Equingam

Package leaflet: Information for the user

Equingam 50 mg/mL concentrate for solution for infusion

human T-lymphocyte anti-lymphocyte immunoglobulins (eATG)
This medicinal product is subject to additional monitoring. This will allow for the rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before taking this medicine because it contains important information for you.

• This patient information leaflet has been written as if addressed directly to the person receiving the medicine. If this medicine is being administered to your child, please replace "you" with "your child" throughout the text.
• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4. Contents of this leaflet:
  1. What Equingam is and what it is used for
  2. What you need to know before being given Equingam
  3. How Equingam is administered
  4. Possible side effects
  5. How to store Equingam
  6. Contents of the pack and other information

1. What Equingam is and what it is used for

Equingam is produced by injecting human thymus cells into horses. It contains immunoglobulins (antibodies) that bind to certain cells of the body's immune system and destroy them. It is used to treat a condition called aplastic anaemia. Aplastic anaemia develops when the body's immune system mistakenly attacks its own cells and the bone marrow is unable to produce sufficient red blood cells, white blood cells, and platelets. When used together with other medicines, Equingam helps the bone marrow to produce these blood cells again. It may also help to avoid the need for blood transfusions. Medicines that suppress the immune system do not cure aplastic anaemia. However, they can relieve its symptoms and reduce complications. These medicines are often used in people who cannot undergo blood and bone marrow stem cell transplants or who are awaiting a bone marrow transplant. Equingam can be used in children aged 2 years and older and in adults.

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

Do not use Equingam

• if you are allergic to the active substance (equine anti-human T-lymphocyte immunoglobulins) or to any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to any other preparation containing equine gammaglobulins.

Warnings and precautions
Only a physician experienced in immunosuppressive therapy should administer Equingam to you. The treatment facility must have trained personnel with access to supportive medical resources. Patients receiving Equingam will be continuously monitored during treatment.
Talk to your doctor or nurse before receiving Equingam

• If you think you have an infection or are experiencing symptoms that may indicate an infection, such as fever, sweating, chills, muscle aches, cough, shortness of breath, warm, red, painful or sore skin, sores on the body, diarrhoea or stomach pain (or any other symptom listed in section 4).
• If you need to be vaccinated. Vaccines may be less effective when administered together with Equingam. Your doctor will decide the best time for you to receive a vaccine. When medicines are made from blood or plasma, certain measures are taken to prevent the transmission of infections to patients. For example:
• Careful selection of blood and plasma donors to exclude those at risk of carrying infections.
• Testing of each donation and plasma batch to identify the presence of viruses/infections.
• Inclusion of steps in the manufacturing process to inactivate or remove viruses.

Despite these measures, when medicines made from human blood or plasma are administered, it is not possible to completely rule out the risk of transmitting infections. This also applies to any unknown or emerging viruses and other types of infections.
Pay special attention during treatment with Equingam
Inform your doctor immediately if you experience any of the following serious and potentially life-threatening side effects related to Equingam (these symptoms are also listed in section 4):

• any serious infection: symptoms may include fever, sweating, chills, muscle aches, cough, shortness of breath, warm, red, painful or sore skin, sores on the body, diarrhoea or stomach pain;
• allergic reactions: symptoms may include widespread skin rash, increased heart rate, difficulty breathing, decreased blood pressure and weakness;
• serum sickness: an allergic reaction causing fever, joint pain, skin rash and swollen lymph nodes;
• the top layer of the skin may peel off from its normal position anywhere on the body;
• fever, swelling, chills, increased heart rate, decreased blood pressure and difficulty breathing. These symptoms may indicate so-called cytokine release syndrome.

Other tests
Your doctor will perform a blood test before you start taking Equingam, as well as during and after treatment, to determine whether you have a low number of white blood cells, a low number of red blood cells or a decrease in platelets. If severe blood cell abnormalities occur, treatment with Equingam may be stopped.
Before treatment, a skin test may be performed to assess your risk of developing severe allergic reactions. This test checks for allergies to any of the components of Equingam. The test results will help your doctor decide whether or not Equingam can be administered.
When patients with aplastic anaemia are treated with Equingam, abnormal results in liver and kidney function tests may occur.
Other medicines and Equingam
Tell your doctor if you are taking, have recently taken or might take any other medicines.
When the dose of corticosteroids and other immunosuppressants is reduced, some reactions to Equingam that were previously masked may appear. You will be closely monitored during Equingam infusion for the possible occurrence of such reactions.
Pregnancy and breastfeeding
Pregnancy
Inform your doctor if you suspect you are pregnant.
It is not known whether Equingam has effects on the foetus during pregnancy. Therefore, it is preferable to avoid using Equingam during pregnancy.
If you become pregnant while taking this medicine, you must inform your doctor immediately.
Women of childbearing potential must use an effective method of birth control (contraception) during treatment with Equingam and for up to 10 weeks after the last dose. Ask your doctor which contraceptive methods are most suitable for you.
Breastfeeding
Inform your doctor if you are breastfeeding or plan to breastfeed.
It is not known whether Equingam passes into breast milk. The risk to the breastfed infant cannot be excluded.
You and your doctor must decide whether you should breastfeed or receive treatment with Equingam.
Driving and using machines
Equingam may affect your ability to drive vehicles and operate machinery. Exercise caution when driving or using machines during treatment with this medicine.
Equingam contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e. essentially 'sodium-free'.
However, it may be prepared with a solution containing sodium. Inform your doctor if you are on a low-salt (sodium) diet.

3. How Equingam is administered

Equingam is infused into a vein by a doctor or healthcare professional. For further information,
you should consult your doctor or pharmacist.
Detailed instructions on the preparation and infusion of Equingam are provided at the end of this leaflet.

Equingam. These instructions are intended for healthcare professionals.

Dosage recommendations are based on body weight (bw).
The recommended total dose is 160 mg/kg bw with additional immunosuppressive therapy.
You may receive Equingam as indicated below:

• 16 mg/kg bw/day for 10 days, or
• 20 mg/kg bw/day for 8 days, or
• 40 mg/kg bw/day for 4 days

Before administration of Equingam, you may be given other medications (such as a
corticosteroid and an antihistamine) to help prevent possible infusion-related adverse effects.
You may also be given a medication to reduce fever.
If you receive more Equingam than you should
Since Equingam will be administered by a doctor or nurse, it is highly unlikely that a dose higher than the recommended dose will be given. If you believe that a higher than prescribed dose of Equingam has been administered, contact your doctor or nurse immediately.
If you have any doubts about the use of this medicine, consult your doctor or nurse.
If you forget to use Equingam
Since Equingam will be administered by a doctor or nurse, it is highly unlikely that you will miss a dose at the scheduled time. If you believe you have not received Equingam at the scheduled time, contact your doctor or nurse immediately.
If you have any doubts about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor immediately if you experience any of the following serious and potentially life-threatening side effects of Equingam (these symptoms, which require you to contact your doctor immediately, are also listed in section 2 above):

• severe infections (very common): symptoms may include fever, sweating, chills, muscle aches, cough, shortness of breath, warm, red or painful skin, or sores on the body, diarrhoea or stomach pain;
• allergic reactions (uncommon): symptoms may include widespread rash, increased heart rate, difficulty breathing, low blood pressure and weakness;
• serum sickness (very common): an allergic reaction causing fever, joint pain, rash and swollen lymph nodes;
• the top layer of skin detaching from its underlying layer at any site on the body (frequency not known).

Other side effects
Very common: may affect more than 1 in 10 people

• low white blood cell count
• skin rashes, skin redness, itching and skin irritation
• pain, including joint pain, back pain, chest pain, muscle pain, pain in hands and feet, hip pain
• fever, chills, headache
• infections (bacterial and viral)
• high or low blood pressure
• diarrhoea, abdominal pain, nausea, vomiting
• swelling of arms or legs
• abnormal liver function tests

Common: may affect up to 1 in 10 people

• breakdown of red blood cells
• enlarged or swollen lymph nodes
• dizziness, fainting, feeling unwell
• epileptic seizure
• tingling or numbness of hands or feet
• fast or slow heart rate
• swelling and pain in part of the body due to a blood clot in a vein
• shortness of breath or difficulty breathing, temporary cessation of breathing
• urticaria (hives)
• nosebleeds
• cough
• fluid in the lungs
• bleeding in the stomach or intestines
• mouth sores, mouth swelling, mouth pain
• increased blood sugar levels
• kidney abnormalities, kidney failure

Uncommon: may affect up to 1 in 100 people

• restlessness
• redness, swelling, pain at infusion site
• swelling around the eyes
• low platelet count

Not known: frequency cannot be estimated from the available data

• painful swelling of the brain, painful swelling of blood vessels
• difficulty moving, muscle stiffness
• confusion, tremors
• heart failure
• blood clot in the blood vessels of the intestine, hole in the intestine (perforation)
• throat spasm, hiccups
• excessive sweating, night sweats
• wound dehiscence (opening of a wound)
• failure of cell development
• loss of strength or energy

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Equingam

Keep this medicinal product out of the sight and reach of children.
The following information is intended for the physician or nurse responsible for the storage,
handling, and disposal of Equingam.
Do not use this medicinal product after the expiry date stated on the packaging after "Exp.". The expiry
date refers to the last day of that month.
Store the vials in a refrigerator (2°C - 8°C). Do not freeze. Keep the vial in its outer packaging to protect
the medicinal product from light.
The diluted solution may be stored at room temperature (20°C - 25°C). The solution must be used within
24 hours (including the infusion time).
From a microbiological standpoint, unless the method of opening/dilution avoids the risk of microbial
contamination, opened vials or medicinal product contained in syringes should be used immediately.
Otherwise, the storage times and conditions prior to use are under the responsibility of the user, and
dilution must be carried out under controlled and validated aseptic conditions.

6. Package contents and other information

What Equingam contains

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

Description of the appearance of Equingam and contents of the pack

Equingam is a sterile, aqueous solution, clear or slightly opalescent, ranging from colourless to pale pink or light brown. During storage, it may develop a slight deposit of granules or floccules.
It is available in a pack of 5 vials, each containing 5 mL of sterile concentrate.

Marketing Authorisation Holder and Manufacturer

Pfizer S.r.l.
Via Isonzo, 71
04100 Latina
Italy

Manufacturer

Pfizer Service Company BV
Hoge Wei 10
Zaventem, 1930
Belgium

For any information about this medicinal product, contact the local representative of the Marketing Authorisation Holder.

This medicinal product is authorised 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, Atgam
Luxembourg, Netherlands, Norway, Poland, Romania, Slovenia, Sweden, United Kingdom (Northern Ireland)
Italy Equingam

Further sources of information

Detailed information on this medicinal product is available on the website of the Italian Medicines Agency (Agenzia Italiana del Farmaco).

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The following information is intended for healthcare professionals only:

Preparation of the infusion solution

Since Equingam is a gammaglobulin, both the concentrate and the diluted solution should be visually inspected for particulate matter or discoloration prior to administration, whenever solution and container permit. The concentrate and the diluted solution are clear or slightly opalescent, ranging from colourless to pale pink or light brown, and both may develop a slight deposit of granules or floccules during storage.

Equingam (diluted or undiluted) must not be shaken, as this may cause excessive foaming and/or protein denaturation. The Equingam concentrate must be diluted by inverting the sterile diluent container to prevent undiluted Equingam from coming into contact with air inside.

Add the total daily dose of Equingam to an inverted bottle or bag containing one of the following sterile diluents:

• 0.9% sodium chloride;
• glucose/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 possible precipitation of Equingam, dilution with glucose solution alone is not recommended.

The recommended concentration of diluted Equingam is 1 mg/mL in the chosen diluent. The concentration must not exceed 4 mg/mL of Equingam.

The diluted Equingam solution should be gently mixed by inversion or rotation to ensure thorough mixing.

Once diluted, for intravenous use only.

Diluted Equingam must be brought to room temperature (20°C–25°C) before infusion. Infusion volumes of 250 mL to 500 mL may be used. Equingam must be administered through a high-flow central vein using an in-line filter (0.2–1.0 micron).

For all Equingam infusions, an in-line filter (not supplied) must be used to prevent administration of insoluble material that may develop in the product during storage.

The solution should be used immediately after dilution. If not used immediately, diluted Equingam should be stored at room temperature (20°C–25°C). The total time in diluted form must not exceed 24 hours (including infusion time).

From a microbiological standpoint, unless the method of opening and dilution prevents the risk of microbial contamination, the product should be used immediately.

Any unused medicinal product and waste material derived from this medicinal product must be disposed of in accordance with local regulations.