Atgam

Package Leaflet: Information for the User

Atgam, 50 mg/ml, concentrate for solution for infusion

Equine anti-human T-lymphocyte immunoglobulin (eATG)
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. To find out more, see section 4.

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

• You should keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What Atgam is and what it is used for

Atgam is made by injecting human thymus cells into horses. It contains antibodies that attach to certain immune system cells in the body and destroy them. It is used to treat a condition called aplastic anemia. Aplastic anemia occurs when the immune system mistakenly attacks its own cells and the bone marrow does not produce enough red blood cells, white blood cells, and platelets. Atgam, when used with other medicines, helps the bone marrow to start producing these blood cells again. It may also help to avoid blood transfusions. Medicines that suppress the immune system do not cure aplastic anemia. However, they can help to relieve the symptoms of the disease and reduce complications. These medicines are often used in people who are not suitable for bone marrow or stem cell transplantation or who are waiting for a bone marrow transplant. Atgam can be used in children from 2 years of age and in adults.

2. What you need to know before you are given Atgam

When you must not be given Atgam

• If you are allergic to the active substance (equine anti-human T-lymphocyte immunoglobulin) or any of the other ingredients of this medicine (listed in section 6).
• If you are allergic to any other product containing equine gamma-globulin.

Warnings and precautions

Only a doctor with experience in immunosuppressive therapy should start treatment with Atgam. The medical institution should have trained personnel with access to necessary medical resources. During treatment with Atgam, patients will be continuously monitored.

Before you start treatment with Atgam, discuss this with your doctor or nurse.

• If you suspect that you have an infection, or have symptoms that may indicate an infection, such as fever, sweating, chills, muscle pain, cough, shortness of breath, increased skin temperature or redness, or skin pain or ulcers, diarrhea, or abdominal pain (or any other symptoms listed in section 4).
• If you need to be vaccinated. The effectiveness of vaccines may be reduced if they are given during treatment with Atgam. Your doctor will decide when it is best to give you a vaccine. When products are made from blood or plasma, certain measures are taken to prevent the transmission of infections to patients. These include:
• careful selection of blood and plasma donors to ensure that people who may carry infections are excluded;
• testing each donation and plasma pool for signs of viruses/infections;
• incorporating steps in the manufacturing process that inactivate or remove viruses. Despite these measures, it cannot be completely excluded that the transmission of infections may occur when using products made from blood or plasma. This also applies to unknown or newly discovered viruses and other types of infections.

During treatment with Atgam, special care must be taken

You should immediately tell your doctor if you experience any of the following serious and potentially life-threatening side effects of Atgam (symptoms requiring immediate contact with a doctor are repeated in section 4):

• severe infections, which may have symptoms such as fever, sweating, chills, muscle pain, cough, shortness of breath, increased skin temperature or redness, or skin pain or ulcers, diarrhea, or abdominal pain;
• allergic reactions, which may have symptoms such as generalized rash, rapid heartbeat, difficulty breathing, decreased blood pressure, and weakness;
• serum sickness: an allergic reaction causing fever, joint pain, skin rash, and swelling of lymph nodes;
• shedding of the skin (the outer layer of the skin) anywhere on the body;
• fever, swelling, chills, rapid heartbeat, decreased blood pressure, and difficulty breathing. These symptoms may suggest a side effect called cytokine release syndrome.

Additional tests

Before starting treatment with Atgam, during treatment, and after treatment, your doctor will order a blood test to check if you have a low number of white blood cells, low number of red blood cells, or low number of platelets. If there are serious abnormalities in the number of blood cells, treatment with Atgam may be discontinued.
To determine if you are at increased risk of severe allergic reactions, skin tests may be performed before starting treatment. Based on the results of these tests, it can be determined if you are allergic to any of the ingredients of Atgam. These results will help your doctor decide if you can be given Atgam.
In patients with aplastic anemia receiving Atgam, abnormalities in liver and kidney function test results may occur.

Atgam and other medicines

Tell your doctor about all medicines you are taking or have recently taken, as well as any medicines you plan to take.
When the dose of corticosteroids and other immunosuppressive medicines is reduced, previously hidden reactions to Atgam may appear. During infusion of Atgam, patients will be closely monitored for the occurrence of these reactions.

Pregnancy and breastfeeding

Pregnancy
If you are pregnant or think you may be pregnant, tell your doctor.
It is not known if Atgam affects the fetus. Therefore, it is recommended to avoid using Atgam during pregnancy.
If you become pregnant while taking this medicine, tell your doctor immediately.
Women of childbearing age must use effective contraception during treatment with Atgam and for up to 10 weeks after the last dose. To get information on suitable methods of contraception, talk to your doctor.
Breastfeeding
If you are breastfeeding or plan to breastfeed, tell your doctor.
It is not known if Atgam passes into human milk. The risk to breastfed children cannot be excluded.
A decision must be made whether to discontinue breastfeeding or discontinue Atgam.

Driving and using machines

Atgam may affect your ability to drive and use machines. Be careful when driving or using machines while taking this medicine.

Atgam contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per total dose, which means it is essentially "sodium-free". However, it may be prepared for administration with a solution containing sodium. Tell your doctor if you are on a low-sodium diet.

3. How Atgam is given

Atgam will be given to you by infusion into a vein by a doctor or a member of the medical staff.
For further information, ask your doctor or pharmacist.
Detailed instructions for the preparation and infusion of Atgam are at the end of this leaflet.
This information is intended for healthcare professionals only.
Dosing recommendations are based on body weight (kg).
The recommended total dose is 160 mg/kg body weight, as part of additional immunosuppressive treatment.
You may receive Atgam according to the following schedules:

• 16 mg/kg body weight/day for 10 days or
• 20 mg/kg body weight/day for 8 days or
• 40 mg/kg body weight/day for 4 days.

Before administration of Atgam, you may be given other medicines (including corticosteroids and antihistamines) to prevent possible side effects related to infusion.
You may also receive a medicine to reduce fever.

Overdose of Atgam

Since Atgam will be given to you by a doctor or nurse, it is very unlikely that you will be given more than the recommended dose. If you think you have been given more Atgam than prescribed, tell your doctor or nurse immediately.
If you have any further questions on the use of this product, ask your doctor or nurse.

Missing a dose of Atgam

Since Atgam will be given to you by a doctor or nurse, it is very unlikely that you will miss a dose. If you think you have missed a dose of Atgam, tell your doctor or nurse immediately.
If you have any further questions on the use of this product, ask your doctor or nurse.

4. Possible side effects

Like all medicines, Atgam can cause side effects, although not everybody gets them.

You should immediately tell your doctor if you experience any of the following serious and potentially life-threatening side effects of Atgam (symptoms requiring immediate contact with a doctor are repeated in section 2 above):

• severe infections (very common), which may have symptoms such as fever, sweating, chills, muscle pain, cough, shortness of breath, increased skin temperature or redness, skin pain, ulcers on the body, diarrhea, or abdominal pain;
• allergic reactions (uncommon), which may have symptoms such as generalized rash, rapid heartbeat, difficulty breathing, decreased blood pressure, and weakness;
• serum sickness (very common): an allergic reaction causing fever, joint pain, skin rash, and swelling of lymph nodes;
• shedding of the skin (the outer layer of the skin) anywhere on the body (frequency not known).

Other side effects

Very common (may affect more than 1 in 10 people)

• low number of white blood cells
• skin rashes, redness, itching, skin irritation
• pain, including joint pain, back pain, chest pain, muscle pain, hand and foot pain, side pain
• fever, chills, headache
• infections (bacterial and viral)
• increased or decreased blood pressure
• diarrhea, abdominal pain, nausea, vomiting
• swelling of hands or feet
• abnormal liver function test results

Common (may affect up to 1 in 10 people)

• breakdown of red blood cells
• enlargement or swelling of lymph nodes
• dizziness, fainting, feeling unwell
• seizures
• tingling or numbness of arms or legs
• rapid or slow heartbeat
• swelling and pain in a part of the body, caused by a local blood clot in a vein
• shortness of breath or difficulty breathing, temporary cessation of breathing
• hives
• nosebleeds
• cough
• fluid accumulation in the lungs
• bleeding from the stomach or intestines
• mouth ulcers, mouth swelling, mouth pain
• increased blood sugar levels
• abnormal kidney function, kidney failure

Uncommon (may affect up to 1 in 100 people)

• agitation
• redness, swelling, pain at the infusion site
• swelling around the eyes
• low number of platelets

Frequency not known (frequency cannot be estimated from the available data)

• painful brain swelling, painful blood vessel swelling
• difficulty moving, muscle stiffness
• confusion, shaking
• heart failure
• blood clots in the intestines, perforation of the intestine
• throat spasm, hiccups
• excessive sweating, night sweats
• wound dehiscence
• failure to develop cells
• loss of strength or energy

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder or its representative.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Atgam

Keep this medicine out of the sight and reach of children.
The following information is intended for the doctor or nurse responsible for storing, preparing, and disposing of Atgam.
Do not use this medicine after the expiry date which is stated on the carton after “EXP”. The expiry date refers to the last day of that month.
Store the ampoules in a refrigerator (2°C - 8°C). Do not freeze. Store the ampoules in the outer carton to protect from light.
The diluted solution can be stored at room temperature (20°C - 25°C). The solution should be used within 24 hours (including infusion time).
From a microbiological point of view, unless the method of opening/ dilution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user. Dilution should be carried out under controlled and validated aseptic conditions.

6. Contents of the pack and other information

What Atgam contains

• The active substance is equine anti-human T-lymphocyte immunoglobulin. Each ampoule of sterile concentrate contains 250 mg of equine anti-human T-lymphocyte immunoglobulin.
• The other ingredients are glycine, water for injections, sodium hydroxide (for pH adjustment), and hydrochloric acid (for pH adjustment) (see section 2 “Atgam contains sodium”).

What Atgam looks like and contents of the pack

Atgam is a clear to slightly opalescent, colorless to pale pink or pale brown, sterile aqueous solution. During storage, a small amount of particulate or flaky sediment may be deposited.
Atgam is available in a carton containing 5 ampoules, each containing 5 ml of sterile concentrate.

Marketing Authorization Holder

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium

Manufacturer

Pfizer Service Company BV
Hoge Wei 10
Zaventem, 1930
Belgium
To obtain more detailed information on this medicine, contact the representative of the Marketing Authorization Holder.
Pfizer Polska Sp. z o.o.
tel. 22 335 61 00

This medicinal product is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Austria, Belgium, Denmark, Finland, France, Germany, Ireland, Latvia, Luxembourg, Netherlands, Norway, Poland, Romania, Slovenia, Sweden, United Kingdom (Northern Ireland)
Atgam
Italy
Equingam

Date of last revision of the leaflet: 10/2023

Other sources of information

Detailed information on this medicinal product is available on the website: http://www.urpl.gov.pl/
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Information intended for healthcare professionals only:
Preparation of the infusion solution
Since Atgam is a gamma-globulin, both the concentrate and the diluted solution should be inspected visually for particulate matter and discoloration prior to administration, whenever the solution and container permit.
The concentrate and diluted solution are clear to slightly opalescent, colorless to pale pink or pale brown, and during storage, a small amount of particulate or flaky sediment may be deposited.
Atgam (both diluted and undiluted) should not be shaken, as this may cause excessive foaming and/or denaturation of the protein. Before administration, the Atgam vial should be entered using a sterile technique and the contents diluted by slowly injecting the sterile diluent into the vial.
Add the total daily dose of Atgam to an inverted bottle or bag containing one of the following sterile diluents:

• 0.9% sodium chloride solution
• glucose solution/sodium chloride solution
• 50 mg/ml (5%) glucose in 0.45% (4.5 mg/ml) sodium chloride solution
• 50 mg/ml (5%) glucose in 0.225% (2.25 mg/ml) sodium chloride solution.

Due to the potential for precipitation of Atgam, it is not recommended to dilute with glucose solution alone.
The recommended concentration of the diluted Atgam solution is 1 mg/ml in the chosen diluent. The concentration of Atgam should not exceed 4 mg/ml.
The diluted Atgam solution should be gently rotated or swirled to mix well.
After dilution, the product is intended for intravenous administration only.
Before starting the infusion, the diluted Atgam solution should reach room temperature (20°C - 25°C). During infusion, volumes ranging from 250 ml to 500 ml can be used. Atgam should be administered through a central vein into a large vessel using a filter (0.2–1.0 micron) incorporated into the infusion line.
During each infusion of Atgam, an in-line filter (not provided) should be used to prevent the introduction of particulate matter into the circulation, which may have formed during storage.
It is recommended that the diluted solution be used immediately. The diluted Atgam solution should be stored at room temperature (20°C - 25°C) if not used immediately. The total time from dilution to use should not exceed 24 hours (including infusion time).
From a microbiological point of view, unless the method of opening and dilution precludes the risk of microbial contamination, this product should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user.
Any unused product or waste material should be disposed of in accordance with local requirements.