PENTAGLOBIN 50 mg /Ml Infusion Solution

Зміст інструкції

1. Pentaglobin 50 mg/ml solution for infusion
   1. What is Pentaglobin and what is it used for
   2. What you need to know before using Pentaglobin
   3. How to use Pentaglobin
   4. Possible side effects
   5. How to store Pentaglobin
   6. Package contents and other information

Pentaglobin 50 mg/ml solution for infusion

Human immunoglobulin
Read this leaflet carefully before using this medicine as 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.
• If any side effects occur, including those not listed in this leaflet, ask your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What is Pentaglobin and what is it used for

Pentaglobin is a medicine derived from human blood, containing antibodies (antibodies are
constituents of the human body's immune defenses). This medicine is available
as an infusion solution, which is administered via a slow intravenous injection.

Pentaglobin is used

• for supportive therapy of severe bacterial infections in association with antibiotic therapy.
• as a therapy to replace missing antibodies (immunoglobulins) in patients with severe acquired immune system deficiency.

2. What you need to know before using Pentaglobin

Do not use Pentaglobin

• if you are allergicto human immunoglobulins or to any of the other ingredients of this medicine (listed in section 6).
• If you have a deficiency of immunoglobulin A, particularly if you have antibodies in your blood directed against immunoglobulins of the IgA type, as this may cause anaphylaxis.

Warnings and precautions
Talk to your doctor or nurse before you are given Pentaglobin:

• if you receive human immunoglobulins for the first time or after a long period of suspensionor if your immunoglobulin preparation has been changed. In these cases, your doctor will keep you under close observation.
• if you have an active infectionor an underlying chronic inflammation;
• if
• you are very overweightor elderly,
• suffer from high blood pressure (hypertension), diabetes or vascular diseases,
• have a high predisposition to forming blood clots,
• you have been bedriddenfor a long time,
• you have a reduced blood volume(hypovolemia) or your blood tends to thicken,
• you have pre-existing kidney diseaseor are using medicines that can have effects harmful to your kidney function. In these cases, there is an increased risk of developing adverse effects. Your doctor may decide to stop therapy with Pentaglobin or to take other precautionary measures (for example, providing a particularly slow infusion rate).

You may be allergic to immunoglobulins without knowing it, even if you have previously tolerated immunoglobulins well. However, true hypersensitivity reactions are rare. Some adverse reactions (e.g. headache, flushing, chills, myalgia, wheezing, tachycardia, back pain, nausea and hypotension) may be related to the infusion rate. If you observe similar reactions during the administration of Pentaglobin, tell your doctor immediately, who will decide whether to reduce the infusion rate or stop the infusion and start the necessary medical measures to treat them.
Information on safety regarding infections
When medicines are produced from human blood or plasma (which is the liquid part of blood), all precautions are taken to prevent the transmission of infectious pathogens to patients.
These include:

• careful selection of blood and plasma donors to ensure exclusion of those at risk of carrying infections
• Analysis of each donation and plasma pools to detect signs of viruses/infections
• The inclusion of steps in the manufacturing process of blood or plasma that can inactivate or remove viruses Despite these measures, the risk of infection transmission following the administration of medicines produced from blood or plasma cannot be completely excluded. This applies even to unknown or emerging viruses or other types of infection.

The measures taken are considered effective against enveloped viruses, such as

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

The measures taken may have limited effectiveness against non-enveloped viruses, such as:

• the hepatitis A virus (HAV),
• parvovirus B19. To date, no correlations have been found between immunoglobulins and infections from hepatitis A virus or parvovirus B19, probably because the antibodies contained in the product exert a protective action against these infections. It is strongly recommended that, each time you are given Pentaglobin, the doctor records the name and batch number of the medicine, to keep track of the batch used. The batch number allows you to trace the specific plasma used as the raw material for the medicine administered to you. If necessary, a connection can be made between you and the material used as raw material.

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

• measles
• rubella
• mumps
• chickenpox.

After the administration of Pentaglobin you should wait three months before being vaccinated; in the case of the measles vaccine, the waiting time may extend up to one year.
Loop diuretics
Avoid concomitant use of loop diuretics (a group of medicines that increase urine production).

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before using this medicine.
The doctor will decide whether you can receive treatment with Pentaglobin during pregnancy or breastfeeding.

Driving and operating machinery
Pentaglobin has minor effects on the ability to drive and operate machinery. If you experience adverse effects during treatment, you should wait for them to resolve before driving or operating machinery.

Pentaglobin contains glucose and sodium
1 ml of solution for infusion contains 25 mg of glucose. This medicine contains 8.75 g of glucose per 350 ml dose for an adult (body weight 70 kg). This should be taken into account in people with diabetes mellitus.
Pentaglobin contains 0.078 mmol/ml (1.79 mg/ml) of sodium (the main component of table salt). This medicine contains 627.6 mg of sodium (the main component of table salt) per daily dose of approximately 350 ml for an adult (body weight 70 kg). This corresponds to approximately 31% of the maximum recommended daily intake with the diet of an adult.

3. How to use Pentaglobin

Pentaglobin will be administered to you by your doctor. The dosage depends on your immune status and the severity of the disease.

The recommended dose is:
Newborns and infants
5 ml (0.25 g) per kg of body weight per day for 3 consecutive days. Further administrations depend on the clinical picture.

Children and adults
For the therapy of severe bacterial infections: 5 ml (0.25 g) per kg of body weight per day for 3 consecutive days. Further administrations depend on the clinical picture.
As therapy to replace missing antibodies (immunoglobulins) in patients with acquired immune deficiency or immune system suppressed by medications or radiation: 3–5 ml (0.15–
0.25 g) per kg of body weight. If necessary, repeat the administration at weekly intervals.
It is infused into a vein (intravenous administration) with the following infusion rates:

Newborns and infants:
1.7 ml per kg of body weight per hour with an infusion pump.

Children and adults:
0.4 ml per kg of body weight per hour,

alternatively: for the first 100 ml 0.4 ml per kg of body weight per hour, then continuously 0.2 ml per kg of body weight per hour until reaching 15.0 ml per kg of body weight over 72 hours.

Examples:

Hepatic insufficiency
There is no evidence to require a dose adjustment.

Renal insufficiency
No dose adjustment unless clinically justified, see the paragraph “Warnings and precautions.”

Elderly
No dose adjustment unless clinically justified.

Route of administration
Pentaglobin is intended for intravenous administration (infusion into a vein).
The medicine must be brought to room temperature or body temperature before use.

If you receive more Pentaglobin than you should
An excessive amount of Pentaglobin can cause fluid overload and increased blood density (hyperviscosity), especially in patients at risk, including children, elderly patients, or those with impaired cardiac or renal function. If you think that you or your child have received an excessive amount of Pentaglobin, talk to your doctor immediately.
If you have any doubts about the use of this medicine, ask 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 have been reported in clinical studies with Pentaglobin:
Common (may affect up to 1 in 10 people):

• low blood pressure
• nausea, vomiting
• increased sweating (hyperhidrosis)

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

• allergic reactions
• skin reactions/allergic dermatitis
• back pain

The following side effects have been reported after marketing of Pentaglobin:
Not known (frequency cannot be estimated from the available data)

• inflammation of the membranes covering the brain and spinal cord (aseptic meningitis)
• decreased red blood cell count (hemolytic anemia)/red blood cell breakdown (hemolysis)
• anaphylactic shock, anaphylactoid reaction, hypersensitivity
• headache, dizziness
• fast heartbeat (tachycardia)
• Skin flushing (erythema)
• Shortness of breath (dyspnea)
• Itching
• acute kidney failure and/or blood test results indicating impaired kidney function (increased serum creatinine levels)
• chills, fever

Children and adolescents
Although the nature and frequency of adverse reactions in neonates and young children are
generally comparable to the adverse reactions observed in other age groups (e.g. infusion
reactions, anaphylactic reactions, hypersensitivity), their clinical presentation in terms of signs and
symptoms reported varies and may also include, for example, changes in heart rate (fast or slow
heartbeat), increased respiratory rate, decreased oxygen saturation, changes in skin color including
pallor and/or cyanosis, decreased muscle tone.

In general, human immunoglobulin preparations can cause the following side effects:

• chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, joint pain, low blood pressure and moderate back pain
• decreased number of red blood cells due to breakdown of these cells in the blood vessels (reversible hemolytic reactions) and (rarely) hemolytic anemia requiring transfusion
• (rarely) a 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 events such as heart attack (myocardial infarction), stroke, blood clots in the pulmonary vessels (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 values indicating that kidney function is impaired and/or acute renal failure
• cases of acute lung injury associated with transfusion (TRALI). This will lead to an accumulation of fluid in the air spaces of the lungs that is not of cardiac origin (non-cardiogenic pulmonary edema). Symptoms include severe difficulty breathing (respiratory distress), increased respiratory rate (tachypnea), abnormally low oxygen levels in the blood (hypoxia) and increased body temperature (fever).

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or nurse. You can also
report side effects directly through 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 Pentaglobin

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label and the package after
Exp.
Store in a refrigerator (2°C–8°C). Do not freeze. Store in the original package to
protect the medicine from light.
Before using the medicine, visually check that the solution is clear or slightly to
moderately milky (opalescent). Pentaglobin must not be used if the solution is
turbid or if it contains deposits.
After opening the container, the infusion solution must be administered
immediately. Discard any unused remaining solution due to the risk of bacterial
contamination.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Pentaglobin contains

• The active substance is human immunoglobulin with a high titre of IgM. 1 ml of solution contains 50 mg of human plasma proteins, of which  95% are immunoglobulins: IgM 6 mg, IgA 6 mg, IgG 38 mg.
• The other components are glucose monohydrate, sodium chloride, water for injections.

Description of the appearance of Pentaglobin and contents of the pack
Pentaglobin is a solution from slightly to moderately opalescent and from colourless to slightly
yellowish in colourless glass vials.
Pentaglobin is available in the following packs:
Each pack contains 1 vial with 10 ml (0.5 g), 50 ml (2.5 g) or 100 ml (5.0) of solution.

Marketing authorisation holder and manufacturer
Biotest Pharma GmbH
Landsteinerstraße 5
63303 Dreieich
Tel.: (06103) 801-0
Fax: (06103) 801-150
Email: [email protected]

The following information is intended exclusively for doctors or healthcare professionals:
Warnings and precautions
Possible complications can often be avoided by ensuring that patients:

• are not sensitive to normal human immunoglobulins; to this end, administer the product initially at a low infusion rate (0.4 ml/kg body weight/hour).
• are kept under close observation throughout the duration of the infusion in order to ascertain any symptoms. In particular, patients treated for the first time with normal human immunoglobulins, those previously treated with a different immunoglobulin preparation or those for whom a long time has elapsed since the previous infusion must be kept under observation in hospital or in a controlled healthcare environment throughout the first infusion and for one hour after the infusion, in order to ascertain any adverse effects and to ensure the possibility of immediate administration of emergency treatment should problems arise. All other patients must be kept under observation for at least 20 minutes after administration.

IVIg therapy requires in all patients

• adequate hydration before starting the IVIg infusion,
• monitoring of diuresis,
• monitoring of serum creatinine levels,
• avoiding the concomitant administration of loop diuretics.

If an adverse reaction occurs, the infusion rate must be reduced or the infusion
must be stopped. The necessary therapy is commensurate with the type and severity of the adverse reaction.
Infusion-related reaction
Certain adverse reactions (e.g. headache, flushing, chills, myalgia, dyspnoea, tachycardia, lower back pain, nausea and hypotension) may be related to the infusion rate. The recommended infusion rates and reported in paragraph "How to use Pentaglobin" must be strictly respected
and patients must be kept under close observation throughout the duration
of the infusion in order to ascertain any symptoms.
Certain adverse effects may occur more frequently:

• in patients treated for the first time with normal human immunoglobulins or, in rare cases, when switching the human normal immunoglobulin product or when a long time has elapsed since the previous infusion.
• In patients with an active infection or with underlying chronic inflammation

Hypersensitivity
Hypersensitivity reactions are rare. Anaphylaxis can develop in patients:

• with undetectable levels of IgA who have anti-IgA antibodies
• who have tolerated previous treatments with normal human immunoglobulins. In case of shock, standard medical measures for shock therapy must be applied. Thromboembolism There is clinical evidence of a correlation between the administration of intravenous immunoglobulins (intravenous immunoglobulin, IVIg) and thromboembolic events, such as myocardial infarction, stroke (including cerebral stroke), pulmonary embolism and deep vein thrombosis, which are believed to be related to a relative increase in blood viscosity due to high immunoglobulin administration in at-risk patients. Caution is required when prescribing and infusing intravenous immunoglobulins in obese patients and patients with pre-existing risk factors for thrombotic events (e.g. advanced age, hypertension, diabetes mellitus and a history of vascular disease or thrombotic episodes, patients with acquired or hereditary thrombophilic disorders, patients with prolonged immobilisation, patients with severe hypovolaemia, patients with diseases that increase blood viscosity).

In patients at risk of thromboembolic adverse effects, IVIg must be administered at the
minimum infusion rate and dose practicable.
Acute renal failure
Cases of acute renal failure have been described in patients treated with IVIg. In most
cases, risk factors were identified, such as pre-existing renal failure, diabetes mellitus,
hypovolaemia, overweight, concomitant use of nephrotoxic drugs or age over 65 years.
Renal parameters must be assessed before IVIg infusion, in particular in patients with
a potentially increased risk of developing acute renal failure and, subsequently, at
appropriate intervals. In patients at risk of acute renal failure, IVIg-based products
must be administered at the minimum infusion rate and dose practicable.
In case of impairment of renal function, discontinuation of IVIg should be considered
There have been cases of renal dysfunction and acute renal failure associated with the use of numerous authorised IVIg preparations containing various excipients, such as sucrose, glucose and maltose, however, the preparations
for which a greater number of cases have been reported are those containing sucrose as
a stabiliser. In at-risk patients, the use of IVIg that do not contain these
excipients may be considered. Pentaglobin does not contain sucrose or maltose but contains glucose (see also the
paragraph “Pentaglobin contains glucose”).
Aseptic meningitis syndrome (AMS)
AMS has been reported in association with IVIg treatment. The syndrome usually manifests
within a period of a few hours to 2 days after treatment with IVIg. The
analysis of cerebrospinal fluid (cerebrospinal fluid, CSF) frequently results positive, with
pleocytosis up to several thousand cells per mm³, predominantly of the granulocytic series, and
elevated protein levels, up to several hundred mg/dl. AMS may occur more
frequently in association with high-dose IVIg treatment (2 g/kg).
Patients presenting these signs and symptoms should be subjected to careful neurological examination, including CSF analysis, to exclude other causes of meningitis.
Discontinuation of IVIg treatment has led to remission of AMS within a few days,
without subsequent damage.
Haemolytic anaemia
Intravenously administered immunoglobulins (IVIg preparations) may contain
antibodies anti-blood group, which may act as haemolysins and induce in vivocoating
of red blood cells (RBC) with immunoglobulins, resulting in a positive direct antiglobulin reaction (Coombs' test) and, rarely, haemolysis. Haemolytic anaemia may develop following IVIg therapy due to intensification of RBC sequestration. Patients treated with
intravenous immunoglobulins must be monitored for the appearance of signs and symptoms of haemolysis.
Neutropenia/Leucopenia
Transient reduction of 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.
Acute lung injury associated with transfusion (TRALI)
Some cases of non-cardiogenic acute pulmonary oedema [transfusion-related acute lung injury (TRALI)] have been reported in patients treated with IVIg. TRALI is characterised by severe hypoxaemia,
dyspnoea, tachypnoea, cyanosis, fever and hypotension. Symptoms associated with TRALI typically develop
during the transfusion or within 6 hours after the transfusion, often within 1-2 hours. Therefore, subjects
receiving IVIg must be monitored and IVIg infusion must be stopped immediately in
case of adverse pulmonary reactions. TRALI is a life-threatening condition requiring immediate admission to intensive care.
Interference with serological tests
After the administration of immunoglobulins, the temporary increase of various passively transferred antibodies in the patient's blood may lead to false positive results in serological tests.
Passive transfer of antibodies anti-erythrocyte antigens, for example A, B, D, may falsify some
serological tests for anti-erythrocyte antibodies, for example the direct antiglobulin test (direct

antiglobulin test, DAT, direct Coombs test).

Special precautions for handling
Pentaglobin may be mixed only with 0.9% NaCl solution.