Consumer medicine information

Evogam

Immunoglobulin, normal (human)

BRAND INFORMATION

Brand name

Evogam

Active ingredient

Immunoglobulin, normal (human)

Schedule

What is in this leaflet

This leaflet answers some common questions about Evogam®.

It does not contain all the available information. If you require further information about this medicine or your treatment, have any questions, or are not sure about something in this leaflet, consult your doctor.

All medicines have benefits and risks. Your doctor has weighed the benefits that Evogam® will have for you against the possible risks.

If you have any concerns about using this medicine, ask your doctor. Follow your doctor's advice even if it is different from what this leaflet says.

Keep this leaflet with the medicine. You may need to read it again.

What Evogam® is used for

Your medicine is Evogam®, a solution for subcutaneous infusion. Evogam® contains human immunoglobulins and is manufactured from human plasma (the liquid component of blood) collected by Australian Red Cross Lifeblood.

Immunoglobulins are also called antibodies and are a type of protein found in the blood. Immunoglobulins are produced by your body’s immune system to fight infections caused by bacteria and viruses. If you do not have enough antibodies you may not be able to fight off diseases. Evogam® can be used as antibody replacement therapy, to correct this lack of antibodies.

Your doctor may have prescribed Evogam® for another reason. Ask your doctor if you have any questions about why it has been prescribed for you.

Before you receive Evogam®

When you must not have it

Do not have Evogam® if you are allergic to:

human immunoglobulin products
glycine.

If you are not sure whether you should be given this medicine talk to your doctor.

Before you are given it

Tell your doctor if you:

are pregnant or breast-feeding
have had any vaccination within the last two weeks
are allergic to any medicine or food
have IgA deficiency
have a history of heart, or blood vessel disease, or blood clots, have thick blood, have been immobile for some time. Also tell the doctor what medicine you are using as some medicines, such as those that contain the hormone estrogen (for example, birth control pills), may increase your risk of developing a blood clot.
have blood group A, B or AB
have any other medical conditions.

If you have not told your doctor about any of the above, tell them before you are given Evogam®.

Your doctor can discuss with you the risks and benefits involved with using this medicine.

About blood products

When medicines are made from human blood or plasma, processes are used to prevent infections being passed from the blood/plasma donor to the person receiving the medicine. These processes include careful selection of the people who donate blood and plasma to make sure that those who might be carrying infections are excluded. In addition each donation and pools of donations are tested for indicators of virus or virus infection(s).

Manufacturers of these medicines also include steps in the processing of blood or plasma that inactivate or remove viruses. Despite these processes, when medicines are prepared from human blood or plasma, the possibility of passing on an infection cannot be totally ruled out. Unknown or new viruses or other types of infection could also be passed on.

The measures taken in the manufacture of this medicine are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, and for the non-enveloped viruses hepatitis A and B19 virus (B19V).

There is reassuring clinical experience regarding the lack of hepatitis A or B19V infections following treatment with immunoglobulin products. The antibodies which are in Evogam® may also make an important contribution to limiting the possibility an infection could be passed on.

Please discuss the risks and benefits of this product with your doctor.

Taking other medicines

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

Some medicines may affect the way other medicines work.

How Evogam® is given

Treatment should be started and supervised by a doctor. Evogam® is administered as an injection or infusion subcutaneously (under the skin). If your doctor decides that you should receive Evogam® at home, they will ensure you receive detailed instructions and training on how to use it.

If you do not understand the instructions ask your doctor or health professional.

How much is given

Your doctor will determine the dose(s) of Evogam® that you will receive, and when you need to have it.

How to prepare it

If your doctor considers that you should receive Evogam® at home, the instructions below should be followed carefully.

Step 1
Prepare Evogam® and equipment

a. Remove from the refrigerator and allow the vial of Evogam® to reach room temperature prior to use, this will take approximately 20-60 minutes.

b. Gather what you need for administration. This may include an infusion pump, administration tubing, subcutaneous needle or catheter set, Y-site connector, alcohol wipes, syringes, vial adapter, gauze or transparent dressing, tape, sharps disposal container, and treatment diary.

c. Check Evogam® vials. Carefully check the liquid in each vial, but do not shake it. Evogam® is clear and colourless or pale-yellow or light-brown. If Evogam® appears to be turbid or to contain sediment, it must not be used. If it is missing the protective cap, or is past its expiry date, it must not be used.

d. Remove the protective cap from the vial and wipe the rubber stopper with an alcohol wipe.

Step 2
Wash hands with soap and water and dry hands thoroughly with a clean towel.

Step 3
Prepare vial adapter

a. Remove the top cover of the vial adapter, leaving the adapter inside the blister pack.

b. Place the Evogam® vial on a flat surface.

c. Place the vial adapter over the top of the vial, using the blister pack to handle the vial adapter. Press down firmly until the vial adapter snaps into place so that it pierces the rubber stopper (see Figure 1).

d. Remove the outer package of the vial adapter and discard. Take care not to touch the exposed end of the device.

Step 4
Prepare syringe

Pull back the plunger of the syringe to fill the syringe with air. The amount of air should be the same as the amount of Evogam® you will transfer from the vial (see Figure 2).

Step 5
Connect to vial

a. Attach the syringe to the vial adapter by twisting the syringe onto the connection.

b. Push the plunger of the syringe down. This will inject the air from the syringe into the airspace of the vial (see Figure 3).

Step 6

Withdraw Evogam® from vial

a. Turn the vial and syringe upside down whilst holding the plunger in, leaving the syringe and vial attached (see Figure 4).

b. Release pressure on the plunger and pull back slowly to fill the syringe with Evogam®.

c. Detach the syringe from the vial adapter with a twist, leaving the vial adapter attached to the vial (see Figure 5).

Repeat Steps 3 to 6 if multiple vials are required to achieve the prescribed dose of Evogam®. The same syringe may be used (to a maximum of 20 mL) but use a new vial adapter for each vial.

Step 7
Prepare infusion tubing

To prime (fill) the tubing, connect the syringe filled with Evogam® to the infusion tubing and gently push on the syringe plunger to fill the tubing with Evogam® (see Figure 6).

Stop priming before Evogam® fluid reaches the needle.

Step 8
Insert needle

a. Select an appropriate infusion site. This may be the abdomen, thigh, upper arm, or side of the hip.

The number and location of injection sites depends on the volume of the total dose. When a dose of more than 20 mL is given, it is advisable to give it in divided doses at different sites, which can be infused at the same time.

b. Clean the injection site(s) as directed by your health care professional.

c. Pinch together the skin around the injection site with two fingers and insert the needle under the skin (see Figure 7).

d. Place sterile gauze and tape or a transparent dressing over the injection site. This will keep the needle from coming out (see Figure 8).

Step 9
Check needle placement

Make sure you are not injecting Evogam® into a blood vessel. To test for this pull the plunger back gently (see Figure 9). If there is blood in the tubing, which would appear as red or pink fluid entering the tubing from the injection site, remove and discard the needle and tubing. Repeat steps beginning with Step 7 using a new needle and tubing, and a new infusion site.

If there is no blood in the tubing, continue to Step 10.

Step 10
Start infusion

Follow the instructions that you have been given by your doctor or nurse to start the infusion, and infuse at the rate you have been instructed.

The recommended initial infusion rate is 10 mL/hr per injection site, with subsequent infusion rate increased as tolerated to a maximum of 20 mL/hr per site.

Step 11
After the infusion

a. Take off the dressing and take the needle out of the injection site, applying light pressure to the injection site.

b. Throw away the Evogam® single-use vial, along with the needle and tubing, in the sharps container. Throw away dressing and tapes in the household waste.

c. Record your treatment. Peel off the removable part of the label of the Evogam® vial and put this label in your treatment diary or logbook. Document the date and time of your infusion, the amount of Evogam® that you infused and the rate of infusion.

If too much is given (overdose)

The effects of an overdose of Evogam® are not known. Please tell your doctor if you accidently use more than instructed.

Things you must do

Tell your doctor if you are planning on having a vaccination.

Evogam® may impair the effect of some virus vaccines such as measles, mumps, rubella and chicken pox for a period of at least six weeks, and up to three months. After receiving this medicine, a period of three months should be allowed before vaccination with some virus vaccines. In the case of measles vaccine, this effect may last for up to one year. Therefore, your vaccinating doctor should check the effectiveness of the measles vaccination.

Tell your doctor if you are about to have any blood tests.

Evogam® may interfere with the results of some tests, resulting in misleading results for some things.

Inform other doctors, dentists, and pharmacists who treat you that you have been given this medicine.

It is important for them to know if they are starting you on any other new medicines.

Side effects

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you experience some of the side effects.

Do not be alarmed by the following lists of possible side effects. You may not experience any of them. If you have any questions, ask your doctor.

Tell your doctor immediately or go to the Accident and Emergency Department at your nearest hospital if you notice any of the following symptoms:

severe headache
neck stiffness
inability to stand bright light
painful eye movements
tingling, numbness or weakness on one side of the body
pain/tenderness, swelling/discolouration of an arm or leg
shortness of breath
chest pain
allergic or anaphylactic reaction, symptoms of which may include:
- swelling of the lips, tongue or eyes
- loss of consciousness
- hives
- difficulty in breathing
feeling very tired
skin becoming yellow
dark urine.

Tell your doctor if you notice any of the following and they worry you:

This list includes the more common side effects of Evogam®. They are usually mild and often reduce over time:

pain, itching, redness or swelling where the injection was given
nausea or vomiting
back and muscle pain
abdominal pain
paleness of skin
diarrhoea
headache
fever or chills
feeling faint (fall in blood pressure)
pain in extremity
fatigue
joint pain.

Other side effects not listed above may also occur in some patients. Tell your doctor if you notice any other effects.

After having Evogam®

Storage

Store at 2°C to 8°C. (Refrigerate. Do not freeze).

Once removed from refrigeration, store below 25°C and use within 2 weeks.

The product must not be returned to refrigeration.

Leave vial in box until ready to use.

Do not use after the expiry date.

Keep it out of the reach and sight of children.

Product description

What it looks like

Evogam® is clear and colourless or pale-yellow or light-brown, and may be turbid in appearance. It is packaged in single use clear glass vials.

Ingredients

Each vial of Evogam® contains a sterile solution comprising 16% plasma proteins of which at least 98% are immunoglobulins. Evogam® does not contain any preservatives, so any unused portion should be discarded immediately. Evogam® is packaged using latex free materials.

Evogam® is available in three different sizes, as shown in the table:

Manufacturer

Evogam® is manufactured in Australia by:

CSL Behring (Australia) Pty Ltd
ABN 48 160 734 761
189-209 Camp Road
Broadmeadows VIC 3047
Australia

Distributor

Australian Red Cross Lifeblood

Date of revision

August 2021

® Registered trademark of CSL Limited

Published by MIMS September 2021

BRAND INFORMATION

Brand name

Evogam

Active ingredient

Immunoglobulin, normal (human)

Schedule

Notes

Distributed by Australian Red Cross Lifeblood

1 Name of Medicine

Normal immunoglobulin (human).

2 Qualitative and Quantitative Composition

Evogam is a sterile preservative-free solution containing 16 g/100 mL of total human plasma protein of which at least 98% is immunoglobulin G (IgG). At least 85% consists of monomers and dimers (typically > 90%) and < 10% of the IgG are aggregates.
The distribution of the IgG subclasses closely resembles that found in normal human plasma (approximate ranges for Evogam: 47.8-58.1% IgG₁, 38.8-49.3% IgG₂, 0.9-1.4% IgG₃, 1.4-2.1% IgG₄).
Evogam contains only trace amounts of IgA, typically < 0.025 mg/mL.
The pH value of the ready-to-use solution is 5.5.
Evogam is manufactured from human plasma collected by Australian Red Cross Lifeblood.
Evogam contains 2.25 g of glycine per 100 mL as a stabiliser.

3 Pharmaceutical Form

Solution for subcutaneous administration.

4 Clinical Particulars

4.1 Therapeutic Indications

Evogam is indicated in adults and children for replacement therapy in:
Primary Immunodeficiency Diseases (PID); and
symptomatic hypogammaglobulinaemia secondary to underlying disease or treatment.

4.2 Dose and Method of Administration

Evogam must be administered subcutaneously.
Treatment should be initiated and monitored under the supervision of a physician experienced in the treatment of immunodeficiency.

Dosage.

The dose and dosage interval must be individualised for each patient based on their measured IgG trough levels and ongoing clinical response. The following dose regimens are given as a guideline.
A weekly dose in the range 0.05-0.15 g/kg body weight is recommended (this corresponds to a total monthly dose of Evogam in the range of 0.2-0.6 g/kg body weight).
As the dose is given by body weight and adjusted to clinical outcome, the dose in the paediatric population is not considered to be different to that of adults.

Administration.

Note.

Evogam contains no antimicrobial preservative. It must, therefore be used immediately after opening the bottle. Use in one patient on one occasion only. Any unused portion should be discarded appropriately. Do not use if the solution has been frozen.
The solution is clear and colourless or pale-yellow or light brown. If Evogam appears to be turbid or to contain sediment, it must not be used. The unopened bottle should be returned to Australian Red Cross Lifeblood.
Evogam must not be administered intravenously. Evogam must be administered via the subcutaneous route, preferentially into the upper outer arms/ upper thighs, abdomen, and/or lateral hip.
Evogam should be brought to room temperature before use.
A common Evogam weekly dose is 0.05-0.15 g (approximately 0.3-0.9 mL) per kg body weight, which may be administered at several infusion sites. When administering Evogam the recommended initial infusion rate is 10 mL/hour per site. The infusion rate may be gradually increased after the first completed infusion up to 20 mL/hour per site as the patient's tolerability and comfort allows. The maximum dose administered during clinical trials was 40 mL/hour using two infusion pumps simultaneously. When large doses are given (> 20 mL), it is advisable to administer them in divided doses at different sites.

Subcutaneous infusion for home treatment.

Home treatment should be commenced and monitored under the supervision of a healthcare professional experienced in the treatment of immunodeficiency.
If the supervising physician believes that home administration is appropriate, the patient or caregiver must be instructed and trained in: subcutaneous administration techniques; the keeping of a treatment diary; recognition of and measures to be taken in the case of severe adverse reactions.

4.3 Contraindications

Evogam is contraindicated in patients with a history of a true anaphylactic reaction to the active substance or to any of the components (e.g. glycine) (see Section 4.4 Special Warnings and Precautions for Use).

4.4 Special Warnings and Precautions for Use

Evogam must be administered subcutaneously. Evogam must not be administered intravenously. It has not been studied for intravenous or intramuscular use.
If Evogam is inadvertently administered into a blood vessel, patients could develop shock. In the case of shock, current medical standards for shock treatment should be observed.
Certain adverse reactions may occur more frequently in patients who receive human normal immunoglobulin for the first time, are switched from an alternative product, or, in rare cases, when there has been a long interval since previous infusion.

Hypersensitivity.

True hypersensitivity reactions to immunoglobulins are rare. Evogam should be used with caution in patients with a known allergy to constituents of the preparation. Evogam contains traces of IgA which rarely may provoke anaphylaxis in IgA deficient patients with anti-IgA antibodies. Patients with anti-IgA antibodies, in whom treatment with subcutaneous IgG product remains the only option, should be treated with Evogam under close medical supervision.
Rarely, human normal immunoglobulin can induce a precipitous fall in blood pressure with anaphylactic reaction, even in patients who had tolerated previous treatment with human normal immunoglobulin. In case of an anaphylactic reaction, the infusion should be stopped immediately and appropriate treatment initiated.

Thromboembolic events.

There is clinical evidence of an association between human immunoglobulin administration and thromboembolic events such as myocardial infarction, cerebral vascular accident (including stroke), pulmonary embolism and deep vein thromboses. Caution should be exercised in prescribing and administering Evogam in patients with pre-existing risk factors for thromboembolic events such as advanced age, estrogen use, in-dwelling vascular catheters, cardiovascular risk factors (including history of atherosclerosis and/or impaired cardiac output), and a history of venous or arterial thrombosis, patients with acquired or inherited hypercoagulable states, patients with prolonged periods of immobilisation, severely hypovolaemic patients and patients with hyperviscosity (including cryoglobulins, fasting chylomicronaemia and/or high triglyceride levels, and monoclonal gammopathies).
In patients at risk for thromboembolic adverse reactions, Evogam should be administered subcutaneously at the minimum rate of infusion and dose possible based on clinical judgement, and these individuals should be monitored for thromboembolic complications. Consideration should also be given to measurement of baseline blood viscosity in individuals at risk for hyperviscosity.

Aseptic meningitis syndrome (AMS).

An Aseptic Meningitis Syndrome (AMS) has been reported to occur infrequently in association with human immunoglobulin administration. The syndrome usually begins within several hours to two days following immunoglobulin 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, predominantly from the granulocytic series, and elevated protein levels. Patients exhibiting such symptoms and signs should receive a thorough neurological examination, including CSF studies, to rule out other causes of meningitis. AMS may occur more frequently in association with high dose (2 g/kg) immunoglobulin treatment. Discontinuation of IVIg treatment has resulted in remission of AMS within several days without sequelae.
It is recommended that the name and batch number of the product are recorded every time the product is administered to a patient in order to maintain a link between patient and the batch of the product.

Reactions reported to have occurred with intravenous immunoglobulin treatment.

The following reactions have been reported to occur with IVIg treatment and may occur with SCIg treatment.

Haemolysis.

Evogam 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 immunoglobulin therapy due to enhanced red blood cells (RBC) sequestration. The following risk factors are associated with the development of haemolysis: high doses, whether given as a single administration or divided over several days, non-O blood groups, and underlying inflammatory conditions. Evogam recipients should be monitored for clinical signs and symptoms of haemolysis, particularly those patients at increased risk. If these occur, appropriate laboratory testing should be undertaken and discontinuation of the IgG treatment should be considered by the treating physician, if haemolysis develops.

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.
Renal function should be monitored in patients at increased risk of developing acute renal failure. If renal function deteriorates, IgG treatment discontinuation should be considered. While these reports of renal dysfunction and acute renal failure have been associated with the use of IVIg products containing excipients such as sucrose, glucose and maltose, those containing sucrose as a stabiliser accounted for a disproportionate share of the total number. Evogam contains glycine but it does not contain sucrose, maltose or glucose.
In patients at risk for acute renal failure, Evogam should be administered subcutaneously at the minimum rate of infusion and dose possible based on clinical judgement.

Pathogen safety.

Evogam is manufactured from human plasma. Products made from human plasma may contain infectious agents, such as viruses and theoretically Creutzfeldt-Jakob disease (CJD) agents. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain infectious agents and by testing for the presence of certain pathogen markers. In addition, two dedicated pathogen reduction steps are included in the manufacturing process of Evogam to reduce the possibility of pathogen transmission. These are pasteurisation (heating at 60°C for 10 hours) and nanofiltration. These steps are effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), and the non-enveloped hepatitis A virus (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. Evogam contains specific antibodies directed against parvovirus B19.
Despite these measures, there remains the potential that such products may transmit disease. There is also the possibility that other known or unknown infectious agents may be present in such products. Vaccination (e.g. hepatitis A and hepatitis B) should be considered where appropriate, for patients in receipt of medicinal products manufactured from human plasma.

Use in the elderly.

Clinical studies of Evogam did not include sufficient numbers of patients aged 65 years and over to determine whether safety of this product is different in this population.

Paediatric use.

Evogam was evaluated in eight children ≤ 13 years in the clinical studies. There were no apparent differences in the safety and efficacy profiles as compared to adults. No paediatric specific dose adjustments were necessary to achieve the desired serum IgG levels. The safety and efficacy of Evogam was not studied in the paediatric population under five years of age.

Effects on laboratory tests.

After immunoglobulin infusion 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. anti-A, anti-B, anti-D) may interfere with some serological tests for red cell allo-antibodies (e.g. Coombs' test), reticulocyte count and haptoglobin.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Immunoglobulin infusion may impair the efficacy of live attenuated virus vaccines such as measles, rubella, mumps and varicella for a period of at least six weeks and up to three months. After infusion of Evogam, an interval of three months should elapse before vaccination with live attenuated virus vaccines. In the case of measles, this impairment may persist for up to one year. Therefore patients receiving measles vaccine should have their antibody status checked. Additionally, immunoglobulins should not be administered for at least two weeks after these vaccines are given.
The interaction of Evogam with other medicines has not been established.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No reproductive toxicity studies have been conducted with Evogam.
The safety of this product for use in human pregnancy has not been established in controlled clinical studies. Evogam should be given to pregnant women only if clearly needed.
The safety of this product for use during lactation has not been established in controlled clinical studies. Immunoglobulins are excreted in breast milk and may contribute to the transfer of protective antibodies to the neonate.

4.7 Effects on Ability to Drive and Use Machines

No effects on the ability to drive and use machines have been observed.

4.8 Adverse Effects (Undesirable Effects)

Patients naive to immunoglobulin may experience a higher frequency of adverse effects including those of a minor nature.
Table 1 summarises treatment related reactions identified in clinical studies of Evogam in 49 individual subjects, of whom 41 were adults and 8 children, from a total of 5694 subcutaneous infusions.
Rarely, human normal immunoglobulins may cause allergic reactions and, in isolated cases, anaphylactic shock, even when the patient has shown no hypersensitivity to previous administration (see Section 4.4 Special Warnings and Precautions for Use). In case of severe reactions, the infusion should be stopped and appropriate treatment initiated. When large doses are given, it is advisable to administer them in divided doses at different sites.
Local tolerability reactions at the infusion site were also assessed in the clinical studies with Evogam. Most subjects reported pain, pruritus, or warmth, erythema, and/or induration being present between 8-12 hours after the infusion. At 72 hours after infusion, the frequency of reported symptoms had markedly decreased. The incidence of all reported tolerability reactions at the infusion site were reported less frequently over the length of the study. The majority of these symptoms reported were of mild or moderate intensity.

Reactions associated with immunoglobulins.

Rare cases of thromboembolic reactions such as myocardial infarction, stroke, pulmonary embolism, deep vein thromboses, and cases of reversible aseptic meningitis have been observed with human normal immunoglobulin.

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

Consequences of an overdose are not known.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Evogam contains the IgG antibodies present in the donor population. It is prepared from pooled plasma collected from not fewer than 1000 donors. It has an IgG subclass distribution closely proportional to normal human plasma.
Evogam contains functionally intact IgG with a broad spectrum of antibodies against infectious agents. The IgG molecules have not been chemically or enzymatically modified and the Fc and Fab functions are retained.
Adequate doses of human normal immunoglobulin restore abnormally low IgG levels to the normal range.

Clinical trials.

Treatment of primary immunodeficiency disease (PID).

The pivotal open-label, prospective, multicentre clinical study conducted in Australia and New Zealand evaluated the efficacy, pharmacokinetics, safety, tolerability and quality of life of Evogam in adult and paediatric subjects with PID. Thirty adult and five paediatric PID subjects, who had been previously treated either with intravenous immunoglobulin (IVIg) monthly (n = 34) or with normal immunoglobulin administered subcutaneously (SCIg; n = 1), were treated with weekly subcutaneous infusions of Evogam for 9 months, at a planned weekly dose calculated to be equivalent to one quarter of the cumulative monthly dose of IVIg (between 0.2-0.6 g/kg/month).
Subjects received a mean weekly dose of 6.83 g (range 3.0-13.5 g), infused subcutaneously via a mean of 2.63 infusion sites (range: 1.0-5.0), over an average duration of 1.53 hours (range: 0.9-2.7 hours).
The primary endpoint was the annual rate of serious bacterial infections (SBIs) including bacteraemia/ sepsis, bacterial meningitis, osteomyelitis/ septic arthritis, bacterial pneumonia and visceral abscess (to a pre-specified upper 99% confidence limit of 1%). The annualised rate of SBI was 0 infections per subject per year for both the per protocol and intention to treat populations, with 99% upper confidence limits of 0.36 and 0.33, respectively. This data is based on the efficacy period (weeks 13-36).
The annual rate of any infections, a secondary endpoint, was 2.80 infections per subject per year.
IgG concentrations were at steady state during the efficacy phase of the study and a repeated measures analysis showed that mean trough concentration of IgG in subjects treated with Evogam (9.11 g/L, 95% CI: 8.68-9.55 g/L) was higher than in their previous treatment (8.30 g/L, 95% CI: 7.82-8.80 g/L; p = 0.0021).
The change from baseline health and treatment related quality of life was assessed in 27 subjects by the SF-36v2 and Life Quality Index (LQI) questionnaires. SF-36v2 results showed a similar health-related quality of life on both the previous treatment and Evogam. LQI scales showed significant improvement in treatment interference and therapy setting, indicating preference for home based SCIg treatment.
Following the pivotal study, an open-label multicentre extension study was conducted (n = 41) in 34 (82.9%) adult and 7 (17.1%) paediatric subjects. The age ranges were 5.9-11.7 in the paediatric group (mean 9.89) and 14.1-68.6 in the adult group (included adolescents; mean 45.25). The primary objective was to assess the safety and tolerability of Evogam in subjects requiring Ig replacement therapy who had either completed the pivotal clinical trial (n = 27), or had switched from alternative IVIg (n = 13) or SCIg (n = 1) therapy. The secondary objective was to monitor serum IgG trough levels, as a surrogate measure of Evogam efficacy in patients with PID. The median duration of treatment was 589.0 days in subjects who switched from previous IVIg therapy and 891.5 days in subjects who transferred from the pivotal study.
At baseline, the mean serum IgG trough level for the 41 enrolled subjects was 9.02 g/L (range: 5.0-13.3). During the treatment period the mean serum IgG trough level was maintained above 8 g/L; based on data from 35 subjects. At the individual subject level, 34 (out of 35) subjects for whom trough level data was available, had IgG trough levels at clinically desirable levels (i.e. ≥ 5 g/L).

5.2 Pharmacokinetic Properties

Following subcutaneous administration of Evogam, peak serum levels are achieved after approximately 8.4 hours.
In a clinical trial with Evogam (n = 31), subjects achieved sustained trough levels (mean 9.11 g/L) over a period of 24 weeks when receiving weekly doses in the range of 0.05-0.15 g/kg.
The pharmacokinetic (PK) parameters of Evogam were evaluated in a subset of 23 subjects (aged 27 to 67 years) with Primary Immunodeficiency Diseases (PID) (see Table 2). A peak IgG concentration of 8.87 g/L and a trough IgG concentration of 8.32 g/L were observed during the 7 day PK evaluation period.
IgG and IgG-complexes are broken down in cells of the reticuloendothelial system.

5.3 Preclinical Safety Data

Genotoxicity.

No genotoxicity studies have been conducted with Evogam.

Carcinogenicity.

No carcinogenicity studies have been conducted with Evogam.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store at 2°C to 8°C (Refrigerate. Do not freeze). Once removed from refrigeration, store below 25°C and use within 2 weeks. Protect from light.
Do not use after the expiry date.

6.5 Nature and Contents of Container

The presentations available for Evogam are summarised in Table 3.
Note that not all presentations may be available.
Evogam is packaged in latex free materials.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

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Consumer medicine information

Evogam

Immunoglobulin, normal (human)

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BRAND INFORMATION