with recurrent bacterial infections: The recommended dose is 2-4 ml (0.2-0.4 g)/kg every three to four weeks.
Hypogammaglobulinaemia in patients after allogeneic haematopoietic stem cell transplantation: The recommended dose is 2-4 ml (0.2-0.4 g)/kg every three to four weeks. The trough levels should be maintained above 5 g/l.
Primary immune thrombocytopenia: There are two alternative treatment schedules:
– 8-10 ml (0.8-1 g)/kg given on day one, this dose may be repeated once within 3 days
– 4 ml (0.4 g)/kg given daily for two to five days.
The treatment can be repeated if relapse occurs.
Guillain Barré syndrome: 4 ml (0.4 g)/kg/day over 5 days.
Kawasaki disease: 16-20 ml (1.6-2.0 g)/kg should be administered in divided doses over two to five days or 20 ml (2.0 g)/kg as a single dose. Patients should receive concomitant treatment with acetylsalicylic acid.
Replacement therapy in adults, and children and adolescents (0-18 years) in:
Primary immunodeficiency syndromes with impaired antibody production.
Hypogammaglobulinaemia and recurrent bacterial infections in patients with chronic lymphocytic leukaemia, in whom prophylactic antibiotics have failed.
Hypogammaglobulinaemia and recurrent bacterial infections in plateau phase multiple myeloma patients who have failed to respond to pneumococcal immunisation.
Hypogammaglobulinaemia in patients after allogeneic haematopoietic stem cell transplantation (HSCT).
Congenital AIDS with recurrent bacterial infections.
Immunomodulation in adults, and children and adolescents (0-18 years) in:
Primary immune thrombocytopenia (ITP), in patients at high risk of bleeding or prior to surgery to correct the platelet count.
Guillain Barré syndrome.
Hypersensitivity to the active substance (human immunoglobulins) or to any of the excipients.
Patients with selective IgA deficiency who developed antibodies to IgA, as administering an IgA-containing product can result in anaphylaxis.
Traceability: In order to improve the traceability of biological medicinal products, the name and the 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 sensitive to human normal immunoglobulin by initially injecting the product slowly (1.4 ml/kg/h corresponding to 0.023 ml/kg/min), 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 at the hospital 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 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 adverse reaction.
Infusion reaction: Certain adverse reactions (e.g. headache, flushing, chills, myalgia, wheezing, tachycardia, lower back pain, nausea, and hypotension) may be related to the rate of infusion. Patients must be closely monitored and carefully observed for any symptoms throughout the infusion period.
Adverse reactions may occur more frequently: 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.
In patients with an untreated infection or underlying chronic inflammation.
Hypersensitivity reactions are rare.
Anaphylaxis can develop in:
Patients with undetectable IgA who have anti-IgA antibodies.
Patients who had tolerated previous treatment with human normal immunoglobulin.
In case of shock, standard medical treatment for shock should be implemented.
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 thrombosis 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 hypovolaemic patients, patients with diseases which increase blood viscosity).
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. 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 years.
Renal parameters should be assessed prior to infusion of IVIg, particularly in patients judged to have a potential increased risk for developing acute renal failure, and again at appropriate intervals. In patients at risk for acute renal failure, IVIg products should be administered at the minimum rate of infusion and dose practicable. In case of renal impairment, IVIg discontinuation should be considered.
While 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 these excipients may be considered. Intratect 100 g/l does not contain sucrose, maltose or glucose.
Aseptic meningitis syndrome (AMS): Aseptic meningitis syndrome has been reported to occur in association with IVIg treatment.
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.
Patients exhibiting such signs and symptoms should receive 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 reaction (Coombs’ test) and, rarely, haemolysis. 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.
Neutropenia/Leukopenia: A transient decrease in neutrophil count and/or episodes of neutropenia, sometimes severe, have been reported after treatment with IVIgs. This typically occurs within hours or days after IVIg administration and resolves spontaneously within 7 to 14 days.
Transfusion related acute lung injury (TRALI): In patients receiving IVIg, there have been some reports of acute non-cardiogenic pulmonary oedema [Transfusion Related Acute Lung Injury (TRALI)]. 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-unit management.
Interference with serological testing: After the administration of immunoglobulin the transitory rise of the various passively transferred antibodies in the patient’s blood may result in misleading positive results in serological testing.
Passive transmission of antibodies to erythrocyte antigens, e.g. A, B, D may interfere with some serological tests for red cell antibodies for example the direct antiglobulin test (DAT, direct Coombs’ test).
Transmissible agents: 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 human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). The measures taken may be of limited value against non-enveloped viruses such as hepatitis A virus 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.
See prescribing information for full details.
Chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, arthralgia, low blood pressure and moderate low back pain.
See prescribing information for full details.
Live attenuated virus vaccines: Immunoglobulin administration may impair for a period of at least 6 weeks and up to 3 months the efficacy of live attenuated virus vaccines such as measles, rubella, mumps and varicella. After administration of this medicinal product, an interval of 3 months should elapse before vaccination with live attenuated virus vaccines. In the case of measles, this impairment may persist for up to 1 year. Therefore patients receiving measles vaccine should have their antibody status checked.
Loop diuretics: Avoidance of concomitant use of loop diuretics.
Paediatric population: It is expected that the same interaction mentioned for the adults may also occur in the paediatric population.
Pregnancy and Lactation
Pregnancy: The safety of this medicinal product for use in human pregnancy has not been established in controlled clinical trials and therefore should only be given with caution to pregnant women and breast-feeding mothers. IVIg products have been shown to cross the placenta, increasingly during the third trimester.
Clinical experience with immunoglobulins suggests that no harmful effects on the course of pregnancy, or on the foetus and the neonate are expected.
Lactation: Immunoglobulins are excreted into human milk. No negative effects on the breastfed newborns/infants are anticipated.
Overdose may lead to fluid overload and hyperviscosity, particularly in patients at risk, including elderly patients or patients with cardiac or renal impairment.
Storage: Do not store above 25°C. Do not freeze. Keep the vial in the outer carton in order to protect from light.
Compatibility: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products, or with any other IVIg products.