ASPAVELI 1080 mg solution for infusion

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, or 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, or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

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

ASPAVELI is a medicine that contains the active substance pegcetacoplan. Pegcetacoplan has been designed to attach to the C3 complement protein, which is a part of the body’s defence system called the ‘complement system’. Pegcetacoplan prevents your body’s immune system from destroying your red blood cells.

ASPAVELI is used to treat adult patients with a disease called paroxysmal nocturnal haemoglobinuria (PNH) who have anaemia as a result of this disease.

In patients with PNH, the ‘complement system’ is overactive and attacks their red blood cells, which can lead to low blood counts (anaemia), tiredness, difficulty in functioning, pain, abdominal pain, dark urine, shortness of breath, difficulty swallowing, erectile dysfunction, and blood clots. By attaching to and blocking the C3 protein, this medicine can stop the complement system from attacking red blood cells and so control symptoms of the disease. This medicine has been shown to increase the number of red blood cells (reduce anaemia), which may improve these symptoms.

• if you are allergic to pegcetacoplan or any of the other ingredients of this medicine (listed in section 6).
• if you have an infection caused by so-called encapsulated bacteria.
• if you are not vaccinated against Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae.

Talk to your doctor, pharmacist or nurse before using ASPAVELI.

Before starting ASPAVELI, inform your doctor if you have any infections.

Because the medicine targets the complement system, which is part of the body’s defences against infection, the use of this medicine increases your risk of infections, including those caused by the so-called encapsulated bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. These are severe infections affecting your nose, throat and lungs or the linings of the brain and can spread throughout the blood and body.

Talk to your doctor before you start ASPAVELI to be sure that you receive vaccination against Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae if you have not had these vaccines in the past. If you have had these vaccines in the past, you might still need additional vaccinations before starting this medicine. These vaccinations should be given at least 2 weeks before beginning therapy. If you cannot be vaccinated 2 weeks beforehand, your doctor will prescribe antibiotics to reduce the risk of infection for 2 weeks after you have been vaccinated. Following vaccination, you may be more closely monitored by your doctor for symptoms of infection.

Infection symptoms

If you experience any of the following symptoms, you should immediately inform your doctor:

• headache and a fever
• fever and a rash
• fever with or without shivers or chills
• shortness of breath
• high heart rate
• clammy skin
• headache with a stiff neck or stiff back
• headache with nausea (feeling sick) or vomiting
• eyes sensitive to light
• muscle aches with flu-like symptoms
• confusion
• extreme pain or discomfort

Make sure that you keep your vaccinations up to date. You should also be aware that vaccines reduce the risk of serious infections, but do not prevent all serious infections. In accordance with national recommendations, your doctor might consider that you need supplementary measures such as antibacterial medicines to prevent infection.

Allergic reactions may appear in some patients. In case of severe allergic reaction, discontinue ASPAVELI infusion and seek medical help immediately. Severe allergic reaction may present as difficulty breathing, chest pain or chest tightness, and/or feeling dizzy/faint, severe itching of the skin or raised lumps on the skin, swelling of the face, lips, tongue and /or throat, which may cause difficulty in swallowing or collapse.

Injection site reactions have been observed with the use of ASPAVELI. You should undergo appropriate training in proper injection technique before self-administering.

During your treatment with ASPAVELI your doctor will perform regular check-ups, including blood tests for lactate dehydrogenase (LDH) levels and tests of renal function, and may adjust your dose if needed.

Use of silica reagents in coagulation tests should be avoided as it can result in artificially prolonged activated partial thromboplastin time (aPTT).

Do not give this medicine to children under 18 years of age as no data are available on its safety and effectiveness in this group.

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

Women of childbearing potential

The effects of the medicine on an unborn child are not known. The use of effective contraception methods is recommended during treatment and up to 8 weeks after treatment by women who are able to get pregnant. Ask your doctor for advice before taking this medicine.

Pregnancy/breast-feeding

ASPAVELI is not recommended during pregnancy and breast-feeding. If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

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

Sorbitol is a source of fructose. If your doctor has told you that you have an intolerance to some sugars or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot break down fructose, talk to your doctor before you take or receive this medicine.

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

The initial recommended dose for adults with PNH is 1 080 mg twice a week. You should take the twice weekly dose on Day 1 and Day 4 of each treatment week. If you are switching to ASPAVELI from another type of PNH medicine, called a C5 inhibitor, you should take ASPAVELI in addition to your current dose of C5 inhibitor as prescribed for 4 weeks. After 4 weeks you should stop taking your C5 inhibitor.

The dose or dosing interval should not be changed without consulting your doctor. Your doctor may adjust your dose to 1 080 mg every third day (e.g., Day 1, Day 4, Day 7, Day 10, Day 13, and so forth) if appropriate. If you think you have missed a dose, speak to your doctor as soon as possible.

ASPAVELI is intended to be given as an infusion (drip) under the skin using an infusion pump. Your first doses of the medicine will be given to you by healthcare professionals in a clinic or treatment centre. If treatment goes well, your doctor may discuss with you the possibility of you giving the medicine yourself at home. If this is appropriate, a healthcare professional will train you or a caregiver how to give the infusion.

The typical infusion time is approximately 30 minutes if you use 2 infusion sites or approximately 60 minutes if using 1 site. The infusion should be started promptly (and completed within 2 hours after preparing the syringe) after drawing this medicinal product into the syringe.

Step 1 Prepare for infusion

Before you start:

1. Remove a single vial carton from the refrigerator. Keep the vial in the carton at room temperature and allow it to warm up for approximately 30 minutes.

a. Do not try to speed up the warming process using a microwave or any other heat source.

2. Find a well-lit, flat work surface area, like a table.
3. Gather your supplies (Figure 1):

A. Syringe system infusion pump and manufacturer’s instructions (not shown)

B. Compatible syringe

C1. Transfer needle OR

C2. Needleless transfer device to draw up product from the vial

D. Infusion set (not shown; varies according to device manufacturer’s instructions)

E. Infusion tubing and Y-connector (if required)

F. Sharps container

G. Alcohol wipes

H. Gauze and tape, or transparent dressing

Thoroughly clean your work surface using an alcohol wipe.

Wash your hands thoroughly with soap and water. Dry your hands.

Step 2 Check the vial and liquid

Remove the vial from the carton. Carefully look at the liquid in the vial. ASPAVELI is a clear, colourless to slightly yellowish liquid. Check for particles or colour changes (Figure 2).

Do not use the vial if:

• The liquid looks cloudy, contains particles, or is dark yellow.
• The protective flip cap is missing or damaged.
• The expiry date (EXP) on the label has passed.

Step 3 Prepare and fill syringe

Remove the protective flip cap from the vial to expose the central portion of the grey rubber stopper of the vial (Figure 3). Throw the cap away.

Clean the stopper with a new alcohol wipe and allow the stopper to dry.

Option 1: If using a needleless transfer device (such as a vial adapter), follow the instructions provided by the device manufacturer.

OR

Option 2: If transfer is done using a transfer needle and a syringe, follow the instructions below:

A. Attach a sterile transfer needle to a sterile syringe.

B. Pull back the plunger to fill the syringe with air, which should be about 20 mL (Figure 4).

C. Make sure the vial is in upright position. Do NOT turn the vial upside down. Push the air-filled syringe with transfer needle attached through the centre of the vial stopper.

D. The tip of the transfer needle should not be in the solution to avoid creating bubbles. (Figure 5).

E. Gently push the air from the syringe into the vial. This will inject the air from the syringe into the vial.

F. Turn the vial upside down (Figure 6).

G. With the transfer needle tip in the solution slowly pull the plunger to fill the syringe with all the liquid (Figure 7).

H. Remove the filled syringe and the transfer needle from the vial.

I. Do not recap the transfer needle. Unscrew the needle and throw it away in the sharps container.

Step 4 Prepare syringe system infusion pump and tubing

Gather the infusion pump supplies and follow the device manufacturer’s instructions to prepare the pump and tubing.

Step 5 Prepare the infusion site(s)

A. Select an area on your abdomen (except for the five centimetres area around the belly button), thighs, hips, or upper arms region for the infusion(s) (Figure 8).

B. Use a different site(s) from the one you used for your last infusion. If there are multiple infusion sites, they should be at least 7.5 cm apart. Rotate infusion sites in between each infusion (Figure 9).

C. Avoid the following infusion areas:

a. Do not infuse into areas where the skin is tender, bruised, red, or hard.

b. Avoid tattoos, scars, or stretch marks.

D. Clean the skin at each infusion site(s) with a new alcohol wipe, starting at the centre and working outward in a circular motion (Figure 10).

E. Let the skin dry.

Step 6 Insert and secure the infusion needle(s)

A. Pinch the skin between your thumb and forefinger around the infusion site (where you intend to place the needle). Insert the needle into the skin (Figure 11). Follow the device manufacturer’s instructions on the angle of the needle.

B. Secure the needle(s) using sterile gauze and tape or a transparent dressing placed over the infusion site(s) (Figure 12).

Step 7 Start infusion

Follow the device manufacturer’s instructions to start the infusion.

Start the infusion promptly after drawing the solution into the syringe.

Step 8 Complete infusion

Follow the device manufacturer’s instructions to complete the infusion.

Step 9 Record infusion

Record your treatment as directed by your healthcare professional.

Step 10 Clean up

A. After the infusion is complete, remove the dressing and slowly take out the needle(s). Cover the infusion site with a new dressing.

B. Disconnect the infusion set from the pump and discard into the sharps container (Figure 13).

C. Throw away all used disposable supplies as well as any unused product and the empty vial as recommended by your healthcare professional.

D. Clean and store the syringe system infusion pump according to the device manufacturer’s instructions.

If you miss a dose, it should be taken as soon as possible; then take the next dose at the regularly planned time.

PNH is a lifelong condition and so it is expected that you will use this medicine for a long time. If you wish to stop using the medicine, please speak to your doctor first. If you stop taking the medicine suddenly, you may be at risk of making your symptoms worse.

If your doctor decides to stop your treatment with this medicine, follow their instructions for how to stop. Your doctor will monitor you closely for at least 8 weeks after stopping treatment for any signs of the destruction of red blood cells (haemolysis) due to PNH. Symptoms or problems that can happen due to destruction of red blood cell include:

• tiredness
• shortness of breath
• blood in the urine
• stomach-area (abdomen) pain
• drop in the number of your red blood cell count
• blood clots (thrombosis)
• trouble swallowing
• erectile dysfunction in males

If you have any of these signs and symptoms, contact your doctor.

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

By reporting side effects you can help provide more information on the safety of this medicine.

The active substance is pegcetacoplan 1 080 mg (54 mg/mL in a 20 mL vial).

The other ingredients are: sorbitol (E 420) (see section 2 “ASPAVELI contains sorbitol”), glacial acetic acid, sodium acetate trihydrate (see section 2 “ASPAVELI contains sodium”), sodium hydroxide (see section 2 “ASPAVELI contains sodium”), and water for injection.

ASPAVELI is a clear, colourless to slightly yellowish solution for subcutaneous infusion (54 mg/mL in a 20 mL vial). Solutions that are cloudy or have particles or colour change should not be used.

ASPAVELI comes in a pack of 1 vial or a multipack of 1 x 8 vials.

Please note that alcohol swabs, needles, and other supplies or equipment are not contained in the pack.

Not all pack sizes may be marketed.