PLITAGAMMA <50 MG/ML Infusion solution

Зміст інструкції

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

Plitagamma 50 mg/ml solution for infusion

Normal human immunoglobulin for intravenous use (IVIg)

Read this leaflet carefully before you start 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.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What is Plitagamma and what is it used for

What is Plitagamma
Plitagamma is a human normal immunoglobulin solution for intravenous use. This
medicinal product belongs to the group of medicines called intravenous immunoglobulins. Immunoglobulins are human antibodies that are also present in the blood.

What is Plitagamma used for
They are used in the treatment of conditions in which the immune system is not functioning properly.
In particular, it is used for:

Treatment of adults, children and adolescents (2-18 years) who do not have a sufficient level of
antibodies (replacement therapy) in the following cases:

• Patients with congenital deficiency in antibody production (Primary Immunodeficiency Syndrome - PID)
• Patients with acquired deficiency in antibody production (secondary immunodeficiencies, AIDS) with severe or recurrent infections, ineffective antibiotic treatment and who have demonstratedinability to produce specific antibodies (PSAF)*or blood IgG levels < 4 g/l *PSAF = inability to produce at least a 2-fold increase in IgG antibody titers to pneumococcal vaccines with polysaccharide and polypeptide antigen.

Treatment of adults, children and adolescents (2-18 years) with autoimmune alterations from some
inflammatory diseases (immunomodulation), in the following situations:

• Patients who do not have sufficient platelets (Primary Immune Thrombocytopenia, ITP), who are at high risk of bleeding or before surgery to correct the platelet count.
• Patients with Guillain Barré syndrome. This is an acute disease, characterized by inflammation of the peripheral nerves, which causes severe muscle weakness, especially in the legs and upper limbs.
• Patients with Kawasaki disease (in combination with acetylsalicylic acid). This is an acute disease that mainly occurs in childhood, characterized by inflammation of blood vessels (arteries) throughout the body.
• Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), a rare and progressive disease that causes weakness of the limbs, numbness, pain and fatigue.
• Multifocal Motor Neuropathy (MMN), a rare disease that causes slow, progressive asymmetric weakness of the limbs, without loss of sensation.

2. What you need to know before using Plitagamma

Do not use Plitagamma

• If you are allergic (hypersensitive) to normal human immunoglobulins or to any of the other ingredients of this medicine (listed in section 6).
• If you have a deficiency of immunoglobulin A (IgA) or have developed antibodies against IgA.
• If you have hereditary fructose intolerance, a rare genetic disease in which the enzyme that metabolizes fructose is missing. In newborns and young children (0-2 years) hereditary fructose intolerance (HFI) may not yet have been diagnosed and in this population the administration of Plitagamma may cause death. Therefore, newborns and young children should not receive this medicine (see special warnings about the excipients at the end of this section).

Warnings and precautions
Talk to your doctor or nurse before using Plitagamma.
The doctor or another healthcare professional will monitor you closely and observe you carefully
during the entire period of the infusion with Plitagamma, and for up to one hour after the end of it,
to verify that there are no undesirable reactions.
Some undesirable effects may occur more frequently:

• if the infusion rate is too high;
• if you suffer from a condition with low levels of antibodies in the blood (hypo- or agammaglobulinemia, with or without IgA deficiency);
• if you receive normal human immunoglobulins for the first time, or if your medicine based on normal human immunoglobulins has been changed, or if a long time has passed since the previous intravenous infusion (e.g., several weeks).
• Allergic reactions are rare. However, you may still be allergic (hypersensitive) to immunoglobulins (antibodies) without knowing it.

This can happen even if you have received human immunoglobulins in the past and have tolerated previous
administrations. This is particularly likely if you do not have enough
immunoglobulins of type IgA in your blood (IgA deficiency with anti-IgA antibodies).
Patients with pre-existing risk factors
Tell your doctor if you have any other illness or unfavorable condition, as immunoglobulins
may increase the risk of thromboembolic events, and in particular of myocardial infarction, stroke,
pulmonary embolism or deep vein thrombosis, as they increase blood viscosity.
In particular, tell your doctor if:

• you have diabetes,
• you have high blood pressure (hypertension),
• you have a history of blood vessel diseases (vascular diseases) or thrombotic episodes,
• you are overweight,
• you have a decrease in blood volume (hypovolemia),
• you have diseases that cause increased blood viscosity,
• you are over 65 years old.

Patients with kidney problems
If you have kidney disease, your doctor should consider whether to discontinue treatment, given that
cases of acute renal failure have been reported in patients undergoing IVIg therapy, generally in
the presence of other risk factors.
Effects on blood tests
After receiving Plitagamma, the results of some blood tests may change for a
certain time, corresponding to the time during which the medicine produces its effect. If you are about to have
a blood test after taking Plitagamma, tell the analyst or doctor that you have taken this
medicine.
In case of an adverse reaction, the doctor will decide whether to reduce the administration rate or to
interrupt the infusion. In addition, the doctor will decide the necessary treatment based on the nature and
severity of the adverse effect.
In case of shock, the doctor must perform the standard treatment for shock. Tell the doctor if
you suffer from any of the conditions described above, the doctor will use particular caution when prescribing and
administering Plitagamma.
Viral safety
When medicines are produced from human plasma or blood, precautionary measures are taken to
prevent infections that could be transmitted to patients. These measures include:

• careful selection of plasma and blood donors, to ensure that those at risk of infection are excluded
• testing each donation and each pool of plasma for viruses or infections
• the inclusion of viral inactivation or removal methods in the plasma or human blood processing process.

Despite these measures, when medicines produced from plasma or human blood are administered,
the possibility of transmitting an infection cannot be completely excluded. This applies to all
viruses of unknown origin, emerging viruses or other types of infections.
The measures taken are considered effective for enveloped viruses, such as the human immunodeficiency virus (HIV), hepatitis B and hepatitis C, as well as for non-enveloped viruses, such as hepatitis A and parvovirus B19.
Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections,
probably because the antibodies against these infections contained in the product have a protective effect.
It is strongly recommended that, whenever Plitagamma is administered, the name and batch number of the medicine are recorded, to maintain a record of the batches used.

Children and adolescents
During the infusion of Plitagamma, vital signs (body temperature, blood pressure, heart rate and respiratory rate) must be monitored.
Newborns and young children (0-2 years) may have hereditary fructose intolerance (HFI), a disease that may not yet have been diagnosed by your doctor. Taking
this medicine may cause death, therefore newborns and young children should not receive this
medicine.

Other medicines and Plitagamma

Tell your doctor or pharmacist if you are taking or have recently taken or might
take any other medicines.

• Normal human immunoglobulins for intravenous use must not be mixed with other medicinal products.
• Effects on vaccines: Plitagamma may reduce the effectiveness of some types of vaccines (live attenuated virus vaccines). In the case of rubella, mumps and varicella, a period of up to 3 months must elapse after the administration of this product before receiving those vaccines. In the case of measles, this period is extended to 1 year. The administration of immunoglobulin may alter the effectiveness of live attenuated virus vaccines such as those for measles, rubella, mumps and varicella for up to 3 months, so an interval of three months must elapse before vaccination with live attenuated virus vaccines (rubella, mumps and varicella). In the case of measles, this weakening of the response can last up to a year. Therefore, in patients receiving the measles vaccine, the level of antibodies must be checked.
• During treatment with Plitagamma, concomitant use of medicines that increase urine production (loop diuretics) should be avoided.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant, are planning a pregnancy, or are breastfeeding with
breast milk, ask your doctor or pharmacist for advice before using this medicine.
The medicine has not been studied in pregnancy, therefore this medicine should be administered
with caution to pregnant women and breastfeeding mothers. Intravenously administered immunoglobulins have been shown to cross the placenta and may affect
the fetus, especially after the third trimester. The use of this medicine in pregnant women has not
suggested harmful effects on the course of pregnancy, on the fetus or on the newborn.
After use of this medicine in breastfeeding mothers, the active ingredient
(immunoglobulins) has been detected in milk and this may protect the newborn from external agents that
enter through the mucous membranes.
The use of this medicine in women has not suggested harmful effects on fertility.

Driving and using machines
During treatment, reactions (e.g. dizziness or nausea) may occur that can affect
the ability to drive vehicles and operate machinery. Patients who experience adverse
reactions during treatment should wait for them to resolve before driving vehicles or operating
machinery.

Plitagamma contains sorbitol
This medicine contains 50 mg of sorbitol per ml.
Sorbitol is a source of fructose. If your doctor has diagnosed you (or your child) with hereditary fructose intolerance, a rare genetic disease, you (or your child) should not take this
medicine.
Patients with hereditary fructose intolerance are unable to transform fructose, the accumulation of which
can cause serious side effects.
Before taking this medicine, tell your doctor if you (or your child) suffer from hereditary fructose intolerance or if the child feels unwell, vomits or has unpleasant reactions such as bloating and
stomach cramps or diarrhea when taking sweet foods or drinks.

Plitagamma contains sodium
This medicine contains less than 7.4 mg of sodium (the main component of table salt) per
100 ml. This is equivalent to 0.37% of the recommended maximum daily intake with the diet of an
adult.

3. How to use Plitagamma

Plitagamma can only be administered by doctors or healthcare professionals, via infusion into a
vein.
The dose to be administered depends on your condition and your body weight and will be determined by your
doctor according to your needs (see the section of instructions for healthcare professionals, at the bottom
of this leaflet).
At the beginning of the infusion, you will receive Plitagamma at a low infusion rate
(0.01-0.02 ml/kg/min). If you tolerate it well, the doctor may gradually increase the infusion rate
(up to 0.1 ml/kg/min).

Use in children and adolescents
The dose in children and adolescents (2-18 years) is not different from that of adults, as it
is established based on the disease and the child's body weight.

If you use more Plitagamma than you should
If you are given more Plitagamma than you should, fluid overload may occur and the
blood may become too thick (hyperviscous). This can happen particularly if you are
a risk patient, an elderly patient, or a patient with heart or kidney problems. Tell your
doctor immediately.
Immunoglobulins can increase blood viscosity and increase the risk of heart attack, stroke, pulmonary embolism or deep vein thrombosis.

If you forget to use Plitagamma
Tell your doctor immediately and follow their instructions.
Do not take a double dose to make up for a missed dose.
If you have any questions 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 everyone will experience them.
Rarely, the following side effects have been reported with medicines based on immunoglobulins:

• chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, arthralgia, hypotension and moderate back pain;
• a sudden drop in blood pressure and, in isolated cases, anaphylactic shock, even if you have not shown hypersensitivity during previous administrations;
• cases of non-infectious inflammation of the tissues lining the Central Nervous System (aseptic meningitis syndrome);
• cases of temporary reduction of red blood cells in the blood (reversible hemolytic anemia/hemolysis);
• cases of transient skin reactions;
• increased creatinine levels in the blood (a parameter that measures kidney function) and/or acute renal failure;
• thromboembolic reactions (formation of blood clots), such as: myocardial infarction, pulmonary embolism, deep vein thrombosis, stroke.
• cases of acute transfusion-related lung injury (TRALI) that causes hypoxia (lack of oxygen), dyspnea (difficulty breathing), tachypnea (rapid breathing), cyanosis (lack of oxygen in the blood), fever and hypotension.

Other side effects

Common (may affect up to 1 in 10 infusions):

• headache;
• fever;
• tachycardia (accelerated heartbeat);
• decreased blood pressure (hypotension);
• decreased minimum blood pressure (diastolic hypotension).

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

• positive Coombs test;
• dizziness (cinetosis);
• hypertension (increased blood pressure);
• systolic hypertension (increased maximum blood pressure);
• diastolic hypertension (increased minimum blood pressure);
• finding of increased maximum blood pressure;
• finding of decreased maximum blood pressure;
• finding of increased body temperature;
• bronchitis;
• nasopharyngitis;
• productive cough;
• wheezing;
• abdominal pain (including upper abdominal pain);
• diarrhea;
• vomiting;
• nausea;
• urticaria;
• pruritus;
• itchy rash;
• back pain;
• myalgia (muscle pain);
• arthralgia (joint pain);
• febrile chills (feeling of cold with shivering in the presence of fever);
• pain;
• reaction at the infusion site;
• pain at the infusion site;
• edema at the infusion site;
• infusion-related reaction.

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

• abnormal behavior;
• migraine;
• blood pressure fluctuations;
• hot flashes (redness);
• cough;
• asthma;
• epistaxis (nosebleed);
• nasal discomfort;
• larynx pain;
• contact dermatitis;
• hyperhidrosis (excessive sweating);
• rash;
• muscle spasms;
• neck pain;
• pain in the extremities;
• urinary retention;
• chills;
• asthenia (fatigue);
• erythema at the infusion site;
• extravasation at the infusion site;
• inflammation at the infusion site;
• pruritus at the infusion site;
• peripheral edema;
• increased alanine aminotransferase (liver transaminase).

Additional side effects in children and adolescents
Compared to adults, a higher percentage of headache, fever,
increased heart rate and low blood pressure have been observed in children.
Assessment of vital signs such as body temperature, heart rate, respiratory
rate and blood pressure in studies on children did not show significant variations
in this population.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please tell
your doctor, pharmacist or nurse. You can also report side effects directly to
adverse .
By reporting side effects, you can help provide more information on the safety of
this medicine.

5. How to store Plitagamma

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 packaging after
“Exp.”.
Do not store at a temperature above 30 ºC. Do not freeze.
The solution must be clear or slightly opalescent. Do not use this medicine if you notice that the
solution is cloudy or contains sediment.
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 Plitagamma Contains

• The active ingredient is normal human immunoglobulin (IVIg). One ml contains 50 mg of normal human immunoglobulins, of which at least 97% consists of IgG.

One 10 ml vial contains: 0.5 g of normal human immunoglobulin
One 50 ml vial contains: 2.5 g of normal human immunoglobulin
One 100 ml vial contains: 5 g of normal human immunoglobulin
One 200 ml vial contains: 10 g of normal human immunoglobulin
One 400 ml vial contains: 20 g of normal human immunoglobulin
Percentage distribution of IgG subclasses (approximate values):
IgG 66.6%
IgG 28.5%
IgG 2.7%
IgG 2.2%
The IgA content is less than 50 micrograms/ml.
Produced from plasma of human donors.

• The other components are D-sorbitol and water for injections (see section 2 for further information on the components).

Description of the Appearance of Plitagamma and Contents of the Pack
Plitagamma is a solution for infusion, clear or slightly opalescent, colorless or pale yellow.
Plitagamma is supplied in:

• Type II glass vial with a stopper (chlorobutylated rubber or chlorobutylated-isoprenic rubber) containing 10 ml of solution
• Type II glass vials with a stopper (chlorobutylated rubber or chlorobutylated-isoprenic rubber) containing 50 ml, 100 ml, 200 ml, or 400 ml of solution

Pack size: 1 vial.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Instituto Grifols, S.A.
Can Guasch, 2 - Parets del Vallès
08150 Barcelona - SPAIN

The following information is intended exclusively for healthcare professionals (for further
information see section 3):
Dosage and Administration
The dose and dosage regimen depend on the indication.
The dose must be adapted to the specific needs of each patient, which are dictated by the
clinical response. The dose based on body weight may require adjustment in underweight or overweight patients.
The recommended dosages are summarised in the following table:

Plitagamma must be administered intravenously at an initial rate of
0.01-0.02 ml/kg/min for the first thirty minutes. If well tolerated, the administration rate may
be gradually increased to a maximum of 0.1 ml/kg/minute.

Paediatric population
Plitagamma is contraindicated in children from 0 to 2 years of age.
Since the dosage for each indication is calculated based on body weight and must
be adjusted based on the clinical outcome of the aforementioned conditions, the dosage in
children and adolescents (2-18 years) is not considered different from that of adults.

Incompatibilities
In the absence of compatibility studies, this medicine must not be mixed with other medicines.
Plitagamma must not be mixed with other drugs or intravenous fluids and must be
administered via a separate intravenous line.

Special Warnings
Sorbitol
One ml of this medicine contains 50 mg of sorbitol.
This medicine should not be administered to patients with hereditary fructose intolerance, as
medicines containing sorbitol/fructose administered intravenously can be life-threatening in these patients.
The medical history of patients should be collected with particular attention to symptoms of hereditary fructose intolerance before administering this medicine.
Hereditary fructose intolerance may not yet be diagnosed in children under 2 years of age. Plitagamma is contraindicated in children under 2 years of age.
In case of accidental administration and suspected fructose intolerance, administration must
be stopped immediately, normal blood glucose must be restored and organ function must be stabilised by intensive care therapy.
No interference with blood glucose determination is expected.

Sodium
This medicine contains less than 7.4 mg of sodium per 100 ml, equivalent to 0.37% of the maximum
recommended daily intake by the WHO, which corresponds to 2 g of sodium for an adult.
It is strongly recommended that, whenever Plitagamma is administered, the name and batch number of the product are recorded, to maintain traceability between the patient and the batch used.

Instructions for Handling and Disposal
The product must be brought to room temperature (not exceeding 30 °C) before use.
The solution must be clear or slightly opalescent. Do not use Plitagamma if you notice that the
solution is cloudy or contains sediment.
Unused medicine and waste derived from such medicine must be disposed of in accordance with
current local regulations.