Consumer medicine information

OCTAGAM 10%

Immunoglobulin, normal (human)

BRAND INFORMATION

Brand name

Octagam 10%

Active ingredient

Immunoglobulin, normal (human)

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using OCTAGAM 10%.

SUMMARY CMI

octagam® 10%

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using octagam® 10%?

Octagam® 10% contains the active ingredient human normal immunoglobulin. Octagam® 10% is used in patients who do not have enough antibodies (proteins that help the body fight infection) in their blood.

For more information, see section 1. Why am I using octagam® 10%? in the full CMI.

2. What should I know before I use octagam® 10%?

Do not use if you have ever had an allergic reaction to any human normal immunoglobulin or to any ingredients listed at the end of the CMI.

Do not use if you have antibodies to human immunoglobulin A in your blood – this may occur if you have human immunoglobulin A deficiency.

There are a number of circumstance in which people may need to use caution when using this medicine. It is important to understand if these apply to you before taking octagam® 10% (see Section 2. What should I know before I use octagam® 10%? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with OCTAGAM® 10% and effect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use octagam® 10%?

Your doctor will administer octagam® 10% as a slow injection (infusion) into a vein.

For more information, see Section 4. How do I use octagam® 10%? in the full CMI.

5. What should I know while using octagam® 10%?

Things you should do
  • Tell your doctor if you become pregnant
  • Tell your doctor if you are to have any blood glucose tests
  • Tell your doctor if you are to receive a vaccine
  • Remind your doctor/pharmacist that you are on octagam® 10% before starting any new medicines

For more information, see Section 5. What should I know while using octagam® 10%? in the full CMI.

6. Are there any side effects?

All medicines can have side effects allthough not everybody will experience them. Do not be alarmed by this list.

Common side effects include chills, headache, fever, vomiting, allergic reactions, nausea, joint/muscle pain, changes in blood pressure, skin rash, fatigue, flushing, sweating, rapid beating of the heart, low back pain and injection site reactions.

Serious potential side effects that require medical attention include sudden signs of allergic reaction (rash, itching/hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing) or signs of blood clot (breathing difficulties, pain/ swelling in legs, chest pain, severe headache, changes in eye sight, slurred speech, dizziness, fainting, sudden weakness/numbness in one side or part of the body).

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

octagam® 10%

Active ingredient: Human Normal Immunoglobulin


Consumer Medicine Information (CMI)

This leaflet provided important information about using octagam® 10%. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using octagam® 10%.

Where to find information in this leaflet:

1. Why am I using octagam® 10%?
2. What should I know before I use octagam® 10%?
3. What if I am taking other medicines?
4. How do I use octagam® 10%?
5. What should I know while using octagam® 10%?
6. Are there any side effects?
7. Product details

1. Why am I using octagam® 10%?

Octagam® 10% is a ready-to-use solution that is infused intravenously (into a vein). It contains human normal immunoglobulins. Immunoglobullins (also known as antibodies) are proteins found in human blood that help your body fight infections caused by bacteria or viruses. You might not be able to fight off infections if you do not have enough antibodies.

Octagam® 10% is used to

  • replace antibodies in patients with no immune system due to a genetic defect or in patients with low or no antibodies due to underlying disease or when medications suppress the immune system
  • modulate the immune system when there is an imbalance (such as conditions where the body attacks its own tissues)
  • treat or prevent infection after a bone marrow transplant

2. What should I know before I useoctagam® 10%?

Warnings

Do not use octagam® 10% if:

  • you are history of allergic to human normal immunoglobulin, or to any of the ingredients listed at the end of this leaflet.
Always check the ingredients to make sure you can use this medicine.
  • you have human immunoglobulin A (IgA) deficiency

Check with your doctor if you:

  • have any other medical conditions, including:
    - kidney disease
    - diabetes
    - heart or blood vessel conditions (such as stroke, heart attack, angina, high blood pressure, or narrowing or hardening of the arteries, high cholesterol, blood clots in your legs (deep vein thrombosis), lungs (pulmonary embolism) or other parts of your body), or if an immediate family member has, or has had any of these conditions
  • have allergies to any other medicines, or if you have ever had an allergic reaction to an injection
  • are taking any medicines for any other condition
  • are taking the contraceptive pill or hormone replacement treatment, as these may increase your risk of developing a blood clot

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

It is not known if octagam® 10% can affect the developing baby when administered to a pregnant woman so the medicine should be given to a pregnant woman only if clearly needed. Immunglobulins pass into breastmilk so octagam® 10% should only be given with caution to breastfeeding mothers

Important information about the ingredients in octagam® 10%

Because this product is made from human blood, there is a risk that it could transmit infectious agents, such as known viruses that can cause disease, or other infectious agents which may not have been discovered yet. The risk that octagam® 10% will transmit an infectious agent has been reduced by screening blood donors for prior expoure to certain viruses, testing all donations for the presence of certain viruses and by including steps in the manufacturing process that are known to remove or inactivate viruses.

Despite these measures, the risk of contamination by viral and other unknown agents can not be totally excluded.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including medicines,vitamins or supplements that you buy without a prescription from your pharmacy, supermarket and health food shop.

Vaccinations: If you are planning on having a vaccination, tell your vaccinating doctor about your treatment with octagam® 10% before receiving any vaccination. Octagam 10% may impair the effects some vaccines such as measles, rubella, mumps and varicella even up to three months later. As such, the use of such vaccines should be delayed for at least three months after octagam® 10% administration.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these interfere with octagam® 10%.

4. How do I use octagam® 10%?

How much to take/use

Your doctor will determine how much octagam® 10% you will need. The amount depends on your illness, your current condition and your body weight.

When to take octagam® 10%

Your doctor will determine how often you will need to use octagam® 10% depending on your illness.

How to use octagam® 10%

Octagam® 10% will be administered by your doctor or healthcare professional.

Octagam® 10% will be given as an infusion, that is, an injection given slowly into the vein.

On the day of your treatment, it is important to make sure you have had sufficient fluids as this will help reduce the chance of side effects. Your infusion of octagam® 10% will begin at a slow rate and if tolerated your doctor or healthcare professional may increase the infusion rate until the administration is complete.

If you use too much octagam® 10%

As octagam® 10% is given to you under the supervision of your doctor or trained medical professional, it is very unlikely that you will receive an overdose. If you experience any side-effects, tell your doctor or nurse immediately.

5. What should I know while using octagam® 10%?

Things you should do

  • tell your doctor immediately if you become pregnant
  • tell your doctor if you are to have a blood or urinary test. The maltose in octagam® 10% can interfere with some blood and urinary glucose tests resulting in falsely elevated glucose readings. Certain antibody levels can rise after octagam® 10% which can result in misleading positive values in some blood tests
  • tell your doctor if you are to receive a live vaccine as octagam® 10% may impair the effect of some vaccines
  • tell your doctor before starting any new medicines

Remind any doctor, dentist or pharmacist you visit that you are using octagam® 10%.

Driving or using machines

Be careful before you drive or use any macines or tools until you know how octagam® 10% affects you.

This medicine is not expected to affect your ability to drive a car or operate machinery.

Looking after your medicine

You will be given octagam® 10% in hospital. You will probably not need to keep this medicine at home. If you are required to keep this medicine at home follow the instuctions on the carton on how to take care of your medicine properly.

Store octagam® 10% in your refrigerator (at 2°C to 8°C). Do not freeze. Keep octagam® 10% in the outer carton provided to protect the medicine from light.

Keep the medicine where children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need this medicine, or it is out of date, take it to any pharmacy for safe disposal.

Do not throw away any medicines via wastewater or household waste.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • General side effects: chills, headache, fever, vomiting, joint/muscle/lower back pain, skin rash, tiredness, weakness
  • Skin reactions: skin rash, flushing sweating
  • Reactions at the infusion site: pain, redness, swelling, itching, and discomfort
Speak to your doctor if you have any of these less serious side effects and they worry you

Individuals may react differently to similar doses of the same product. Most side effects tend to be related to the rate of infusion and are likely to reduce or disappear when the rate is slowed down or the infusion stopped.

Serious side effects

Serious side effectsWhat to do
  • Allergic or anaphylactic reaction symptoms:
    - feeling light-headed, dizzy or faint (signs of a fall in blood pressure)
    - skin rash and itchiness
    - swelling of the mouth or throat, throat tightness
    - difficulty breathing, wheezing
  • Meningitis like symptoms:
    - Severe headache with nausea,and/or vomiting
    - drowsiness
    - neck stiffness
    - fever
    - sensitivity to light
  • Symptoms of blood clots:
    - chest pain or a feeling of heaviness on your chest which may radiate to the left arm
    - unusual, severe or long-lasting headache
    - shortness of breath difficulty breathing, wheezing
    - swelling of the face, lips or tongue or other parts of the body
    - sudden changes in eyesight (such as loss of vision or blurred vision)
    - slurred speech or any other difficulties affecting speech
    - dizziness or fainting
    - sudden weakness or numbness in one side or part of the body
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects

A condition called aseptic meningitis syndrome may occur occasionally after receiving this medicine. It usually begins within several hours to two days following treatment. The signs include severe headache (migraine-like), neck stiffness, drowsiness, fever, inability to stand bright light, painful eye movements, and nausea and vomiting. The condition reverses without ill effects when treatment is stopped. You may be more susceptible to this syndrome if you suffer from migraine headaches.

In rare cases, the use of octagam® 10% may lead to the formation of blood clots. Very occasionally blood clots may cause serious permanent disabilities, or may even be fatal. Blood clots can form in the veins or the arteries and may result in conditions related to the site of the blood clot, such as heart attack or stroke. The most common symptoms of blood clots are listed in the table of serious side effects.

Tell your doctor, nurse or pharmacist if you notice anything else that may be making you feel unwell.

Other sides effects not listed here may also occur in some people

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What octagam® 10% contains

Active ingredient
(main ingredient)
Human normal immunoglobulin
Other ingredients
(inactive ingredients)
Maltose
Tributyl phosphate
Octoxinol 9
Water for injections
Human immunoglobulin A (IgA)

Do not take this medicine if you are allergic to any of these ingredients.

What octagam® 10% looks like

Octagam® 10% is a clear, slightly opalescent solution. It is supplied in glass bottles.

Octagam® 10% is available in the following fill sizes:
20 mL AUST R 155601
50 mL AUST R 155602
100 mL AUST R 155603
200 mL AUST R 155604

Who distributes octagam® 10%

Octagam® 10% is supplied by:

Octapharma Australia Pty. Ltd.
Jones Bay Wharf
42/26-32 Pirrama Road
Pyrmont NSW 2009
Australia

Medical Enquiries: 1800 780 169 (Australia toll free)
Email: [email protected]

This leaflet was prepared in January 2021.

® Registered trademark of Octapharma AG

Published by MIMS March 2021

BRAND INFORMATION

Brand name

Octagam 10%

Active ingredient

Immunoglobulin, normal (human)

Schedule

S4

 

1 Name of Medicine

Human normal immunoglobulin.

2 Qualitative and Quantitative Composition

Octagam 10% contains 100 mg/mL of human normal immunoglobulin with a purity of at least 95% immunoglobulin G (IgG), and a broad spectrum of antibodies against infectious agents. It is composed of the following distribution of IgG subclasses (approx. values): IgG1 60%, IgG2 32%, IgG3 7%, IgG4 1%.
Octagam 10% contains ≤ 3% polymers. Monomer and dimer content is ≥ 90%.
The human immunoglobulin A (IgA) content is ≤ 0.4 mg/mL. Octagam 10% is contraindicated in patients with IgA deficiency (for further details, see Section 4.3 Contraindications).
Octagam 10% contains all the IgG activities which are present in the normal population. It is prepared from pooled plasma from more than 3,500 donors.
For a full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for intravenous infusion.
The solution is clear or slightly opalescent.

4 Clinical Particulars

4.1 Therapeutic Indications

Replacement therapy.

Primary immunodeficiency syndromes: congenital agammaglobulinaemia and hypogammaglobulinaemia, common variable immunodeficiency, severe combined immunodeficiencies, Wiskott Aldrich syndrome.
Myeloma or chronic lymphocytic leukaemia with severe secondary hypogammaglobulinaemia and recurrent infections.
Children with congenital acquired immune deficiency syndrome (AIDS) who have repeated bacterial infections.

Immunomodulation.

Idiopathic thrombocytopenic purpura, in adults or children with a high risk of bleeding or prior to surgery to correct the platelet count.
Guillain-Barre syndrome.
Kawasaki disease.

Allogeneic bone marrow transplantation.

4.2 Dose and Method of Administration

Dose.

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 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, followed by at least 0.2 g/kg every three weeks.
The dose required to achieve a trough level of 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 2 to 4 weeks.
Trough levels should be measured in order to adjust the dose and dosage interval.

Replacement therapy in myeloma or chronic lymphatic 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 every three to four weeks.

Idiopathic thrombocytopenic purpura.

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

Guillain-Barre syndrome.

0.4 g/kg/day for 3 to 7 days. Experience in children is limited.

Kawasaki disease.

1.6-2 g/kg should be administered in divided doses over two to five days or 2 g/kg as a single dose. 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 transplant. 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/week, starting seven days before transplantation and for up to 3 months after transplantation.
In the case of persistent lack of antibody production, dosage of 0.5 g/kg/month is recommended until antibody level returns to normal.
The dosage recommendations are summarised in Table 1.

Method of administration.

Octagam 10% should be infused intravenously at an initial rate of 0.6 to 1.2 mL/kg/hour for 30 minutes. If well tolerated, the rate of administration may gradually be increased to a maximum of 7.2 mL/kg/hour.
If large volumes are administered, the product should be warmed to room or body temperature before use.
The solution should be clear or slightly opalescent. Do not use solutions which are cloudy or have deposits.
Octagam 10% does not contain an antimicrobial agent. Once the container has been opened the contents should be used immediately. Product is for single use in one patient only.
In order to infuse any product that may remain in the infusion tubing at the end of the infusion the tubing may be flushed with either 0.9% saline or 5% dextrose solution.
Any unused product should be disposed of in accordance with Special Precautions for Disposal.

4.3 Contraindications

Hypersensitivity to homologous immunoglobulins, especially in very rare cases of IgA deficiency, when the patient has antibodies against IgA. Octagam 10% is contraindicated in any patient who has a history of an allergic reaction to any human normal immunoglobulin preparation or to any constituent of Octagam 10%.

4.4 Special Warnings and Precautions for Use

Certain severe adverse drug reactions may be related to the rate of infusion. The recommended infusion rate must be closely followed (see Section 4.2 Dose and Method of Administration). Patients must be closely monitored and carefully observed for any symptoms throughout the infusion period.
Certain adverse reactions may occur more frequently:
with a high infusion rate;
in patients with hypo- or agammaglobulinaemia, with or without IgA deficiency;
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 patient are:
not sensitive to human normal immunoglobulin by initially infusing the product slowly (0.6 to 1.2 mL/kg/hour);
carefully monitored for any symptoms throughout the infusion period. In particular, patients naive to human normal immunoglobulin, patients switched from an alternative intravenous human normal immunoglobulin (IVIg) product to Octagam 10% 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.
If allergic or anaphylactic type reactions occur, the infusion should be stopped immediately and appropriate treatment instituted. In case of shock, the current medical standards for shock treatment should be observed.

Hypersensitivity and anaphylactic reactions.

True hypersensitivity reactions are rare. They can occur in very seldom 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.

Thromboembolic events.

Arterial and venous thromboembolic events have been reported in association with Octagam, particularly in those with known risk factors (see Section 4.8 Adverse Effects (Undesirable Effects)). The pathogenesis of thromboembolic events associated with IVIg's is assumed to be multifactorial. A relative increase in blood viscosity from the high influx of immunoglobin and/or the presence of procoagulant factors in the immunoglobulin solution are two possible mechanisms. There was an increased rate of thromboembolic events reported in 2010 associated with Octagam. The unexpected presence of factor XIa appeared to be the main cause for the thromboembolic events. Corrective measures in the manufacturing process of Octagam have been implemented. Arterial thromboembolic events included myocardial infarction and stroke. Most arterial thromboembolic events occurred during Octagam infusion or within the first 24 hours postinfusion. Venous thromboembolic events included deep vein thromboses and pulmonary embolism. Most venous thromboembolic events occurred within 72 hours post-Octagam infusion.
Caution should be exercised in prescribing and infusing IVIg in patients with pre-existing risk factors for arterial and venous thromboembolic events such as obesity, smoking, advanced age, hypertension, diabetes, a history of atherosclerosis/ vascular disease or thrombotic events, hyperlipidaemia, multiple cardiovascular risk factors, impaired cardiac output, pregnancy and the puerperium, oestrogen containing hormone replacement therapy or oral contraceptive, acquired or inherited thrombophilic disorders, prolonged periods of immobilisation, hypovolemia, surgery, central venous catheterisation, active malignancy and/or known or suspected hyperviscosity.
The potential risks and benefits of IVIg's, including Octagam, should be weighed against those of alternative therapies for all patients for whom IVIg administration is being considered. Baseline assessment of blood viscosity should be considered in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronaemia/ markedly high triglycerides, or monoclonal gammopathies. Patients should be monitored closely for signs and symptoms of thromboembolism, particularly during and for 72 hours after Octagam infusion. Rapid rates of IVIg infusion may be a risk factor for thromboembolic events. The recommended infusion rate should not be exceeded. For patients judged to be at risk of developing thromboembolic events, administer Octagam at the minimum rate of infusion practicable. The decision to take antithrombotic prophylactic measures is a clinical decision that requires a careful assessment of individual patients' underlying risk factors.

Renal dysfunction.

Cases of renal dysfunction, acute renal failure, osmotic nephrosis and death have been reported in patients receiving IVIg therapy. In most cases, risk factors have been identified, such as pre-existing renal insufficiency, diabetes mellitus, hypovolemia, sepsis, overweight, concomitant nephrotoxic medicinal products or age over 65.
In patients at risk of acute renal failure or thromboembolic adverse reactions, 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 the 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 not containing sucrose may be considered.
In all patients, IVIg administration requires: adequate hydration prior to the infusion of IVIg, monitoring of urine output, monitoring of serum creatinine levels, avoidance of concomitant use of loop diuretics.

Aseptic meningitis syndrome.

Aseptic meningitis syndrome (AMS) has been reported to occur infrequently in association with IVIg treatment. The syndrome usually begins within several hours to two days following IVIg treatment. It is characterised by symptoms and signs including severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, and nausea and vomiting. 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 g/L. Patients exhibiting such symptoms and signs should receive a thorough neurological examination, including CSF studies, to rule out other causes of meningitis. It appears that patients with a history of migraine may be more susceptible. Discontinuation of IVIg treatment has resulted in remission of AMS within several days without sequelae.

Haemolysis.

IVIg products can contain blood group antibodies which may act as haemolysins and induce in vivo coating of red blood cells (RBC) with immunoglobulin, causing a positive direct antiglobulin reaction and, rarely, haemolysis. Haemolytic anaemia can develop subsequent to IVIg therapy due to enhanced RBC sequestration (see Section 4.8 Adverse Effects (Undesirable Effects)). IVIg recipients should be monitored for clinical signs and symptoms of haemolysis.
In patients with a normal acid base compensatory mechanism, the acid load delivered by the largest dose of the preparation would be neutralised by the buffering capacity of whole blood alone, even if the dose were to be infused instantaneously. In patients with limited or compromised acid base compensatory mechanisms including neonates, consideration should be given to the effect of the additional acid load that the preparation might present.

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 manufacturing process for Octagam 10% includes a three stage viral inactivation/ removal process, which includes two dedicated viral inactivation steps (solvent/ detergent treatment followed by incubation at low pH at 37°C for 24-26 hours) and a cold ethanol fractionation process, which also contributes to viral removal/ inactivation.
Viral removal and inactivation procedures performed during the manufacturing process may be of limited value against nonenveloped viruses such as hepatitis A virus or parvovirus B19.
Parvovirus B19 infection may be serious for pregnant women (foetal infection) and for individuals with immunodeficiency or increased erythropoiesis (e.g. haemolytic anaemia).
There is a 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.
The manufacturing process was investigated for the capacity to decrease the amount of an experimental agent of transmissible spongiform encephalopathy (TSE), considered as a model for the vCJD and CJD agents. The manufacturing process of Octagam 10% has been shown to decrease the amount of this experimental model agent. The TSE reduction step is the precipitation and separation of fraction I + III.
Vaccination for patients in receipt of medicinal products made from human plasma should be considered where appropriate.
It is strongly recommended that every time Octagam 10% 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 use.

The safety of Octagam 10% for paediatric use has not been established in controlled clinical trials.

Effects on laboratory tests.

Interference with serological testing.

After injection of human normal immunoglobulin the transitory rise of 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 or D may interfere with some serological tests for red cell allo-antibodies, for example the antiglobulin test (e.g. Coombs' test), reticulocyte count and haptoglobin.

Blood glucose testing.

Some types of blood glucose testing systems (for example, those based on the glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ) or glucose dye oxidoreductase methods) falsely interpret the maltose contained in Octagam 10% as glucose. This may result in falsely elevated glucose readings and, consequently, in the inappropriate administration of insulin, resulting in life threatening or even fatal hypoglycemia. Also, cases of true hypoglycemia may go untreated if the hypoglycemic state is masked by falsely elevated glucose readings. Accordingly, when administering Octagam 10% or other parenteral maltose containing products, the measurement of blood glucose must be done with a glucose specific method.
The product information of the blood glucose testing system, including that of the test strips, should be carefully reviewed to determine if the system is appropriate for use with maltose containing parenteral products. If any uncertainty exists, contact the manufacturer of the testing system to determine if the system is appropriate for use with maltose containing parenteral products.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Live attenuated virus vaccines.

Human normal 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 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.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data are available.
The safety of Octagam 10% 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 breastfeeding mothers. Clinical experience with human normal immunoglobulins suggests that no harmful effects on the course of pregnancy, or on the foetus and the neonate are to be expected.
Immunoglobulins are excreted into the milk and may contribute to the transfer of protective antibodies to the neonate.

4.7 Effects on Ability to Drive and Use Machines

There is no indication that human normal immunoglobulins may impair the ability to drive and use machines.

4.8 Adverse Effects (Undesirable Effects)

In general, various allergic and hypersensitivity type of reactions and headache, chills, back pain, chest pain, fever, cutaneous reactions, vomiting, arthralgia, low blood pressure and nausea may occasionally occur. Reactions to IVIg tend to be related to the dose and rate of infusion.
The following adverse effects (Table 2) have been identified in clinical trials with Octagam (5 and 10%). Within each frequency grouping, undesirable effects are presented in the internationally agreed order.
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 (see Section 4.4 Special Warnings and Precautions for Use).
Very rarely: thromboembolic reactions such as myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis have been observed. For further information, see Section 4.4 Special Warnings and Precautions for Use.
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.
Table 3 lists adverse effects that have been identified during postapproval use of Octagam (5% and 10%). Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency.
For information on viral safety, see Section 4.4 Special Warnings and Precautions for Use.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

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

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: immune sera and immunoglobulins: immunoglobulins, normal human, solution for intravenous infusion.
ATC Code: J06B A02.

Mechanism of action.

Octagam 10% has a distribution of IgG subclasses closely proportional to that in native human plasma. Adequate doses of this medicinal product may restore abnormally low IgG levels to the normal range.
The mechanism of action in indications other than replacement therapy is not fully elucidated, but includes immunomodulatory effects.

Clinical trials.

Octagam 10% is a human normal immunoglobulin solution ready for intravenous administration (IVIg) developed as a new strength of the essentially similar Octagam 5%. Having in mind that both products have similar biochemical characteristics, it is reasonable to conclude that both products are equally efficacious. No differences concerning the efficacy of Octagam 10% are to be expected. Nevertheless efficacy data are presented, derived from an ongoing study in patients suffering from ITP.
In a prospective, open label, multicentre phase III trial (GAM10-02), the efficacy and safety of Octagam 10% was studied in patients suffering from idiopathic (immune) thrombocytopenic purpura (ITP). Octagam 10% was infused on 2 consecutive days at a dose of 1 g/kg/day, and patients were observed for a period of 21 days and at a follow-up visit on day 63 postinfusion. Haematology parameters were assessed on days 2 to 7, 14 and 21.
In agreement with national health agencies, a descriptive interim analysis has been performed following the completion of 31 subjects. The final analysis of results will be presented in subsequent study reports. From 31 subjects included in the interim analysis, 15 were subjects with chronic ITP, 15 were newly diagnosed, and 1 subject was incorrectly enrolled in the study (had no ITP) and was therefore excluded from the efficacy analysis.
In total, 25 subjects (83%) showed a clinical response (defined as an increase in platelets to at least 50 x 109/L within 7 days after treatment). A higher clinical response rate was seen in the newly diagnosed cohort (93%) than in the chronic ITP cohort (73%). In subjects with a response, the median time to platelet response was 2 days, with a range of 1 to 5 days.
In 24 subjects (77%), Octagam 10% was given at the maximum allowed infusion rate of 0.06 mL/kg/min. Following a Protocol Amendment, 2 patients of the presented analysis received the product at a rate of 0.08 mL/kg/min which was uneventful in both cases. In the continuation of this ongoing study, 22 subjects have been treated with the maximum allowed infusion rate of 0.12 mL/kg/min. These administrations were not related to a higher incidence of adverse reactions.
In 9 of 62 infusions (14.5%) treatment related AEs were observed. The most common drug related AE was headache, followed by tachycardia and pyrexia. There was no case of haemolysis related to the study drug. Pretreatment to alleviate infusion related intolerability was not given.

5.2 Pharmacokinetic Properties

Absorption.

Human normal immunoglobulin is immediately and completely bioavailable in the recipient's circulation after intravenous administration.

Distribution.

Octagam 10% is distributed relatively rapidly between plasma and extravascular fluid, after approximately 3-5 days equilibrium is reached between the intra- and extravascular compartments.

Metabolism.

Human normal immunoglobulin has an average half-life ranging of 26 to 41 days, as measured in immunodeficient patients. This half-life may vary from patient to patient, in particular in primary immunodeficiency.

Excretion.

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

5.3 Preclinical Safety Data

Genotoxicity.

Clinical experience provides no evidence for genotoxic potential of human normal immunoglobulin.

Carcinogenicity.

Clinical experience provides no evidence for genotoxic potential of human normal immunoglobulin.

6 Pharmaceutical Particulars

6.1 List of Excipients

Maltose, human immunoglobulin A (IgA), tributyl phosphate, octoxinol 10, water for injections.

6.2 Incompatibilities

Octagam 10% must not be mixed with other medicinal products.

6.3 Shelf Life

Shelf life is 3 years.

6.4 Special Precautions for Storage

Store at 2°C to 8°C. (Refrigerate. Do not freeze.)
Protect from light.
Do not use after expiry date.
Once removed from refrigeration, the product may be stored up to 9 months at ≤ +25°C. In this case the product expires at the end of the 9 month period; the new date of expiry should be noted on the outer carton. The product may not be returned to refrigerated storage after storage at ≤ +25°C.
Octagam 10% doesn't contain any antimicrobial agent. It must, therefore, be used immediately after opening; any remaining contents must be discarded (see Section 6.6 Special Precautions for Disposal).

6.5 Nature and Contents of Container

The primary container is made of type II glass closed with a bromobutyl rubber stopper. Each container contains 100 mg/mL solution for infusion.
The product is supplied in the following vial sizes: 1 injection vial with 20 mL; 1 infusion bottle with 50 mL; 1 infusion bottle with 100 mL; 1 infusion bottle with 200 mL.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

No data available.

CAS number.

None assigned.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes