5 mg/ml powder for infusion liquid, solution
Rabbit anti-human thymocyte immunoglobulin
What Thymoglobuline is and what it is used for
Thymoglobuline is designed as a freeze-dried powder for infusion solution, solution (25 mg – carton with 1 vial).
After reconstitution with 5 ml water for injections, the solution contains 5 mg rabbit ATG/ml (concentrate).
Thymoglobuline is a so-called anti-human thymocyte immunoglobulin, made from blood from rabbits that have received an injection of cells from the thymus gland from humans.
When a patient receives an organ transplant, an immune reaction occurs (one of the body’s defense reactions that recognizes foreign substances entering the body) to get rid of the organ (reject it).
Thymoglobuline belongs to a group of medicines called immunosuppressants, which help prevent transplanted organs from being rejected. These medications change the body’s defense mechanism and help it accept the transplanted organ. Immunosuppressive agents can also be used to treat other unwanted immune reactions.
Thymoglobuline is used for immunosuppression in transplantation: to treat the rejection of a transplanted kidney when the rejection cannot be treated well enough with other medicines, called corticosteroids.
What you need to know before receiving Thymoglobuline
Do not use Thymoglobuline
- if you have an active acute or chronic infection that prevents any further immunosuppression (as Thymoglobuline lowers the body’s ability to fight infection ).
- if you know that you are allergic to rabbit proteins or to any of the other ingredients of this medicine (see section 6).
Warnings and precautions
Thymoglobuline must always be used under strict medical supervision in a hospital.
During treatment with Thymoglobuline, the doctor will take regular blood tests and other tests to check your health. Because of the way this medicine works, it can affect your blood and other organs.
Talk to a doctor or nurse before receiving Thymoglobuline if:
- you have ever had an allergic reaction to animals or other medicines? The doctor will monitor you closely and stop the treatment if there are any signs of an allergic reaction to Thymoglobuline.
- you have any blood disorders, such as thrombocytopenia (lower than a normal number of platelets in the blood) or leukopenia (lower than a normal number of white blood cells in the blood). Your dose depends on the number of white blood cells or platelets in the blood, which is checked before, during, and after treatment.
Thymoglobuline is often used in combination with other immunosuppressive drugs. Following the use of these combinations, there have been reports of infection, reactivation of infection, and sepsis (blood poisoning, a severe infection that is in the blood and spreads throughout the body).
In aplastic anemia, the immunosuppressive treatment contributes to the risk of infection (especially fungal infection) associated with the aplastic anemia itself.
The use of immunosuppressive drugs, including Thymoglobuline, may increase the risk of developing cancer, including lymphoma or lymphoproliferative disorders (abnormal increase in the number of white blood cells).
The safety of immunization with live attenuated vaccines after thymoglobulin therapy has not been studied; therefore, immunization with attenuated live vaccines is not recommended if you have recently received Thymoglobuline (see also “Use of other medicines”).
Risk of transmission of infection
Components of human blood (formaldehyde-treated red blood cells), as well as thymus cells, are used in the manufacturing process for Thymoglobuline. When medicines are prepared from human blood or plasma, special measures are taken to prevent infection from being transmitted to patients. These measures include carefully selecting blood and plasma donors to ensure that people at risk of being carriers are excluded, as well as testing individual donations and plasma pools (collection of blood plasma from several blood donors) for signs of virus/infection. The manufacturers of these products also include steps in the processing of blood and plasma that can inactivate or separate viruses. Despite these measures, the risk of transmission of infections when administering medicinal products made from components of human blood cannot be completely ruled out. This risk also applies to new, hitherto unknown viruses and other types of infection.
The measures taken are considered effective against enveloped viruses such as human immunodeficiency virus ( HIV ), hepatitis B virus, hepatitis C virus, and for non-enveloped viruses, HAV and parvovirus B19.
When you are given Thymoglobuline, it is recommended that the product name and batch number be recorded to enable the tracking of the product used.
Other medicines and Thymoglobuline
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including those obtained without a prescription.
If you use Thymoglobuline together with other immunosuppressive drugs (e.g. combination treatment with ciclosporin, tacrolimus, or mycophenolate mofetil), there is a risk that the body’s defense system is weakened too much (so-called overimmunosuppression). The doctor must therefore know if you are using any of these medicines.
Blood or blood products must not be administered together with Thymoglobuline.
Avoid vaccinating yourself during or soon after treatment with Thymoglobuline without first discussing it with your doctor as it may cause side effects or not work.
Thymoglobuline with food and drink
It is unlikely that food and drink will affect the medicine.
Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.
Pregnancy
Thymoglobuline should not be used by pregnant women, unless this is necessary, as the effects are unknown.
Breast-feeding
Avoid breastfeeding if you receive Thymoglobuline because it can pass into the breast milk and affect the baby.
Driving ability and use of machinery
Avoid driving or using tools or machines because Thymoglobuline can make you feel sick, tired, or dizzy.
You are responsible for assessing whether you are fit to drive a motor vehicle or perform work that requires increased vigilance. One of the factors that can affect your ability in these respects is the use of drugs due to their effects and/or side effects. A description of these effects and side effects can be found in other sections. Read all the information in this leaflet for guidance. Discuss with a doctor or pharmacist if you are unsure.
Thymoglobuline contains sodium
This medicine contains 4 mg of sodium (the main ingredient in common/table salt) per vial. This corresponds to 0.2% of the maximum recommended daily intake of sodium for adults.
How to use Thymoglobuline
Your medicine is given to you by a doctor or nurse in a hospital. Thymoglobuline is given through a plastic tube ( catheter ) directly into the blood ( intravenous infusion ) over at least 4 hours. It may take longer to give the first dose.
The dose you receive may vary and depends on your weight, and if you are receiving other medications at the same time. In general, patients receive 1.5 mg for each kilogram they weigh each day for 3 to 14 days, which equates to a total dose of 4.5 to 21 mg/kg.
The doctor or nurse will check you regularly while you are receiving the first dose as this is when you are most likely to have side effects. They check if you have a rash, take your pulse, and blood pressure and check your breathing. Sometimes the doctor may also want to test your blood to check the number of blood cells. If you have a low white blood cell count, the doctor may also give medicines to prevent or treat infections; if you have a low platelet count, your doctor may give you a platelet transfusion.
The doctor can change the dose of Thymoglobuline if you experience side effects.
Other medicines that the doctor may give you
The doctor may give you certain other medicines before, or at the same time as you receive Thymoglobuline. These medicines are used to prevent or treat possible side effects and may include:
- Antipyretics (such as paracetamol ) to reduce fever
- Corticosteroids (eg hydrocortisone ) to prevent organ rejection and side effects
- Antihistamines (eg cetirizine) to prevent an allergic reaction
- Heparin to reduce the risk of blood clots
If you have used too much Thymoglobuline
It is unlikely that you would receive too much Thymoglobuline, as you will be closely monitored by a doctor or nurse during treatment. If this still happens, you may have thrombocytopenia (lower than a normal number of platelets ) or leukopenia (lower than a normal number of white blood cells). This means that you may have a fever, chills, sore throat, and mouth ulcers and that you bleed or bruise more easily than usual.
What should the doctor do if you have missed a dose of Thymoglobuline?
The doctor gives the next dose at the usual time and does not give a double dose to compensate for forgotten single doses.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell the doctor immediately if you get any of the following symptoms in connection with the infusion of Thymoglobuline:
- Skin rash, hives
- Difficulty breathing, wheezing
- Stomach ache
- Swelling of the face, tongue, or throat
- Nausea, vomiting
- Headache
- Fever, chills
- Low or high blood pressure
- Feeling of illness
This could be a sign of an allergic reaction or a serious, acute infusion-related reaction.
Side effects listed below have been reported:
Very common (may affect more than 1 in 10 users):
- Low white blood cell count; low platelet count
- Fever
- Infection
- Low red blood cell count ( anemia )
Common (may affect up to 1 in 10 users):
- Diarrhea, difficulty swallowing, nausea, vomiting
- Tremors
- Serum sickness is a disease caused by antibodies against Thymoglobuline and causes skin rash, itching, hives, joint pain, and/or muscle pain and develops within 5–15 days. Serum sickness is usually mild and resolves without treatment or with a short course of steroids.
- Muscle pain
- Malignancy you
- Shortness of breath
- Itching, rash
- Low blood pressure
- Increase in certain liver enzymes in your blood
Uncommon side effects (may affect up to 1 in 100 users) :
- Liver damage (liver failure)
Has been reported (occurring in an unknown number of users):
- Increased bilirubin in the blood (elevation of laboratory parameters)
During treatment with Thymoglobuline, some patients experience a temporary, transient increase in certain liver values in laboratory tests that show how well the liver is working.
When Thymoglobuline has been administered in combination with other immunosuppressive drugs, there have been cases of infection, activation of a previous infection, and reduced number of certain white blood cells with concomitant fever, and sepsis (blood poisoning). In rare cases, these infections have been fatal. In rare cases, malignant diseases and tumors have also occurred, sometimes with fatal outcomes. These side effects only occurred when several immunosuppressive drugs were combined.
How Thymoglobuline should be stored
Your medicine is kept in the hospital by a doctor or nurse, out of the sight and reach of children.
Unopened vials of Thymoglobuline are stored in a refrigerator (2–8°C) and must not be frozen.
The doctor or nurse checks that the product has not passed the expiry date before diluting it.
Thymoglobuline should not be used if there are particles in the vial that do not disappear when the vial is rotated.
Contents of the packaging and other information
Contents declaration
Thymoglobuline contains 25 mg of the active substance, rabbit anti-human thymocyte immunoglobulin. It also contains mannitol, glycine, and sodium chloride (salt).
Appearance and package sizes of the medicine
Thymoglobuline is supplied in a glass bottle containing a creamy white powder. Before using the powder, it must be mixed with 5 milliliters (ml) of sterile water so that it becomes a liquid. Each milliliter (ml) contains 5 mg of rabbit anti-human thymocyte immunoglobulin. The prepared solution is clear or slightly opalescent.
This liquid is then mixed with sodium chloride or glucose solution so that it can be slowly given (infused) into the blood through a plastic tube ( catheter ) into a large vein.
Each pack contains one vial.
Marketing Authorization Holder :
Genzyme Europe BV
Paasheuvelweg 25
1105 BP Amsterdam
Netherlands
Manufacturer:
Genzyme Polyclonals SAS
23 boulevard Chambaud de la Bruyère
69007 Lyon
France
or
Genzyme Ireland Ltd.
IDA Industrial Park
Old Kilmeaden Road
Waterford
Ireland