Prolastin

Package leaflet: Information for the user

Prolastin

1000 mg powder and solvent for solution for infusion
Human alpha -protease inhibitor
Please read all of this leaflet carefully before you start using this medicine because 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 other people, even if their symptoms seem identical to yours, as it may be harmful to them.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What Prolastin is and what it is used for

Prolastin belongs to a class of compounds known as proteinase inhibitors.
Alpha-1-proteinase inhibitor (alpha-1-PI) is a substance produced by the body that inhibits certain substances known as elastases, which damage the lungs. In the case of an inherited deficiency of alpha-1-PI, an imbalance occurs between alpha-1-PI and elastase. This imbalance may lead to progressive destruction of lung tissue and the development of pulmonary emphysema. Pulmonary emphysema is an abnormal swelling of the lungs accompanied by destruction of lung tissue. Prolastin is used to restore the balance between alpha-1-PI and elastases in the lungs, thereby preventing the progression of pulmonary emphysema.
Prolastin is indicated for chronic therapy in patients with alpha-1-proteinase inhibitor deficiency, as specifically diagnosed by their physician.

2. What you should know before using Prolastin

Do not use Prolastin

• if you are allergic (hypersensitive) to the active substance, alpha-1 proteinase inhibitor, or to any of the other components of Prolastin (listed in section 6).
• if you have a deficiency of certain immunoglobulins (IgA), as severe allergic reactions, up to anaphylactic shock, may occur in such cases.

Warnings and precautions

• Talk to your doctor, pharmacist, or nurse before using Prolastin.
• Inform your doctor if you have severely weakened heart function (heart failure). Special caution is required, as Prolastin may cause a temporary increase in blood volume.

Allergic reactions (hypersensitivity)
Rarely, hypersensitivity reactions to Prolastin may occur even if you have previously tolerated alpha-1 proteinase inhibitor well.
Your doctor will inform you about the signs of allergic reactions and what to do if they occur (see also section 4).
If you experience any signs of an allergic reaction during the infusion of the medicine, inform your doctor or nurse immediately.

Information on safety regarding the risk of infections
When medicines are manufactured from human blood or plasma, special precautions are taken to prevent transmission of infections to patients. These include:

• careful selection of blood and plasma donors to ensure that donors at risk of transmitting infections are excluded,
• testing for markers of viruses/infections in individual donations and plasma pools,
• inclusion of manufacturing steps that are effective in inactivating or removing viruses. Despite these measures, however, the risk of transmitting infections cannot be completely ruled out when administering medicines derived from human blood or plasma. This also applies to unknown or emerging viruses and other types of infections. The measures taken are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus. The measures may have limited effectiveness against non-enveloped viruses such as hepatitis A virus and parvovirus B19. Parvovirus B19 infection may be severe in pregnant women (fetal infection) and in individuals with a weakened immune system or suffering from certain forms of anemia (e.g. sickle cell anemia or hemolytic anemia).

If you are regularly or repeatedly treated with plasma-derived proteinase inhibitors, your doctor may recommend that you consider vaccination against hepatitis A and B.
It is strongly recommended that, each time you are administered Prolastin, the name and batch number of the product be recorded to maintain traceability of the batch used.

Smoking
Since the effectiveness of Prolastin in the lungs may be impaired by tobacco smoke, smoking cessation is strongly recommended.

Children and adolescents
There are no data available on the use of Prolastin in children and adolescents under 18 years of age.

Other medicines and Prolastin
No interactions between Prolastin and other medicines are currently known.
Inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including those not requiring a prescription.

Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
There is no experience with the use of Prolastin during pregnancy. Inform your doctor if you are pregnant or planning to become pregnant.
It is not known whether Prolastin is excreted in breast milk. Consult your doctor if you are breastfeeding.

Driving and using machines
There are no indications that Prolastin impairs the ability to drive or operate machinery.

Prolastin contains sodium
Prolastin 1,000 mg contains approximately 110.4 mg of sodium (the main component of table salt).
For a patient weighing 75 kg, the recommended dose corresponds to 24.84% of the maximum daily sodium intake recommended in an adult diet. Speak with your doctor or pharmacist if you have been advised to follow a low-salt (low-sodium) diet.

3. How to use Prolastin

After reconstitution with the solvent supplied in the package, Prolastin is administered as an intravenous infusion. The first infusions of Prolastin will be supervised by a physician experienced in chronic obstructive lung diseases.

Home treatment
After the initial infusions, Prolastin may also be administered by a healthcare professional, but only after receiving adequate training. Your treating physician will decide whether you are suitable for home treatment and will ensure that the healthcare professional is properly instructed on:

• how to prepare and administer the reconstituted infusion solution (see the illustrated instructions at the end of this leaflet),
• how to maintain sterility of the medicinal product (aseptic infusion techniques),
• how to keep a treatment diary,
• how to recognize adverse reactions, including signs of allergic reactions, and what actions to take if such reactions occur (see also section 4).

Dosage
The amount of Prolastin administered is based on your body weight. A weekly dose of 60 mg of active substance per kg of body weight (which corresponds, for a patient weighing 75 kg, to 180 mL of reconstituted infusion solution containing 25 mg/mL of human alpha*1-proteinase inhibitor) is usually sufficient to maintain protective levels of alpha*1-proteinase inhibitor in serum, thereby preventing further progression of pulmonary emphysema.

Your treating physician will determine the duration of treatment. To date, there are no indications suggesting a need to limit the duration of treatment.

If you feel that the effect of Prolastin is too strong or too weak, discuss this with your doctor or pharmacist.

If you use more Prolastin than you should
The consequences of overdose are not currently known.

• If you think you have used more Prolastin than you should, inform your doctor or healthcare professional, who will take appropriate measures.

If you forget to use Prolastin

• Consult your doctor to determine whether the missed dose should be administered.
• Do not administer a double dose to make up for the forgotten infusion.

If you stop using Prolastin
If treatment with Prolastin is discontinued, your condition may worsen. If you decide to stop Prolastin treatment prematurely, consult your treating physician.

If you have any doubts about the use of this medicinal product, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Prolastin can cause side effects, although not everybody gets them.
If side effects occur during the infusion of Prolastin, the infusion must be slowed down or
stopped according to the nature and severity of the side effects.

Possible serious side effects
In rare cases (may affect up to 1 in 1,000 people), hypersensitivity reactions may occur; in very rare cases (may affect up to 1 in 10,000 people), these reactions may present as anaphylactic reactions of any type, even if you have not shown signs of allergy during previous infusions.
Inform your doctor or nurse immediately if you experience any of the following signs:

• Skin rash, hives, itching,
• Difficulty swallowing,
• Swelling of the face or mouth,
• Flushing,
• Difficulty breathing (dyspnea),
• Drop in blood pressure,
• Changes in heart rate,
• Chills.

The doctor or healthcare professional will decide whether to slow down or completely stop the infusion and will initiate any necessary appropriate treatments.
In case of home treatment, stop the infusion immediately and contact your doctor or healthcare professional.

The following side effects have been observed during treatment with Prolastin:
Uncommon (may affect up to 1 in 100 people):

• Chills, fever, flu-like symptoms, chest pain
• Hives
• Dizziness, sensation of "empty head", headache
• Difficulty breathing (dyspnea)
• Skin rash
• Nausea
• Joint pain (arthralgia)

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

• Hypersensitivity reactions
• Rapid heartbeat (tachycardia)
• Low blood pressure (hypotension)
• High blood pressure (hypertension)
• Back pain

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

• Anaphylactic shock

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor,
pharmacist, or nurse. You can also report side effects directly via the national reporting system at 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 Prolastin

Store below 25°C.
Do not freeze.
The reconstituted solution must not be refrigerated and should always be used within 3 hours after preparation.
Any unused medicine should be discarded.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Keep this medicine out of the sight and reach of children.
Do not use Prolastin after the expiry date stated on the vial label and packaging.
The expiry date refers to the last day of that month.

6. Package contents and other information

What Prolastin contains

• The active substance is human alpha-1-proteinase inhibitor (i.e. derived from human blood or plasma).
• The other components are sodium chloride, sodium dihydrogen phosphate, water for injections (solvent/diluent).

Description of the appearance of Prolastin and contents of the pack
Alpha-1-proteinase inhibitor is a white, light yellow or light brown powder or friable mass.
After reconstitution with water for injections, the solution should be clear to slightly opalescent, colourless, light green, light yellow or light brown, and free from visible particles.
1 mL of reconstituted solution contains 25 mg of alpha-1-proteinase inhibitor.
A single pack of Prolastin 1000 mg, powder and solvent for solution for infusion, contains:

• 1 vial containing 1000 mg of human alpha-1-proteinase inhibitor.
• 1 vial containing 40 mL of solvent (water for injections).
• 1 transfer device for reconstitution.

The multiple pack of Prolastin 1000 mg contains:

• 4 single packs of Prolastin 1000 mg, powder and solvent for solution for infusion.

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

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Prolastin: Austria, Italy, Greece, the Netherlands, Poland, Portugal
Prolastin 1000 mg: France, Germany, Ireland
Prolastina: Croatia, Cyprus, Czech Republic, Denmark, Finland, Norway, Spain, Slovakia, Sweden
Pulmolast 1000 mg: Belgium.
(AIFA): http://www.agenziafarmaco.it.

Information for healthcare professionals and for patients suitable for home treatment:
Preparation of the reconstituted infusion solution:

1. Perform the procedure under aseptic conditions (cleanliness and sanitation) to maintain sterility. Carry out the reconstitution procedure on a flat working surface.
2. Ensure that the vials containing Prolastin powder and the solvent (sterile water for injections) are at room temperature (20–25 °C).
3. Remove the protective caps from the Prolastin vial and from the solvent vial, and wipe the rims and stoppers with an alcohol swab. Allow the rubber stoppers to dry.

10. If more than one vial is required to achieve the required dose, repeat the above instructions using another product package containing a new transfer adapter. Do not reuse the adapter.

Complete dissolution must be achieved within approximately 5 minutes for the 1,000 mg Prolastin presentation.
Use only a solution that is clear to slightly opalescent, colorless, pale green, pale yellow, or
pale brown, and free of visible particles. Prolastin must not be mixed with other infusion solutions.
The reconstituted solution must always be administered within 3 hours after preparation.
The reconstituted solution must be administered by slow intravenous infusion using an appropriate intravenous infusion set (not included). The infusion rate must not exceed 0.08 mL per kg of body weight (equivalent to 6 mL in a 75 kg patient) per minute.

Package leaflet: Information for the user

Prolastin

4 000 mg powder and solvent for solution for infusion
5 000 mg powder and solvent for solution for infusion
Active substance: Human alpha-\protease inhibitor

Please read this leaflet carefully before using this medicine because 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 give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

1. What Prolastin is and what it is used for
2. What you need to know before using Prolastin
3. How to use Prolastin
4. Possible side effects
5. How to store Prolastin
6. Package contents and other information

1. What Prolastin is and what it is used for

Prolastin belongs to a class of compounds known as protease inhibitors.
Alpha-protease inhibitor (alpha-PI) is a substance produced by the body that inhibits certain substances known as elastases, which damage the lungs. In the case of an inherited deficiency of alpha-PI, there is an imbalance between alpha-PI and elastases. This can lead to progressive destruction of lung tissue and the development of pulmonary emphysema. Pulmonary emphysema is an abnormal swelling of the lungs, accompanied by destruction of lung tissue. Prolastin is used to restore the balance between alpha-PI and elastases in the lung, thereby preventing the worsening of pulmonary emphysema.
Prolastin is indicated for chronic therapy in patients with alpha-protease inhibitor deficiency in specific forms as diagnosed by their physician.

2. What you need to know before using Prolastin

Do not use Prolastin

• if you are allergic (hypersensitive) to the active substance, alpha-proteinase inhibitor, or to any of the other components of Prolastin (listed in section 6).
• if you have a deficiency of certain immunoglobulins (IgA), as severe allergic reactions, up to anaphylactic shock, may occur in such cases.

Warnings and precautions

• Talk to your doctor, pharmacist, or nurse before using Prolastin.
• Inform your doctor if you have severely weakened heart function (heart failure). Special caution is required, as Prolastin may cause a temporary increase in blood volume.

Allergic reactions (hypersensitivity)
Rarely, hypersensitivity reactions to Prolastin may occur, even if you have previously tolerated alpha-proteinase inhibitor well. Your doctor will inform you about the signs of allergic reactions and what to do if they occur (see also section 4). If you experience any signs of an allergic reaction during the infusion, inform your doctor or nurse immediately.

Safety information regarding infection risk
When medicines are manufactured from human blood or plasma, particular precautions are taken to prevent transmission of infections to patients. These include:

• careful selection of blood and plasma donors to ensure that donors at risk of transmitting infections are excluded,
• testing for markers of viruses/infections in individual donations and plasma pools,
• inclusion of manufacturing steps that are effective in inactivating or removing viruses.

Despite these measures, however, the risk of transmitting infections cannot be completely ruled out when administering medicines derived from human blood or plasma. This also applies to unknown or emerging viruses and other types of infections.

The measures taken are considered effective against enveloped viruses, such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus. The measures may have limited effectiveness against non-enveloped viruses, such as hepatitis A virus and parvovirus B19. Parvovirus B19 infection may be severe in pregnant women (fetal infection) and in individuals with a weakened immune system or suffering from certain forms of anemia (e.g., sickle cell anemia or hemolytic anemia).

If you are regularly or repeatedly treated with plasma-derived proteinase inhibitors, your doctor may recommend that you consider vaccination against hepatitis A and B.
It is strongly recommended that, each time Prolastin is administered to you, the name and batch number of the product be recorded, in order to maintain traceability of the product batch used.

Smoking
Since the effectiveness of Prolastin in the lungs may be impaired by tobacco smoke, smoking cessation is strongly recommended.

Children and adolescents
There are no available data on the use of Prolastin in children and adolescents under 18 years of age.

Other medicines and Prolastin
No interactions between Prolastin and other medicines are currently known.
Inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including those not requiring a prescription.

Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
There is no experience with the use of Prolastin during pregnancy. Inform your doctor if you are pregnant or planning to become pregnant.
It is not known whether Prolastin is excreted in human milk. Consult your doctor if you are breastfeeding.

Driving and use of machines
There are no indications that Prolastin impairs the ability to drive or operate machinery.

Prolastin contains sodium
Prolastin 4,000 mg contains approximately 441.6 mg of sodium (a main component of table salt).
Prolastin 5,000 mg contains approximately 552.0 mg of sodium (a main component of table salt).
For a patient weighing 75 kg, a recommended dose corresponds to 24.84% of the maximum daily sodium intake recommended in an adult diet. Talk to your doctor or pharmacist if you have been advised to follow a low-salt (low-sodium) diet.

3. How to use Prolastin

After reconstitution with the solvent supplied in the package, Prolastin is administered as an intravenous infusion. The first infusions with Prolastin will be supervised by a physician experienced in chronic obstructive lung diseases.

Home treatment
After the initial infusions, a healthcare provider may administer Prolastin, but only after receiving adequate training. Your treating physician will decide whether you are suitable for home treatment and will ensure that the healthcare provider is instructed on:

• how to prepare and administer the reconstituted infusion solution (see the illustrated instructions at the end of this leaflet),
• how to maintain sterility of the medicine (aseptic infusion techniques),
• how to keep a treatment diary,
• how to recognize adverse reactions, including signs of allergic reactions, and what actions to take should such reactions occur (see also section 4).

Dosage
The amount of Prolastin you receive is based on your body weight. A weekly dose of 60 mg of active substance per kg of body weight (which corresponds, for a patient weighing 75 kg, to 180 mL of reconstituted infusion solution containing 25 mg/mL of human alpha*1-proteinase inhibitor) is usually sufficient to maintain protective levels of alpha*1-proteinase inhibitor in serum, thereby preventing further progression of pulmonary emphysema.

Your treating physician will decide the duration of treatment. To date, there are no indications suggesting a need to limit the duration of treatment.

If you feel that the effect of Prolastin is too strong or too weak, discuss this with your doctor or pharmacist.

If you use more Prolastin than you should
The consequences of overdose are currently unknown.

• If you think you have used more Prolastin than you should, inform your doctor or healthcare provider, who will take appropriate measures.

If you forget to use Prolastin

• Consult your doctor to determine whether the missed dose should be administered.
• Do not take a double dose to make up for the missed infusion.

If you stop using Prolastin
If treatment with Prolastin is stopped, your condition may worsen. If you decide to discontinue treatment with Prolastin prematurely, consult your treating physician.

If you have any doubts about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Prolastin can cause side effects, although not everybody gets them.
If side effects occur during Prolastin infusion, the infusion must be slowed down or stopped depending on the nature and severity of the side effects.

Possible serious side effects
In rare cases (may affect up to 1 in 1,000 people), hypersensitivity reactions may occur; in very rare cases (may affect up to 1 in 10,000 people), these reactions may present as anaphylactic reactions of any type, even if you have not previously shown signs of allergy during prior infusions.

Inform your doctor or nurse immediately if you experience any of the following symptoms:

• Skin rash, hives, itching
• Difficulty swallowing
• Swelling of the face or mouth
• Flushing
• Difficulty breathing (dyspnea)
• Drop in blood pressure
• Changes in heart rate
• Chills

Your doctor or healthcare provider will decide whether to slow down or completely stop the infusion and will initiate any necessary appropriate treatments.
In case of home treatment, stop the infusion immediately and contact your doctor or healthcare provider.

The following side effects have been observed during treatment with Prolastin:
Uncommon (may affect up to 1 in 100 people):

• Chills, fever, flu-like symptoms, chest pain
• Hives
• Dizziness, sensation of "empty head", headache
• Difficulty breathing (dyspnea)
• Skin rash (rash)
• Nausea
• Joint pain (arthralgia)

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

• Hypersensitivity reactions
• Rapid heartbeat (tachycardia)
• Low blood pressure (hypotension)
• High blood pressure (hypertension)
• Back pain

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

• Anaphylactic shock

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please consult your doctor, pharmacist, or nurse. You may also report side effects directly via the national reporting system at 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 Prolastin

Store below 25°C. Do not
freeze.
The reconstituted solution must not be refrigerated and must always be used within 3 hours after preparation. Any unused medicine must be discarded.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Keep this medicine out of the sight and reach of children.
Do not use Prolastin after the expiry date stated on the vial label and packaging. The expiry date refers to the last day of that month.

6. Package contents and other information

What Prolastin contains

• The active substance is human alpha-*1-protease inhibitor (i.e. derived from human blood or plasma).
• The other components are sodium chloride, sodium dihydrogen phosphate, water for injections (solvent/diluent). Description of the appearance of Prolastin and package contents

Alpha-*1-protease inhibitor is a white, light yellow or light brown powder or friable mass.
After reconstitution with water for injections, the solution should be from clear to slightly opalescent, colourless, light green, light yellow or light brown, and free from visible particles.
1 mL of reconstituted solution contains 25 mg of alpha-*1-protease inhibitor.
Single pack contains:
Prolastin 4,000 mg powder and solvent for solution for infusion:

• 1 vial containing 4,000 mg of human alpha-*1-protease inhibitor powder.
• 1 vial containing 160 mL of solvent (water for injections).
• 1 transfer device for reconstitution.

Prolastin 5,000 mg powder and solvent for solution for infusion:

• 1 vial containing 5,000 mg of human alpha-*1-protease inhibitor powder.
• 1 vial containing 200 mL of solvent (water for injections).
• 1 transfer device for reconstitution.

Marketing Authorization Holder and Manufacturer
Instituto Grifols, S.A.
Can Guasch, 2 - Parets del Vallès 08150
Barcelona - SPAIN
This medicinal product is authorized in the European Economic Area Member States under the following
names:
Prolastin [4000 mg/5000 mg]: Austria, Ireland, Italy, France, Germany, Greece, Netherlands, Poland, Portugal
Prolastina [4000 mg/5000 mg]: Croatia, Czech Republic, Denmark, Finland, Norway, Slovakia, Spain, Sweden
Pulmolast [4000 mg/5000 mg]: Belgium.
Detailed information on this medicinal product is available on the website of the Italian Medicines Agency (AIFA): http://www.agenziafarmaco.it .
Information for healthcare professionals and for patients eligible for home treatment:
Preparation of the reconstituted infusion solution:

1. Perform the procedure under aseptic conditions (cleanliness and sanitation) to maintain sterility. Carry out the reconstitution procedure on a flat working surface.
2. Ensure that the vials containing Prolastin powder and the solvent (sterile water for injections) are at room temperature (20 – 25 °C).
3. Remove the protective caps from the Prolastin vial and from the solvent vial, and clean the rims and stoppers with an alcohol swab. Allow the rubber stoppers to dry.

10. If more than one vial is required to achieve the required dose, repeat the instructions above using another product package containing a new transfer adapter. Do not reuse the adapter.

Complete dissolution must be achieved within approximately 15 minutes for Prolastin 4,000 mg or 5,000 mg.
Use only a solution that is clear to slightly opalescent, colorless, pale green, pale yellow, or pale brown,
and free from visible particulate matter. Prolastin must not be mixed with other infusion solutions.
The reconstituted solution must always be administered within 3 hours of preparation.
The reconstituted solution should be administered by slow intravenous infusion using an appropriate intravenous infusion set (not included). The infusion rate must not exceed 0.08 mL per kg of body weight (equivalent to 6 mL in a 75 kg patient) per minute.