Prospecto: information for the user

Megalotect 100 U/ml solution for perfusion

Human anticitomegalovirus immunoglobulin

Read this prospect carefully before starting to use this medication, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only to you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospect. See section 4.

1. What isMegalotectand for what it is used

2. What you need to know before starting to useMegalotect

3. How to useMegalotect

4. Possible adverse effects

5. Conservation ofMegalotect

6. Contents of the package and additional information

Megalotect

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

Megalotect is administered to patients undergoing immunosuppressive treatment (treatment to suppress the immune system), particularly after an organ transplant, to prevent the clinical manifestation of cytomegalovirus infection.

Your doctor will consider the concomitant use of antiviral agents with Megalotect.

Do not use Megalotect

• if you areallergicto human immunoglobulinor to any of the other components of this medication (listed in section6).
• if you have a deficiency of immunoglobulin A, particularly if you have antibodies against immunoglobulin A in your blood, as this may lead to anaphylaxis.

Warnings and precautions

Consult your doctor, pharmacist or nurse before administeringMegalotect.

• if you are to be administered human immunoglobulinfor the first time or after a prolonged interruption of treatment,or ifyou have changed the immunoglobulin product. In these cases, the frequency of adverse reactions may be higher and your doctor will monitor you closely.
• if you areallergicto immunoglobulins (see the section «Do not useMegalotect»). You may be allergic to immunoglobulins without knowing it, even if you have been administered them previously and tolerated them well. However, hypersensitivity reactions are rare.
• if you have an untreated infection or a prolonged (chronic) underlying inflammation
• if you
• • areoverweightorobese, or
  • arean elderly patient,
  • havehigh blood pressure(hypertension),diabetesorvascular disease,
  • have agreater tendency to blood coagulation,
  • have beenbedridden for a long time,
  • havelow blood volume(hypovolemia) or yourblood density is higher than normal,
  • have apre-existing kidney diseaseortake medications that can damage the kidneys.

In these cases, there is a higher risk of adverse effects. Your doctor may interrupt treatment with Megalotect or take other precautions (e.g. a particularly low infusion rate).

Reactions to infusion

If you notice any of the following signs of a reaction during the infusion of Megalotect, that is, headache, hot flushes, chills, muscle pain, wheezing, rapid heart rate, lower back pain, nausea, low blood pressure, inform your doctor immediately.

Inform your doctor immediatelyif you notice these reactions during the administration ofMegalotect. He will decide whether to reduce the infusion rate or stop it completely, and initiate the necessary medical measures to treat these reactions.

Information on safety with respect to infections

Megalotectis prepared with human plasma (the liquid part of the blood). When administering medications derived from blood or human plasma, certain measures must be taken to prevent the transmission of infections to patients. The blood of all donors is analyzed to detect viruses and infections. Additionally, the processing of the blood or plasma includes steps that can inactivate or eliminate viruses.

Despite these measures, when administering medications derived from blood or human plasma, the possibility of transmission of infectious agents cannot be ruled out entirely.

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 are of limited value against viruses such as

• parvovirus B19.

Until now, immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections. This is because the antibodies contained in Megalotect protect against these infections.

We strongly recommend that you note the name and batch number of each dose of Megalotect that you are administered. The batch number provides information on the raw materials used in your medication. This allows, if necessary, to establish a relationship between you and the raw material used.

Children and adolescents

The special warnings and precautions for adults are also valid for children and adolescents.

Other medicationsandMegalotect

Inform your doctor or pharmacist if you are using, have used recently or may have to use any other medication.

Megalotectmay reduce the effectiveness of certainvaccines, e.g. the effectiveness of vaccines against

• measles
• rubella
• mumps
• chickenpox

If you have been administeredMegalotect, wait at least 3months before receiving certain vaccines, and at least one year before receiving a measles vaccine.

Please avoid using diuretics withMegalotect.

Children and adolescents

It is expected that the interactions mentioned for adults will be the same for children and adolescents.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant or intend to become pregnant, consult your doctor or pharmacist before using this medication.

Your doctor will decide whetherMegalotectcan be used during pregnancy and breastfeeding.

Driving and operating machinery

The influence ofMegalotecton your ability to drive and operate machinery is small. If you experience adverse effects during treatment, wait until they resolve before driving or operating machinery.

Your treating doctor will administerMegalotect.

The recommended dose is 1ml per kg of body weight and day for adults, children, and adolescents.

The medication will be administered at least a total of 6times, in intervals of 2 or 3weeks. Your doctor will decide the exact number of infusions you need and when to start treatment.

Megalotectis administered through a "drip" (infusion) in a vein.This medication must be at room temperature or body temperature before use.

If you use more Megalotect than you should

An excess ofMegalotectmay cause fluid overload and blood hyperviscosity (thickening), especially if you are over 65years old and/or have heart or kidney failure.

If you think you have received moreMegalotectthan you should, consult your doctor as soon as possible.

In case of overdose or accidental ingestion, call the Toxicological Information Service immediately, phone 915620420.

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

The following side effects have been reported spontaneously with Megalotect:

Unknown: The frequency cannot be estimated from the available data

• Anemia (hemolytic anemia)
• Severe allergic reactions, such as anaphylactic shock, anaphylactic reactions, anaphylactoid reactions, hypersensitivity
• Headache, dizziness
• Vomiting
• Skin reactions such as exanthema, abnormal skin redness, itching
• Joint pain
• Laboratory test results indicating renal function deterioration (elevated serum creatinine levels) and/or acute renal insufficiency
• Chills, fever, fatigue

Generally, normal human immunoglobulin preparations can cause the following adverse reactions (in decreasing frequency):

• Chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, joint pain, low blood pressure, and moderate lower back pain
• Decreased red blood cell count due to destruction in blood vessels (reversible hemolytic reactions) and (rarely) hemolytic anemia requiring blood transfusion
• (Rarely) sudden drop in blood pressure and in isolated cases anaphylactic shock
• (Rarely) transient skin reactions (including cutaneous lupus erythematosus, unknown frequency)
• (Very rarely) thromboembolic reactions such as heart attack (myocardial infarction), stroke, pulmonary embolism, deep vein thrombosis
• Cases of acute transient inflammation of the protective membranes covering the brain and spinal cord (aseptic spinal meningitis)
• Cases of laboratory test results indicating renal dysfunction and/or sudden renal insufficiency
• Cases of acute lung injury related to transfusion (TRALI, in English). This causes the accumulation of non-cardiogenic fluid in the lung air spaces (non-cardiogenic pulmonary edema). You would experience significant breathing difficulty (respiratory distress), rapid breathing (tachypnea), abnormally low oxygen concentration in the blood (hypoxia), and increased body temperature (fever).

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is possible adverse effects that do not appear in this prospectus. You can also report them directly through the Spanish System of Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the box and vial after CAD.

Store in refrigerator (between 2°C and 8°C). Store in the original packaging to protect it from light.

Do not freeze.

The product must be visually inspected before use: the solution must be transparent or slightly opalescent (with a milky appearance) and colorless or pale yellow. Do not use Megalotect if the solution is turbid or sediment has formed.

The medication must be used immediately after opening.

Medicines should not be thrown down the drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This way, you will help protect the environment.

Composition of Megalotect

The active principle ishuman anticytomegalovirus immunoglobulin (CMVIG).

1ml of the solution contains:

50mg of human plasma proteins, of which at least 96% is immunoglobulin G (IgG), with a content of antibodies against cytomegalovirus (CMV) of 100U*.

Each vial with 10ml contains:500mg of human plasma proteins (of which at least 96% is immunoglobulin G), with a content of antibodies against CMV of 1,000U*.

Each vial with50mlcontains:2,500mg of human plasma proteins (of which at least 96% is immunoglobulin G), with a content of antibodies against CMV of 5,000U*.

The distribution of IgG subclasses is approximately 65% IgG1, 30% IgG2, 3% IgG3, 2% IgG4.

The maximum content of immunoglobulin A (IgA) is 2,000micrograms/ml.

* units of the reference preparation of the Paul Ehrlich Institute

The other components areglycine and water for injection.

Appearance of the product and contents of the package

Megalotectis a transparent or slightly opalescent (with a milky appearance), colorless or slightly yellowish solution in glass vials.

Megalotectis available in the following package sizes:

One box contains 1vial with 10ml (1,000U)of perfusion solution

One box contains 1vial with 50ml (5,000U)of perfusion solution

Only some package sizes may be commercially available.

Holder of the marketing authorization and responsible for manufacturing

Biotest Pharma GmbH

Landsteinerstraße 5

63303 Dreieich

Germany

Phone: + 49 6103 801-0

Fax: + 49 6103 801-150

Email:[email protected]

For more information about this medicinal product, please contact the local representative of the marketing authorization holder:

Grifols Movaco, S.A.

Can Guasc, s/n – Parets del Vallès

08150 Barcelona

Spain

This medicinal product is authorized in the member states of the European Economic Area with the following names:

Croatia, Germany, Hungary:Cytotect CP Biotest

Austria:Cytotect CP Biotest 100 E/ml Infusionslösung

Italy:Cytomegatect

Spain:Megalotect 100 U/ml solución para perfusión

Greece, Poland, Portugal:Megalotect CP

Belgium, Netherlands:Megalotect 100 E/ml

Slovenia:Megalotect 100 e./ml raztopina za infundiranje

Date of the last review of this leaflet:05/2023.

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This information is intended solely for healthcare professionals:

Dosage and administration

The administration should be initiated on the day of the transplant. If the transplant is of bone marrow, the prophylaxis can also be planned to start up to 10days before the intervention, especially in patients who are seropositive for CMV. At least a total of 6doses should be administered at intervals of 2 to 3weeks.

Administration

Intravenous.

Megalotect should be infused intravenously at an initial rate of 0.08ml/kg PC/h for 10minutes. In case of adverse reaction, the rate of administration should be reduced or the infusion stopped. If well tolerated, the rate of administration can be gradually increased to a maximum of 0.8ml/kgPC/h for the remaining time of the infusion.

Warnings and precautions

The rate of infusion may be related to certain severe reactions to the drug. The recommended infusion rate should be followed in detail. Patients will be closely monitored and closely observed for any symptoms during the infusion period.

Some adverse reactions may occur more frequently

• at a high infusion rate
• in patients receiving human immunoglobulin for the first time or, in rare cases, in patients who have replaced the immunoglobulin product or in cases where it has been a long time since the last infusion.

Adverse reactions can often be prevented by ensuring that patients

• are not sensitive to human immunoglobulin. To do this, the product should be injected slowly initially (0.08ml/kg body weight/hour).
• are closely monitored during the infusion period to detect any symptoms. In particular, patients who have not been treated with human immunoglobulin before, patients who have undergone other treatments with human immunoglobulin intravenous products (IgIV) or when it has been a long time since the last infusion, should be monitored in the hospital during the first infusion and during the first hour after the first infusion to detect possible adverse effects. Other patients should be observed for at least 20minutes after administration.

In case of an adverse reaction, the infusion rate should be reduced or the infusion stopped. The necessary treatment depends on the type of adverse reaction and the nature and severity of the adverse reaction.

In case of shock, standard medical treatment should be applied.

For all patients, treatment with immunoglobulin requires

• adequate hydration before starting the infusion of immunoglobulin,
• monitoring of urine output,
• monitoring of serum creatinine levels,
• avoiding the simultaneous use of diuretics.

Hypersensitivity

Reactions of hypersensitivity are rare. They can occur in patients with anti-IgA antibodies.

Anaphylaxis can develop in patients

• with undetectable IgA who haveanti-IgA antibodies
• who have tolerated previous treatment with human immunoglobulin

In case of shock, standard medical treatment should be applied.

Thromboembolism

There is clinical evidence of an association between the administration of intravenous immunoglobulin (IgIV) and episodes of thromboembolism, such as myocardial infarction, stroke, pulmonary embolism, and deep vein thrombosis. It is assumed that these events are related to a relative increase in blood viscosity due to the high influx of immunoglobulin in at-risk patients. Caution should be exercised when prescribing and infusing immunoglobulins in obese patients and in patients with pre-existing risk factors for thrombotic events (such as advanced age, hypertension, diabetes mellitus, and a history of vasculopathy or thrombotic episodes, patients with acquired or hereditary thrombophilic diseases, patients who have been immobilized for prolonged periods, patients who are severely hypovolemic, patients with diseases that increase blood viscosity).

In patients at risk of thromboembolic adverse reactions, IgIV products should be administered at the minimum infusion rate and minimum dose possible.

Acute renal failure

Cases of acute renal failure have been reported in patients treated with intravenous immunoglobulin (IgIV). In most cases, the risk factors have been identified, such as pre-existing renal insufficiency, diabetes mellitus, hypovolemia, obesity, concomitant administration of nephrotoxic medications, or age over 65.

Before infusing IgIV, renal parameters should be evaluated, especially in patients considered to be at higher risk of developing acute renal failure and, again, at appropriate intervals. In patients at risk of acute renal failure, IgIV products should be administered at the minimum infusion rate and dose possible.

In case of renal failure, the administration of the immunoglobulin product should be interrupted.

Although reports of renal dysfunction and acute renal failure have been associated with the use of many medications with IgIV authorized that contain different excipients such as sucrose, glucose, and maltose, those that contained sucrose as a stabilizer represented a disproportionate part of the total number. In at-risk patients, consider using immunoglobulin products that do not contain these excipients. Megalotect does not contain sucrose, glucose, or maltose.

Asymptomatic aseptic meningitis (AAM)

AAM has been reported in association with treatment with intravenous immunoglobulins (IgIV). AAM usually begins several hours to 2days after starting treatment with IgIV. In most cases, cerebrospinal fluid analysis is positive with pleocytosis of up to several thousand cells per mm3, predominantly granulocytic series, and high protein concentrations of up to several hundred mg/dl. AAM occurs more frequently in association with treatment with high doses of IgIV (2g/kg).

Patients who show these signs and symptoms should be subjected to an exhaustive neurological examination, including cerebrospinal fluid studies, to exclude other causes of meningitis.

Discontinuation of IgIV treatment has resulted in the resolution of AAM within several days without sequelae.

Hemolytic anemia

Intravenous immunoglobulins (IgIV) may contain antibodies against blood groups that act as hemolysins and induce the in vivo coating of red blood cells with immunoglobulin, causing a positive direct antiglobulin test (Coombs test) and, exceptionally, hemolysis. Hemolytic anemia can develop as a consequence of treatment with IgIV and be potentiated by erythrocyte sequestration. Patients treated with IgIV should be monitored for signs and symptoms of hemolysis.

Neutropenia/Leucopenia

After treatment with IgIV, a transient decrease in the number of neutrophils and/or episodes of neutropenia, sometimes severe, have been reported. This usually occurs in the hours or days following administration of IgIV, and resolves spontaneously within 7 to 14days.

Transfusion-related acute lung injury (TRALI)

In some cases, TRALI has been reported in patients who have received IgIV. TRALI is characterized by severe hypoxia, dyspnea, tachypnea, cyanosis, fever, and hypotension. Symptoms of TRALI usually develop during or within 6hours after infusion, often within the first 1-2hours. Therefore, patients receiving IgIV should be closely monitored and the infusion of IgIV should be immediately stopped in case of adverse pulmonary reactions. TRALI is a potentially fatal disease that should be treated immediately in the intensive care unit.

Interference with serological tests

After administration of immunoglobulin, the transient increase in different antibodies transferred passively to the patient's blood may cause false-positive results in serological tests.

The passive transfer of antibodies to erythrocyte antigens, e.g., A, B, and D, may interfere with some serological tests for erythrocyte antibodies, e.g., the direct antiglobulin test (Coombs test).

Incompatibilities and special precautions for handling

This medicinal product should not be mixed with other medicinal products, or IgIV products.

The medicinal product should be used immediately after opening.

This medicinal product should be at room temperature or body temperature before use.

Products should be visually inspected before administration. The solution should be transparent or slightly opalescent and colorless or pale yellow. Do not use a solution that is turbid or has sediment.