Human Normal Immunoglobulin 5% w/v Taj Pharma

Human Normal Immunoglobulin 5% w/v Taj Pharma

  1. Name of the medicinal product

Human Normal Immunoglobulin 5% w/v Taj Pharma
Human Normal Immunoglobulin 10% w/v Taj Pharma

  1. Qualitative and quantitative composition

Human normal immunoglobulin (IVIg)

One ml contains: Human normal immunoglobulin 50mg or 100mg (purity of at least 95% IgG).

Distribution of the IgG subclasses (approximate values):

IgG1 62 %
IgG2 31 %
IgG3 6 %
IgG4 1 %

The maximum IgA content is 10 micrograms per ml (typically ~4 micrograms per ml).

  1. Pharmaceutical form

Human Immunoglobulin is a colourless sterile liquid for intravenous administration.

  1. Clinical particulars

4.1 Therapeutic indications

Replacement therapy in adults, and children and adolescents 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 with recurrent bacterial infections

Immunomodulation in adults, and children and adolescents 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

4.2 Posology and method of administration

Replacement therapy should be initiated and monitored under the supervision of a physician experienced in the treatment of immunodeficiency. Treatment at home should be similarly supervised, with the patient fully assessed and trained in hospital prior to self-infusion at home.

Posology

The dose and dose 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 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 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; congenital 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 transplantation

The 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 thrombocytopenia

There are two alternative treatment schedules:

  • 0.8 – 1 g/kg given 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 syndrome

0.4 g/kg/day over 5 days.

Kawasaki Disease

1.6 – 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 – starting dose:

0.4 – 0.8 g/kg

– thereafter:

0.2 – 0.8 g/kg

 

 

every 3 – 4 weeks to obtain IgG trough level of at least 5 – 6 g/l

Replacement therapy in secondary immunodeficiency 0.2 – 0.4 g/kg every 3 – 4 weeks to obtain IgG trough level of at least 5 – 6 g/l
Congenital AIDS 0.2 – 0.4 g/kg every 3 – 4 weeks
Hypogammaglobulinaemia (< 4 g/l) in patients after allogeneic haematopoietic stem cell transplantation 0.2 – 0.4 g/kg every 3 – 4 weeks to obtain IgG trough level above 5 g/l
Immunomodulation:

Primary immune thrombocytopenia

 

0.8 – 1 g/kg

or

0.4 g/kg/day

 

on day 1, possibly repeated once within 3 days

 

for 2 – 5 days

Guillain Barré syndrome 0.4 g/kg/day for 5 days
Kawasaki disease 1.6 – 2 g/kg

or

2 g/kg

in divided doses over 5 days in association with acetylsalicylic acid

in one dose in association with acetylsalicylic acid

Paediatric population

The posology in children and adolescents 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 administration

For intravenous use.

Human Immunoglobulin should be infused intravenously, at an initial rate of 0.01 – 0.02 ml/kg/minute (0.6 – 1.2 ml/kg/hour) for 15 minutes. If well tolerated (see section 4.4), the rate of administration may be increased to 0.04 ml/kg/minute (2.4 ml/kg/hour) for 15 minutes, then to 0.06 ml/kg/minute (3.6 ml/kg/hour) for 15 minutes, followed by a maximum of 0.08 ml/kg/minute (4.8 ml/kg/hour).

4.3 Contraindications

Hereditary fructose intolerance (see section 4.4).

Babies and young children (see section 4.4).

Hypersensitivity to the active substance or to any of the excipients (see section 4.4).

Hypersensitivity to human immunoglobulins, especially in patients with antibodies against IgA.

4.4 Special warnings and precautions for use

This medicinal product contains 50mg of sorbitol per ml as an 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, as they may not yet have been exposed to fructose-containing foods such as fruit or sucrose and infusion of sorbitol may be fatal. Therefore, babies and young children who have not been exposed to fructose containing foods or sucrose should not receive this medicine until it is known whether they can metabolise fructose.

In other patients, in case of inadvertent administration and suspicion of fructose intolerance, the infusion has to be stopped immediately, normal glycaemia has to be re-established and organ function has to be stabilised by means of intensive care.

Certain severe adverse reactions may be related to the rate of infusion. The recommended infusion rate given under section 4.2 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 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.

Potential complications can often be avoided by ensuring that patients:

  • are not sensitive to human normal immunoglobulin by initially injecting the product slowly (0.01 – 0.02 ml/kg/min)
  • are carefully monitored for any symptoms throughout the infusion period. In particular, patients naïve 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.

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. In case of shock, standard medical treatment for shock should be implemented.

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.

Hypersensitivity

True 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 had tolerated previous treatment with human normal immunoglobulin.

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 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).

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.

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. Human Immunoglobulin does not contain sucrose, maltose or glucose.

In patients at risk for acute renal failure, IVIg products should be administered at the minimum rate of infusion and dose practicable.

Transfusion related acute lung injuries (TRALI)

There have been reports of TRALI i.e. noncardiogenic pulmonary oedema, in patients administered IVIg products.

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 hundredmg/dl.

AMS may occur more frequently in association with high-dose (2 g/kg) IVIg treatment.

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 (See section 4.8.).

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 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) and for the non-enveloped hepatitis A (HAV) and parvovirus B19 viruses.

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 Human Immunoglobulin 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

This medicinal product contains 50mg of sorbitol per mL as an excipient. Patients with rare hereditary problems of fructose intolerance should not take this medicine. Special precautions should be taken with babies and young children because this fructose intolerance may not yet be diagnosed and may be fatal.

Home therapy

Human Immunoglobulin must only be used by patients themselves at home after thorough training in hospital by a qualified health care professional, expert in infusion of IVIg products. The patient should first be stabilised on the product under supervision in hospital.

4.5 Interaction with other medicinal products and other forms of interaction

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.

Paediatric population

There are no known interactions that are specific to the paediatric population or any subset of the paediatric population.

4.6 Fertility, 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 to be expected.

Breast-feeding

Immunoglobulins are excreted into the milk and may contribute to protecting the neonate from pathogens which have a mucosal portal of entry.

Fertility

Clinical experience with immunoglobulins suggests that no harmful effects on fertility are to be expected.

4.7 Effects on ability to drive and use machines

The ability to drive and operate machines may be impaired by some adverse reactions associated with Human Immunoglobulin. Patients who experience adverse reactions during treatment should wait for these to resolve before driving or operating machines.

4.8 Undesirable effects

Summary of the safety profile

Adverse 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 with respect to transmissible agents, see Section 4.4.

Tabulated list of adverse reactions

The 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 Human Immunoglobulin

MedDRA Standard System Organ Class Undesirable effects Frequency
Metabolism and nutrition Fluid retention, dehydration Common
Decreased appetite, iron deficiency Uncommon
Psychiatric disorders Insomnia Uncommon
Nervous system disorders Headache Very common
Dizziness, Common
Migraine, hypoaesthesia, paraesthesia, lethargy Uncommon
Ear and labyrinth Vertigo Common
Tinnitus Uncommon
Cardiac disorders Palpitations, tachycardia Common
Vascular disorders Hypertension, hypotension Common
Thrombosis, hot flush, Uncommon
Respiratory, thoracic and mediastinal disorders Nasal congestion Common
Bronchospasm, epistaxis, pharyngolaryngeal pain, Uncommon
Gastrointestinal disorders Vomiting, nausea, diarrhoea, abdominal pain Common
Abdominal distension, constipation, stomatitis Uncommon
Skin and subcutaneous tissue disorders Erythema multiforme, urticaria, pruritus Uncommon
Musculoskeletal, connective tissue disorders and bone disorders Arthralgia, myalgia, muscle spasms, back pain, neck pain, Common
Musculoskeletal stiffness, pain in extremity Uncommon
General disorders and administration site conditions Pyrexia Very common
Chills, chest discomfort/ pain, fatigue, asthenia, infusion site reaction, infusion site erythema , pain Common
Investigations Coombs’ direct test positive, anaemia/haemoglobin decreased Common
Anti-erythrocyte antibody positive, white blood cell count increased, urinary haemosiderin positive, gastric pH decreased Uncommon

Description of selected adverse reactions

None of the reported adverse reactions to Human Immunoglobulin warrant separate description.

Paediatric population

Of the 50 patients in the clinical study of Human Immunoglobulin in primary immunodeficiency (GMX01), seven were aged less than 18 years (age range 9 to 17 years). A separate paediatric clinical study of Human Immunoglobulin in primary immunodeficiency (GMX04) treated 25 patients aged less than 18 years (age range 3 to 16 years). Of the 35 patients in the clinical study of Human Immunoglobulin in chronic immune thrombocytopenia (ITP) (GMX02), three were aged less than 18 years (age range 6 to 17 years). The frequency, type and severity of adverse reactions in children are similar to those in adults.

Other special populations

Certain patient groups may be at increased risk of hypersensitivity reactions, thromboembolism or acute renal failure. Caution should be exercised when infusing IVIg in obese patients or those with advanced age, hypertension, diabetes mellitus, history of vascular disease or thrombotic episodes, acquired or inherited thrombophilic disorders, prolonged periods of immobilisation, severe hypovolaemia, diseases which increase blood viscosity, pre-existing renal insufficiency or those receiving concomitant nephrotoxic medicinal products; see section 4.4 for details.

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.

4.9 Overdose

Overdose may lead to fluid overload and hyperviscosity, particularly in patients at risk, including elderly patients or patients with cardiac or renal impairment.

  1. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: immune sera and immunoglobulins: immunoglobulins, normal human, for intravascular administration.

Human normal immunoglobulin contains mainly immunoglobulin G (IgG) with a broad spectrum of antibodies against various infectious agents.

Human normal immunoglobulin contains the IgG antibodies present in the normal population. It is usually prepared from pooled plasma from not fewer than 1,000 donations. It has a distribution of immunoglobulin G subclasses closely proportional to that in native human plasma. Adequate doses of this medicinal product may restore abnormally low immunoglobulin G levels to the normal range.

The mechanism of action in indications other than replacement therapy is not fully elucidated, but includes immunomodulatory effects.

A phase III, multicentre, non-randomized, open-label study in 50 predominantly adult subjects with primary immunodeficiency diseases (PID), where Human Immunoglobulin was infused at a dose of 300 to 800mg/kg every 21 or 28 days, concluded that Human Immunoglobulin was well tolerated and efficacious and therefore suitable for the management of subjects with PID. There were no serious acute bacterial infections during the 12 months of treatment, and the most commonly reported adverse reactions were headache (18 patients), nausea (6 patients), pyrexia (6 patients) and fatigue (6 patients).

A later phase III, open-label, multicentre clinical study investigating the safety and efficacy of Human Immunoglobulin infused at a dose of 1 g/kg/day for two consecutive days in 35 subjects with chronic immune thrombocytopenic purpura (ITP) showed Human Immunoglobulin to be an effective treatment, and hence its efficacy in immunomodulation. The most commonly reported adverse reactions were headache (10 patients), vomiting (6 patients) and pyrexia (5 patients).

Paediatric population

Study above, comprised predominantly of adult subjects with PID and included seven patients aged less than 18 years (9 – 17 years inclusive). There were no reports of serious adverse reactions in any of the paediatric subjects.

Study above in ITP included three subjects aged less than 18 years (6 – 17 years inclusive). One of the paediatric subjects (aged six years) experienced a serious adverse reaction (headache, with vomiting and dehydration).

A phase III, multicentre, non-randomized, open-label paediatric study in 25 children and adolescent subjects (aged 3-16 years inclusive) with primary immunodeficiency diseases (PID), where Human Immunoglobulin was infused at a dose of 300 to 800mg/kg every 21 or 28 days, concluded that Human Immunoglobulin was well tolerated and efficacious in children with PID.

There were two serious acute bacterial infections reported during the 12 months of treatment, and the most commonly reported adverse reactions were headache (8 patients), hypotension (4 patients), pyrexia (3 patients) and tachycardia (3 patients).

The European Medicines Agency has waived the obligation to submit the results of studies with Human Immunoglobulin in all subsets of the paediatric populations in ITP (see section 4.2 for information on paediatric use).

5.2 Pharmacokinetic properties

Human normal immunoglobulin is immediately and completely bioavailable in the recipient’s circulation after intravenous administration. It is distributed relatively rapidly between plasma and extravascular fluid, and after approximately 3 – 5 days equilibrium is reached between the intra- and extravascular compartments. At steady state Human Immunoglobulin has a median half-life in adults of 31.3 days (range 21.1 days to 42.7 days). This half-life may vary from patient to patient, in particular in primary immunodeficiency.

IgG and IgG-complexes are broken down in cells of the reticuloendothelial system.

Paediatric population

Pharmacokinetic data is available from 25 paediatric patients across the two PID studies: GMX01 (2/50 patients were included in the paediatric PK analysis) and GMX04 (23/25 patients were included in the PK analysis). At steady state Human Immunoglobulin was shown to have a median half-life in children of 35.5 days (range 24.2 to 76.2 days).

5.3 Preclinical safety data

Immunoglobulins are normal constituents of human plasma and therefore toxicity testing in heterologous species is of no relevance. Human Immunoglobulin contains highly purified immunoglobulins and has been tested in non-clinical haemodynamic monitoring studies. There was no evidence of effects on blood pressure or heart rate at infusion rates similar to those used clinically. At higher infusion rates of approximately 2- to 7-fold those used clinically, a hypertensive effect was found. No other preclinical studies have been carried out.

  1. Pharmaceutical particulars

6.1 List of excipients

D-sorbitol, Glycine, Sodium, Chloride, Acetate, Polysorbate 80

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

36 months if stored unopened in the dark at temperatures between 2°C and 25°C.

Human Immunoglobulin should be used immediately after opening (see section 4.2).

6.4 Special precautions for storage

Human Immunoglobulin should be stored at temperatures between 2°C and 25°C in its carton.

DO NOT FREEZE.

Do not use after the expiry date printed on the label. The conditions of expired or incorrectly stored product cannot be guaranteed. Such product may be unsafe and should not be used.

6.5 Nature and contents of container

Human Immunoglobulin is a sterile colourless liquid immunoglobulin G supplied as 2.5 g, 5 g, 10 g and 20 g doses. The product is contained in a clear glass bottle with an integral sling, closed with a stopper and oversealed with a tamper-evident cap.

6.6 Special precautions for disposal and other handling

The product should be brought to room temperature before use.

The solution should be clear or slightly opalescent and colourless or pale yellow. Solutions that are cloudy or have deposits should not be used.

Any unused product or waste material should be disposed of in accordance with local requirements.

 

  1. MANUFACTURED IN INDIA BY:
    TAJ PHARMACEUTICALS LTD.
    Mumbai, India
    Unit No. 214.Old Bake House,
    Maharashtra chambers of  Commerce Lane,
    Fort, Mumbai – 400001
    at:Gujarat, INDIA.
    Customer Service and Product Inquiries:
    1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
    Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
    E-mail: tajgroup@tajpharma.com

 

Human Normal Immunoglobulin 5% w/v, 10% w/v Taj Pharma

 

PACKAGE LEAFLET: INFORMATION FOR THE USER
Human normal immunoglobulin

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor, pharmacist or nurse.
  • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
  • If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

  1. What Human Immunoglobulin is and what it is used for
  2. What you need to know before you use Human Immunoglobulin
  3. How to use Human Immunoglobulin
  4. Possible side effects
  5. How to store Human Immunoglobulin
  6. Contents of the pack and other information

1. What Human Immunoglobulin is and what it is used for

Human Immunoglobulin is a solution containing the active substance called human normal immunoglobulin (a protein in the body used to fight infections) which is obtained from blood plasma from screened donors. These donors are selected from carefully screened and healthy donors. The product is given by injection into a vein (intravenous infusion). It can be given in a hospital or for use at home and is only available on a doctor’s prescription.

Human Immunoglobulin is used to treat several illnesses. Your doctor will advise you what you are receiving Human Immunoglobulin for. This medicine is used to replace antibodies which are missing from your body in primary antibody deficiencies (lack of certain proteins protective against infection that you may either have been born with or may develop during life) such as:

  • agammaglobulinaemia (deficiency of gamma globulins in the blood),
  • hypogammaglobulinaemia (low levels of immunoglobulin G (IgG), with or without low IgA and/or IgM),
  • common variable immunodeficiency (failure of the immune system to produce antibodies against infections),
  • severe combined immunodeficiency (a severe genetic disorder of the immune system making you susceptible to infections),
  • Wiskott Aldrich syndrome (hereditary disorder with signs of eczema, recurring infections, and a decrease in the number of white blood cells).

Human Immunoglobulin is also used to replace antibodies in secondary antibody deficiencies caused by:

  • chronic lymphocytic leukaemia (cancer of the blood where too many white blood cells are produced),
  • some other bone marrow cancers,
  • AIDS in children born with the disease, when repeated infections occur.

Human Immunoglobulin is also used for the treatment of:

  • Idiopathic thrombocytopenic purpura (ITP, a blood platelet disorder),
  • Kawasaki disease (disorder of the blood vessels and heart in children),
  • Guillain Barré syndrome (disorder of peripheral nerves), bone marrow transplant, as an immunoglobulin supplement.
  1. What you need to know before you use Human Immunoglobulin Do not use Human Immunoglobulin
  • if you suffer from hereditary fructose intolerance,
  • for babies and young children who may have a fruit sugar intolerance,
  • if you are allergic to human normal immunoglobulin or any of the other ingredients of this medicine (listed in Section 6). If you do experience an allergic reaction, seek medical attention immediately,
  • if you have developed antibodies to IgA. Your doctor will advise you if this affects you.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Human Immunoglobulin if any of the following conditions applies to you.

  • fruit sugar intolerance,
  • diabetes,
  • obesity,
  • kidney disorder,
  • stroke (now or in the past),
  • heart complaint (now or in the past),
  • are elderly,
  • taking other medicines,
  • pregnant or breast-feeding.

You may need to be monitored closely during treatment and the dose may have to be altered.

With immunoglobulin treatments, you may get lung damage related to the treatment called Transfusion Related Acute Lung Injury (TRALI). If you get shortness of breath and find yourself having to breathe rapidly during or within several hours of your infusion, tell your doctor or nurse immediately as these symptoms may need urgent treatment.

Immunoglobulin infusions may also interfere with immunisation with certain virus vaccines such as measles, rubella, mumps and varicella for a period of at least 6 weeks and up to 3 months. In the case of measles, this impairment may persist for up to a year. If you need a blood test during this period, tell your doctor when you last had an injection of Human Immunoglobulin, as false positive results may occur with certain tests. This medicine will raise the level of various antibodies in your blood for several weeks or longer.

Other medicines and Human Immunoglobulin

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Driving and using machines

Some side effects of Human Immunoglobulin may affect your ability to drive or operate machinery. Wait for side effects to resolve before you drive or operate machines.

Human Immunoglobulin contains D-sorbitol, sodium chloride, glycine, sodium acetate and polysorbate 80.

If you know you are unable to digest fructose (a certain type of sugar, sometimes called fruit sugar) then do not use Human Immunoglobulin. Also, this medicine should not be used in babies or very young children until they are known to be able to digest fructose. Sucrose (table sugar) contains fructose.

Please note:

When medicines are made from human blood or plasma, certain measures are put in place to prevent infections being passed on to patients. These include:

  • careful selection of blood and plasma donors to make sure those at risk of carrying infections are excluded,
  • the testing of each donation and pools of plasma for signs of virus/infections,
  • the inclusion of steps in the processing of the blood or plasma that can inactivate or remove viruses.

Despite these measures, when medicines prepared from human blood or plasma are administered, the possibility of passing on infection cannot be totally excluded. This also applies to any unknown or emerging viruses or other types of infections.

The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus and hepatitis C virus, and for the non-enveloped hepatitis A and parvovirus B19 viruses.

Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections possibly because the antibodies against these infections, which are contained in the product, are protective.

It is strongly recommended that every time you receive a dose of Human Immunoglobulin the name and batch number of the medicine are recorded in order to maintain a record of the batches used.

  1. How to use Human Immunoglobulin

Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not sure.

Do not exceed the recommended dose. See below for full dosage recommendations. Your doctor will decide the appropriate dose. Do not add any other medicines or fluids to Human Immunoglobulin.

The medicine is given by intravenous injection (infusion) using a giving set which your doctor or nurse will provide. The maximum safe rate of infusion is determined by your body weight. An infusion rate of 0.01 – 0.02 ml/kg/minute is recommended for the first 15 minutes, gradually increasing it to 0.08 ml/kg/minute.

To reduce the risk of side effects, the infusion rate in the first 15 minutes must be low (0.01 –

0.02 ml/kg/minute). Some severe side effects may be caused by injecting the product too quickly.

The recommended infusion rate must be checked closely and you must be carefully observed for any symptoms throughout this period. If you feel unwell, tell your doctor and the infusion will either be slowed or stopped until you feel better.

You should remain with another person for at least 20 minutes after the infusion is complete or for an hour if it is the first time you have had this product.

Dosage recommendations:

  • antibody deficiency disease: the dosage is at first 0.4 – 0.8 g/kg body weight, then 0.2 – 0.8 g/kg body weight every 3 to 4 weeks, depending on your clinical response and measurements of immunoglobulins in the bloodstream.
  • bone marrow cancers (including leukaemia) and children born with AIDS resulting in antibody deficiencies: 2 – 0.4 g/kg body weight every 3 to 4 weeks.
  • Idiopathic thrombocytopenic purpura (ITP): 8 – 1 g/kg body weight as a single dose, sometimes repeated within 3 days. A dose of 0.4 g/kg may be administered daily for 2 – 5 days.

Guillain Barré syndrome: 0.4 g/kg/day for 5 days.

  • Kawasaki disease: 6 to 2 g/kg body weight split into several doses over 2 – 5 days or 2 g/kg body weight as a single dose. Aspirin should usually be given as well. Your doctor will decide the appropriate dose and whether you should take aspirin.
  • after bone marrow transplant: 2 – 0.4 g/kg body weight every 3 to 4 weeks.

Bring the medicine to room temperature for at least 2 hours before infusion. Do not use if there are any particles in the medicine or it is discoloured. Contact your doctor if you are not sure if your medicine is fit for use.

The product does not contain any additives to prevent the growth of germs once it has been opened. Therefore the infusion should begin immediately after piercing the cap.

This product is for single injection only. Safely throw away any used materials or unused solution. To help you, your doctor will provide instructions and a box.

If you use more Human Immunoglobulin than you should

If you use more Human Immunoglobulin than you should there is no cause for alarm. However, if you feel unwell afterwards or have any discomfort, tell your doctor.

If you forget to use Human Immunoglobulin

Do not take a double dose to make up for a forgotten dose.

If you stop using Human Immunoglobulin

You should consult your doctor if you begin to feel unwell. If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

  1. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. If you feel unwell, you must tell your doctor immediately.

The risk of side effects can be minimised by making sure that the infusion rate in the first 15 minutes is low (0.01 – 0.02 ml/kg/minute) (see Section 3 “How to use Human Immunoglobulin”).

The following side effects have been reported to occur:

Very common side effects (affecting more than 1 in 10 people)

  • headache
  • high temperature

Common side effects (affecting less than 1 in 10 and more than 1 in 100 people)

  • vomiting or feeling sick
  • dizziness or vertigo
  • body pain, back pain or neck pain
  • muscle pain or spasms
  • joint pain
  • raised or lowered blood pressure
  • raised pulse rate
  • palpitations
  • diarrhoea
  • stomach pain or acidity

nose congestion

  • chills
  • skin rash or itching
  • chest discomfort/pain
  • pain, redness or inflammation at infusion site
  • fluid retention
  • pins & needles or numbness
  • blood test (Coombs’) positive
  • insomnia
  • dehydration
  • anaemia

Uncommon side effects (affecting less than 1 in 100 and more than 1 in 1,000 people)

  • blood clots
  • tiredness or weakness
  • wheeze
  • migraine
  • muscle or joint stiffness
  • decreased appetite
  • ringing in ears
  • hot flushes
  • sore throat
  • mouth ulcers
  • nose bleeds
  • bloating
  • constipation
  • increased white blood cell count (shown by blood test)
  • antibody against red blood cells (shown by blood test)
  • positive urine test for haemosiderin, an iron storage compound (related to anaemia)
  • iron deficiency

Rare side effects (affecting less than 1 in 1,000 and more than 1 in 10,000 people)

  • sudden fall in blood pressure which could be serious
  • severe allergic reaction that may cause difficulty in breathing or swallowing
  • kidney failure

If you are using this medicine at home and you feel unwell during the infusion, stop the infusion and contact your doctor immediately. If you feel unwell during an infusion in hospital tell the doctor or nurse immediately. The rate of infusion will probably then be slowed until you feel better. The rate of infusion may then be slowly increased to half that achieved when you started to feel unwell. If you still feel unwell, the infusion should be stopped, but may be resumed after about an hour when you are feeling better.

Reporting of side effects

If you get any side effects talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

  1. How to store Human Immunoglobulin

Keep this medicine out of the sight and reach of children.

The medicine should be stored in its carton, between 2°C and 25°C.

Do not freeze.

Do not use this medicine if you notice the solution is cloudy or has deposits.

Do not use this medicine after the expiry date which is stated on the label. The expiry date refers to the last day of that month.

Disposal

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away any medicines you no longer use. These measures will help protect the environment.

  1. Contents of the pack and other information What Human Immunoglobulin contains

The active substance is human normal immunoglobulin, mainly immunoglobulin G (IgG) and is obtained from blood plasma from screened donors. These donors are selected from the USA.

The other ingredients are D-sorbitol, glycine, sodium chloride, sodium acetate and polysorbate 80 (see also Section 2 “Human Immunoglobulin contains D-sorbitol, sodium chloride, glycine, sodium acetate and polysorbate 80”).

Human Immunoglobulin is slightly acidic, but this will not have any unpleasant effects as your blood will neutralise it rapidly.

The maximum amount of sodium is 50 mmol/l.

The IgA content of Human Immunoglobulin is less than 10 micrograms/ml (typically about 4 micrograms/ml). Human Immunoglobulin has a composition of the different types of IgG immunoglobulins similar to that in blood.

What Human Immunoglobulin looks like and contents of the pack;

Human Immunoglobulin is a sterile, colourless liquid.

This product comes in 2.5 g, 5 g, 10 g and 20 g dose sizes, with a sling to hold the bottle during infusion.

  1. MANUFACTURED IN INDIA BY:
    TAJ PHARMACEUTICALS LTD.
    Mumbai, India
    Unit No. 214.Old Bake House,
    Maharashtra chambers of  Commerce Lane,
    Fort, Mumbai – 400001
    at:Gujarat, INDIA.
    Customer Service and Product Inquiries:
    1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
    Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
    E-mail: tajgroup@tajpharma.com

 

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Taj Generics (Taj Pharma) provides a wide range of products to the Indian market, including an extensive range of generics and specialty products; Our products cover a vast array of therapeutic categories, and we offer an extensive range of dosage forms and delivery systems including oral solids, controlled-release, steriles, injectables, topicals, liquids, transdermals, semi-solids and high-potency products. Our Generics portfolio offers over 1500 products in the major therapeutic areas of gastro-intestinal, cardiovascular, pain management, oncology, anti-infectives, paediatrics and dermatology.