Package Leaflet: Information for the User

Plangamma 100mg/mlInfusion Solution

Normal Human Immunoglobulin (igiv)

Read this leaflet carefully before you start using this medicine, because it contains important information for you.

-Keep this leaflet, as 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. It may harm them.

-If you experience any side effects, talk to your doctor, pharmacist or nurse. See section 4.

1.What isPlangammaand what it is used for

2.What you need to know beforeusingPlangamma

3.How to usePlangamma

4.Possible side effects

5.Storage ofPlangamma

6.Contents of the pack and additional information

What isPlangamma

Plangammacontains normal human immunoglobulin. This medication belongs to a class of medications called intravenous immunoglobulins. These are used to treat conditions in which the immune system does not function correctly in the face of diseases.

What is it used forPlangamma

Treatment in adults, children, and adolescents (2-18 years) who lack sufficient antibodies (replacement therapy). There are two groups:

• Patients with Primary Immunodeficiency Syndrome (SIP), a congenital deficiency of antibodies (group 1).

• Patients with Secondary Immunodeficiency Syndrome (SIS) in patients who suffer from severe or recurrent infections, who do not respond to antimicrobial treatment and whohave demonstrated a deficiency of specific antibodies (PSAF)*or a serum level of <4

*PSAF= inability to duplicate the antibody titer of IgG against the pneumococcal polysaccharide and polypeptide antigens.

Treatment in adults, children, and adolescents (2-18 years) with certain autoimmune diseases (immunomodulation). They are classified into five groups:

• Primary immune thrombocytopenia, when the number of platelets in the bloodstream is drastically reduced. Platelets are an important part in the coagulation process, and a reduced number of platelets can cause bleeding and hematomas. This product is also used in patients with a high risk of bleeding or before a surgical intervention, to increase the number of platelets.

• Guillain-Barré Syndrome, in which the immune system attacks the nerves and prevents them from functioning correctly.

• Kawasaki Disease (in this case, in combination with acetylsalicylic acid), a childhood disease in which the blood vessels (arteries) of the body become enlarged.

• Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), a rare and progressive disease that causes weakness in the limbs, numbness, pain, and fatigue.

• Multifocal Motor Neuropathy (MMN), a rare disease that causes slow, asymmetric, progressive weakness in the limbs without sensory loss.

No usePlangamma

• If you are allergic to human immunoglobulins or to any other component of this medication (including those listed in section 6).

• If you have a deficiency of IgA immunoglobulin in your blood or have developed antibodies to IgA.

• If you have fructose intolerance, a rare genetic disorder in which the enzyme responsible for breaking down fructose is not produced. In babies and young children (0-2 years), hereditary fructose intolerance (HFI) may not have been diagnosed and could be fatal, so they should not receive this medication. (See special precautions on excipients at the end of this section).

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Plangamma.

Some adverse reactions may occur more frequently:

• if administered at a high infusion rate.
• if you have hypogammaglobulinemia or agammaglobulinemia (a condition characterized by low levels of immunoglobulin in the blood) with or without IgA deficiency.
• if you receive Plangamma for the first time, or have changed from a normal human immunoglobulin product (IgIV), or have had a long period of time (e.g. several weeks) since the last infusion. You will be closely monitored for up to one hour after the infusion to detect possible adverse reactions.

Allergic reactions are rare. These may occur in isolated cases if you do not have sufficient IgA immunoglobulin in your blood or if antibodies to IgA have developed.

Patients with pre-existing risk factors

Please inform your doctor if you have any other underlying medical condition and/or disease, as patients with pre-existing risk factors for thrombotic events require increased caution. In particular, inform your doctor if you have:

• diabetes
• high blood pressure
• history of vascular disease or thrombotic events
• obesity
• decreased blood volume
• diseases that increase blood viscosity
• age 65 years or older

Patients with kidney problems

If you have kidney problems, your doctor should consider whether to suspend treatment, as cases of acute kidney failure have been reported in patients receiving IgIV, usually in patients with risk factors.

Consult your doctor, even if any of the circumstances mentioned above have occurred at any time.

Effects on blood tests

After receiving Plangamma, the results of certain blood tests (serological tests) may be altered for some time. If you have a blood test after receiving Plangamma, please inform the analyst or your doctor that you have received this medication.

Special safety precautions

When medications are prepared from human blood or plasma, a series of measures must be taken to prevent the possible transmission of infections to patients. These measures include:

• a careful selection of blood and plasma donors to ensure the exclusion of donors at risk of infection,

• analysis of each donation and plasma mixture to detect possible viruses or infections,

• inclusion of a series of steps in the processing of blood or plasma that can inactivate or eliminate viruses.

Despite these measures, when medications are prepared from human blood or plasma, it is not possible to rule out the transmission of infections completely. This also applies to unknown or emerging viruses and other types of infections.

The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, and for non-enveloped viruses of hepatitis A and parvovirus B19.

Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections, possibly because the antibodies against these infections, as contained in the medication, are protective.

It is highly recommended that each time Plangamma is administered to a patient, the name of the medication and the batch number administered be recorded in order to maintain a relationship between the patient and the product batch.

Children and adolescents

Monitor vital signs (body temperature, blood pressure, heart rate, and respiratory rate) during the infusion of Plangamma.

Use of Plangamma with other medications

?Inform your doctor or pharmacist if you are taking or have recently taken other medications.

?Effects on vaccines: Plangamma may reduce the effectiveness of certain types of vaccines (live attenuated virus vaccines). In the case of rubella, mumps, and varicella, a period of up to 3 months should elapse after receiving this medication and before receiving these vaccines. In the case of measles, the period is up to 1 year.

• Concomitant use with medications that increase water excretion from the body (diuretics) should be avoided during treatment with Plangamma.

Pregnancy and lactation

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

Driving and operating machinery

Patients may experience reactions (such as dizziness or nausea) during treatment that may affect their ability to drive and operate machinery.

Plangamma contains sorbitol

This medication contains 50 mg of sorbitol per ml. If your doctor has informed you that you suffer from intolerance to some sugars, contact them before using this medication.

In people over 2 years with difficulty tolerating fructose, a spontaneous reaction to foods containing fructose may occur, which can lead to the following symptoms: vomiting, gastrointestinal disturbances, apathy, growth retardation, and weight loss. Therefore, patients should be examined for symptoms of hereditary fructose intolerance before receiving Plangamma.

Plangamma contains sodium

This medication contains less than 23 mg of sodium (1 mmol) per vial; this is,essentially“sodium-free”. However, depending on the required dose, the patient may receive more than one vial.

Plangamma is for intravenous administration (venous injection). You can administer it yourself if you have previously received complete training from hospital staff. You must perform the infusion exactly as you have been taught to avoid the presence of germs. Never administer an injection when alone; always have an adult present.

The dose you receive will depend on your illness and your weight and will be calculated by your doctor (see section “Instructions for healthcare professionals” at the end of the prospectus).

At the beginning of the infusion, you will receivePlangammaat a low speed(0.01ml/kg/min). If you tolerate it well, your doctor may gradually increase the infusion speed(up to 0.08ml/kg/min).

Use in children

The dose in children is not considered to be different from that of adults, as it depends on the illness and the child's weight.

If you receive morePlangammathan you should

If you receive morePlangammathan you should, your body may suffer from fluid overload. This can occur especially if you are a high-risk patient, for example if you are elderly or have cardiac or renal problems. Consult your doctor immediately.

If you forgot to usePlangamma

Consult your doctor or pharmacist immediately and follow their instructions.

You should not administer a double dose to compensate for a missed dose.

If you have any other questions about the use of thismedication, ask your doctor,pharmacistor nurse.

Like all medicines, Plangammacan cause side effects, although not everyone will experience them.

In isolated cases, the following adverse reactions have been described with immunoglobulin preparations.Inform your doctor if you experience any of the following adverse reactions during or after infusion:

• Brisk descent of blood pressure and, in isolated cases, anaphylactic shock (whose symptoms are skin rash, hypotension, palpitations, wheezing, cough, sneezing and difficulty breathing, among others), even in patients who have not shown hypersensitivity to previous administrations.
• Temporal non-infectious meningitis (whose symptoms are headache, fear or sensitivity to light, neck stiffness).
• Temporal reduction in the number of red blood cells in the blood (reversible hemolytic anemia/hemolysis).
• Transient skin reactions (skin adverse reactions).
• Increased serum creatinine levels (test that measures kidney function) and/or acute kidney failure (whose symptoms are lower back pain, fatigue, decreased urine output).
• Thromboembolic reactions such as myocardial infarction (pressure in the chest area with a sensation that the heart is beating very quickly), stroke (weakness in the face, arms or legs, difficulty speaking or understanding others when they speak), pulmonary embolism (shortness of breath, chest pain and fatigue) and deep vein thrombosis (pain and swelling in a limb).
• Acute transfusion-related lung injury (TRALI, in English) that causes hypoxia (lack of oxygen), dyspnea (difficulty breathing), tachypnea (rapid breathing), cyanosis (lack of oxygen in the blood), fever and decreased blood pressure.

Other side effects:

Very common (may affect more than 1 in 10 people):

• Headache

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

• Tachycardia (increased heart rate)
• Hypotension (decreased blood pressure)
• Nausea
• Back pain
• Muscle pain
• Pain
• Fever (increased body temperature)
• Tremors (sensation of chills)

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

• Common cold (flu)
• Urinary tract infection
• Decreased red and white blood cells
• Loss of appetite
• Dizziness
• Radicular syndrome (neck or back pain and other symptoms such as numbness, tingling and weakness in arms and legs)
• Vasovagal syncope (temporary loss of consciousness)
• Tremors
• Conjunctivitis (inflammation of the conjunctiva of the eyes)
• Maculopathy (disease of the macula, in the retina of the eyes)
• Photophobia (excessive sensitivity to light)
• Ear pain
• Dizziness
• Increased or decreased blood pressure
• Flush (redness)
• Hematoma
• Thrombosis
• Nasal discharge (excess mucus)
• Pain in the nasal passages
• Wheezing
• Abdominal pain (including upper abdominal pain and abdominal distension)
• Diarrhea
• Flatulence
• Vomiting
• Acne
• Ecchymosis (hematoma on the skin)
• Erythema (redness of the skin)
• Pruritus
• Skin rash
• Arthralgia (joint pain)
• Muscle spasms or muscle stiffness
• Neck pain
• Pain in the limbs
• Thoracic discomfort/male
• Sensation of cold
• Fatigue
• Chills
• Reaction associated with injection and reaction at the injection site (including erythema, pain, itching and swelling at the infusion site)
• Fatigue
• Nervous state
• Pseudogripal syndrome
• Discomfort
• Peripheral edema
• Decreased hemoglobin
• Increased heart rate

Unknown frequency (cannot be estimated from available data):

• Dyspnea (difficulty breathing)
• Rubefaction (redness of the skin)

Other side effects in children and adolescents

It was observed that the proportion of headache, chills, fever, nausea, vomiting, decreased blood pressure, increased heart rate and back pain was higher in children than in adults.A case of cyanosis (lack of oxygen in the blood) was reported in a child, but not in adults.

The side effects may decrease if Plangamma 100mg/mlis administered instead of Plangamma 50 mg/ml. Consult your doctor if the side effects increase.

Reporting of side effects

If you experience any type of side effect, consultyour doctor,pharmacistor nurse,even if it is a possible side effect that does not appear in this leaflet.You can also report them directly through theSpanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keepthis medicationout of the sight and reach of children.

Do not usethis medicationafter the expiration date that appears on the label and carton after CAD.

Do not store at a temperature above30 °C. Do not freeze.

The solution must be transparent or slightly opalescent. Do not usethis medicationif the solution is cloudy or has sediment.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of containers and medications you no longer need. In this way, you will help protect the environment.

Composition ofPlangamma

-The active principle is normal human immunoglobulin (IgIV). One ml contains 100mg of normal human immunoglobulin, of which at least 97% is IgG.

Each vial of 50ml contains: 5g of normal human immunoglobulin

Each vial of 100ml contains: 10g of normal human immunoglobulin

Each vial of 200ml contains: 20g of normal human immunoglobulin

The percentage of IgG subclasses is approximately 66.6%IgG1, 27.9%IgG2, 3.0%IgG3and 2.5%IgG4. The IgA content is less than 100micrograms/ml.

-The remaining components are sorbitol and water for injectable preparations (see section 2 for more information on components).

Appearance of the product and contents of the container

Plangammais a perfusion solution.The solution is transparent or slightly opalescent, colorless or pale yellow.

Plangamma is presented in vials of 5g/50ml, 10g/100ml and 20g/200ml.

Container size: 1vial

Only some container sizes may be marketed.

Marketing authorization holder and manufacturer responsible

Grifols, S.A.

Can Guasc, 2 - Parets del Vallès

08150 Barcelona - Spain

Last review date of thisleaflet 03/2020

The detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.es/

This information is intended solely for healthcare professionals (see section 3 for more information):

Dosage and administration

The dose and dosing regimen depend on the indication.

A personalized dosing regimen may be necessary for each patient based on clinical response. The dose based on body weight may require adjustment in patients with low body weight or obesity. The following dosing regimen may be used as a guide.

The recommended dosage is described in the following table:

Plangamma should be administered intravenously at an initial rate of0.01ml/kg/min for the first 30minutes. If well tolerated, increase the rate to 0.02ml/kg/min for the next 30minutes. Again, if well tolerated, increase the rate to 0.04ml/kg/min for the third 30minutes. If the patient tolerates the administration, the rate can be increased by 0.02ml/kg/min at 30minute intervals, up to a maximum of 0.08ml/kg/min.

It has been proven that the frequency of IgIV adverse reactions increases with infusion rate. The infusion rate should be slow in initial administrations. If no adverse reactions occur, the infusion rate for subsequent administrations can be gradually increased to reach the maximum rate. For patients who have experienced adverse reactions, it is recommended to reduce the infusion rate in subsequent administrations, limiting the maximum rate to 0.04ml/kg/min or administering IgIV at a concentration of 5%.

Pediatric population

Since the dosage for each indication is based on body weight and adjusted according to clinical response, the dosage in children does not differ from that recommended for adults.

Incompatibilities

Plangamma should not be mixed with other medications or intravenous solutions and should be administered through a separate intravenous route.

Special precautions

Sorbitol

Each ml of this medicine contains 50mg of sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.

In infants and young children (0-2 years), fructose intolerance may not have been diagnosed and could be fatal, so they should not receive this medicine.

In people over 2 years of age with fructose intolerance, a spontaneous aversion to fructose-containing foods may develop, leading to the appearance of some symptoms (such as vomiting, gastrointestinal disturbances, apathy, growth retardation and weight loss). Therefore, a detailed history of symptoms of fructose intolerance should be taken for each patient before receiving Plangamma.

If administered without this check and fructose intolerance is suspected, the infusion should be stopped immediately, the blood glucose level should be restored to normal, and the patient's organ function should be stabilized with intensive care.

No interference with blood glucose level determination is expected.

It is highly recommended that each timePlangammais administered to a patient, the name of the medicine and the batch number administered should be recorded to maintain a relationship between the patient and the product batch.

Handling and disposal instructions

The product should reach room temperature(not exceeding 30°C)before use.

The solution should be transparent or slightly opalescent. Do not use Plangamma if the solution is turbid or contains sediment.

The elimination of unused medicine and all materials that have come into contact with it will be carried out in accordance with local regulations.