PIASKY 340 mg INJECTABLE SOLUTION AND PERFUSION SOLUTION

2. What you need to know before you use Piasky

Do not use Piasky

• if you are allergic to crovalimab or any of the other ingredients of this medicine (listed in section 6).
• if you have a meningococcal infection (a serious infection caused by the bacterium Neisseria meningitidisthat can affect the membranes covering the brain and spinal cord and spread through the blood).
• if you have not been vaccinated against meningococcal infection, unless you are going to receive preventive treatment with antibiotics until 2 weeks after receiving this vaccine.

Do not use Piasky if you are in any of the above situations. If you are not sure, consult your doctor, pharmacist, or nurse before using Piasky.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting treatment with Piasky.

Severe meningococcal infections

Piasky may increase the risk of meningococcal infections caused by a bacterium called Neisseria meningitidis, as it blocks a part of the immune system. This includes severe infections such as septicemia (blood poisoning) and meningitis (inflammation of the membranes covering the brain and spinal cord).

• Tell your doctor immediately if you have any of the following symptoms, which may be signs of meningococcal infection:

• Fever
• Feeling unwell (nausea)
• Vomiting
• Headache
• Confusion or irritability
• Stiff back or neck
• Muscle pain, with flu-like symptoms
• Sensitivity to light
• Rashes or spots on the skin

Consult your doctor before starting treatment with Piasky to ensure that your vaccination against meningococcal infections is up to date; it is necessary to have received complete vaccination at least 2 weeks before starting treatment with Piasky. Your doctor may decide that you need to be revaccinated, even if you were vaccinated in childhood.

If you have not received complete vaccination, but need to receive Piasky immediately, you should be vaccinated as soon as possible. To reduce the risk of infection, your doctor will prescribe antibiotics from the moment you start treatment with Piasky until 2 weeks after vaccination.

Vaccination may not always prevent this type of infection. Your doctor may decide that you need additional measures to prevent infection.

Patient Information Card

Your doctor will give you a “Patient Information Card”that mentions the signs of meningococcal infection and sepsis:

• carry it with you at all times during treatment with Piasky, and
• for 11 months after the last dose of Piasky.

Other severe infections

Piasky may also increase the risk of other severe infections, such as infections caused by Streptococcus pneumoniaeand Haemophilus influenzae.

• Tell your doctor, pharmacist, or nurse if you have any of the following symptoms, which may be signs of infection:

• Fever
• Cough
• Chest pain
• Fatigue
• Shortness of breath
• Painful rash
• Sore throat
• Painful urination
• Feeling of weakness or general malaise

Consult your doctor before starting treatment with Piasky to ensure that your vaccinations against Streptococcus pneumoniaeand Haemophilus influenzaeare up to date; it is necessary to have received complete vaccination at least 2 weeks before starting treatment with Piasky. Your doctor may decide that you need to be revaccinated, even if you were vaccinated in childhood.

If you have not received complete vaccination, but need to receive Piasky immediately, you should be vaccinated as soon as possible. To reduce the risk of infection, your doctor will prescribe antibiotics from the moment you start treatment with Piasky until 2 weeks after vaccination.

It is possible that your doctor may recommend that you receive other vaccinations before treatment. Consult your doctor before starting treatment.

Reaction due to switching from another C5 inhibitor

Before using Piasky, tell your doctor if you have ever received treatment with any other C5 inhibitor. This is because you may have a type of temporary reaction, known as an immune complex-mediated type III reaction, during the first 30 days after switching from receiving another C5 inhibitor to receiving Piasky. This can also happen if you stop using Piasky and switch to receiving a different C5 inhibitor.

• Tell your doctor if you have any signs of this type of reaction, such as:

• joint pain or other problems related to muscles, bones, or tissues
• numbness or tingling or a feeling of pins and needles, especially in the hands and feet
• rash or other skin problems
• fever

Infusion and injection reactions

When Piasky is administered by intravenous infusion (drip into a vein) or subcutaneous injection (injection under the skin), you may have infusion or injection reactions. Tell your doctor or nurse immediately if you have any of the following, which may be signs of an infusion or injection reaction:

• Headache
• Back pain
• Pain at the infusion site and other sites
• Swelling
• Bruising or bleeding
• Redness of the skin
• Itching and rash

You may also have an allergic reaction to the infusion or injection. Tell your doctor or nurse immediately if you have any of the following signs of severe allergic reactions:

• Chest tightness or wheezing
• Shortness of breath
• Fever or chills
• Severe dizziness or fainting
• Swelling of the lips, tongue, or face
• Itching of the skin, hives, or rash

If you have had an infusion or injection reaction, including an allergic reaction, you must confirm with your doctor or nurse whether treatment with Piasky should continue or not.

Discontinuation of treatment with Piasky

If you stop treatment with Piasky and do not switch to another treatment for PNH, tell your doctor immediately if you develop symptoms that are signs of intravascular hemolysis (destruction of red blood cells in the blood vessels), including:

• Symptoms of anemia (low red blood cell levels), such as fatigue or lack of energy and dark urine
• Abdominal pain
• Difficulty swallowing
• Difficulty having or maintaining an erection (erectile dysfunction)
• Kidney malfunction
• Blood clot formation with symptoms such as progressive swelling of a leg or difficulty breathing without having performed strenuous activities

Formation of antibodies (immunogenicity)

The immune system may produce antibodies (proteins that the body produces to fight against an unwanted substance) against crovalimab, which may lead to a reduced or lost response to Piasky. You must tell your doctor immediately if you have any of the following symptoms:

• Symptoms of anemia (low red blood cell levels), such as fatigue or lack of energy and dark urine
• Abdominal pain
• Difficulty swallowing
• Difficulty having or maintaining an erection (erectile dysfunction)
• Kidney malfunction
• Blood clot formation with symptoms such as progressive swelling of a leg or difficulty breathing without having performed strenuous activities

Children and adolescents

Do not give Piasky to children under 12 years of age or who weigh less than 40 kg. This is because it has not been studied in this group.

Other medicines and Piasky

Tell your doctor, pharmacist, or nurse if you are using, have recently used, or might use any other medicines.

In particular, you must tell your doctor if you are currently receiving treatment or if you have ever been treated with any other C5 inhibitor. This is because you may have a type of temporary reaction, known as an immune complex-mediated type III reaction (see “Warnings and precautions”).

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

There is no information on the use of Piasky in pregnant women, and the effects on the fetus are unknown. Your doctor will inform you of the possible risks of using Piasky during pregnancy.

If you are breastfeeding, it is unknown whether Piasky passes into breast milk, but considering its characteristics, it is expected to pass into breast milk. Your doctor will inform you of the possible risks of using Piasky during breastfeeding.

Driving and using machines

Piasky has no or negligible influence on the ability to drive and use machines.

3. How to use Piasky

Follow the instructions for administration of this medicine exactly as told by your doctor. If you are not sure, consult your doctor again.

Vaccines administered before using Piasky

At least 2 weeks before starting treatment with Piasky, your doctor will administer a vaccine against meningococcal infections if you have not been vaccinated before or if you are not up to date with vaccination.

If you start treatment with Piasky less than 2 weeks after receiving this vaccine, your doctor will prescribe antibiotics for at least 2 weeks after vaccination to reduce the risk of infection.

How to use Piasky

Piasky is administered by intravenous infusion (drip into a vein) or subcutaneous injection (injection under the skin).

Only the first dose will be administered by intravenous infusion by a healthcare professional. Subsequent doses will be administered by subcutaneous injection. Once you have been taught how to do it, you can self-inject, or your caregiver can administer the subcutaneous injection of Piasky, without medical supervision.

Your doctor or nurse will teach you or your caregiver how to prepare this medicine and how to administer the subcutaneous injections. Read carefully and follow the instructions provided in the “Instructions for use” at the end of this leaflet.

When to use Piasky

A healthcare professional will administer your first dose on day 1. This is the first loading dose and is higher than the doses that will be administered later during treatment. Additional loading doses will be administered on days 2, 8, 15, and 22.

From then on, Piasky will be administered on day 29 and then every 4 weeks by subcutaneous injection. These are the maintenance doses.

If you were previously receiving another medicine for PNH called a “complement inhibitor”, the first loading dose of Piasky should be administered at the time when the next dose of that medicine was scheduled to be administered.

How much Piasky to use

Your doctor will prescribe a dose and treatment plan based on your weight.

If you weigh 40 kg or more, but less than 100 kg:

• The first loading dose on day 1 will be 1,000 mg, administered by intravenous infusion over 60 minutes.
• Subsequent loading doses on days 2, 8, 15, and 22 will be 340 mg, administered by a single subcutaneous injection.
• You will receive a maintenance dose of 680 mg, administered by two subcutaneous injections on day 29 and then every 4 weeks.

If you weigh 100 kg or more:

• The first loading dose on day 1 will be 1,500 mg, administered by intravenous infusion over 90 minutes.
• Subsequent loading doses on days 2, 8, 15, and 22 will be 340 mg, administered by a single subcutaneous injection.
• You will receive a maintenance dose of 1,020 mg, administered by three subcutaneous injections on day 29 and then every 4 weeks.

The maintenance dose may change if your body weight changes during treatment with Piasky. Consult your doctor if your weight exceeds or falls below 100 kg. Your doctor or nurse should continuously monitor your weight.

If you use more Piasky than you should

If you think you have used more Piasky than prescribed, consult your doctor, pharmacist, or nurse.

If you forget to use Piasky

For the treatment to be fully effective, it is very important to use Piasky as prescribed.

• If you do not attend a scheduled appointment with your doctor or nurse to receive the injections, you should schedule another one immediately.
• If you or your caregiver forget to administer part of the dose or the entire dose of Piasky at home, the missed dose or the remainder of the missed dose should be administered as soon as possible, and the next dose should be administered at the usual scheduled time. Do not administer a double dose to make up for the missed dose. If you are unsure, consult your doctor, pharmacist, or nurse.

If you stop treatment with Piasky

Do not stop treatment with Piasky unless you have discussed it with your doctor. This is because stopping treatment will stop the effect of the medicine, which may cause the symptoms of PNH to recur or worsen.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Your doctor will discuss the possible adverse effects and explain the risks and benefits of Piasky before treatment.

Piasky may cause some adverse effects that you should immediately report to your doctor. The most serious adverse effects are meningococcal infection and severe allergic reaction.

• If you have any of the following signs of meningococcal infection, you should immediately inform your doctor:

• Fever
• Discomfort (nausea or vomiting)
• Headache
• Confusion or irritability
• Stiff back or neck
• Muscle pains, with pseudo-flu-like signs or symptoms
• Eye sensitivity to light
• Rashes or spots on the skin

• If you experience any of the following signs of severe allergic reaction, you should immediately inform your doctor:

• Chest tightness or wheezing
• Shortness of breath
• Fever or chills
• Severe dizziness
• Mild fainting
• Swelling of the lips, tongue, or face
• Itching of the skin, hives, or rash

Very common(may affect more than 1 in 10 people):

• Fever
• A reaction due to the change from another C5 inhibitor (type III hypersensitivity mediated by immune complexes; symptoms may include redness, itching, or skin pain)
• Nasal and throat infection (upper respiratory tract). Symptoms may include runny nose, sneezing, irritated throat, and cough
• Infusion reactions
• Headache

Common(may affect up to 1 in 10 people):

• Allergic reactions (hypersensitivity)
• Urinary tract infection
• Lung infection (pneumonia)
• Injection site reaction
• Irritated throat and runny nose (nasopharyngitis)
• Joint pain (arthralgia)
• Abdominal pain
• Diarrhea
• Extreme fatigue/weakness (asthenia)
• Fatigue
• Rash

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

• Bacterial infection (bacteremia)
• Kidney infection (pyelonephritis)
• Severe reaction to an infection (sepsis), which may be accompanied by severe low blood pressure (septic shock)
• Local reaction at the injection site
• Respiratory tract infection

Inform your doctor, pharmacist, or nurse if you experience any of the aforementioned adverse effects. If you are unsure what the aforementioned side effects are, ask your doctor to explain them to you.

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is an adverse effect that is not listed in this prospectus. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Piasky

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

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

Store in a refrigerator (between 2 °C and 8 °C). Once removed from the refrigerator, unopened vials in the original packaging can be stored at room temperature (up to 30 °C) for a maximum of 7 days. Do not freeze.

Keep the vial in the outer packaging to protect it from light.

Do not store loaded syringes of this medicine. Loaded syringes with Piasky should be used immediately.

Do not use this medicine if you notice that it is cloudy, discolored, or contains particles.

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

More details are provided in the "Instructions for use". Read them carefully before using the Piasky vial.

6. Container Contents and Additional Information

Piasky Composition

• The active ingredient is crovalimab. Each glass vial contains 340 mg of crovalimab in 2 ml of solution. Each ml of injectable and infusion solution contains 170 mg of crovalimab.

• The other components are histidine, aspartic acid, arginine hydrochloride, poloxamer 188, and water for injectable preparations.

Product Appearance and Container Contents

Piasky is a clear to very opalescent and almost colorless to yellowish-brown injectable and infusion solution.

Each Piasky container contains 1 glass vial of 2 ml.

Marketing Authorization Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer

Roche Pharma AG

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu.

The leaflet can be found on the European Medicines Agency website in all languages of the European Union/European Economic Area.

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1. Instructions for Use

Before Using the Vial

Read all of these instructions for usebefore you or your caregiver start using the Piasky vial and each time you are prescribed it again. They may contain new information. This information does not replace your doctor's consultation about your illness or treatment.

Your doctor may decide that you or your caregiver can administer the Piasky injections.

• In that case, your doctor or nurse will teach you or your caregiver how to inject the Piasky dose correctly.
• Do notuse the Piasky vial until your doctor or nurse has taught you or your caregiver how to inject it correctly.
• Do notinject the medication into a vein (intravenous injection).

Storage and Handling

• Store the Piasky vial in its original packaging in the refrigerator between 2 °C and 8 °C until it is ready for use.
• Unopened Piasky vials in their original packaging can be stored at room temperature up to 30 °C for a maximum of 7 days.
• Keep the Piasky vial in the outer packaging to protect it from light.
• Once removed from the packaging, keep the Piasky vial away from direct sunlight.
• Keep Piasky vials, syringes, and needles out of the reach of children.
• Each Piasky vial, syringe, and needle can only be used once.
• Keep your hands away from the needle tip during use and disposal.
• Do notfreeze the vial. Do notuse the vial if it has been frozen. Dispose of the vial safely in a puncture-resistant container (see step 43) and contact your doctor or pharmacist.
• Do notuse the vial if it has been at room temperature, up to 30 °C, for more than 7 days. Dispose of the vial safely in a puncture-resistant container (see step 43) and contact your doctor or pharmacist.
• Do notstore loaded Piasky syringes. Any loaded syringe with the medication should be used immediately.
• Do notshake the vial.
• Do notreuse the vial, syringe, or needles for another injection.
• Do notshare the syringe or needles with others.

Full Dose and Number of Injections

Your Piasky dose may require up to 3 consecutive injections. You may need up to 3 Piasky vials to receive a full dose.

• Your doctor or pharmacist will tell you or your caregiver how many injections you need and how often you should inject the medication.
• If the prescribed Piasky dose is 680 mg, administer 2 separate consecutive injections.
• If the prescribed Piasky dose is 1020 mg, administer 3 separate consecutive injections.
• Always use a new Piasky vial for each injection.
• If you are unsure of the dose, ask your doctor or pharmacist.
• Do notsplit your full dose if you do not have all the Piasky vials you need. Contact your doctor or pharmacist.

Materials Needed for 1 Injection

This list is for a single injection.Adjust the number of materials based on the number of injections needed (see the "Full Dose and Number of Injections" section above).

Included in the Packaging:

• 1 Piasky vial

Not Included in the Packaging:

• 18G single-bevel transfer needle or 21G standard needle.
• 25G, 26G, or 27G injection needle with safety protector. The needle length should be between 9 mm (3/8) and 13 mm (½).
• 2 or 3 ml syringe
• 2 alcohol swabs (one for the skin and one for the vial)
• 1 cotton ball or sterile gauze
• 1 small adhesive bandage
• 1 puncture-resistant container (see step 43)

Open the Packaging

1. Remove the required number of Piasky packaging from the refrigerator. Open the packaging and remove the vial(s).

1. Place the vial(s) on a clean and flat surface.

• Do notuse the vial if the packaging is damaged or if the perforation for opening is broken. Dispose of the vial safely in a puncture-resistant container (see step 43) and contact your doctor or pharmacist.

Check the Vial(s)

1. Check the expiration date (EXP) on the vial(s).

1. Check the appearance of the medication.

The medication should be clear to very opalescent and almost colorless to yellowish-brown.

1. Check if the vial(s) have any damage, such as cracks or scratches.

• Do notuse them if the expiration date (EXP) has passed.
• Do notuse it if the medication is cloudy, discolored, or contains particles.
• Do notuse the vial if it is cracked or broken.
• If you notice any of the above, dispose of the vial safely in a puncture-resistant container (see step 43) and contact your doctor or pharmacist.

Warming Time

1. Place the vial(s) on a clean and flat surface for 30 minutes, protected from direct sunlight. This allows the medication to reach room temperature.

If the vial is not at room temperature, the cold medication may make it difficult to extract from the vial and inject later. It could also cause discomfort.

• Do notspeed up the warming process in any way; e.g., in a microwave, with hot water, or by exposing it to direct sunlight.
• Do notremove the vial cap while it reaches room temperature.

Gather the other materials

1. Gather the other materials while the vial reaches room temperature.

This list is for a single injection.Adjust the quantity of materials based on the number of injections needed.

Note: The color of the materials may not be the same as in the images.

• 1 transfer needle
• 1 injection needle with safety protector
• 1 syringe
• 2 alcohol swabs: one for the skin and one for the vial
• 1 cotton ball or sterile gauze
• 1 small adhesive bandage
• 1 puncture-resistant container

Choose the Injection Site

1. Piasky should only be injected into the stomach (abdomen) area.

Make sure not to administer the injection in the same place multiple times.Each injection should be given at a minimum distance of 5 cm from the area used for the previous injection.

• Do notinject into the arm or thigh.
• Do notinject within 5 cm of the navel.
• Do notadminister the injection in moles, scars, or areas where the skin is sensitive, bruised, red, hard, or damaged.

Clean the Injection Site

1. Wash your hands with water and soap.

1. Clean the injection site with an alcohol swab and let it air dry.

• Do nottouch, fan, or blow on the cleaned area.

Clean the Vial Top

1. Remove the color cap from the vial. Dispose of the color cap in the puncture-resistant container (see step 43).

1. Clean the rubber stopper with the other alcohol swab.

• Do nottouch the rubber stopper after cleaning it.

Attach the Transfer Needle

1. Remove the syringe and transfer needle from their packaging.

1. Push and turn the transfer needle until it is fully attached to the syringe.

Do not remove the needle cap.

• Do notuse the injection needle (with the safety protector) to withdraw the medication.

Fill the Syringe with Air

1. With the cap still on the needle, slowly pull the plunger back and fill the syringe with air up to the 2 ml line.

Note: The vial does not contain air. The injected air will facilitate the extraction of the medication and prevent the plunger from moving.

Remove the Transfer Needle Cap

1. Hold the syringe by the center and carefully remove the needle cap from the syringe.

1. Place the cap on a flat surface.

You will need to put the cap back on the needle after transferring the medication.

• Do notdiscard the cap.
• Do nottouch the needle or let the needle touch any surface after removing the cap.

Inject Air into the Vial

1. Hold the vial on a flat surface and insert the entire needle directly into the center of the rubber stopper.

1. Keep the needle in the vial and turn the vial over.

1. Make sure the needle tip is above the medication.

1. With the vial on top, push the plunger to inject air into the vial.

1. Continue pressing down on the plunger with your fingers to prevent it from moving.

• Do notinject air into the medication, as bubbles may form in it.

Transfer All the Medication

1. Slide the needle tip down so that it is inside the medication.

1. Slowly pull the plunger back to transfer all the medicationto the syringe.

• Do notcompletely remove the needle from the vial.
• Do notcompletely remove the plunger from the syringe.

Remove Air Bubbles

1. If you see air bubbles or an air-filled space in the syringe, gently tap the side of the syringe with your finger until the bubbles rise to the top of the syringe.

1. Slowly push the plunger up to return the air bubbles to the vial.

If you introduce some medication into the vial while doing this, slowly pull the plunger back (more slowly this time) to transfer all the medication from the vial (steps 23 and 24).

Replace the Transfer Needle Cap

1. Remove the syringe from the vial.

1. With one hand, place the needle into the cap on a flat surface.

1. Once the needle is covered, lift the syringe and press the cap to ensure it is fully attached to the needle.

• Do nothold the cap with your fingers while sliding the needle into it.

Remove the Transfer Needle

1. Hold the syringe and turn the transfer needle to remove it.