Cytomegatetect

Package leaflet: Information for the user

Cytomegatect 100 U/ml solution for infusion

Human anti-cytomegalovirus immunoglobulin
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

Cytomegatect

• belongs to the group of immunoglobulins. These medicines contain antibodies (antibodies are part of the body's immune system).
• contains antibodies directed against cytomegalovirus.
• is a solution for infusion administered as an intravenous "drip" (infusion) into a vein.

Cytomegatect is given for the prevention of clinical manifestations of cytomegalovirus infection in patients receiving immunosuppressive therapy (a treatment that suppresses the immune system), particularly in patients who have received a transplant.
During administration of Cytomegatect, your doctor will consider the concomitant use of appropriate antiviral agents.

Do not use Cytomegatect
if you are allergic to human cytomegalovirus immunoglobulin or to any of the other
components of this medicine (listed in section 6).
if you have immunoglobulin A (IgA) deficiency, especially if you have antibodies against IgA
in your blood, as this may cause anaphylaxis.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before you are given Cytomegatect

• if you are receiving human immunoglobulins for the first time or after a long period without treatment, or if your immunoglobulin preparation has been changed. In these cases, adverse reactions may occur more frequently and your doctor will monitor you closely.
• if you are allergic to immunoglobulins (see section “Do not use Cytomegatect”). You may be allergic to immunoglobulins without knowing it, even if you have previously received immunoglobulins and tolerated them well. However, hypersensitivity reactions are rare.
• if you have an untreated infection or a long-standing (chronic) underlying inflammation
• if
• you are very overweight or elderly,
• you have high blood pressure (hypertension), diabetes, or vascular diseases,
• you have a high tendency to form blood clots,
• you have been bedridden for a long time,
• you have low blood volume (hypovolemia) or your blood tends to thicken,
• you have pre-existing kidney disease or are taking medicines that may have harmful effects on the kidneys. In these cases, the risk of developing adverse effects is higher. Your doctor may decide to stop treatment with Cytomegatect or take other precautionary measures (for example, using a particularly slow infusion rate).

Infusion reactions
If during the infusion of Cytomegatect you experience any of the following signs of a reaction—such as headache, flushing, chills, muscle pain, wheezing, rapid heartbeat, back pain, nausea, or low blood pressure—inform your doctor immediately.
Inform your doctor immediately if you notice such reactions during administration of Cytomegatect. The doctor will decide whether to reduce the infusion rate or stop the infusion completely and initiate the necessary medical measures to manage the reactions.

Information on safety regarding infections
Cytomegatect is made from human plasma (the liquid part of blood). When medicines are manufactured from human blood or plasma, certain precautions are taken to prevent transmission of infections to patients through the administration of the medicine. All blood donors are tested for viruses and infections. In addition, the manufacturing process includes steps that can inactivate or remove viruses.
Despite these measures, the risk of transmitting infections through medicines made from human blood or plasma cannot be completely excluded.
The measures taken are considered effective against viruses such as

• human immunodeficiency virus (HIV),
• hepatitis A virus (HAV),
• hepatitis B virus (HBV),
• hepatitis C virus (HCV).

The measures taken may have limited effectiveness against viruses such as

• parvovirus B19.

To date, no associations have been found between immunoglobulins and infections caused by hepatitis A virus or parvovirus B19, probably because the antibodies contained in Cytomegatect provide protective activity against these infections.
It is strongly recommended that, for each dose of Cytomegatect administered, the name and batch number of the medicine be recorded. The batch number allows tracing back to the specific starting material used for the medicine administered to you. Therefore, if necessary, a link can be established between you and the material used as starting substance.

Children and adolescents
The same special warnings and precautions for use apply to children and adolescents as mentioned for adults.

Other medicines and Cytomegatect
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Cytomegatect may reduce the effectiveness of certain vaccines, such as vaccines against

• measles
• rubella
• mumps
• varicella. After receiving Cytomegatect, you should wait up to 3 months before being vaccinated with certain vaccines; and up to 1 year in the case of the measles vaccine.

Avoid concomitant use of loop diuretics (commonly known as water tablets) with Cytomegatect.
Children and adolescents
Interactions similar to those observed in adults are expected in children and adolescents.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Your doctor will decide whether Cytomegatect can be used during pregnancy or breastfeeding.

Driving and using machines
Cytomegatect may have a slight effect on the ability to drive or operate machinery. If you experience any adverse effects during treatment, you should wait until they resolve before driving or operating machinery.

Cytomegatect is administered by your treating physician.
The recommended dose is 1 ml per kg of body weight per day for adults, children, and adolescents.
You will receive this medicine for a total of at least 6 times, at intervals of 2-3 weeks. Your doctor will
determine exactly how many infusions you need and when to start treatment.
Cytomegatect is administered as an intravenous "drip" (infusion). The medicine must be brought to room or body temperature before use.
If you receive more Cytomegatect than you should
An excessive amount of Cytomegatect may increase fluid volume and cause hyperviscosity (thickening) of the blood, particularly if you are over 65 years of age and/or have reduced cardiac or renal function.
If you think you have received more Cytomegatect than you should have, speak to your doctor as soon as possible.
If you have any doubts about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects of Cytomegatect are based on spontaneous reports:
Not known: frequency cannot be estimated from the available data

• Anaemia (haemolytic anaemia)
• Severe allergic reaction such as anaphylactic shock, anaphylactic reactions, anaphylactoid reactions, hypersensitivity
• Headache, dizziness
• Vomiting
• Skin reactions including rash, abnormal redness of the skin, itching
• Joint pain
• Blood test results indicating impaired kidney function (increased serum creatinine) and/or acute kidney failure
• Chills, fever, fatigue

Normal human immunoglobulin preparations can generally cause the following side effects (in decreasing order of frequency):

• chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, joint pain, low blood pressure, and moderate back pain
• reduction in the number of red blood cells due to their destruction within blood vessels (haemolytic reactions (reversible)) and (rarely) haemolytic anaemia requiring transfusion
• (rarely) sudden drop in blood pressure and, in isolated cases, anaphylactic shock
• (rarely) transient skin reactions (including cutaneous lupus erythematosus – frequency not known)
• (very rarely) thromboembolic reactions such as heart attack (myocardial infarction), stroke, blood clots in the blood vessels of the lungs (pulmonary embolism), blood clots in a vein (deep vein thrombosis)
• cases of temporary acute inflammation of the protective membranes covering the brain and spinal cord (reversible aseptic meningitis)
• cases of blood test results indicating impaired kidney function and/or acute kidney failure
• cases of acute transfusion-related lung injury (TRALI). This leads to a build-up of fluid, unrelated to the heart, in the lung alveoli (non-cardiogenic pulmonary edema). You will experience severe breathing difficulty (respiratory distress), increased breathing rate (tachypnea), abnormally low levels of oxygen in the blood (hypoxia), and increased body temperature (fever).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the Italian Medicines Agency (Agenzia Italiana del Farmaco)
Website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cytomegatect

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the outer packaging and on the
vial after Exp.
Store in the refrigerator (2 °C - 8 ºC). Keep in the original packaging to protect the
medicine from light.
Do not freeze.
Before use, the product should be inspected visually. The solution should be clear or slightly opalescent (milky) and colourless or pale yellow. Do not use Cytomegatect if the solution is cloudy or contains precipitates.
The medicine should be used immediately after first opening.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Cytomegatect contains
The active substance is: human anti-cytomegalovirus immunoglobulin (CMVIG)
1 ml of solution contains:
50 mg of human plasma proteins, of which immunoglobulin G (IgG) ≥ 96%,
with an anti-cytomegalovirus (CMV) antibody content of 100 U*.
Each 10 ml vial contains: 500 mg of human plasma proteins (of which at least 96%
immunoglobulin G), with an anti-CMV antibody content of 1,000 U*.
Each 50 ml vial contains: 2,500 mg of human plasma proteins (of which at least 96%
immunoglobulin G), with an anti-CMV antibody content of 5,000 U*.
The percentage distribution of IgG subclasses is approximately 65% IgG1, 30% IgG2, 3% IgG3, 2% IgG4.
Maximum content of immunoglobulin A (IgA) is 2,000 micrograms/ml.
* units of the reference preparation of the Paul-Ehrlich-Institute
Other components are: glycine, water for injections.

Description of the appearance of Cytomegatect and contents of the pack
Cytomegatect is a clear or slightly opalescent (milky), colourless or pale yellow solution, contained in colourless glass vials.
Cytomegatect is available in the following pack sizes:
One box containing 1 vial with 10 ml (1,000 U) of infusion solution.
One box containing 1 vial with 50 ml (5,000 U) of infusion solution.
It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder and Manufacturer
Biotest Pharma GmbH
Landsteinerstr. 5
63303 Dreieich
Germany
Tel.: +49 6103 801-0
Fax: +49 6103 801-150
E-mail: [email protected]

This medicinal product is authorised in the European Economic Area countries under the
following names:
Croatia, Germany, Hungary: Cytotect CP Biotest
Austria: Cytotect CP Biotest 100 E/ml Infusionslösung
Italy: Cytomegatect
Spain: Megalotect
Greece, Poland, Portugal: Megalotect CP
Belgium, Netherlands: Megalotect 100 E/ml
Slovenia: Megalotect 100 e./ml raztopina za infundiranje

The following information is intended exclusively for healthcare professionals:

Dosage and administration
Administration should begin on the day of transplantation. In the case of bone marrow transplantation, prophylaxis may start up to 10 days before transplantation, particularly in CMV-seropositive patients. A total of at least six doses should be administered at intervals of 2–3 weeks apart.

Route of administration
For intravenous use.
Cytomegatect is administered intravenously at an initial infusion rate of 0.08 ml/kg body weight/h for 10 minutes. In case of adverse reaction, reduce the infusion rate or discontinue the infusion. If the product is well tolerated, the infusion rate may be gradually increased up to a maximum of 0.8 ml/kg body weight/h for the remainder of the infusion.

Warnings and precautions
Certain severe adverse reactions may be related to the infusion rate. The recommended infusion rate must be strictly observed, and patients must be closely monitored and observed for the onset of symptoms throughout the entire duration of the infusion. Certain adverse reactions may occur more frequently in cases of:

• high infusion rate,
• patients receiving normal human immunoglobulin for the first time, or, rarely, when switching to a different normal human immunoglobulin preparation, or after a long interval since the previous infusion.

Potential complications can often be avoided by ensuring that patients:

• are not sensitive to normal human immunoglobulin by starting with a slow initial infusion rate (0.08 ml/kg body weight/h),
• are closely monitored for any symptoms during the infusion period. In particular, patients who have never been treated with normal human immunoglobulin, patients previously treated with another intravenous human immunoglobulin (IVIg), or those who have had a long interval since the last infusion, must be monitored in hospital during the first infusion and for the first hour after completion of the infusion to detect potential adverse signs. All other patients should be observed for at least 20 minutes after administration.

In case of adverse reactions, the infusion rate should be reduced or the infusion stopped. The required treatment depends on the nature and severity of the adverse reaction. In case of shock, standard medical treatment for shock should be initiated.

For all patients, administration of IVIg requires:

• adequate hydration before starting the IVIg infusion,
• monitoring of urinary output,
• monitoring of serum creatinine levels,
• avoidance of concomitant use of loop diuretics.

Hypersensitivity
Hypersensitivity reactions are rare and may occur in patients with anti-IgA antibodies.
Anaphylaxis may develop in patients:

• with undetectable IgA who have anti-IgA antibodies,
• who have previously tolerated treatment with human immunoglobulin.

In case of shock, standard medical treatment for shock should be initiated.

Thromboembolism
There is clinical evidence of an association between intravenous immunoglobulin (IVIg) administration and thromboembolic events such as myocardial infarction, cerebrovascular accident (stroke), pulmonary embolism, and deep vein thrombosis. In at-risk patients, these events are believed to be related to the rapid influx of immunoglobulins, leading to a relative increase in blood viscosity. Caution should be exercised when prescribing and infusing immunoglobulins in the following patient groups: overweight patients and patients with pre-existing risk factors for thrombotic events (such as advanced age, hypertension, diabetes mellitus, history of vascular disease or thrombotic episodes, patients with acquired or hereditary thrombophilic disorders, patients undergoing prolonged immobilization, patients with severe hypovolemia, and patients with conditions that increase blood viscosity).
In patients at risk of thromboembolic adverse reactions, IVIg products should be administered at the lowest possible infusion rate and dose.

Acute renal failure
Cases of acute renal failure have been reported in patients receiving intravenous immunoglobulin (IVIg) therapy. In most cases, risk factors such as pre-existing renal insufficiency, diabetes mellitus, hypovolemia, overweight, concomitant nephrotoxic therapy, or age over 65 years have been identified.
Renal function parameters should be checked before IVIg infusion, particularly in patients considered at potentially increased risk of developing acute renal failure, and repeated at appropriate intervals. In patients at risk of acute renal failure, IVIg products should be administered at the lowest feasible infusion rate and dose.
In the presence of renal dysfunction, discontinuation of immunoglobulin therapy should be considered.
Although cases of renal dysfunction and acute renal failure have been associated with the use of many authorized IVIg products containing various excipients such as sucrose, glucose, and maltose, products containing sucrose as a stabilizer have been linked to an unusually high proportion of total cases. In at-risk patients, the use of immunoglobulin products free from these excipients may be considered. Cytomegatect does not contain sucrose, glucose, or maltose.

Aseptic meningitis syndrome (AMS)
AMS has been reported in association with intravenous immunoglobulin (IVIg) therapy. The syndrome usually begins within several hours to 2 days after IVIg treatment. Cerebrospinal fluid (CSF) analyses often show pleocytosis up to several thousand cells/mm³, predominantly granulocytes, and elevated protein levels up to several hundred mg/dL. AMS may occur more frequently with high-dose IVIg treatment (2 g/kg). Patients presenting with such signs and symptoms should undergo a thorough neurological evaluation, including CSF analysis, to exclude other causes of meningitis. Discontinuation of IVIg therapy has led to resolution of AMS within a few days without sequelae.

Hemolytic anemia
Intravenous immunoglobulins (IVIg) may contain blood group-specific antibodies that can act as hemolysins and induce in vivo coating of erythrocytes with immunoglobulins, resulting in a positive direct antiglobulin test (Coombs test) and, rarely, hemolysis. Hemolytic anemia may develop following IVIg therapy due to increased sequestration of erythrocytes. Patients receiving IVIg should be monitored for clinical signs and symptoms of hemolysis.

Neutropenia/Leukopenia
Transient reduction in neutrophil count and/or episodes of neutropenia, sometimes severe, have been reported after IVIg treatment. This typically occurs within hours or days of IVIg administration and resolves spontaneously within 7–14 days.

Transfusion-related acute lung injury (TRALI)
Cases of acute non-cardiogenic pulmonary edema [Transfusion-Related Acute Lung Injury (TRALI)] have been reported in patients receiving IVIg. TRALI is characterized by severe hypoxia, dyspnea, tachypnea, cyanosis, fever, and arterial hypotension. TRALI symptoms usually develop during or within 6 hours after infusion, often within 1–2 hours. Therefore, recipients of IVIg should be monitored, and IVIg infusion should be immediately stopped in case of pulmonary adverse reactions. TRALI is a potentially life-threatening condition requiring immediate management in an intensive care unit.

Interference with serological tests
Following administration of immunoglobulin, the transient increase in various passively transferred antibodies in the patient's blood may lead to false-positive results in serological tests.
Passive transfer of antibodies directed against erythrocyte antigens, such as A, B, and D, may interfere with certain serological tests for anti-erythrocyte antibodies, such as the direct antiglobulin test (DAT, direct Coombs test).

Incompatibilities and special handling precautions
This medicinal product must not be mixed with other medicinal products or with any other product containing IVIg.
The medicinal product should be used immediately after first opening.
The medicinal product should be brought to room or body temperature before use.
Before administration, the solution should be visually inspected. The solution should be clear or slightly opalescent and colorless or pale yellow. Turbid solutions or those containing precipitates must not be used.