Search The Medical Knowledge Base

Drug Details

SANDOGLOBULIN

• Drug Class Description
  Intravenous immunoglobulins.
• Generic Name
  Human Normal Immunoglobulin [intravenous]
• Presentation
  Solution for infusion Sandoglobulin NF Liquid is a clear or slightly opalescent, colourless or pale yellow solution.
• Description
  Sandoglobulin® NF Liquid, 120 mg/ml solution for infusion
• Indications
  

  Replacement therapy in:

  Primary immunodeficiency syndromes such as:

  - congenital agammaglobulinaemia and hypogammaglobulinaemia

  - common variable immunodeficiency

  - severe combined immunodeficiency

  - Wiskott-Aldrich syndrome Myeloma or chronic lymphocytic leukaemia with severe secondary hypogammaglobulinaemia and recurrent infections Children with congenital AIDS and recurrent infections Immunomodulation Idiopathic thrombocytopenic purpura (ITP), in children or adults at high risk of bleeding or prior to surgery to correct the platelet count. Guillain-Barré syndrome Kawasaki disease Allogeneic bone marrow transplantation

• Adult Dosage
  

  Posology

  The dose and dosage regimen is dependent on the indication.

  In replacement therapy the dosage may need to be individualised for each patient dependent on the pharmacokinetic and clinical response.

  The daily dose should not exceed 1g/kg body weight (b.w.).

  The following dosage regimens are given as a guideline.

  Replacement therapy in primary immunodeficiency syndromes

  The dosage regimen should achieve a trough level of IgG (measured before the next infusion) of at least 4-6 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 b.w. followed by at least 0.2 g/kg b.w. every three weeks.

  The dose required to maintain a trough level of 6 g/l is of the order of 0.2-0.8 g/kg b.w./month. The dosage interval when steady state has been reached varies from 2-4 weeks.

  Trough levels should be measured in order to adjust the dose and dosage interval.

  Replacement therapy in myeloma or chronic lymphocytic leukaemia with severe secondary hypogammaglobulinaemia and recurrent infections; replacement therapy in children with AIDS and recurrent infections

  The recommended dose is 0.2-0.4 g/kg b.w. every three to four weeks.

  Idiopathic thrombocytopenic purpura

  For the treatment of an acute episode, 0.8-1 g/kg b.w. on day one, which may be repeated once within 3 days, or 0.4 g/kg b.w. daily for two to five days. The treatment can be repeated if relapse occurs.

  The mean duration of platelet response was 6 days in chronic ITP patients. Monitoring of platelet counts from day 7 onwards is recommended for patients with clinical symptoms, especially active bleedings.

  Guillain-Barré syndrome

  0.4 g/kg b.w./day for 3 to 7 days.

  Experience in children is limited.

  Kawasaki disease

  1.6-2.0 g/kg b.w. should be administered in divided doses over two to five days. Patients should receive concomitant treatment with acetylsalicylic acid.

  Allogeneic bone marrow transplantation

  Human normal immunoglobulin treatment can be used as part of the conditioning regimen and after the transplantation.

  For the treatment of infections and prophylaxis of graft versus host disease, dosage is individually tailored. The starting dose is normally 0.5 g/kg b.w./week, starting seven days before transplantation and for up to 3 months after transplantation.

  In case of persistent lack of antibody production, dosage of 0.5 g/kg b.w./month is recommended until antibody level returns to normal.

  The dosage recommendations are summarised in the following table:

  Indication	Dose	Frequency of injections
  Replacement therapy in primary immunodeficiency	- starting dose: 0.4-0.8 g/kg b.w. - thereafter: 0.2-0.8 g/kg b.w.
  		every 2-4 weeks to obtain IgG trough level of at least 4-6 g/l
  Replacement therapy in secondary immunodeficiency	0.2-0.4 g/kg b.w.	every 3-4 weeks to obtain IgG trough level of at least 4-6 g/l
  Children with AIDS<	0.2-0.4 g/kg b.w.	every 3-4 weeks
  Immunomodulation:
  Idiopathic thrombocytopenic purpura	0.8-1 g/kg b.w.	on day 1, possibly repeated once within 3 days
  	or
  	0.4 g/kg b.w./d	for 2-5 days
  Guillain-Barré syndrome	0.4 g/kg b.w./d	for 3-7 days
  Kawasaki disease	1.6-2 g/kg b.w.	in several doses for 2-5 days in association with acetylsalicylic acid
  Allogeneic bone marrow transplantation:
  - treatment of infections and prophylaxis of graft versus host disease	0.5 g/kg b.w.	every week from day -7 up to 3 months after transplantation
  - persistent lack of antibody production	0.5 g/kg b.w.	every month until antibody levels return to normal

  Method of administration

  Sandoglobulin NF Liquid should be infused by the intravenous route only.

  It should be infused at an initial rate of 0.3 ml/kg b.w./h (0.6 mg/kg b.w./min) for 60 minutes. If well tolerated, the rate may be gradually increased to a maximum of 2 ml/kg b.w./h (4 mg/kg b.w./min). In patients who have previously tolerated Sandoglobulin NF Liquid well, it can be infused at an initial rate of 0.5 ml/kg b.w./h (1 mg/kg b.w./min) for 30 minutes. If well tolerated, the rate may be gradually increased to a maximum of 2 ml/kg b.w./h (4 mg/kg b.w./min).

• Contra Indications
  

  Hypersensitivity to any of the components.

  Hypersensitivity to homologous immunoglobulins, especially in the very rare cases of IgA deficiency when the patient has antibodies against IgA.

  Sandoglobulin NF Liquid contains the excipients L-isoleucine and L-proline and is contraindicated in patients with maple syrup urine disease (MSUD) and hyperprolinaemia.

• Special Precautions
  

  Certain severe adverse drug reactions may be related to the rate of infusion.

  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 IVIg 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 rare 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 initially injecting the product slowly ( 0.5 ml/kg b.w./h);

  - 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 hypovolaemic patients, 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, 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, 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. Sandoglobulin NF Liquid contains no carbohydrates like sucrose or maltose.

  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 a clinical study in paediatric patients with acute ITP, a transient slight-to-moderate decrease in Hb levels has been observed in some children after administration of Sandoglobulin NF Liquid. In these patients, a follow-up of Hb is recommended.

  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.

  Sandoglobulin NF Liquid contains the excipient L-isoleucine. Intake of L-isoleucine is contraindicated in patients with maple syrup urine disease (MSUD). This disease is a hereditary disorder of metabolism of oxidative decarboxylation. An increase of L-isoleucine may induce metabolic acidosis and may lead to cerebral damage.

  Nicotinamide is a water soluble vitamin and forms an essential constituent of the normal human body. There is no known contraindication. Nicotinamide serum concentrations of 0.64 mmol/l measured after infusion of 1g/kg b.w. of Sandoglobulin NF Liquid is well tolerated. Higher serum concentrations may be associated with headache and nausea.

  Sandoglobulin NF Liquid also contains as excipient the non-essential amino acid L-proline and is therefore contraindicated in patients with hyperprolinaemia. Hyperprolinaemia is a very rare disease and there are only a few families known world-wide with hyperprolinaemia. Hyperprolinaemic patients show an increased concentration of proline in the plasma and an increased urinary excretion of proline, hydroxyproline and glycine. The medical consequences appear to be moderate in most cases, however, an increased incidence of renal disease is observed in some cases and neurological symptoms and disturbance of mental development in others.

  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. They 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 Sandoglobulin NF 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.

• Interactions
  

  Live attenuated virus vaccines

  Immunoglobulin administration may impair the efficacy of live attenuated virus vaccines such as measles, mumps, rubella and varicella for a period of at least 6 weeks and up to 3 months. After administration of this 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.

  Interference with serological testing

  After 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 allo-antibodies (e.g. Coombs test).

  Drug interactions

  Patients treated with phenytoin concomitantly should be carefully monitored, as there has been a published report of hepatic toxicity with concurrent administration of nicotinamide and phenytoin.

  Formal interaction studies of nicotinamide with cardiac drugs such as β-blockers and vasodilators have not been performed.

• Adverse Drug Reactions
  

  With human normal immunoglobulin for intravenous administration, adverse reactions such as chills, headache, 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, isolated cases of reversible haemolytic anaemia/haemolysis and rare cases of transient cutaneous reactions have been observed with human normal immunoglobulin.

  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.

  Clinical trial data

  In phase II and III clinical studies AEs suspected to be related to the product (ADRs) were reported by 44 of the 81 patients (54%) who received Sandoglobulin NF Liquid. ADRs were reported more often in patients with ITP than with PID, and the overall most commonly reported ADR was headache. All ADRs were expected for IVIg therapy. They are summarised and categorised according to MedDRA System Organ Classes (SOCs) and frequency in the following table, whereby frequency rates are based on a total of 521 infusions administered.

  Frequency of ADRs in 81 patients receiving Sandoglobulin NF Liquid in Phase II and III clinical studies (ADR frequency based on a total of 521 infusions)

  MedDRA System Organ Class<	MedDRA Preferred Term	ADR Frequency Category
  Infections and infestations	Upper respiratory tract infection	Uncommon (1/1000 and <1/100)
  Nervous system disorders	Headache	Very common (1/10)
  	Dizziness	Common (1/100 and <1/10)
  Respiratory, thoracic and mediastinal disorders	Pharyngolaryngeal pain	Uncommon
  Gastrointestinal disorders	Nausea, abdominal pain upper	Common
  	Vomiting	Uncommon
  Musculoskeletal and connective tissue disorders	Myalgia, arthralgia, back pain	Common
  General disorders and administration site conditions	Fatigue, pyrexia, chills, malaise, pain	Common
  	Feeling hot, influenza-like illness	Uncommon
  Ear and labyrinth disorders	Ear pain	Uncommon

  In a clinical study in paediatric patients with acute ITP, a transient slight-to-moderate decrease in Hb levels has been observed in some children after administration of Sandoglobulin NF Liquid. In these patients, a follow-up of Hb is recommended.