PROLASPLAN 1000 mg POWDER AND SOLVENT FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Prolasplan 1000 mg powder and solvent for solution for infusion

alpha1-antitrypsin

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 further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the package leaflet

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

1. What is Prolasplan and what is it used for

Prolasplan contains alpha1-antitrypsin and belongs to a group of medicines called "protease inhibitors".

Alpha1-antitrypsin is a normal component of human blood, whose function is to inhibit the activity of some enzymes such as elastases that can damage the lungs. When there is a hereditary deficiency of alpha1-antitrypsin, there is an imbalance between alpha1-antitrypsin and elastases. This can lead to progressive destruction of lung tissue and develop pulmonary emphysema. Pulmonary emphysema is an abnormal enlargement of the lung, accompanied by destruction of lung tissue.

Prolasplan is indicated to restore the balance between alpha1-antitrypsin and elastases in the lung, and consequently, prevent further deterioration in pulmonary emphysema.

This medicine is used as chronic treatment in certain types of patients with alpha1-antitrypsin deficiency as determined by their doctor.

2. What you need to know before you use Prolasplan

Do not use Prolasplan

• If you are allergic (hypersensitive) to alpha1-antitrypsin or any of the other components of this medicine (listed in section 6).
• If you have a deficiency of certain immunoglobulins, known as IgA, as severe allergic reactions may develop that can lead to anaphylactic shock.

Warnings and precautions

• Consult your doctor, pharmacist, or nurse before starting to use Prolasplan.
• Tell your doctor if you have severe heart failure (heart failure). Caution is required, as Prolasplan may cause a transient increase in blood volume.

Allergic reactions (hypersensitivity)

Rarely, allergic reactions to Prolasplan may occur, although you have previously been administered human alpha1-antitrypsin inhibitors and have tolerated them well.

Your doctor will inform you about the symptoms of allergic reactions and tell you what to do if you experience them (see also section 4).

If you experience any symptoms of an allergic reaction during the infusion of the medicine, inform your doctor or nurse immediately.

Information on safety regarding the risk of infections

To prevent the transmission of infectious diseases due to the use of medicines derived from human blood or plasma, standard measures are taken that include:

• careful selection of blood and plasma donors to ensure the exclusion of donors at risk of infection,
• analysis of each donation and plasma pool to detect possible viruses or infections
• inclusion of stages in the manufacturing process to inactivate/eliminate viruses.

Despite this, when medicines derived from human blood or plasma are administered, the possibility of transmitting infectious agents cannot be entirely excluded. This also applies to emerging or unknown viruses and other pathogens.

These procedures are considered effective against enveloped viruses, such as the human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus. The inactivation/elimination procedures may have limited value for non-enveloped viruses such as hepatitis A virus or parvovirus B19. Parvovirus B19 infection can have serious consequences in pregnant women (fetal infection) and in patients with immunodeficiency or increased erythropoiesis (e.g., in case of hemolytic anemia).

If you receive chronic treatment with medicines derived from human plasma (such as protease inhibitors), it is recommended that you be vaccinated against hepatitis A and B.

It is strongly recommended that each time you are administered Prolasplan, the name and batch number of the medicine be recorded; this allows tracking of patients who have received each batch of product.

Smoking

Since the efficacy of Prolasplan is compromised by the presence of tobacco smoke in the lungs, it is recommended that patients quit smoking.

Children and adolescents

There is no experience with the use of Prolasplan in children or adolescents under 18 years of age.

Use of Prolasplan with other medicines

No interactions between Prolasplan and other medicines are known.

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

Pregnancy and breastfeeding

Consult your doctor or pharmacist before using a medicine.

There are no controlled clinical trials on the use of this medicine during pregnancy.

Inform your doctor if you are pregnant or think you may be pregnant.

It is unknown whether Prolasplan passes into breast milk, so it should not be administered to women during breastfeeding.

Consult your doctor if you are breastfeeding.

Driving and using machines

No effects on the ability to drive or use machines have been observed.

Prolasplan contains sodium

Prolasplan contains approximately 110.4 mg of sodium (main component of common table salt) per vial. In the case of a 75 kg patient, this is equivalent to 24.84% of the maximum recommended daily sodium intake for an adult. Consult your doctor or pharmacist if you have been advised to follow a low-salt diet.

3. How to use Prolasplan

Follow the instructions for administration of this medicine exactly as indicated by your doctor. If in doubt, consult your doctor again.

Treatment with alpha1-antitrypsin should be performed or supervised by specialist doctors in chronic obstructive pulmonary disease.

After dissolving the powder with the solvent included in the package, the reconstituted solution should be administered by intravenous infusion. A specialist doctor in chronic obstructive pulmonary disease will supervise the first infusions with this medicine.

Dose

The amount of Prolasplan administered is based on your body weight.

A weekly dose of 60 mg of the active substance per kg of body weight is recommended (in the case of a 75 kg patient, this dose is equivalent to 180 ml of the reconstituted solution for infusion and contains 25 mg of human alpha1-antitrypsin per ml).

Your doctor will indicate the duration of your treatment, as the need to limit the duration of treatment has not been established to date.

If you feel that the effect of Prolasplan is too strong or too weak, consult your doctor.

Home treatment

After the first infusions, a specialist doctor may decide that you are suitable for home treatment. The medicine may also be administered by a healthcare professional, but only after receiving adequate training. Your doctor will ensure that the healthcare professional is provided with adequate training regarding:

• how to prepare and administer the reconstituted solution for infusion (see the illustrated instructions at the end of this leaflet,

• how to maintain the product sterile (aseptic infusion techniques),
• how to record the treatment,

• how to identify side effects, including symptoms of allergic reactions and the measures to be taken if such effects occur (see also section 4).

If you use more Prolasplan than you should

The effects of an overdose are unknown to date.

Inform your doctor or healthcare professional if you think you have used more Prolasplan than you should, so they can take the necessary measures. You can also call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount administered.

If you forget to use Prolasplan

• Do not administer a double dose to make up for the missed infusion.
• Consult your doctor if you should administer the missed dose.

If you stop treatment with Prolasplan

If you stop treatment with this medicine, your disease may worsen. Consult your doctor immediately if you want to stop treatment with this medicine.

If you have any further questions on 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.

If side effects occur during the infusion of Prolasplan, the infusion should be suspended or interrupted, depending on the nature and severity of the side effect.

Serious side effects

Rarely, allergic reactions (hypersensitivity) may occur (may affect up to 1 in 1,000 people), and in some very rare cases, these reactions may occur as anaphylaxis of any type (may affect up to 1 in 10,000 people), even if you have not experienced allergy symptoms in previous infusions.

Tell your doctor or nurse immediatelyif you notice any of the following symptoms:

• rash, hives, itching,
• difficulty swallowing,
• swelling of the face or mouth,
• redness,
• difficulty breathing (dyspnea),
• low blood pressure,
• abnormal heartbeat,
• chills

Your doctor or healthcare professional will decide whether to reduce or interrupt the infusion and initiate the necessary treatment.

In the case of home treatment, interrupt the infusion immediatelyand contact your doctor or healthcare professional.

During treatment with Prolasplan, the following side effects have been observed:

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

• Chills, fever, flu-like symptoms, chest pain.
• Hives (urticaria).
• Dizziness, dizziness, headache.
• Difficulty breathing (dyspnea).
• Skin rashes.
• Nausea.
• Joint pain (arthralgia).

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

• Allergic reactions.
• Fast heart rate (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 effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Medicines and Healthcare Products Agency (AEMPS) website: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Prolasplan

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

Store at a temperature below 25°C. Do not freeze.

Do not refrigerate the solution after reconstitution. The reconstituted solution must be used within 3 hours of preparation. Unused product should be discarded.

Do not use this medicine after the expiry date stated on the vial label and carton after EXP. The expiry date is the last day of the month stated.

Do not use the reconstituted solution of this medicine if you notice it is cloudy or has sediment.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

Composition of Prolasplan

• The active substance is human alpha1-antitrypsin (derived from human blood or plasma).
• The other components are sodium chloride, sodium dihydrogen phosphate, water for injections (solvent/diluent).

Appearance of the product and pack contents

Human alpha1-antitrypsin is a white to beige powder.

The reconstituted solution is clear.

1 ml of the reconstituted solution contains 25 mg of human alpha1-antitrypsin.

The Prolasplan pack contains:

• 1 vial with powder containing 1000 mg of human alpha1-antitrypsin.
• 1 vial with 40 ml of solvent (water for injections).
• 1 Mix2Vial transfer device for reconstitution.

Marketing authorisation holder and manufacturer

Instituto Grifols, S.A.

Can Guasc, 2 - Parets del Vallès

08150 Barcelona

Spain

Date of last revision of this leaflet: May 2021

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency for Medicines and Healthcare Products (AEMPS) http://www.aemps.es/

This information is intended for healthcare professionals and patients suitable for home treatment.

Preparation of the reconstituted solution for infusion:

1. Use aseptic conditions (cleaning and disinfection) to maintain sterility. Reconstitute the medicine on a flat work surface during preparation of the solution.
2. Make sure the powder and solvent vials (sterile water for injections) are at room temperature (20-25°C) before use.
3. Remove the protective cap from the powder vial and clean the top of the stopper with an alcohol swab. Let the rubber stopper dry.
4. Repeat this step with the vial of sterile water.
5. Open the sterile package of the Mix2Vial by removing the cap (Figure 1). Do not remove the device from its wrapper.
6. Place the solvent vial in a vertical position on a flat surface. Holding the solvent vial firmly, press the blue terminal of the Mix2Vial downwards until the spike pierces the stopper (Figure 2).
7. Remove the transparent wrapper from the Mix2Vial and discard it (Figure 3).
8. Place the powder vial in a vertical position on a flat surface and invert the solvent vial with the Mix2Vial still attached.
9. Holding the powder vial firmly on a flat surface, press the transparent terminal of the Mix2Vial downwards until the spike pierces the stopper (Figure 4). The solvent will automatically transfer to the powder vial by vacuum.

Note: If the Mix2Vial is connected at an angle, the vacuum in the product vial may be lost, and the solvent may not transfer to the product vial. If the vacuum is lost, use a sterile syringe and needle to draw the sterile water from the solvent vial and inject it into the powder vial, directing the flow against the vial wall.

1. With the solvent and powder vials still attached to the Mix2Vial, gently rotate (Figure 5) until the powder is completely dissolved. Do not shake to avoid foam formation. The reconstituted solution should be clear. Do not use it if you notice particles or abnormal coloration.
2. Since more than one vial of product will be needed to achieve the required dose, repeat the above instructions using an additional package with a new Mix2Vial. Do not reuse the Mix2Vial.
3. Remove the Mix2Vial (Figure 6) and administer the product using aseptic technique.

The total dissolution should be obtained in 5 minutes.

Only clear solutions should be used. Prolasplan should not be mixed with other infusion solutions. The reconstituted solution should be used within 3 hours of preparation.

The reconstituted solution should be administered by slow intravenous infusion, using an infusion set (not included) suitable for this purpose. The infusion rate should be less than 0.08 ml per kg of body weight per minute (equivalent to 6 ml per minute for a 75 kg patient).