- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
Replacement therapy in adults, and children and adolescents (0-18 years) in:• Primary immunodeficiency syndromes with impaired antibody production (see section 4.4).• 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 and 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 • Kawasaki disease.
PosologyThe dose and dosage regimen is dependent on the indication. In replacement therapy the dose may need to be individualised for each patient dependent on the pharmacokinetic and clinical response. The following dosage regimens are given as a guideline.
Replacement therapy in primary immunodeficiency syndromesThe dose regimen should achieve a trough level of IgG (measured before the next infusion) of at least5 to 6 g/L. Three to six months are required after the initiation of therapy for equilibration to occur. The recommended starting dose is 0.4 - 0.8 g/kg given once, followed by at least 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 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; congenial AIDS with recurrent bacterial infections.The recommended dose is 0.2 - 0.4 g/kg every three to four weeks.
Hypogammaglobulinaemia in patients after allogeneic haematopoietic stem cell transplantationThe recommended dose is 0.2-0.4 g/kg every three to four weeks. The trough levels should be maintained above 5 g/L
Primary immune thrombocytopeniaThere are two alternative treatment schedules: • 0.8 - 1 g/kg on day one; this dose may be repeated once within 3 days, • 0.4 g/kg given daily for two to five days. The treatment can be repeated if relapse occurs.
Guillain Barré Syndrome0.4 g/kg/day over 5 days. Kawasaki Disease1.6 - 2.0 g/kg should be administered in divided doses over two to five days or 2.0 g/kg as a single dose. Patients should receive concomitant treatment with acetylsalicylic acid.The dosage recommendations are summarised in the following table:
|Indication||Dose||Frequency of injections|
|Replacement therapy in primary immunodeficiency Replacement therapy in secondary immunodeficiency Congenital AIDS Hypogammaglobulinaemia (<4 g/L) in patients after allogeneic haematopoietic stem cell transplantation||- starting dose: 0.4 - 0.8 g/kg - thereafter: 0.2 - 0.8 g/kg 0.2 - 0.4 g/kg 0.2 - 0.4 g/kg 0.2 - 0.4 g/kg||Every 3 - 4 weeks to obtain IgG trough level of at least 5- 6 g/L Every 3 - 4 weeks to obtain IgG trough level of at least-5 - 6 g/L Every 3 - 4 weeks Every 3-4 weeks to obtain IgG trough level above 5g/L.|
|Immunomodulation: Primary immune thrombocytopenia Guillain Barré Syndrome Kawasaki disease||0.8 - 1 g/kg or 0.4 g/kg/d 0.4 g/kg/d 1.6 - 2 g/kg or 2 g/kg||On day 1, possibly repeated once within 3 days For 2 - 5 days For 5 days In divided doses over 2 - 5 days in association with acetylsalicylic acid In one dose in association with acetylsalicylic acid|
Paediatric populationThe posology in children and adolescents (0-18 years) is not different to that of adults as the posology for each indication is given by body weight and adjusted to the clinical outcome of the above mentioned conditions.
Method of administrationFor intravenous use.Vigam Liquid should be infused intravenously at an initial rate of 0.01 - 0.02 mL/kg/minute for 30 minutes. If well tolerated (see section 4.4), the rate of administration may be gradually increased to 0.04 mL/kg/minute up to a maximum of 3 mL/minute..
HypersensitivityTrue 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 anaphylactic reaction, even in patients who tolerated previous treatment with human normal immunoglobulin.
ThromboembolismThere 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 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, 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 failureCases 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. 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 these excipients may be considered. Vigam Liquid contains sucrose In patients at risk for acute renal failure, IVIg products should be administered at the minimum rate of infusion and dose practicable.
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 (2g/kg) IVIg treatment.
Haemolytic anaemiaIVIg products can obtain 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. (See section 4.8)
Interference with serological testingAfter injection 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 agentsStandard 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. The measures taken may be of limited value against non-enveloped viruses such as 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 strongly recommended that every time that Vigam Liquid 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 populationThe listed warnings and precautions apply to both adults and children.
Live attenuated virus vaccinesImmunoglobulin 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.
Paediatric populationThe listed interaction(s) apply to both adults and children
PregnancyThe 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 to be expected.
Breast-feedingImmunoglobulins are excreted into the milk and may contribute to protecting the neonate from pathogens which have a mucosal portal of entry.
FertilityClinical experience with immunoglobulins suggests that no harmful effects on fertility are to be expected.
Summary of the safety profileAdverse reactions such as chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, arthralgia, low blood pressure and moderate low back pain may occur occasionally. Rarely, human normal immunoglobulins may cause a sudden fall in blood pressure and, in isolated cases, anaphylactic shock, even when the patient has shown no hypersensitivity to previous administration. Cases of reversible aseptic meningitis and rare cases of transient cutaneous reactions have been observed with human normal immunoglobulin. Reversible haemolytic reactions have been observed in patients especially those with blood groups A, B, and AB. Rarely, haemolytic anaemia requiring transfusion may develop after high dose IVIg treatment (see also Section 4.4). Increase in serum creatinine level and/or acute renal failure have been observed.Very rarely: Thromboembolic reactions such as myocardial infarction, stroke, pulmonary embolism, deep vein thromboses.For safety information with respect to transmissible agents,, see Section 4.4.
Tabulated list of adverse reactionsThe table presented below is according to the MedDRA system organ classification (SOC and Preferred Term Level). Frequencies have been evaluated according to the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Frequency of Adverse Reactions (ADRs) in clinical studies with Vigam Liquid
|MedDRA System Organ Class (SOC)||Adverse Reaction||Frequency|
|Nervous system disorders||Headache||Common|
|Vascular disorders||Hypertension NOS Hypotension NOS||Common Common|
|Respiratory, thoracic and mediastinal disorders||Pharyngitis||Common|
|Gastrointestinal disorders||Vomiting Nausea||Common Common|
|Skin and subcutaneous tissue disorders||Dermatitis exfoliative NOS Rash macular Urticaria NOS||Common Common Common|
|Musculoskeletal and connective tissue disorders||Arthralgia||Common|
|General disorders and administration site conditions||Pyrexia Infusion site pain/inflammation Lethargy Fatigue||Very common Common Common Common|
Description of selected adverse reactionsNone of the reported adverse reactions to Vigam® Liquid warrant separate description
Paediatric populationFrequency, type and severity of adverse reactions in children are expected to be the same as in adults Reporting of Suspected adverse reactions.Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/ risk balance of the medicinal product. Healthcare professional are asked to report any suspected adverse reactions via the Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard
Paediatric populationThere is no clinical data on the pharmacodynamics of Vigam Liquid in children.
Paediatric populationThere is no clinical data on the pharmacokinetics of Vigam Liquid in children.
|POM||Version Code: VLS12|
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