MEGALOTECT 100 U/ml Solution

Contents of the leaflet

1. Package Leaflet: Information for the User
2. Megalotect CP, 100 U/ml, Solution for Infusion
   1. Read the package leaflet carefully before using the medicine, as it contains important information for the patient.
3. What is Megalotect CP and what is it used for
4. Important information before using Megalotect CP
   1. When not to use Megalotect CP
   2. Warnings and precautions
   3. Megalotect CP and other medicines
   4. Pregnancy, breastfeeding, and fertility
   5. Driving and using machines
5. How to use Megalotect CP
   1. Receiving more than the recommended dose of Megalotect CP
6. Possible side effects
   1. The following side effects have been reported spontaneously during the use of Megalotect CP:
   2. Frequency not known (cannot be estimated from the available data)
   3. Immunoglobulin products for intravenous use may generally cause the following side effects:
   4. Uncommon (may affect up to 1 in 100 people):
   5. Rare (may affect up to 1 in 1,000 people):
   6. Very rare (may affect up to 1 in 10,000 people):
   7. Frequency not known (cannot be estimated from the available data)
   8. Reporting side effects
7. How to store Megalotect CP
8. Contents of the pack and other information
   1. What Megalotect CP contains
   2. What Megalotect CP looks like and contents of the pack
   3. Marketing authorization holder and manufacturer
   4. This medicinal product is authorized in the Member States of the European Economic Area under the following names:
   5. Date of last revision of the package leaflet: 07/2018.
   6. Information intended for healthcare professionals only:
   7. Pharmaceutical incompatibilities and special precautions

Package Leaflet: Information for the User

Megalotect CP, 100 U/ml, Solution for Infusion

Human cytomegalovirus immunoglobulin

Read the package leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Table of Contents of the Package Leaflet:

• 1. What is Megalotect CP and what is it used for
• 2. Important information before using Megalotect CP
• 3. How to use Megalotect CP
• 4. Possible side effects
• 5. How to store Megalotect CP
• 6. Contents of the pack and other information

1. What is Megalotect CP and what is it used for

Megalotect CP

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

Megalotect CP is given to patients receiving immunosuppressive treatment (treatment to suppress the immune system) to prevent clinical symptoms of cytomegalovirus infection, especially in patients after organ transplants. The doctor will consider concomitant use of appropriate antiviral medications during administration of Megalotect CP.

2. Important information before using Megalotect CP

When not to use Megalotect CP

• if the patient is allergicto human immunoglobulin or any of the other ingredients of this medicine (listed in section 6).
• if the patient is allergicto human immunoglobulin, especially if they have antibodies against immunoglobulin A (IgA).

Warnings and precautions

Before receiving Megalotect CP, discuss with your doctor, pharmacist, or nurse,

• if the patient is receiving human immunoglobulin for the first time or after a long break, or if the patient's immunoglobulin-containing medicine is being changed. In these cases, the doctor will closely monitor the patient.
• if the patient is allergicto immunoglobulins (see "When not to use Megalotect CP").
• if the patient
• is overweightor is elderly,
• has high blood pressure(hypertension), diabetes, or vascular disease,
• has a greater tendency to blood clotting in vessels,
• has been bedridden for a long time,
• has low blood volume(hypovolemia) or if the patient's blood is thickened,
• has kidney diseaseor is taking medicines that may harm kidney function. In these cases, more side effects may occur. If necessary, the doctor will stop treatment with Megalotect CP or take other precautions (e.g., reduce the infusion rate).

Hypersensitivity reactions
The patient may be allergic to immunoglobulins and not know about it. Hypersensitivity reactions can
occur even if the patient has previously received human immunoglobulins and tolerated them well.
However, true hypersensitivity reactions are rare. In these rare cases, hypersensitivity reactions (anaphylactic reactions) may occur, such as sudden drop in blood pressure or shock
(see also section 2 "Warnings and precautions", anaphylactic reactions,
If the patient notices such reactions during administration of Megalotect CP, they should immediately
tell their doctor.The doctor will decide whether to reduce the infusion rate or stop the infusion and take necessary medical measures to treat them.
Safety information regarding infections
Megalotect CP is made from human plasma (the liquid part of blood). When medicines are made from human blood or plasma, certain precautions are taken to prevent the transmission of infections to patients. All blood donors are tested for the presence of viruses and infectious diseases. Additionally, measures are taken to inactivate or remove viruses.
Despite these precautions, it cannot be completely ruled out that the transmission of infectious agents may occur when administering medicines obtained from human blood or plasma.
The measures taken are considered effective against enveloped viruses, such as:

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

The effectiveness of these measures may be limited for non-enveloped viruses, such as:

• parvovirus B19.

No association has been found between immunoglobulins and viral hepatitis A or parvovirus B19 infection. This is probably because the antibodies against these infections contained in Megalotect CP have a protective effect.
It is strongly recommended that each time a patient receives a dose of Megalotect CP, the doctor records the name and batch number of the medicine. The batch number provides information about the starting materials used in the medicine. If necessary, this allows the patient to be linked to the starting material used.
Children and adolescents
Special warnings and precautions for use listed for adults should also be taken into account for children and adolescents.

Megalotect CP and other medicines

Tell your doctor about all medicines you are taking, or have recently taken, and about any medicines you plan to take.
Megalotect CP may reduce the effectiveness of some vaccines, such as vaccines against

• measles
• rubella
• mumps
• chickenpox(varicella) After receiving Megalotect CP, it may be necessary to wait up to 3 months before receiving some vaccines and up to 1 year before receiving the measles vaccine.

Children and adolescents
It is expected that interactions listed for adults may also occur in children and adolescents.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, ask your doctor or pharmacist for advice before taking this medicine.
Your doctor will decide whether you can be treated with Megalotect CP during pregnancy and breastfeeding.

Driving and using machines

Some side effects associated with the administration of Megalotect CP may impair the ability to drive and use machines. If you experience side effects during treatment, wait until they resolve before driving or using machines.

3. How to use Megalotect CP

Megalotect CP is administered by a doctor.
The recommended dose is 1 ml per kilogram of body weight per day for adults, children, and adolescents.
The patient will receive this medicine at least 6 times at intervals of 2-3 weeks. The doctor will decide how many infusions the patient will need and when to start treatment.
Megalotect CP is administered in a "drip" (infusion) into a vein. The medicinal product should reach room temperature or body temperature before use.

Receiving more than the recommended dose of Megalotect CP

Too much Megalotect CP can lead to fluid overload and increased blood viscosity (thickening), especially in patients over 65 years of age and (or) patients with kidney function disorders.
If you think you have received too much Megalotect CP, you should discuss this with your doctor as soon as possible.
If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

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

The following side effects have been reported spontaneously during the use of Megalotect CP:

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

• temporary anemia (reversible hemolytic anemia),
• hypersensitivity reactions and allergic reactions (e.g., skin reactions, feeling of heat, chills, itching, shortness of breath) with sudden drop in blood pressure, in single cases with anaphylactic shock, even if no reactions occurred during previous administration of the medicine (see also section 2 "Warnings and precautions", anaphylactic reactions,
• headache,
• vomiting,
• skin reactions,
• joint pain
• blood test results indicating impaired kidney function (increased creatinine levels in the blood) and (or) acute kidney failure,
• chills, fever

Immunoglobulin products for intravenous use may generally cause the following side effects:

Uncommon (may affect up to 1 in 100 people):

• headache, dizziness
• nausea, vomiting
• joint pain, mild back pain
• low blood pressure
• chills, fever
• allergic reactions

Rare (may affect up to 1 in 1,000 people):

• transient skin reactions
• hypersensitivity reactions with sudden drop in blood pressure and in isolated cases with anaphylactic shock, also in patients who did not react to previous treatment (see also section 2 "Warnings and precautions").

Very rare (may affect up to 1 in 10,000 people):

• thromboembolic reactions, such as
• heart attack,
• stroke,
• blockage of blood vessels in the lungs by a blood clot (pulmonary embolism)
• blood clot in a vein (deep vein thrombosis)

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

• temporary anemia
• red blood cell destruction (hemolysis)
• blood test results indicating impaired kidney function (increased creatinine levels in the blood) and (or) acute kidney failure
• transient aseptic meningitis (reversible aseptic meningitis)

Children and adolescents
It is expected that the frequency, type, and severity of side effects in the pediatric population will be similar to those in adults.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocides
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
e-mail: [email protected]
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of this medicine.

5. How to store Megalotect CP

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after "Expiry date".
Store in a refrigerator (2°C-8°C). Store in the outer carton to protect from light.
Do not freeze.
Check the medicine before use. The solution should be clear or slightly opalescent (milky-shiny) and colorless or pale yellow. Do not use Megalotect CP if the solution is cloudy or contains sediment.
The medicinal product should be used immediately after opening the package.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Megalotect CP contains

The active substance is human cytomegalovirus immunoglobulin (CMVIG).
1 ml of solution contains:
50 mg of human plasma protein, of which at least 96% is immunoglobulin G (IgG),
with an antibody content against cytomegalovirus (CMV) of 100 U*.
Each vial of 10 ml of the medicine contains: 500 mg of human plasma protein (of which at least 96% is immunoglobulin G), with an antibody content against CMV of 1000 U.
Each vial of 50 ml of the medicine contains: 2500 mg of human plasma protein (of which at least 96% is immunoglobulin G), with an antibody content against CMV of 5000 U.
The subclass distribution of IgG is approximately: 65% IgG1, 30% IgG2, 3% IgG3, 2% IgG4.
The maximum content of immunoglobulin A (IgA) is 2000 micrograms/ml.
* reference units of the Paul Ehrlich Institute
The other ingredients are glycine and water for injections.

What Megalotect CP looks like and contents of the pack

Megalotect CP is a clear or slightly opalescent (milky-shiny) solution, colorless or pale yellow, in colorless glass vials.
Megalotect CP is available in the following pack sizes:
One carton containing 1 vial of 10 ml (1000 U) solution for infusion.
One carton containing 1 vial of 50 ml (5000 U) solution for infusion.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Biotest Pharma GmbH
Landsteinerstraße 5
63303 Dreieich
Germany
Phone: +49 6103 801-0
Fax: +49 6103 801-150
Email: [email protected]

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Croatia, Germany, Hungary, Spain:
Cytotect CP Biotest
Austria:
Cytotect CP Biotest 100 E/ml Infusionslösung
Italy:
Cytomegatect
Greece, Poland, Portugal:
Megalotect CP
Belgium, Netherlands:
Megalotect 100 E/ml
Slovenia:
Megalotect 100 e./ml solution for infusion

Date of last revision of the package leaflet: 07/2018.

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Information intended for healthcare professionals only:

Dosing and administration
Administration should be started on the day of transplantation. For bone marrow transplantation, prophylaxis may also be considered to start up to 10 days before transplantation, especially in CMV-seropositive patients. A total of at least 6 single doses should be administered at intervals of 2-3 weeks.
Method of administration
The medicinal product Megalotect CP should be administered as an intravenous infusion with an initial rate of 0.08 ml/kg body weight/hour for 10 minutes. If tolerated well, the infusion rate can be gradually increased to a maximum of 0.8 ml/kg body weight/hour until the end of the infusion.
Warnings and precautions
Certain serious side effects may be caused by the infusion rate. The recommended infusion rate should be strictly followed. During the infusion, patients should be closely monitored and observed for any symptoms.
Certain side effects may occur more frequently

• with high infusion rates,
• in patients who receive human immunoglobulin for the first time or in rare cases in patients who have their immunoglobulin product changed or in patients with a long break in treatment.

Complications can be avoided by ensuring that patients:

• do not have hypersensitivity to human immunoglobulin through initial slow (0.08 ml/kg body weight/hour) administration of the product,
• are closely monitored during infusion for any symptoms. In particular, patients not previously treated with normal human immunoglobulin, patients receiving alternative immunoglobulin products, and those with a long period since the last infusion should be monitored during and for one hour after the first infusion to detect possible side effects. All other patients should be observed for at least 20 minutes after administration.

In case of a side effect, the infusion rate should be reduced or the infusion stopped. The required treatment depends on the type and severity of the side effect.
In case of shock, current standard medical treatment for shock should be applied.
In all patients, administration of immunoglobulins requires:

• adequate hydration before starting the immunoglobulin infusion,
• monitoring of diuresis,
• monitoring of serum creatinine levels,
• avoidance of concomitant use of loop diuretics.

Hypersensitivity
True hypersensitivity reactions are rare. They may occur in patients with antibodies against IgA.
The use of immunoglobulins is not indicated in patients with selective IgA deficiency, if the IgA deficiency is the only abnormal finding.
Administration of immunoglobulin may rarely cause a drop in blood pressure with anaphylactic reaction, even in patients who have previously tolerated immunoglobulin treatment well.
Thromboembolic complications
There is clinical evidence suggesting a link between the administration of intravenous immunoglobulins (IVIg) and thromboembolic events, such as myocardial infarction, stroke, pulmonary embolism, and deep vein thrombosis. It is assumed that the administration of high doses of immunoglobulin to patients at risk leads to a relative increase in blood viscosity. Caution should be exercised when recommending and infusing intravenous immunoglobulins to obese patients and patients with existing risk factors for thrombotic events (such as advanced age, hypertension, diabetes, vascular disease, or a history of thrombotic events, patients with acquired or congenital predispositions to thrombosis, patients after prolonged immobilization, patients with severe hypovolemia, and patients with diseases characterized by increased blood viscosity).
In patients with existing risk factors for thromboembolic side effects, intravenous immunoglobulin products should be administered at the lowest possible infusion rate and in the smallest possible dose.
Acute kidney failure
Cases of acute kidney failure have been reported in patients receiving intravenous immunoglobulin treatment. In most cases, risk factors were identified, such as pre-existing kidney failure, diabetes, hypovolemia, overweight, concomitant use of nephrotoxic medicinal products, or patient age over 65 years.
In case of kidney function disorders, consideration should be given to discontinuing the immunoglobulin product.
Cases of kidney function disorders and acute kidney failure have been observed after administration of several registered intravenous immunoglobulin products containing different excipients, such as sucrose, glucose, and maltose, and products containing sucrose as a stabilizer accounted for the majority of such cases. In patients at risk, consideration can be given to using immunoglobulin products that do not contain these ingredients. The medicinal product Megalotect CP does not contain sucrose, glucose, or maltose.
In patients with existing risk factors for acute kidney failure, intravenous immunoglobulin products should be administered at the lowest possible infusion rate and in the smallest possible dose.
Aseptic meningitis syndrome (AMS)
Aseptic meningitis syndrome (AMS) has been reported in association with intravenous immunoglobulin (IVIg) treatment. Discontinuation of intravenous immunoglobulin treatment resulted in remission of AMS within a few days without sequelae. The syndrome usually occurs within a few hours to 2 days after starting intravenous immunoglobulin treatment. In cerebrospinal fluid examinations, pleocytosis is often found in the number of up to several thousand cells/mm, mainly of the granulocytic series, and increased protein levels up to several hundred mg/dl. AMS may occur more frequently in association with high-dose intravenous immunoglobulin treatment (2 g/kg).
Hemolytic anemia
Intravenous immunoglobulins (IVIg) may contain antibodies against blood groups, which can act as hemolysins and cause in vivocoating of red blood cells with immunoglobulins, resulting in a positive direct antiglobulin test (Coombs test) and rarely hemolysis.
Hemolytic anemia may develop after intravenous immunoglobulin treatment due to increased red blood cell sequestration. Patients receiving intravenous immunoglobulins should be monitored for clinical signs and symptoms of hemolysis.
Effect on serological test results
A transient increase in the level of various passively transferred antibodies in the patient's blood after injection of immunoglobulin may lead to false-positive results in serological tests.
Passive transfer of antibodies against erythrocyte antigens, such as A, B, and D, may interfere with the results of certain serological tests for the presence of antibodies against red blood cells, such as the direct antiglobulin test (DAT, direct Coombs test).

Pharmaceutical incompatibilities and special precautions

Do not mix the medicinal product with other medicinal products.
The medicinal product should be used immediately after opening the package.
The medicinal product should reach room temperature or body temperature before use.
Products should be inspected visually before administration. The solution should be clear or slightly opalescent and colorless or pale yellow. Do not use solutions that are cloudy or contain sediment.