Rimphisia

Package Leaflet: Information for the User

Rymphysia, 500 mg, powder and solvent for solution for infusion

Rymphysia, 1000 mg, powder and solvent for solution for infusion

Human alpha1-proteinase inhibitor
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. To find out more, see section 4.

Read all of 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 further questions, ask your doctor or pharmacist.
• 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 or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

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

1. What Rymphysia is and what it is used for

What Rymphysia is

This medicine contains the active substance human alpha1-proteinase inhibitor, which is a normal component of human blood and is found in the lungs. Its main function in the lungs is to protect lung tissue by inhibiting the action of a certain enzyme called neutrophil elastase. Neutrophil elastase can cause damage if its action is not controlled (for example, if the patient has a deficiency of alpha1-proteinase inhibitor).

What Rymphysia is used for

This medicine is used in adults with a diagnosed severe deficiency of alpha1-proteinase inhibitor (also known as alpha1-antitrypsin deficiency), who have developed a lung disease called emphysema. Emphysema occurs when the lack of alpha1-proteinase inhibitor leads to a condition in which neutrophil elastase is not properly controlled, causing damage to the small air sacs in the lungs through which oxygen enters the body. As a result of this damage, the lungs do not function properly.
Regular use of this medicine increases the concentration of alpha1-proteinase inhibitor in the blood and lungs, thereby protecting the lungs, limiting the action of neutrophil elastase, and thus slowing the progression of emphysema. It should not be expected that the medicine will reverse the damage that has already occurred.

2. What you need to know before you use Rymphysia

When not to use Rymphysia

• if you are allergic to human alpha1-proteinase inhibitor or any of the other ingredients of this medicine (listed in section 6).
• if you have been found to have a deficiency of immunoglobulins A (IgA) in your blood and you have antibodies against these immunoglobulins.

If any of the above applies to you, do not use Rymphysia.

Warnings and precautions

Before starting treatment with Rymphysia, discuss it with your doctor or other healthcare professional.

Information on allergic reactions

You may be allergic to Rymphysia, even if you have previously received similar medicines and tolerated them well.

• In some cases, a severe allergic reaction may occur.
• Your doctor will inform you about the symptoms of allergic reactions (such as chills, fever, rapid heartbeat, low blood pressure, dizziness, rash, hives, itching, difficulty breathing or swallowing, as well as swelling of the hands, face, or mouth) - see also "Allergic reactions" in section 4.
• If the reaction is severe, your doctor may decide to reduce the infusion rate or discontinue the infusion altogether. Then, they may administer appropriate treatment for the symptoms of the allergic reaction.

Tell your doctor or other healthcare professional immediately if you notice any of the above reactions during the infusion. If you are being treated at home and/or self-administering, stop the infusion immediately and contact your doctor or other healthcare professional.

Risk of infection

Rymphysia is made from human blood plasma (the liquid part of the blood from which the blood cells have been removed).
When medicines are made from human blood or plasma, certain measures are taken to prevent the transmission of infections to patients. These include:

• careful selection of blood and plasma donors to ensure that donors who may be carrying infections are excluded,
• testing each donated sample and plasma pools for signs of infection,
• including steps in the manufacturing process that inactivate or remove viruses.

However, despite these precautions, when medicines are prepared from human blood or plasma, it cannot be completely excluded that the transmission of an infection may occur. This also applies to unknown or new viruses or 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, as well as non-enveloped viruses such as hepatitis A virus and parvovirus B19.
To improve the identification of biological medicinal products, the name and batch number of the administered product should be clearly recorded.
If you are regularly/repeatedly receiving alpha-proteinase inhibitors from human plasma, your doctor may recommend that you consider vaccination against hepatitis A and B.
Smoking
Tobacco smoke is a significant risk factor for the development and progression of emphysema, so it is strongly recommended to quit smoking and avoid passive smoking.

Children and adolescents

This medicine is not intended for use in children and adolescents under 18 years of age.

Rymphysia and other medicines

Tell your doctor or other healthcare professional about all medicines you are taking, have recently taken, or might take, including those obtained without a prescription and herbal medicines.
This is necessary because Rymphysia may affect the action of some other medicines. Also, some medicines may affect the action of Rymphysia.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or other healthcare professional for advice before taking this medicine.
Because alpha1-proteinase inhibitor is a normal component of human blood, it is not expected that the recommended dose of this medicine will have a harmful effect on the developing fetus.
However, due to the lack of available data on the safety of Rymphysia during pregnancy, if you are pregnant, this medicine should only be used with caution.
It is not known whether Rymphysia passes into human breast milk. If you are breastfeeding, your doctor will discuss the risks and benefits of using this medicine with you.
There are no data on the effects on fertility, but since alpha1-proteinase inhibitor is a normal component of human blood, no adverse effect on fertility is expected when Rymphysia is used at the recommended dose.

Driving and using machines

Rymphysia may have a minor influence on the ability to drive and use machines. If you experience dizziness or fatigue, do not drive or operate tools or machines.

Rymphysia contains sodium

Rymphysia, 500 mg, powder and solvent for solution for infusion:

• The medicine contains 108 mg of sodium (the main component of common salt) per vial of 25 ml solution. This corresponds to 5.4% of the maximum recommended daily intake of sodium in the diet for adults.

Rymphysia, 1000 mg, powder and solvent for solution for infusion:

• The medicine contains 216 mg of sodium (the main component of common salt) per vial of 50 ml solution. This corresponds to 10.8% of the maximum recommended daily intake of sodium in the diet for adults.

3. How to use Rymphysia

Rymphysia is administered by intravenous infusion. The first infusions of the medicine will be supervised by a healthcare professional with experience in the treatment of alpha1-proteinase inhibitor deficiency.

Treatment at home and/or self-administration by the patient

After the first infusions of Rymphysia, the medicine may be administered by the patient themselves or their caregiver, but only after receiving proper training. If your doctor decides that you can use the treatment at home and/or self-administer the medicine, they will train you or your caregiver in the following:

• how to prepare and administer the medicine (see the instructions at the end of this leaflet),
• how to maintain asepsis (rules for performing infusions under aseptic conditions),
• how to keep a treatment diary,
• how to recognize side effects, including symptoms of allergic reactions and what measures to take in case of such effects (see also section 2 and section 4).

Your doctor or other healthcare professional will regularly check the patient's and/or caregiver's infusion technique to ensure that the medicine is always properly prepared and administered.

Dose

The dose of Rymphysia administered to the patient depends on their body weight. The recommended dose is 60 mg per kilogram of body weight; this dose should be administered once a week. The infusion will last approximately 15-30 minutes. Your doctor will determine the appropriate dose and infusion rate based on your body weight and tolerance of the infusion.

Overdose

If you think you have used too much Rymphysia, contact your doctor or other healthcare professional, who will decide on the appropriate action. The consequences of overdose are unknown.

Missed dose

If you miss an infusion, take the next dose as soon as possible and continue using the medicine at the regular intervals recommended by your doctor or other healthcare professional.
Do not take a double dose to make up for a missed dose.

Stopping treatment with Rymphysia

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Such side effects may occur even if you have previously received similar medicines and tolerated them well. With this medicine, the following side effects may occur:

Allergic reactions

Tell your doctor or other healthcare professional immediately if you notice any of the following severe side effects during the infusion, as you may need urgent medical attention:

• chills or fever,
• rapid heartbeat, low blood pressure, or dizziness,
• rash, hives, or itching,
• difficulty breathing or swallowing, as well as swelling of the hands, face, or mouth.

Tell your doctor or other healthcare professional immediately if you notice any of the above severe side effects.
If the reaction is severe, your doctor or other healthcare professional may decide to reduce the infusion rate or discontinue the infusion altogether. Then, they may administer appropriate treatment for the symptoms of the allergic reaction.
If you are being treated at home and/or self-administering, stop the infusion immediately and contact your doctor or other healthcare professional.

• Allergic reactions are uncommonand may affect up to 1 in 100 people.
• Severe allergic reactions are rareand may affect up to 1 in 10,000 people.
• Allergic reactions may occur even if no symptoms of allergy have appeared in previous infusions.

Other side effects

Tell your doctor or other healthcare professional immediately if you notice any of the following side effects:
Very common:may affect more than 1 in 10 people

• bronchitis (persistent cough that may produce mucus, wheezing, difficulty breathing);
• upper respiratory tract infection (common cold, flu-like illness);
• headache;
• cough;
• sore throat (throat and larynx pain);

Common:may affect up to 1 in 10 people

• altered sense of taste (taste disturbance);
• discomfort in the head, migraine;
• drowsiness;
• eye disorders (conjunctivitis, eye irritation, and vision disturbances);
• runny nose (rhinitis);
• throat irritation;
• bloating, diarrhea, mouth ulcers, vomiting;
• chest pain or discomfort;
• fever and malaise (flu-like illness);
• pain or discomfort at the infusion site;
• feeling very tired and sleepy;
• discomfort, pain, or tenderness of muscles (muscle pain);
• general feeling of discomfort, illness, or unease - without clear cause (malaise);

Frequency not known:frequency cannot be estimated from the available data

• feeling weak;
• feeling unwell;
• reaction at the infusion site, such as bruising, pain, and rash;

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Side effects can be reported to the Medicines and Healthcare products Regulatory Agency (MHRA) using the Yellow Card Scheme (www.mhra.gov.uk/yellowcard). You can also report side effects directly via the internet at www.mhra.gov.uk/yellowcard. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Rymphysia

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the outer carton and on the label 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. Store in the original package to protect from light.
After reconstitution, the resulting solution should be used immediately. If this is not possible, the solution can be stored at room temperature (up to 25°C) for up to 3 hours. Do not freeze the prepared solution.

6. Contents of the pack and other information

What Rymphysia contains

• Active substanceis human alpha1-proteinase inhibitor. One vial contains approximately 500 mg or 1000 mg of human alpha1-proteinase inhibitor.
• Other ingredientsare: sodium chloride, sodium dihydrogen phosphate monohydrate, and sodium hydroxide.
• Solvent: sterile water for injection.

What Rymphysia looks like and contents of the pack

Powder and solvent for solution for infusion.
This medicine is a white or off-white to light greenish-yellow powder.
After reconstitution with water for injection, the solution should be clear, colorless, or slightly yellow to greenish-yellow and should not contain any visible particles.
One pack contains:
Rymphysia, 500 mg, powder and solvent for solution for infusion:

• One vial of Rymphysia 500 mg powder
• One vial of solvent with 25 ml of sterile water for injection
• One sterile double-ended needle for transfer
• One sterile filter with a pore size of 20 microns

Rymphysia, 1000 mg, powder and solvent for solution for infusion:

• One vial of Rymphysia 1000 mg powder
• One vial of solvent with 50 ml of sterile water for injection
• One sterile double-ended needle for transfer
• One sterile filter with a pore size of 20 microns

Marketing Authorisation Holder

Takeda Pharma Sp. z o.o.
ul. Prosta 68
00-838 Warszawa
Tel.: +48 22 306 24 47
[email protected]

Manufacturer

Takeda Manufacturing Austria AG
Industriestrasse 67
1221 Vienna
Austria

This medicinal product is authorised in the Member States of the European Economic Area under the following names:

Country

Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Italy, Latvia, Luxembourg, Norway, Poland, Portugal, Romania, Spain, Sweden: Rymphysia

Date of last revision of the leaflet: 02/2023.

Information intended for healthcare professionals and trained caregivers and/or patients:

General instructions

• Rymphysia is intended for intravenous use only.
• Reconstitution, administration, and any handling of the product should be carried out with caution and asepsis to maintain the sterility of the product.
• Before reconstitution, allow Rymphysia and the solvent to reach room temperature.
• After reconstitution, Rymphysia should be stored at room temperature and administered within three (3) hours of reconstitution. Partially used vials should be discarded and not stored for future use. The solution does not contain a preservative.
• Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Reconstitution

• 1. Remove the caps from the solvent and product vials.
• 2. Wipe the exposed surfaces of the vial stoppers with alcohol.
• 3. Remove the protective cover from one end of the double-ended transfer needle. Insert the exposed end of the needle through the center of the solvent vial stopper.
• 4. Remove the plastic protective cover from the other end of the double-ended transfer needle, which is embedded in the solvent vial stopper. To minimize foaming, invert the solvent vial and insert the exposed end of the needle through the center of the product vial stopper at an angle, ensuring that the solvent vial remains above the product vial. Insertion at an angle directs the solvent stream to the vial wall. See the diagram below. The vacuum in the vial is sufficient to transfer all of the solvent.
• 5. Separate the two vials by removing the solvent vial from the transfer needle. This equalizes any slight negative pressure that may have developed in the product vial. Then, remove the double-ended transfer needle from the product vial and discard the needle in an appropriate sharps container.
• 6. Stand the vial upright and allow the solution to dissolve; gently rotate the vial until the powder is completely dissolved. Reconstitution takes no more than five (5) minutes for the 500 mg vial and no more than ten (10) minutes for the 1000 mg vial. Note: Do not shake the vial contents. Do not invert the vial until ready to withdraw the solution.
• 7. The reconstituted product is colorless or slightly yellow to greenish-yellow.
• 8. Occasionally, a few small visible particles may remain in the reconstituted product. These will be removed by the sterile filter with a pore size of 20 microns provided with the product.

Administration

• 1. Before administration, inspect the reconstituted product for particulate matter and discoloration.

• 2. The contents of several vials can be transferred to an empty, sterile container for intravenous solutions. This should be done using aseptic technique and a sterile needle that is not provided with the product.
• 3. To minimize the risk of developing harmful microorganisms, Rymphysia should be administered within three (3) hours of reconstitution. Any unused solution should be discarded.
• 4. Rymphysia should be administered separately, without mixing with any other agents or diluents.

Infusion rate

• The recommended infusion rate is 0.08 ml/kg body weight per minute. The infusion rate can be adjusted according to the patient's clinical response and tolerance, but should not exceed 0.2 ml/kg body weight per minute.
• If side effects occur, reduce the infusion rate or stop the infusion. After the symptoms have resolved, the infusion can be restarted at a rate tolerated by the patient.