Plitalfa

Package leaflet: Information for the user

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

1. What Plitalfa is and what it is used for

Plitalfa belongs to a class of compounds known as protease inhibitors.
Human alpha-protease 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-protease inhibitor, an imbalance occurs between the alpha-protease inhibitor and elastase. This imbalance 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.
Plitalfa is used to restore the balance between human alpha-protease inhibitor and elastase in the lungs, thereby preventing the worsening of pulmonary emphysema.
Plitalfa is indicated for chronic therapy in patients with alpha-protease inhibitor deficiency in specific forms as diagnosed by your doctor.

2. What you need to know before using Plitalfa

Do not use Plitalfa

• if you are allergic (hypersensitive) to the active substance, alpha*1-proteinase inhibitor, or to any of the other components of Plitalfa (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 Plitalfa.
• Inform your doctor if you have severely weakened heart function (heart failure). Special care is needed, as Plitalfa may cause a temporary increase in blood volume.

Allergic reactions (hypersensitivity)
Rarely, hypersensitivity reactions to Plitalfa may occur even if you have previously tolerated the alpha*1-proteinase inhibitor well in earlier administrations.
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 this medicine, inform your doctor or nurse immediately.

Information on safety regarding the risk of infections
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 donors at risk of transmitting infections are excluded,
• testing for markers of viruses/infections in individual donations and plasma pools,
• inclusion of steps in the manufacturing process 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. Infection with parvovirus B19 may be severe in pregnant women (fetal infection) and in individuals with weakened immune systems or certain forms of anemia (e.g. sickle cell anemia or hemolytic anemia).
If you are treated regularly or repeatedly with plasma-derived proteinase inhibitors, your doctor may recommend that you consider vaccinations against hepatitis A and B.
It is strongly recommended that each time Plitalfa is administered to you, the product name and batch number are recorded, in order to maintain traceability of the batch used.

Smoking
Since the effectiveness of Plitalfa 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 Plitalfa in children and adolescents under 18 years of age.

Other medicines and Plitalfa
No interactions between Plitalfa 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 Plitalfa during pregnancy. Inform your doctor if you are pregnant or planning to become pregnant.
It is not known whether Plitalfa is excreted in human milk. Consult your doctor if you are breastfeeding.

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

Plitalfa contains sodium
Plitalfa 1,000 mg contains approximately 110.4 mg of sodium (the main component of table salt). In a patient weighing 75 kg, the recommended dose corresponds to 24.84% of the maximum daily sodium intake recommended in the 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 Plitalfa

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

Home treatment
After the initial infusions, a healthcare provider may administer Plitalfa, but only after having received adequate training. Your treating physician will decide whether you are suitable for home treatment and will ensure that the healthcare provider 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 the measures to be taken if such reactions occur (see also section 4).

Dosage
The amount of Plitalfa you receive is based on your body weight.
A weekly dose of 60 mg of active substance per kg of body weight (which, for a patient weighing 75 kg, corresponds to 180 mL of reconstituted infusion solution containing 25 mg/mL of human alpha -proteinase inhibitor) is usually sufficient to maintain protective levels of alpha -proteinase inhibitor in serum, thereby preventing further progression of pulmonary emphysema.
Your treating physician will determine the duration of treatment. Currently, there are no recommendations regarding the need to limit the duration of treatment.
If you feel that the effect of Plitalfa is too strong or too weak, discuss this with your doctor or pharmacist.

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

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

If you forget to use Plitalfa

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

If you stop using Plitalfa
If treatment with Plitalfa is discontinued, your condition may worsen. If you decide to stop treatment with Plitalfa earlier than planned, consult your treating physician.
If you have any questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Plitalfa can cause side effects, although not everyone experiences them.
If side effects occur during Plitalfa infusion, the infusion must be paused or stopped depending on the nature and severity of the side effects.

Possible serious side effects

Rarely (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 to prior infusions.

Immediately inform your doctor or nurse if you experience any of the following signs:

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

The doctor or healthcare provider will decide whether to slow down or completely stop the infusion and will initiate any necessary 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 Plitalfa:

Uncommon (may affect up to 1 in 100):

• 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):

• 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):

• Anaphylactic shock

Reporting of side effects

If you experience any side effect, including those not listed in this leaflet, talk to 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 Plitalfa

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 should 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 Plitalfa after the expiry date stated on the vial label and packaging.

6. Package contents and other information

What Plitalfa contains

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

Description of the appearance of Plitalfa and the contents of the pack
The alpha-1-proteinase inhibitor is a white, light yellow or light brown hygroscopic 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 the reconstituted solution contains 25 mg of alpha-1-proteinase inhibitor.
The Plitalfa 1,000 mg powder and solvent for infusion solution pack contains:

• 1 vial containing 1,000 mg of human alpha-1-proteinase inhibitor powder.
• 1 vial containing 40 mL of solvent (water for injections).
• 1 transfer device for reconstitution.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Grifols Italia S.p.A.
Via Torino, 15
56010 Vicopisano
Pisa – ITALY
Manufacturer:
Instituto Grifols, S.A.
Can Guasc, 2 - Parets del Vallès
08150 Barcelona - SPAIN

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

1. Perform 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 Plitalfa powder and solvent (sterile water for injections) are at room temperature (20–25°C).
3. Remove the protective caps from the Plitalfa vial and the solvent vial, and clean the rims and stoppers with an alcohol swab. Allow the rubber stoppers to dry.

4. Open the sterile packaging of the transfer device by completely removing the lid. Do not remove the device from the packaging.	5. Place the solvent vial upright on a flat surface and hold it firmly. Without removing the outer packaging, push the blue end of the transfer adapter downward until the tip penetrates the stopper and clicks into place. Do not rotate.	6. Remove and discard the transparent outer packaging from the transfer adapter.
7. Place the Plitalfa powder vial upright on the surface. Invert the transfer adapter and solvent vial assembly by 180°. Push the transparent/white end of the adapter downward—without rotating—until the tip penetrates the stopper and clicks into place.	8. Due to the vacuum in the powder vial, the solvent transfer will begin automatically. Wait for the complete transfer of the solvent. Remove the adapter with the attached solvent vial by tilting it at an angle of approximately 45°.	9. Gently swirl the Plitalfa vial until the powder is completely dissolved. Do not shake, to avoid foaming. Do not touch the stopper. Proceed with aseptic administration of the product.

10. If more than one vial is required to obtain the desired 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.
Use only a solution that is clear to slightly opalescent, colourless, or pale green, pale yellow, or pale brown, and free from visible particles.
Plitalfa 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 as a slow intravenous infusion using a suitable 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.