Respreeza

Package leaflet: Information for the user

Respreeza 1000 mg powder and solvent for solution for infusion, 4000 mg powder and solvent for solution for infusion, 5000 mg powder and solvent for solution for infusion

Human alpha-proteinase inhibitor
Please read all of this leaflet carefully before you use 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 or healthcare professional.
• 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 or healthcare professional. See section 4.

Contents of this leaflet:

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

1. What Respreeza is and what it is used for

What Respreeza is
This medicine contains as its active substance human alpha -proteinase inhibitor, which is a normal
component of blood found in the lungs. In the lungs, its main function is to protect lung tissue by
limiting the activity of a specific enzyme called neutrophil elastase. Neutrophil elastase can cause
damage if its activity is not kept under control (for example, if you have an alpha -proteinase inhibitor deficiency).

What Respreeza is used for
This medicine is used in adults with severe alpha -proteinase inhibitor deficiency (an inherited disease also known as alpha -antitrypsin deficiency) who have developed a lung disease called emphysema.

Emphysema occurs when a lack of alpha -proteinase inhibitor leads to a condition in which neutrophil elastase is not properly controlled, damaging the small air sacs in the lungs through which oxygen passes into the body. Due to this damage, the lungs do not function properly.
By using this medicine regularly, levels of alpha -proteinase inhibitor in the blood and lungs increase, thereby slowing the progression of emphysema.

2. What you should know before using Respreeza

Do not take Respreeza

• if you are allergic to alpha-proteinase inhibitor or to any of the other ingredients of this medicine (listed in section 6).
• if you have been found to have a deficiency of certain blood proteins called immunoglobulin A (IgA) and have developed antibodies against them.

Warnings and precautions
Talk to your doctor or healthcare professional before using Respreeza.
Information about allergic reactions: when might it be necessary to slow down or stop the infusion?
You may be allergic to human alpha-proteinase inhibitor even if you have previously taken alpha-proteinase inhibitors and tolerated them well. In some cases, severe allergic reactions may occur. Your doctor will inform you about the signs of allergic reactions (for example, chills, flushing, rapid heartbeat, drop in blood pressure, dizziness, rash, hives, itching, difficulty breathing or swallowing, as well as swelling of the hands, face, or mouth) (see also section 4).
Immediately inform your doctor or healthcare professional if you experience any of these reactions during infusion of the medicine. Depending on the nature and severity of the reaction, your doctor may decide to slow down or completely stop the infusion and initiate appropriate treatment.
If you are self-administering the medicine or receiving treatment at home, immediately stop the infusion and contact your doctor or healthcare professional.

Information on safety regarding infections
Respreeza is derived from human plasma (the liquid part of blood, from which cells have been removed).
Since blood can transmit infections, when medicines are made from human blood or plasma, certain measures are taken to prevent infections from being present in the medicine and transmitted to patients. These measures include:

• careful selection of blood and plasma donors to ensure that those at risk of carrying infections are excluded,
• testing of donated blood and plasma samples to avoid using material showing signs of viruses/infections,
• inclusion in the processing of blood or plasma of steps that can inactivate or remove viruses.

The measures taken are considered effective against viruses such as human immunodeficiency virus (HIV), hepatitis A virus, hepatitis B virus, hepatitis C virus, and parvovirus B19.
However, despite these measures, when medicines prepared from human blood or plasma are administered, the possibility of transmitting an infection cannot be completely ruled out. This also applies to unknown or emerging viruses or other types of infections.
Your doctor may advise you to consider vaccination against hepatitis A and B if you regularly/repeatedly receive plasma-derived proteinase inhibitors.
It is strongly recommended to record the name and batch number of the product each time you receive a dose of Respreeza, to keep a record of the batches used.

Smoking
Since tobacco smoke is a major risk factor for the development and progression of emphysema, it is strongly advised to stop smoking and to avoid passive smoking.

Children and adolescents
This medicine must not be used in children and adolescents under 18 years of age.

Other medicines and Respreeza
Inform your doctor or healthcare professional if you are taking, have recently taken, or might take any other medicines.

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or healthcare professional for advice before taking this medicine.
Since alpha-proteinase inhibitor is a normal component of human blood, the recommended dose of this medicine is not expected to harm the unborn baby. However, because there are no available data on the safety of Respreeza during pregnancy, this medicine should be given during pregnancy only with caution.
It is not known whether Respreeza passes into breast milk. If you are breastfeeding, your doctor will discuss with you the risks and benefits of taking this medicine.
There are no data regarding the effect on fertility, but since alpha-proteinase inhibitor is a normal component of human blood, no adverse effects on fertility are expected when using Respreeza at the recommended dose.

Driving and using machines
Dizziness may occur after administration of this medicine. If you feel dizzy, do not drive or operate machinery until the dizziness has resolved (see section 4).

Respreeza contains sodium
This medicine contains approximately 37 mg of sodium per 1000 ml vial of Respreeza, 149 mg of sodium per 4000 ml vial of Respreeza, and 186 mg of sodium per 5000 ml vial of Respreeza, equivalent to 1.9%, 7.4%, and 9.3% respectively of the maximum daily intake of 2 g of sodium recommended by the WHO for adults. Your doctor or healthcare professional will take this into account if you are on a sodium-controlled diet.

3. How to use Respreeza

After reconstitution, Respreeza is administered by intravenous infusion. The first infusions will be supervised by a healthcare professional experienced in the treatment of alpha-\proteinase inhibitor deficiency.

Home treatment/self-administration
After the initial infusions, you or your caregiver may administer Respreeza, but only after receiving adequate training. If your doctor decides that you are suitable for home treatment/self-administration, they will teach you:

• how to prepare and administer the medicine (see the illustrated instructions at the end of this leaflet in the section "Information for healthcare professionals and patients eligible for home treatment/self-administration")
• how to keep the product sterile (aseptic infusion techniques)
• how to maintain a treatment diary
• how to recognize adverse reactions, including signs of allergic reactions, and the actions to take if these occur (see also section 2 and section 4).

Your doctor or healthcare professional will regularly review the infusion technique used by you or your caregiver to ensure that treatment is being performed appropriately.

Dosage
The amount of Respreeza you receive is based on your body weight. The recommended dose is 60 mg per kg of body weight, administered once weekly.
The infusion solution is usually administered over approximately 15 minutes (approximately 0.08 ml of solution per kg of body weight per minute). Your doctor will determine the appropriate infusion rate for you, based on your body weight and your tolerance to the infusion.

If you use more Respreeza than you should
The consequences of an overdose are unknown.
Inform your doctor or healthcare professional if you think you have used more Respreeza than prescribed.
Your doctor or healthcare professional will take appropriate measures.

If you forget to use Respreeza
Take the next dose as soon as possible and continue at regular intervals as directed by your doctor or healthcare professional.
Do not take a double dose to make up for a missed dose.

If you stop using Respreeza
Do not stop treatment with this medicine without consulting your doctor or healthcare professional. If treatment with Respreeza is stopped, your condition may worsen.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. These side effects may occur even if you have previously taken alpha-proteinase inhibitors and tolerated them well.
Some side effects may be serious:
Allergic reactions have been observed uncommonly (may affect up to 1 in 100 people). Such reactions may progress, very rarely (may affect up to 1 in 10,000 people), to severe allergic reactions, even if you did not show signs of allergy during previous infusions.
Immediately inform your doctor or healthcare professional if you notice signs of allergic reactions (for example, chills, flushing, rapid heartbeat, drop in blood pressure, dizziness, rash, itching, hives, difficulty breathing or swallowing, and swelling of the hands, face, or mouth) during administration of Respreeza. Depending on the nature and severity of the reaction, your doctor or healthcare professional may decide to slow down or completely stop the infusion and initiate appropriate treatment for the reaction.
If you are self-administering or receiving treatment at home, immediately stop the infusion and contact your doctor or healthcare professional.

Other side effects may include:
Commonly (may affect up to 1 in 10 people)
Dizziness, headache, shortness of breath (dyspnea), nausea.
Uncommonly (may affect up to 1 in 100 people)
Altered sensation of touch with burning, tingling, or numbness in the hands, arms, legs, or feet (paraesthesia), flushing, hives, scaly skin rash, and rash all over the body, physical weakness (asthenia), infusion site reactions (such as burning, stinging sensation, pain, swelling, or redness at the infusion site (haematoma)).
Very rarely (may affect up to 1 in 10,000 people)
Reduced sensation of touch with burning, tingling, or numbness in the hands, arms, legs, or feet (hypoesthesia), excessive sweating (hyperhidrosis), itching, chest pain, chills, fever (pyrexia).
Frequency not known (frequency cannot be estimated from the available data)
Pain in the lymph nodes (oval-shaped tissue masses distributed throughout the body, which may be palpable for example in the armpit, groin, or neck areas), facial swelling, swelling of the eyes and lips.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or healthcare professional. You can also report side effects directly via the national reporting system at https://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 Respreeza

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the outer carton and on the labels of the vials after Exp. The expiry date refers to the last day of that month.
Do not store above 25°C. Do not freeze.
After reconstitution, the solution should be used immediately. If this is not possible, solutions may be stored for up to 3 hours at room temperature (up to 25°C). Do not freeze the reconstituted solution.

6. Package Contents and Other Information

What Respreeza Contains

• The active substance is human alpha1-proteinase inhibitor. One vial contains approximately 1000 mg, 4000 mg, or 5000 mg of human alpha1-proteinase inhibitor.
• The other components are sodium chloride, monosodium phosphate monohydrate, and mannitol (see section 2). Solvent: Water for injections.

Description of the Appearance of Respreeza and Contents of the Package
The medicine is a white to off-white powder.
After reconstitution with water for injections, the solution should be clear, colorless to pale yellow, and free from visible particles.
Presentations:
A package contains:
Respreeza 1000 mg powder and solvent for solution for infusion:

• 1 single-use vial containing powder
• 1 solvent vial containing 20 ml of water for injections
• 1 transfer set 20/20 (Mix2Vial set) for reconstitution

Respreeza 4000 mg powder and solvent for solution for infusion:

• 1 single-use vial containing powder
• 1 solvent vial containing 76 ml of water for injections
• 1 transfer set 20/20 (Mix2Vial set) for reconstitution
  Administration set (inner box):
• 1 intravenous infusion set
• 1 butterfly device
• 3 alcohol-impregnated swabs

Respreeza 5000 mg powder and solvent for solution for infusion:

• 1 single-use vial containing powder
• 1 solvent vial containing 95 ml of water for injections
• 1 transfer set 20/20 (Mix2Vial set) for reconstitution
  Administration set (inner box):
• 1 intravenous infusion set
• 1 butterfly device
• 3 alcohol-impregnated swabs

Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
CSL Behring GmbH
Emil-von-Behring-Strasse 76
D-35041 Marburg
Germany
For further information about this medicinal product, contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
CSL Behring NV CentralPharma Communications UAB Tel:
Tél/Tel: +32 15 28 89 20 +370 5 243 0444
България Luxembourg/Luxemburg
МагнаФарм България CSL Behring NV
Тел: +359 2 810 3949 Tél/Tel: +32 15 28 89 20
Česká republika Magyarország
CSL Behring s.r.o. CSL Behring Kft.
Tel: +420 702 137 233 Tel.: +36 1 213 4290
Danmark Malta
CSL Behring AB AM Mangion Ltd.
Tlf: +46 8 544 966 70 Tel: +356 2397 6333
Deutschland Nederland
CSL Behring GmbH CSL Behring BV
Tel: +49 6190 75 84810 Tel: +31 85 111 96 00
Eesti Norge
CentralPharma Communications OÜ CSL Behring AB
Tel: +3726015540 Tlf: +46 8 544 966 70
Ελλάδα Österreich
CSL Behring ΕΠΕ CSL Behring GmbH
Τηλ: +30 210 7255 660 Tel: +43 1 80101 1040
España Polska
CSL Behring S.A. CSL Behring Sp. z.o.o.
Tel: +34 933 67 1870 Tel.: +48 22 213 22 65
France Portugal
CSL Behring SA CSL Behring Lda
Tél: +33 1 53 58 54 00 Tel: +351 21 782 62 30
Hrvatska România
Marti Farm d.o.o. Prisum Healthcare S.R.L.
Tel: +385 1 5588297 Tel: +40 21 322 01 71
Ireland Slovenija
CSL Behring GmbH EMMES BIOPHARMA GLOBAL s.r.o.-
Tel: +49 6190 75 84700 podružnica v Sloveniji
Tel:+ 386 41 42 0002
Ísland Slovenská republika
CSL Behring AB CSL Behring Slovakia s.r.o.
Sími: +46 8 544 966 70 Tel: +421 911 653 862
Italia Suomi/Finland
CSL Behring S.p.A. CSL Behring AB
Tel: +39 02 34964 200 Puh/Tel: +46 8 544 966 70
Κύπρος Sverige
CSL Behring EΠE CSL Behring AB
Τηλ: +30 210 7255 660 Tel: +46 8 544 966 70
Latvija
CentralPharma Communications SIA
Tel: +371 6 7450497

More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.

The following information is intended exclusively for healthcare professionals and patients
eligible for home treatment/self-administration
General Instructions

• Reconstitution must be performed according to the instructions provided below.
• The product must be reconstituted, administered, and handled carefully using aseptic technique to maintain sterility.
• Do not use the sterile support devices supplied for reconstitution and administration if their packaging is open or damaged.
• The powder must be reconstituted with the solvent (water for injections).
• Complete reconstitution of the powder must be achieved within 5 minutes (1000 mg presentation) or 10 minutes (4000 mg and 5000 mg presentations).
• Inspect the reconstituted solution for the presence of particles and discoloration prior to administration.
• The reconstituted solution must be clear, colorless to slightly yellow, and free from visible particles.

Follow the steps below for the preparation and reconstitution of Respreeza:

1. Ensure that the Respreeza vial and the vial of water for injectable preparations are at room temperature (up to 25°C).
2. Remove the plastic flip-off cap from the vial of water for injectable preparations.
3. Clean the rubber stopper of the water for injectable preparations vial with an antiseptic such as an alcohol-impregnated swab and allow it to dry.
4. Open the Mix2Vial set by removing the lid (Figure 1). Do not remove the Mix2Vial set from its packaging.	Figure 1
5. Place the vial of water for injectable preparations on a clean, flat surface and hold it firmly. Take the Mix2Vial set with its packaging and vertically pierce the water vial with the blue tip of the Mix2Vial set (Figure 2).	Figure 2
6. Carefully remove the packaging from the Mix2Vial set by gripping the edge and pulling it vertically upward. Make sure to remove only the packaging and not the Mix2Vial set (Figure 3).	Figure 3
7. Remove the plastic flip-top cap from the Respreeza vial.
8. Clean the rubber stopper of the Respreeza vial with an antiseptic such as an alcohol-impregnated swab and allow it to dry.
9. Place the Respreeza vial on a flat, stable surface. Invert the water vial connected to the Mix2Vial set and vertically pierce the Respreeza vial with the transparent tip of the Mix2Vial set (Figure 4). The water for injectable preparations will automatically flow into the Respreeza vial. NOTE: Ensure that all the water has been transferred into the Respreeza vial.	Figure 4
10. Follow the steps below to remove the entire Mix2Vial set from the Respreeza vial: •With one hand, firmly hold the Respreeza vial as shown in Figure 5. •With the other hand, firmly hold the water vial for injectable preparations and the blue part of the Mix2Vial set. •Bend the entire Mix2Vial set to one side until it disconnects from the Respreeza vial (Figure 5). Dispose of the water vial for injectable preparations together with the entire Mix2Vial set.	Figure 5
11. Gently rotate the Respreeza vial until the powder is completely dissolved (Figure 6). DO NOT SHAKE. Avoid touching the rubber stopper of the vial.	Figure 6
12. Visually inspect the reconstituted solution. The solution should be clear, colorless to slightly yellow, and free of visible particles. Do not use solutions that are discolored, cloudy, or contain particles.
13. If more than one Respreeza vial is required to achieve the required dose, repeat steps 1 to 11 above using an additional kit containing an unused Mix2Vial set. Use a separate, unused Mix2Vial set and a vial of water for injectable preparations for each Respreeza vial.
14. Reconstituted solutions may be administered sequentially directly from the vial, or alternatively, the reconstituted solutions may be transferred prior to administration into an infusion container (e.g., intravenous infusion bag or glass vial; not supplied) using a commercially available intravenous transfer set (not supplied). Use an aseptic technique when transferring the reconstituted solution into an infusion container.

Administration
The reconstituted solution must be administered using an intravenous infusion set (supplied with the 4000 mg and 5000 mg packs).

1. Ensure that both the vent cap and the flow regulator of the intravenous infusion set are closed. Pierce the Respreeza vial VERTICALLY with the tip of the intravenous infusion set by gently rotating the tip, or connect it to an infusion container.
2. Raise the Respreeza vial/infusion container or hang it on an infusion stand.
3. Prime the drip chamber by squeezing it until the Respreeza solution fills the chamber to approximately half full.
4. Open the vent cap of the intravenous infusion set.
5. Slowly open the flow regulator of the intravenous infusion set and allow the Respreeza solution to flow until it reaches the end of the tubing, ensuring no air bubbles remain.
6. Close the flow regulator.
7. Disinfect the injection site with an antiseptic such as an alcohol-impregnated swab before carefully inserting the butterfly needle into the vein. Ensure that no air bubbles remain in the rest of the butterfly device tubing.
8. Connect the end of the intravenous infusion set to the butterfly device and reopen the flow regulator.
9. Infuse the reconstituted solution into the vein. The solution should be infused at an infusion rate of approximately 0.08 ml per kg of body weight per minute, adjusted according to your response and comfort. The recommended dose of 60 mg per kg of body weight will require approximately 15 minutes for infusion.

A Respreeza vial is for single use only.
Any unused medicine and waste material derived from this medicine must be disposed of as directed by your doctor or healthcare professional.