Consumer medicine information

Gamunex

Immunoglobulin, normal (human)

BRAND INFORMATION

Brand name

Gamunex

Active ingredient

Immunoglobulin, normal (human)

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Gamunex.

What is in this leaflet

This leaflet answers some common questions about GAMUNEX®. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you receiving GAMUNEX® against the benefits they expect it will have for you.

If you have any concerns about receiving this medicine, ask your doctor or pharmacist.

Keep this leaflet. You may need to read it again.

What GAMUNEX® is used for

GAMUNEX® is used to replace antibodies (used to fight infections) in people with conditions that impair the body’s ability to make antibodies. These conditions include:

  • Primary Immunodeficiency Diseases.
  • Symptomatic Hypogammaglobulinaemia secondary to underlying disease or treatment.

GAMUNEX® is also used to modulate the immune system in people whose immune systems are not working well. These conditions include

  • Idiopathic Thrombocytopaenic Purpura (ITP), in patients at high risk of bleeding or prior to surgery to correct the platelet count.
    People with ITP have antibodies that do not work properly and may need treatment with GAMUNEX® to raise blood platelet counts to prevent bleeding or prior to undergoing surgery.
  • Guillain Barré Syndrome (GBS).
  • Chronic Inflammatory Demyelinating Polyneuropathy (CIDP).
  • Kawasaki disease.

This medicine belongs to a group of medicines called immunoglobulins.

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

Before you receive GAMUNEX®

When you must not receive it

You should not receive GAMUNEX® if:

  • you have an allergy to immunoglobulin or any of the ingredients listed at the end of this leaflet.
  • you have severe immunoglobulin A (IgA) deficiency (which may also cause a severe allergic reaction to this medicine).

Some of the symptoms of an allergic reaction may include:

  • shortness of breath,
  • wheezing or difficulty breathing,
  • swelling of the face, lips, tongue or other parts of the body,
  • rash, itching or hives on the skin,
  • loss of consciousness.

You should not receive this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, it should be returned to your pharmacist for disposal.

If you are not sure whether this medicine is suitable for you talk to your doctor.

Before you receive it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • renal (kidney) impairment or disease,
  • diabetes mellitus,
  • volume depletion,
  • sepsis (bacterial infection in the blood or tissues),
  • paraproteinaemia (abnormal proteins in the blood),
  • hypertension (high blood pressure),
  • are bed or chair bound,
  • atherosclerosis (thickening/hardening of the blood vessel walls),
  • heart conditions,
  • blood clotting disorders such as thrombosis (clotting in the blood vessels).

Tell your doctor if you are aged over 65 years.

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. It is not known whether GAMUNEX® can affect the developing baby when administered to a pregnant woman or can affect fertility. GAMUNEX® should be given to a pregnant woman only if clearly needed.

Immunoglobulins pass into breast milk and should only be given with caution to breastfeeding mothers.

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

If you have not told your doctor about any of the above, tell him/her before you receive GAMUNEX®.

Special warning

Because this product is made from human blood, it may carry a risk of transmitting infectious agents, e.g. viruses that can cause disease. The plasma is sourced from US plasma centers licensed by the FDA. The risk that GAMUNEX® will transmit an infectious agent has been reduced by screening blood donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses. Despite these measures, immunoglobulin products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products.

Taking other medicines

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

Tell your doctor if you are taking an oestrogen medication (such as for birth control). Some medicines and GAMUNEX® may interfere with each other. These include:

  • live viral vaccines such as measles, mumps and rubella. GAMUNEX® may interfere with the response to these vaccines. Therefore the use of such vaccines should be deferred until approximately 6 months after GAMUNEX® administration.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while receiving this medicine.

How GAMUNEX® is given

The treating medical professional will give your GAMUNEX® as slow injections (infusions) into the veins. Alternatively, some conditions such as Primary Immunodeficiency Diseases in adult patients can be treated by having patients self-administer GAMUNEX® in their own home, with slow injections under the skin (subcutaneous infusions).

If you are self-administering GAMUNEX® with subcutaneous injections, be sure to closely follow all instructions from your doctor. They may differ from the information contained in this leaflet. You will take GAMUNEX® through infusions given just below the skin (in the subcutaneous tissue). As directed by your physician, one or more injection sites on your body will be selected. The number and location of the injection sites depends on the amount you need to receive. Typically, people use 1 to 4 needles in different locations on your body at one time. You may use up to 8 needles as directed by your doctor. The needles are attached with a tube to the pump. You will need to have infusions once a week.

Instructions for administering GAMUNEX® are shown below. Only use GAMUNEX® by yourself after you have been instructed by your doctor or healthcare professional.

If you do not understand any of the instructions you have been given, ask your doctor, nurse or pharmacist for help.

Steps for Subcutaneous Administration

Before Using GAMUNEX®

  • Do not shake the vials.
  • Prior to use, allow the solution to come to room temperature (20°C to 25°C). This can take 60 minutes or longer.
  • Do not use the vial if:
    - the tape over the carton ends is broken.
    - the solution is cloudy, discolored or contains particles. The solution should be clear to opalescent, and colorless to pale yellow.
    - the band around the vial neck and cap is damaged or missing.
    - the expiration date has passed.
  • Sanitize your infusion set-up area by preparing a clean, flat, non-porous surface such as a kitchen counter. Avoid using porous surfaces such as wood. Clean the surface with an alcohol wipe using a circular motion from the center outward.

Step 1:
Wash and dry your hands thoroughly before administering GAMUNEX®

  • Your healthcare provider may recommend that you use antibacterial soap or that you wear gloves.

Step 2:
Remove the protective cap and sanitize the rubber stopper

  • Remove the protective cap from the vial to expose the central portion of the rubber stopper.
  • Wipe the rubber stopper with alcohol and allow to dry.

Step 3:
Use aseptic technique when preparing and administering GAMUNEX®

  • Do not allow your fingers or other objects to touch the inner stem of the plunger, the syringe tip, or other areas that will come in contact with your GAMUNEX® solution. This is called aseptic technique and is designed to prevent transmission of germs.
  • Using aseptic technique, attach each needle to the syringe tip.

Step 4:
Prepare the syringe and draw GAMUNEX® solution into syringe

  • Remove cap from needle.
  • Pull the syringe plunger back to the level matching the amount of GAMUNEX® to be withdrawn from the vial.
  • Place the GAMUNEX® vial on a clean flat surface and insert the needle into the center of the vial stopper.
  • Inject air into the vial. The amount of air should match the amount of GAMUNEX® to be withdrawn.
  • Turn the vial upside down and withdraw the correct amount of GAMUNEX®. If multiple vials are required to achieve the correct dose, repeat Step 4.

Step 5:
Fill the pump reservoir and prepare the infusion pump

  • Follow the pump manufacturer’s instructions for filling the pump reservoir and preparing the infusion pump, administration tubing and Y-site connection tubing, if needed.
  • Be sure to prime the administration tubing to ensure that no air is left in the tubing or needle by filling the tubing/needle with GAMUNEX®. To prime, hold the syringe in one hand and the administration tubing’s capped needle in the other. Gently squeeze on the plunger until you see a drop of GAMUNEX® exit from the needle.

Example Equipment

Step 6:
Select the number and location of infusion sites

  • Select one or more infusion sites as directed by your healthcare provider.
  • The number and location of injection sites depends on the volume of the total dose.

Step 7:
Prepare the infusion site

  • Cleanse the infusion site(s) with antiseptic solution using a circular motion working from the center of the site and moving to the outside.
  • Sites should be clean, dry, and at least 5 centimetres apart.

Step 8
Insert the needle

  • Grasp the skin between two fingers and insert the needle into the subcutaneous tissue.

Step 9:
Do not inject GAMUNEX® into a blood vessel

  • After inserting each needle into tissue (and before your infusion), make sure that a blood vessel has not been accidentally entered. To do this, attach a sterile syringe to the end of the primed administration tubing. Pull back on the syringe plunger and watch for any blood flowing back into administration tubing.
  • If you see any blood, remove and discard the needle and administration tubing.

  • Repeat priming and needle insertion steps using a new needle, administration tubing and a new infusion site.
  • Secure the needle in place by applying sterile gauze or transparent dressing over the site.

Step 10:
Repeat for other sites, as needed

  • If using multiple, simultaneous infusion sites, use Y-site connection tubing and secure to the administration tubing.

Step 11:
Infuse GAMUNEX® following the pump manufacturer’s instructions for the infusion pump

Step 12:
After infusion, turn off pump and dispose of used supplies

  • Follow manufacturer’s instructions to turn off pump.
  • Undo and discard any dressing or tape.
  • Gently remove the inserted needle(s) or catheter(s).
  • Discard any unused solution in an appropriate waste container as instructed.
  • Discard any used administration equipment in an appropriate waste container.
  • Store your supplies in a safe place.
  • Follow manufacturer’s instructions to care for the infusion pump.

Step 13:
Record each infusion

  • Remove the peel-off label with the product lot number and expiration date from the GAMUNEX® vial and use this to complete the patient record.
  • Remember to bring your journal with you when you visit your physician or healthcare provider.

Be sure to tell your doctor about any problems you have doing your infusions. Your doctor may ask to see your journal, so be sure to take it with you each time you visit the doctor’s office.

How much GAMUNEX® is given

Your doctor will calculate the dose of GAMUNEX® that you are to receive. Your dose will depend on factors such as your condition, body weight and response to the medicine.

If you miss a dose

If you miss a dose talk to your doctor and arrange another visit as soon as possible.

If you are not sure what to do, ask your doctor or pharmacist.

If you receive too much (overdose)

Overdose may lead to fluid overload and increased viscosity (“thickness”) of the blood.

Immediately telephone your doctor or the Poisons Information Centre (telephone13 11 26) for advice, or go to Accident and Emergency at the nearest hospital if you think that you may have self-administered too much GAMUNEX®. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are receiving GAMUNEX®

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are receiving GAMUNEX® therapy.

Tell any other doctors, dentists, and pharmacists who treat you that you are being treated with this medicine.

If you are going to have surgery, tell the surgeon or anaesthetist that you are being treated with this medicine. It may affect other medicines used during surgery.

If you become pregnant while receiving this medicine, tell your doctor immediately.

If you are about to have any blood tests, tell your doctor that you are receiving this medicine. It may interfere with the results of some tests.

Keep all of your doctor’s appointments so that your progress can be checked. Your doctor may do some tests from time to time to make sure the medicine is working and to prevent unwanted side effects.

Things you must not do

If you are self-administering GAMUNEX®, do not stop using it or change the dosage without checking with your doctor.

Things to be careful of

You should immediately tell your doctor if you experience any of the following during treatment with GAMUNEX®:

  • decreased urine output,
  • sudden weight gain,
  • fluid retention/oedema,
  • shortness of breath.

Side Effects

Tell your doctor or nurse as soon as possible if you do not feel well while you are being treated with GAMUNEX®.

This medicine helps most people with the conditions listed at the start of this leaflet, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Some side effects are more common with the first dose of GAMUNEX®.

If you are over 65 years of age you may have an increased chance of getting side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor, nurse or pharmacist to answer any questions you may have.

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

  • chills,
  • headache,
  • dizziness,
  • mild fever,
  • nausea,
  • vomiting,
  • diarrhoea,
  • sore throat, cough or nasal congestion,
  • pain or reaction at the injection site.

The above side effects are usually mild and short-lived

Tell your doctor as soon as possible if you notice any of the following:

  • mild skin reaction such as rash, itching,
  • tiredness or loss of strength/energy,
  • pain in the abdomen,
  • joint pain,
  • mild back or shoulder pain,
  • infections.

The above list includes more serious side effects that may require medical attention.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • severe allergic reaction (with symptoms such as shortness of breath, wheezing or difficulty breathing, swelling of the face, lips, tongue or other parts of the body, loss of consciousness),
  • difficulty breathing,
  • severe headache, stiff neck, drowsiness, fever, sensitivity to light, painful eye movements, nausea and vomiting (these may be signs of aseptic meningitis),
  • severe tiredness or generalised weakness, lightheadedness, dark urine, jaundice (yellow skin and eyes) and/or pale complexion (these may be signs of haemolytic anaemia),
  • fluid retention/oedema (swelling) or decreased urine output (these may be signs or impaired kidney function),
  • chest pain or discomfort that worsens on deep breathing, unexplained rapid pulse, unexplained shortness of breath, numbness or weakness on one side of the body, or swelling, pain, or warmth and redness of the arm or leg (these could be signs of a blood clot).

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are rare.

Tell your doctor or nurse if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

Some side effects (for example, low blood pressure, impairment of renal function with elevation of serum creatinine) can only be found when your doctor does tests from time to time to check your progress.

After receiving GAMUNEX®

If you need to keep your GAMUNEX® at home follow these instructions for storage and disposal.

Storage

Store GAMUNEX® in the refrigerator (2ºC to 8ºC). Do not freeze.

Do not use after the expiry date.

Tape over carton ends must be unbroken.

Do not use if the band around vial neck and cap is damaged or missing.

Do not use if turbid.

Solution that has been frozen should not be used.

Once removed from the fridge GAMUNEX® can be stored below 25ºC for use within 6 months.

Discard unused portion. Do not store after entry into vial.

Keep it where children cannot reach it.

Disposal

If your doctor tells you to stop using this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

GAMUNEX® is a clear solution which is colourless to pale yellow. It is available in glass vials.

Ingredients

In each vial of GAMUNEX® is a sterile solution containing 10% blood proteins of which at least 98% is immunoglobulin.

It also contains:

  • water for injections
  • glycine.

This medicine does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Australian Registration Numbers

10 mL AUST R 116689

25 mL AUST R 117237

50 mL AUST R 117238

100 mL AUST R 117239

200 mL AUST R 117240

400 mL AUST R 371434

Not all pack sizes may be marketed.

Sponsor

Grifols Australia Pty Ltd
5/80 Fairbank Road,
Clayton South, Victoria 3169
Australia

This leaflet was updated 16 September 2022

® = Registered Trademark of Grifols.

Published by MIMS November 2022

BRAND INFORMATION

Brand name

Gamunex

Active ingredient

Immunoglobulin, normal (human)

Schedule

S4

 

1 Name of Medicine

Normal immunoglobulin (human), 10%, for intravenous or subcutaneous administration.

2 Qualitative and Quantitative Composition

Gamunex normal immunoglobulin (human), 10%, solution for intravenous or subcutaneous administration.
One mL contains: normal immunoglobulin (human) 100 mg (purity of at least 98% IgG).
Each vial of 10 mL contains: 1 g of human normal immunoglobulin.
Each vial of 25 mL contains: 2.5 g of human normal immunoglobulin.
Each vial of 50 mL contains: 5 g of human normal immunoglobulin.
Each vial of 100 mL contains: 10 g of human normal immunoglobulin.
Each vial of 200 mL contains: 20 g of human normal immunoglobulin.
Each vial of 400 mL contains: 40 g of human normal immunoglobulin.
Distribution of the IgG subclasses (average values): IgG1 62.8%; IgG2 29.7%; IgG3 4.8%; IgG4 2.7%.
The maximum IgA content is 84 microgram/mL.
Produced from plasma of human donors.
For a full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Dosage form: injection.
The solution is clear to opalescent, colourless to pale yellow.

4 Clinical Particulars

4.1 Therapeutic Indications

Replacement therapy in: primary immunodeficiency (PI) diseases; symptomatic hypogammaglobulinaemia secondary to underlying disease or treatment.
Immunomodulation in: idiopathic thrombocytopaenic purpura (ITP), in patients at high risk of bleeding or prior to surgery to correct the platelet count; Guillain-Barré syndrome (GBS); chronic inflammatory demyelinating polyneuropathy (CIDP); Kawasaki disease.

4.2 Dose and Method of Administration

Gamunex is recommended for administration by intravenous infusion for all indications. Gamunex can also be administered by subcutaneous infusion for replacement therapy in primary immunodeficiency indications only. Safety and efficacy of subcutaneous administration has not been demonstrated for other indications.

Dosage.

Replacement therapy in primary immunodeficiency (PI) diseases.

Intravenous (IV).

Gamunex doses between 300 and 600 mg/kg (3 and 6 mL/kg), which represented the dose range for 92% of the subjects in the larger efficacy trial, may be used for infection prophylaxis. The dose should be individualized taking into account dosing intervals (e.g. 3 or 4 weeks) and Gamunex dose (between 300 and 600 mg/kg). A target serum IgG trough level (i.e. prior to the next infusion) of at least 5 g/L has been proposed in the literature, however no randomized controlled trial data are available to validate this recommendation. See Clinical trials.

Subcutaneous (SC).

The weekly SC Gamunex dose for replacement therapy in primary immunodeficiency diseases may be initiated with a dose comparable to the IVIg replacement dose adjusted for previous IV treatment interval. The dose and dosage interval must be individualised based on measured IgG trough levels and ongoing clinical response.
Replacement therapy in symptomatic secondary hypogammaglobulinaemia. The recommended dose is 200 to 400 mg/kg every 3 to 4 weeks, to obtain a trough level of at least 5 to 6 g/L.
Idiopathic thrombocytopaenic purpura (ITP). Gamunex may be administered at a total dose of 2 g/kg, divided in two doses of 1 g/kg (10 mL/kg) given on two consecutive days or into five doses of 0.4 g/kg (4 mL/kg) given on five consecutive days. If after administration of the first of two daily 1 g/kg (10 mL/kg) doses, an adequate increase in the platelet count is observed at 24 hours, the second dose of 1 g/kg body weight may be withheld. Likewise, subsequent 0.4 g/kg doses maybe withheld when an adequate increase in platelet count is observed.
The high dose regimen (1 g/kg x 1-2 days) is not recommended for individuals with expanded fluid volumes or where fluid volume may be a concern.
Guillain-Barré syndrome (GBS). 400 mg/kg (4 mL/kg) on three to seven consecutive days. The treatment should commence within 14 days of the onset of symptoms.
Only limited experience is available of use of intravenous immunoglobulins in children with Guillain-Barré syndrome.
Chronic inflammatory demyelinating polyneuropathy (CIDP). Loading dose: 2 g/kg (20 mL/kg) in divided doses over 2 to 4 consecutive days.
Maintenance dose: 1 g/kg administered over 1 day (10 mL/kg) or divided into two doses of 500 mg/kg (5 mL/kg) given on two consecutive days, every 3 weeks.
Only limited experience is available of use of intravenous immunoglobulins in children with CIDP.
Clinical studies of Gamunex did not include sufficient numbers of subjects aged 65 and over to determine a precise treatment effect.
Kawasaki disease. 1.6 to 2 g/kg (16 to 20 mL/kg) as a single infusion or in divided doses over 2 to 5 days.

Administration.

If dilution is required, Gamunex may be diluted with 5% dextrose in water (D5/W). Do not dilute with saline.
Gamunex should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if turbid and/or if discoloration is observed.
For intravenous or subcutaneous administration, Gamunex should be at room temperature during administration.

Intravenous (IV).

It is recommended that Gamunex should initially be infused at a rate of 0.01 mL/kg per minute (1 mg/kg per minute) for the first 30 minutes. If well tolerated, the rate may be gradually increased to a maximum of 0.08 mL/kg per minute (8 mg/kg per minute). If side effects occur, the rate may be reduced, or the infusion interrupted until symptoms subside. The infusion may then be resumed at the rate which is comfortable for the patient.
For patients judged to be at increased risk for developing renal dysfunction, it may be prudent to reduce the amount of product infused per unit time by infusing Gamunex at a rate less than 8 mg/kg/min (0.08 mL/kg/min). No prospective data are presently available to identify a maximum safe dose, concentration, and rate of infusion in patients determined to be at increased risk of acute renal failure. In the absence of prospective data, recommended doses should not be exceeded and the concentration and infusion rate should be the minimum level practicable. Reduction in dose, concentration, and/or rate of administration in patients at risk of acute renal failure has been proposed in the literature in order to reduce the risk of acute renal failure.
Only 18 gauge needles should be used to penetrate the stopper for dispensing product from 10 mL vial sizes; 16 gauge needles or dispensing pins should only be used with 25 mL vial sizes and larger. Needles or dispensing pins should only be inserted within the stopper area delineated by the raised ring. The stopper should be penetrated perpendicular to the plane of the stopper within the ring. See Table 1.
Content of vials may be pooled under aseptic conditions into sterile infusion bags and infused within 8 hours after pooling.
If dilution is required, Gamunex may be diluted with 5% dextrose in water (D5/W). Do not dilute with saline.
It is recommended to infuse Gamunex using a separate line by itself, without mixing with other intravenous fluids or medications the subject might be receiving. The Gamunex infusion line can be flushed with 5% dextrose in water (D5/W) or 0.9% sodium chloride for injection.
Avoid simultaneous administration of Gamunex and heparin through a single lumen delivery device due to Gamunex, heparin incompatibilities. Flush heparin lock (hep-lock) through which Gamunex was administered with 5% dextrose in water (D5/W) or 0.9% sodium chloride for injection, and do not flush with Heparin. See Table 2.

Subcutaneous (SC).

Subcutaneous infusion for home treatment should only be used for replacement therapy in patients with PI and should be initiated by a physician experienced in the guidance of patients for home treatment. Provide the patient with instructions on subcutaneous infusion for home treatment, if the physician believes that home administration is appropriate for the patient. Include the type of equipment to be used along with its maintenance, proper infusion techniques, selection of appropriate infusion sites (e.g. abdomen, thighs, upper arms, and/or lateral hip), maintenance of a treatment diary, and measures to be taken in case of adverse reactions in the patient instructions.
It is recommended that Gamunex should be infused at a rate of 20 mL/hr per infusion site.
In clinical study 060001, the mean volume administered per infusion site was 34 mL (17-69 mL) and the majority of infusions were administered at a rate of 20 mL/hr per site. Multiple simultaneous infusion sites were enabled by administration tubing and Y-site connection tubing. Most subjects utilized 4 infusion sites per infusion with abdomen and thighs being the most commonly used sites.
Prior to use, allow the solution to reach ambient room temperature. Gamunex should be inspected visually for discoloration and particulate matter prior to administration. Do not shake. Do not use if the solution is cloudy or has particulates. Check the product expiration date on the vial. Do not use beyond the expiration date.
See Figure 1.
1. Use aseptic technique when preparing and administering Gamunex for injection.
2. Remove the protective cap from the vial to expose the central portion of the rubber stopper.
3. Wipe the rubber stopper with alcohol and allow to dry.
4. Using a sterile syringe and needle, prepare to withdraw Gamunex by first injecting air into the vial that is equivalent to the amount of Gamunex to be withdrawn. Then withdraw the desired volume of Gamunex. If multiple vials are required to achieve the desired dose, repeat this step. (Figure 1a.)
5. Follow the manufacturer's instructions for filling the pump reservoir and preparing the pump, administration tubing and Y-site connection tubing, if needed. Be sure to prime the administration tubing to ensure that no air is left in the tubing or needle by filling the tubing/ needle with Gamunex.
6. Select the number and location of injection sites. (Figure 1b.)
7. Cleanse the injection site(s) with antiseptic solution using a circular motion working from the center of the site and moving to the outside. Sites should be clean, dry, and at least two inches apart. (Figure 1c.)
8. Grasp the skin between two fingers and insert the needle into the subcutaneous tissue. (Figure 1d.)
9. Repeat priming and needle insertion steps using a new needle, administration tubing and a new infusion site. Secure the needle in place by applying sterile gauze or transparent dressing over the site. (Figure 1e.)
10. If using multiple, simultaneous injection sites, use Y-site connection tubing and secure to the administration tubing.
11. Infuse Gamunex following the manufacturer's instructions for the pump. (Figure 1f.)

General.

A number of factors could reduce the efficacy of this product or even result in an ill effect following its use. These include improper storage and handling of the product, diagnosis, dosage, method of administration, and biological differences in individual subjects. Because of these factors, it is important that this product be stored properly and that the directions be followed carefully during use.
Product is for single use in one patient only. Discard any residue.
To reduce microbiological hazard, use as soon as practicable after entering the vial or after dilution. Visually inspect each vial before use. Do not use if turbid. Solution that has been frozen should not be used.

4.3 Contraindications

Gamunex is contraindicated in individuals with known anaphylactic or severe systemic response to human immunoglobulin or any of the excipients of the product. This applies in particular to individuals with severe, selective IgA deficiencies (serum IgA < 0.05 g/L) who have known antibodies against IgA (anti-IgA antibody), due to the risk of severe immediate hypersensitivity reactions including anaphylaxis.

4.4 Special Warnings and Precautions for Use

Certain undesirable effects may be related to the rate of infusion. The recommended infusion rate should therefore be followed (see Section 4.2 Dose and Method of Administration). Patients should be carefully observed during the infusion and for at least 20 minutes afterwards.
Certain adverse effects may occur more frequently:
with a high infusion rate;
in patients with hypo- or agammaglobulinaemia with or without IgA deficiency;
in patients who are receiving human normal immunoglobulin for the first time or, in rare cases, when the immunoglobulin product is switched or after a prolonged interval without treatment.
Potential complications can often be avoided by ensuring:
that patients are not hypersensitive to human normal immunoglobulin by initially infusing Gamunex slowly (0.1 mL/kg body weight per hour);
that patients are carefully monitored for any symptoms throughout the infusion period. In particular, patients receiving human immunoglobulin for the first time and those switched from a different immunoglobulin or not having received treatment for some time should be monitored for possible undesirable effects during the first infusion and for one hour afterwards;
the use of glucose solution for dilution prior to infusion should be carefully considered for patients suffering from latent diabetes, diabetes or in patients on a low sugar diet.
If undesirable effects occur, the infusion rate should be reduced or the infusion should be suspended until the symptoms have disappeared. If the symptoms persist even after suspending the infusion, suitable treatment should be instituted. In the event of anaphylactic shock, treatment with the product should be discontinued immediately and current standard medical treatment for shock should be implemented.

Infection risk.

Because this product is made from human blood, it may carry a risk of transmitting infectious agents, e.g. viruses that can cause disease. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses. Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections.
The capacity of the manufacturing process to remove and/or inactivate enveloped and nonenveloped viruses has been validated by laboratory spiking studies on a scaled down process model, using the following enveloped and nonenveloped viruses: human immunodeficiency virus, type I (HIV-1) as the relevant virus for HIV-1 and HIV-2; bovine viral diarrhoea virus (BVDV) as a model for hepatitis C virus (HCV); pseudorabies virus (PRV) as a model for large DNA viruses (e.g. herpes viruses); Reo virus type 3 (Reo) as a model for nonenveloped viruses and for its resistance to physical and chemical inactivation; hepatitis A virus (HAV) as a relevant nonenveloped virus, and porcine parvovirus (PPV) as a model for human parvovirus B19.
The measures taken are considered effective for enveloped viruses such as HIV, HBV, and HCV. The measures taken may be of limited value against nonenveloped viruses such as HAV and/or 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.
Additionally, the manufacturing process was investigated for its capacity to decrease the infectivity of an experimental agent of transmissible spongiform encephalopathy (TSE), considered as a model for the vCJD and CJD agents. Several of the individual production steps in the Gamunex manufacturing process have been shown to decrease TSE infectivity of that experimental model agent. These studies provide reasonable assurance that low levels of CJD/vCJD agent infectivity, if present in the starting material, would be removed.
It is strongly recommended that every time that Gamunex is administered to a patient, the name and batch number of the product are recorded using the supplied tear off labels in order to maintain a link between the patient and the batch of the product.

Anaphylaxis.

Gamunex should be administered only intravenously or subcutaneously. On rare occasions, treatment with an immune globulin preparation may cause a precipitous fall in blood pressure and a clinical picture of anaphylaxis, even when the patient is not known to be sensitive to immune globulin preparations. Adrenalin and other appropriate supportive care should be available for the treatment of an acute anaphylactic reaction.
True anaphylactic reactions to Gamunex may occur in recipients with documented prior histories of severe allergic reactions to intramuscular immunoglobulin, but some subjects may tolerate cautiously administered intravenous immunoglobulin without adverse effects. Very rarely an anaphylactoid reaction may occur in subjects with no prior history of severe allergic reactions to either intramuscular or intravenous immunoglobulin.

Aseptic meningitis syndrome.

An aseptic meningitis syndrome (AMS) has been reported to occur infrequently in association with human normal immunoglobulin intravenous treatment. The syndrome usually begins within several hours to two days following human normal immunoglobulin intravenous treatment. It is characterized by symptoms and signs including severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea and vomiting.
AMS may occur more frequently in association with high dose (2 g/kg) and or rapid infusion of human normal immunoglobulin intravenous treatment. Discontinuation of human normal immunoglobulin intravenous treatment has resulted in remission of AMS within several days without sequelae.

Haemolysis.

Human normal immunoglobulin intravenous (IGIV) 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 and, rarely, haemolysis. Haemolytic anaemia can develop subsequent to IGIV therapy due to enhanced red blood cells sequestration. IGIV recipients should be monitored for clinical signs and symptoms of haemolysis.
The following risk factors may be related to the development of haemolysis: high doses (such as ≥ 2 gram/kg, single administration or divided over several days) and non-O blood group. Underlying inflammatory state in an individual patient may increase the risk of haemolysis, but its role is uncertain.
Gamunex may contain low levels of antiblood group A and B antibodies primarily of the IgG4 class. Direct antiglobulin tests (DAT or direct Coombs tests), which are carried out in some centres as a safety check prior to red blood cell transfusions, may become positive temporarily. Gamunex does not contain irregular antibodies to Rhesus antigens or other non-ABO RBC antigens. Haemolytic events were not detected in association with positive DAT findings in clinical trials.
Monitor patients for clinical signs and symptoms of haemolysis, particularly patients with risk factors noted above. Consider appropriate laboratory testing in higher risk patients, including measurement of haemoglobin or haematocrit prior to infusion and within approximately 36 to 96 hours postinfusion. If clinical signs and symptoms of haemolysis or a significant drop in haemoglobin or haematocrit have been observed, perform additional confirmatory laboratory testing. If transfusion is indicated for patients who develop haemolysis with clinically compromising anaemia after receiving IGIV, perform adequate cross matching to avoid exacerbating ongoing haemolysis.

Thrombotic events.

Thrombotic events have been reported in association with IGIV (see Section 4.8 Adverse Effects (Undesirable Effects)). This association is assumed to be related to a relative increase in blood viscosity through the influx of immunoglobulin in at risk patients. Caution should be exercised in prescribing and infusing IGIV in obese patients and in patients with pre-existing risk factors for thrombotic events (such as advanced age, hypertension, diabetes mellitus, a history of vascular disease/ atherosclerosis or venous or arterial thrombosis, impaired cardiac output, hypercoagulable conditions, prolonged periods of immobilization, use of oestrogens, indwelling central vascular catheters, hyperviscosity, severe hypovolaemia and/or diseases which may increase blood viscosity). The potential risks and benefits of IGIV should be weighed against those of alternative therapies for all patients for whom IGIV 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 triacylglycerols (triglycerides), or monoclonal gammopathies. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity.

Haematoma formation.

Do not administer Gamunex subcutaneously in patients with ITP because of the risk of haematoma formation.

Information for patients.

Patients should be instructed to immediately report symptoms of decreased urine output, sudden weight gain, fluid retention/ oedema, and/or shortness of breath (which may suggest kidney damage) to their physicians.

Use in renal impairment.

Human normal immunoglobulin intravenous products have been reported to be associated with acute renal dysfunction, acute renal failure, acute tubular necrosis, proximal tubular nephropathy, osmotic nephrosis and death. Patients predisposed to acute renal failure include patients with any degree of pre-existing renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinaemia, or patients who are overweight or receiving known nephrotoxic drugs. Especially in such patients, IGIV products should be administered at the minimum concentration available and the minimum rate of infusion practicable. While these reports of renal dysfunction and acute renal failure have been associated with the use of many of the licensed IGIV products, those containing sucrose as a stabilizer accounted for a disproportionate share of the total number. Gamunex does not contain sucrose. Glycine, a natural amino acid, is used as a stabilizer. See Section 4.2 Dose and Method of Administration for important information intended to reduce the risk of acute renal failure.
Patients must not be volume depleted prior to the initiation of the infusion of IGIV. Concomitant use of loop diuretics must be avoided. Periodic monitoring of renal function and urine output is particularly important in patients judged to have a potential increased risk for developing acute renal failure. Renal function, including measurement of blood urea nitrogen (BUN)/serum creatinine, should be assessed prior to the initial infusion of Gamunex and again at appropriate intervals thereafter. If renal function deteriorates, discontinuation of the product should be considered. For patients judged to be at risk for developing renal dysfunction, it may be prudent to reduce the amount of product infused per unit time by infusing Gamunex at a rate less than 8 mg IG/kg/min (0.08 mL/kg/min).
Increases in creatinine and blood urea nitrogen (BUN) have been observed as soon as one to two days following infusion with human normal immunoglobulin intravenous products, predominantly with products containing sucrose as stabilizer. Progression to oliguria and anuria requiring dialysis has been observed, although some patients have improved spontaneously following cessation of treatment.

Use in the elderly.

See Section 4.4 Special Warnings and Precautions for Use, Use in renal impairment.

Paediatric use.

No data available.

Effects on laboratory tests.

Interference with serological testing.

After injection of immunoglobulin the transitory rise of the various passively transferred antibodies in the patient's blood may result in misleading positive results in serological testing. Passive transmission of antibodies to erythrocyte antigens e.g. A, B, D may interfere with some serological tests for red cell allo-antibodies (e.g. Coombs test), reticulocyte count and haptoglobin.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Antibodies in Gamunex may interfere with the response to live viral vaccines such as measles, mumps and rubella. Therefore, use of such vaccines should be deferred until approximately 6 months after Gamunex administration.
Avoid simultaneous administration of Gamunex and heparin through a single lumen delivery device due to Gamunex, heparin incompatibilities. Flush heparin lock (hep-lock) through which Gamunex was administered with 5% dextrose in water (D5/W) or 0.9% sodium chloride for injection, and do not flush with heparin.
Please see Section 4.2 Dose and Method of Administration for other drug interactions.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No studies have been conducted on the effects of Gamunex on fertility.
Animal reproduction studies have not been conducted with Gamunex. It is not known whether Gamunex can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Gamunex should be given to a pregnant woman only if clearly needed.
 The safety of Gamunex for use in human lactation has not been established in controlled clinical trials. Immunoglobulins are excreted into breast milk and Gamunex should only be given with caution to breastfeeding mothers.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

The following drug related adverse events were compiled from clinical trials with Gamunex.

Intravenous administration (PI, ITP, CIDP).

See Table 3.
The following adverse effects have been reported in clinical trials with Gamunex in rare frequencies (≥ 0.01% and < 0.1%): haemolytic anaemia, dyspnoea, sinusitis, skin exfoliation, anxiety, myalgia, haemoglobin decreased, dyspepsia, contusion, dermatitis, flushing, musculoskeletal stiffness, palmar erythema, aphonia.

Subcutaneous administration (PI).

Treatment of primary immunodeficiency by the subcutaneous route (study 060001).

Adverse events occurring in study 060001 were divided into 2 types: 1) local infusion site reactions, and 2) noninfusion site adverse events. Table 4 displays those adverse events occurring in ≥ 2% of infusions during the SC phase of the study.
Drug related adverse events occurring in ≥ 5% of subjects are shown in Table 5. All local infusion site reactions were a priori considered drug related.
Table 6 shows the frequency of drug related adverse events per infusion that occurred at a rate ≥ 0.01.
There were no serious bacterial infections in the SC phase of study 060001.
Local infusion site reactions with SC Gamunex consisted primarily of mild to moderate erythema, pain and swelling. No serious local infusion site reactions were observed. The majority of local infusion site reactions resolved within 3 days. The number of subjects experiencing an infusion site reaction and the number of infusion site reactions decreased substantially over time as subjects received continued weekly SC infusions. At the beginning of the SC phase, a rate of approximately 1 infusion site reaction per infusion was reported, whereas at the end of the study this rate was reduced to 0.5 infusion site reactions per infusion, a reduction of 50%. See Figure 2.

Post-marketing.

The following post-marketing serious adverse events have been reported. See Table 7.
Some cases of haemolytic anaemia, especially in association with pre-existing renal impairment, were severe and required blood component transfusion.
In isolated instances, impairment of renal function with elevation of serum creatinine, to the point of acute renal failure, may occur in the context of administration of immunoglobulins (see Section 4.4 Special Warnings and Precautions for Use, Use in renal impairment).
Very rarely: thromboembolic events such as myocardial infarction, stroke, pulmonary embolism and deep vein thromboses have been reported in association with immunoglobulins in patients at risk (see Section 4.4 Special Warnings and Precautions for Use, Thrombotic events).

Transfusion related acute lung injury (TRALI).

There have been reports of noncardiogenic pulmonary oedema [transfusion related acute lung injury (TRALI)] in patients administered IGIV. TRALI is characterized by severe respiratory distress, pulmonary oedema, hypoxaemia, normal left ventricular function, and fever and typically occurs within 1-6 hrs after transfusion. Patients with TRALI may be managed using oxygen therapy with adequate ventilatory support.
IGIV recipients should be monitored for pulmonary adverse reactions. If TRALI is suspected, appropriate tests should be performed for the presence of antineutrophil antibodies and anti-HLA antibodies in both the product and patient serum.

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

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

Replacement therapy (PI). Gamunex supplies a broad spectrum of opsonic and neutralizing IgG antibodies against bacteria or their toxins.
Immunomodulation therapy.

ITP.

The mechanism of action of high doses of immunoglobulins in the treatment of ITP has not been fully elucidated.

CIDP.

The precise mechanism of action in CIDP has not been fully elucidated.

Clinical trials.

Primary immunodeficiency (PI).

Efficacy in primary immunodeficiency was assessed in two trials. The first trial was a randomised comparison with Gamimune N, a previous version of the product manufactured using a solvent/ detergent method of viral inactivation. Patients received Gamunex IV infusion for 9 months at 100-600 mg/kg every 3-4 weeks. Patients were aged 35 years on average and 70% were male. The primary efficacy endpoint was the proportion of patients with at least one of the following validated infections: pneumonia, acute sinusitis and acute exacerbations of chronic sinusitis. Seventy three of the 87 patients were evaluable for efficacy. Thirteen patients (18%) developed at least one validated sinopulmonary infection, 4 with pneumonia, 4 with acute sinusitis and 5 with exacerbation of chronic sinusitis. Fifty six patients (77%) developed any infection (validated plus clinically defined nonvalidated). The annual rate of infection was 0.25 for validated sinopulmonary infections and 2.88 for any infection. Patients spent 14% of their time on prophylactic antibiotics, 10% on therapeutic antibiotics, 1.1% off school or work, 0.7% on physicians' visits and 0.2% in hospital. The results were comparable with Gamimune N and other similar products.
The mean trough serum IgG concentration was 7.8 g/L. The relationship between trough serum IgG concentration and incidence of validated and any infection is shown in Table 8.
The second trial was uncontrolled, in 19 subjects of whom 17 were evaluable. Median age was 14 years, range 6-60, and 82% were male. The dose and dose interval of Gamunex were similar to the previous study. The duration of treatment was 6 months. The average number of infections per patients was 3, range 1-5, and the average number of days off work or school due to infection was 3, range 0-14. Antibiotics were used for an average of 21 days, which was higher than for other similar products. However, the number of subjects was small and the data were not seasonally adjusted. There were no serious infections or hospitalisations due to infection. The mean trough serum IgG concentration was 7.5 g/L.

Treatment of primary immunodeficiency by the subcutaneous (SC) route.

In a single sequence, crossover trial, the pharmacokinetics, safety, and tolerability of subcutaneously administered Gamunex in subjects with primary immunodeficiency were evaluated. The objectives of the study were to determine a dose of weekly subcutaneously administered Gamunex that produces steady-state AUC of plasma total IgG that is noninferior to that of the regularly administered IV dose of Gamunex. Subjects were required to have been receiving Gamunex 200-600 mg/kg IV every 3-4 weeks for at least 3 months, at which time they entered the IV phase of the study. PK profiling around the IV dose occurred and subjects were crossed over to weekly SC infusions. The weekly SC dose was determined by multiplying the total IV dose by 1.37 and dividing the resultant new total dose by 3 or 4 depending on the previous IV interval. A total of 32 and 26 subjects, respectively, had plasma total IgG concentration vs. time profiles for assessment of steady-state PK parameters after IV and SC administration. In contrast to plasma total IgG levels observed with monthly IV Gamunex treatment (rapid peaks followed by a slow decline), the plasma IgG levels in subjects receiving weekly SC Gamunex therapy were relatively stable. See Figure 3.
The primary PK endpoint (AUC of plasma total IgG) following IV and SC administration is summarized in Table 9.
In order to test noninferiority, the geometric least squares mean (LSM) ratio, SC vs. IV administration, was analyzed using ANOVA. The result showed that the point estimate for the geometric LSM ratio of AUCSC vs. AUCIV was 0.888, with a 90% confidence interval (CI) of 0.861-0.917. The lower bound of the 90% confidence interval is above 0.80 indicating that the SC dose is noninferior to the IV dose. In addition, the 90% CI is within the limit of 0.80-1.25, a criterion for concluding "bioequivalence" between the two treatments (SC and IV doses).
The mean trough concentration (mean Ctrough) of plasma total IgG following IV and SC administration are presented in Table 10.
The IV infusions prior to the SC phase of this study allowed steady-state conditions for the SC phase to be achieved much earlier (by week 5), due to the loading dose effect of the IV doses.
SC administration was evaluated in three pediatric subjects (age range 13-15) with PI. This number of pediatric subjects was too small for separate evaluation of pharmacokinetics and safety to determine whether they respond differently from adults. Efficacy and safety in pediatric patients using the SC route of administration have not been established.
SC administration should not be used in patients with idiopathic thrombocytopaenic purpura due to risk of haematoma formation.

Idiopathic thrombocytopaenic purpura (ITP).

The mechanism of action of high doses of immunoglobulins in the treatment of idiopathic thrombocytopaenic purpura (ITP) has not been fully elucidated. Several lines of evidence suggest that Fc receptor blockade of phagocytes as well as down regulation of autoreactive B cells by anti-idiotypic antibodies provided by IGIV may constitute the main mechanisms of action.
Efficacy in idiopathic thrombocytopenic purpura was assessed in two trials. In the first trial, 49 patients with platelet counts ≤ 20 x 109/L were treated with Gamunex IV infusion 1 g/kg/day for two consecutive days. The mean age of patients was 34 years and 25% were male. Children (age ≤ 18 years) made up 24% of the study population. The primary efficacy variable was platelet response, defined as an increase in platelet count to ≥ 50 x 109/L within 7 days of the first dose of Gamunex. Forty three patients (88%) achieved a response. Responses of at least 7 days duration occurred in 33 patients (67%). Sixty eight percent of patients had new bleeding episodes. The results were comparable with other similar products.
In the second study, 18 patients with platelet count ≤ 20 x 109/L were treated with Gamunex IV infusion 1 g/kg day for two consecutive days. The mean age of patients was 42 years and 39% were male. All were adults. The primary efficacy variable was platelet response, defined differently to the previous trial. It was an increase in platelet count to ≥ 50 x 109/L on at least one occasion within 21 days of the first dose of Gamunex. Fifteen patients (83%) responded. The median duration of response was 13 days, range 1-21 days. Fifteen patients (83% had bleeding sites at the start of treatment. Bleeding resolved in all but two patients; however, new bleeding sites developed in three patients (epistaxis x 1, purpura x 2), two of which later resolved. The results were comparable with other similar products.

Clinical trials conducted with Gamunex on patients with chronic inflammatory demyelinating polyneuropathy (CIDP).

The IVIG-C CIDP efficacy trial (ICE study), a double blind, randomised, placebo controlled study investigated the efficacy and safety of Gamunex in the treatment of CIDP. A total of 117 (adult) CIDP patients were randomised to receive either Gamunex or placebo every three weeks. Loading dose was 2 g/kg; maintenance dose was 1 g/kg (administered intravenously).
Responder rates (determined by improvement in INCAT disability score and maintenance of ≥ 1 improvement over the 24 week efficacy period) were significantly higher in the Gamunex group (54%), compared to the placebo group (21%, p = 0.0002). Muscle strength as measured by the MRC score and grip strength, as well as sensation as measured by the ISS score improved significantly more in the Gamunex group compared to placebo.
In view of the limited number of patients ≥ 65 years included in the study, a precise treatment effect could not be determined with regard to the INCAT score; for grip strength, a statistically significant treatment effect was shown in favour of Gamunex.
Of the responders, less than half responded after the loading dose (by week 3), but most responded after the second dose (by week 6). Nonresponders were crossed over to the alternative treatment, for again up to a maximum of 24 weeks of therapy.
All responders were rerandomised in an extension phase for another 6 months period of maintenance therapy with either Gamunex or placebo. Of the former responders to Gamunex, the actual relapse rate was significantly higher in the patients randomised to placebo (42%) than in those randomised to Gamunex (13%, p = 0.012).
The ICE study has shown short-term and long-term efficacy of Gamunex in the treatment of CIDP (see Table 11 and Figure 4).

5.2 Pharmacokinetic Properties

Pharmacokinetic parameters were determined in a trial in 17 patients with primary immunodeficiency stabilized on Gamunex intravenous infusion at a mean dose of 417 mg/kg, range 234-593 mg/kg, and dose interval of 3-4 weeks. The mean age of patients was 36 years and range 19-59. Seventy one percent were male.
Serum IgG concentration was measured following the third infusion of the product. Serum IgG peaked at a median of 2.3 hours after starting the infusion. The concentration time curve was then biphasic with a distribution phase of about 5 days characterised by a fall in serum IgG concentration to 65-75% of the peak and an elimination phase of median half-life 36 days. Other pharmacokinetic parameters are given in Table 12.
Pharmacokinetic parameters were determined in a trial in subjects with primary immunodeficiency stabilized on Gamunex subcutaneous infusion at a dose equivalent to 1.37 times the intravenous dose. See Table 13.

5.3 Preclinical Safety Data

Genotoxicity.

No genotoxicity studies have been conducted on Gamunex.

Carcinogenicity.

No carcinogenicity studies have been conducted on Gamunex.

6 Pharmaceutical Particulars

6.1 List of Excipients

Water for injections; glycine.
See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

Avoid simultaneous administration of Gamunex and heparin through a single lumen delivery device due to Gamunex, Heparin incompatibilities. Flush heparin lock (hep-lock) through which Gamunex was administered with 5% dextrose in water (D5/W) or 0.9% sodium chloride for injection, and do not flush with Heparin.

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

Gamunex may be stored for 36 months at 2°C - 8°C, and may be stored at temperatures not to exceed 25°C for up to 6 months anytime during the 36 month shelf life, after which the product must be used immediately or discarded.
Refrigerate. Do not freeze.
Do not use after expiration date.
Tape over carton ends must be unbroken.
Do not use if band around vial neck and cap is damaged or missing.

6.5 Nature and Contents of Container

Gamunex, normal immunoglobulin (human) 10% solution for intravenous or subcutaneous administration, is supplied in single-dose vials in the following sizes:
10 mL: 1 gram protein; 25 mL: 2.5 gram protein; 50 mL: 5 gram protein; 100 mL: 10 gram protein; 200 mL: 20 gram protein; 400 mL: 40 gram protein.

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.

Immunoglobulin (IgG), is a glycoprotein of approximately 150 kD in molecular weight, consisting of four disulfide-linked polypeptide chains: two light chains of 25 kD and two heavy chains of 55 kD. Disulfide linkage of the amino terminal portions of each pair of light and heavy chain forms an antigen binding site, resulting in two such sites per molecule. The carboxyl terminal portions of the heavy chains are likewise disulfide-linked, forming the carbohydrate-bearing Fc portion of the molecule that can interact with complement, and for which various phagocytes and B lymphocytes bear receptors. The three resulting domains of the protein are arranged in the shape of a "Y". The IgG molecule contains 2.9% carbohydrate by weight and has an isoelectric point of 6.8.
The amino terminal portions of all four chains in IgG contain regions with variable amino acid sequences, responsible for conferring the broad specificity of a population of antibody molecules against diverse antigens. In addition, IgG light and heavy chains contain alternate constant regions which divide the antibody population into four distinct subclasses. The major subclass is IgG1 (54 to 70% of the total IgG), whose molecules are effective in activating complement, and tend to be produced in response to protein antigens. IgG2 makes up approximately 20 to 28% of the total IgG molecules, and does not activate complement.
Antibodies produced in response to carbohydrate antigens are predominantly of this subclass. IgG3 represents 5 to 6% of the total IgG, and shares IgG1's ability to activate complement. IgG3 is also produced in response to protein antigens. IgG4 does not activate complement, and represents a late antibody response (3 to 4% of the total IgG) to either chronic or high levels of antigen exposure.

CAS number.

227945-81-5.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes