Kanuma

Package leaflet: Information for the user

KANUMA 2 mg/mL concentrate for solution for infusion

sebelipase alfa
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while being treated with this medicine, either for yourself or for the child. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before receiving 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.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor. See section 4.

Contents of this leaflet:

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

1. What KANUMA is and what it is used for

KANUMA contains the active substance sebelipase alfa. Sebelipase alfa is similar to lysosomal acid lipase (LAL), an enzyme naturally present in the body that helps break down fats.
It is used to treat patients of all ages with lysosomal acid lipase deficiency (LAL deficiency).
LAL deficiency is a genetic disease that causes liver damage, high levels of cholesterol in the blood, and other complications due to the accumulation of certain types of fats (cholesteryl esters and triglycerides).

How KANUMA works
This medicine is an enzyme replacement therapy, meaning it replaces the missing or defective LAL enzyme in patients with LAL deficiency. This medicine works by reducing the buildup of fat that causes medical complications, including impaired growth, liver damage, and heart complications. It also improves fat levels in the blood, including elevated levels of LDL cholesterol (bad cholesterol) and triglycerides.

2. What you should know before receiving KANUMA

Do not receive KANUMA

• If you or the child have previously experienced potentially life-threatening allergic reactions to sebelipase alfa that cannot be managed if the medicine is administered again, or if you have had allergic reactions to egg or to any of the other components of this medicine (listed in section 6).

Warnings and precautions

• While being treated with KANUMA, you or the child may experience adverse reactions during or in the hours following the infusion (see section 4). This so-called “infusion reaction” can sometimes be serious and may include an allergic reaction that could be life-threatening and require immediate medical treatment. When you or the child first receive KANUMA, you must be monitored by a healthcare professional for 1 hour to detect any signs of an infusion reaction. If you or the child experience a severe infusion reaction of this type, seek immediate medical attention. If you or the child experience an infusion reaction, additional medicines may be administered to treat or prevent future reactions. These may include antihistamines, fever-reducing medicines, and/or corticosteroids (a type of anti-inflammatory medicine). If the infusion reaction is severe, the doctor may decide to stop the KANUMA infusion and initiate appropriate medical treatment.

• During treatment, proteins in the blood directed against KANUMA, known as “anti-drug antibodies,” may develop. If you notice a reduction in the effectiveness of KANUMA, speak with your doctor.

• This medicine may contain egg proteins. If you or the child have an egg allergy or a history of egg allergy, inform your doctor or nurse (see section Do not receive KANUMA).

Other medicines and KANUMA
Tell your doctor if you or the child are using, have recently used, or might use any other medicines.

Pregnancy
There are no data on the use of sebelipase alfa in pregnant women. As a precautionary measure, KANUMA should not be administered if you are pregnant.

Breast-feeding
It is not known whether sebelipase alfa is excreted in human milk. Inform your doctor if you are breast-feeding or plan to breast-feed. Your doctor will help you decide whether to discontinue breast-feeding or the treatment with KANUMA, taking into account the benefits of breast-feeding for the child and the benefits of KANUMA for the mother.

If you are pregnant, suspect you may be pregnant, planning a pregnancy, or are breast-feeding, ask your doctor for advice before taking this medicine.

Driving and using machines
KANUMA may have a slight influence on the ability to drive vehicles or operate machinery. Dizziness is one of the side effects of sebelipase alfa and may affect the ability to drive or operate machinery.

KANUMA contains sodium
When diluted with sodium chloride 9 mg/mL (0.9%) solution for infusion for intravenous administration, this medicine contains 33 mg of sodium (the main component of table salt) at the recommended dose. This corresponds to 1.7% of the maximum recommended daily dietary intake of sodium for an adult. Inform your doctor if you or the child are on a low-sodium diet.

3. How KANUMA is administered

The dose you or your child will receive depends on your body weight.
Neonates (less than 6 months of age)
For neonatal patients with signs and symptoms of disease, the recommended initial dose is 1 mg/kg or
3 mg/kg once weekly. Dose adjustments may be considered based on the child's response to treatment.
Children and adults
The recommended dose is 1 mg per kg of body weight administered every other week via intravenous infusion
(endovenously). Dose adjustments may be considered depending on how you or your child respond to treatment.
Each infusion will take approximately 1–2 hours. Your doctor or nurse may monitor you or your child for an additional hour after the infusion. KANUMA should be initiated as early as possible and is intended for long-term use.
KANUMA will be administered to you or your child by your doctor or nurse through an intravenous infusion into a vein. The medicine must be diluted before it is given to you or your child.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Side effects have been observed during or immediately after administration of the medicine (infusion reactions). The most serious side effects have included allergic reactions (very commonly observed [may affect more than 1 in 10 newborns under 6 months of age]; and commonly observed [may affect up to 1 in 10] in children and adults), with symptoms including difficulty breathing, rapid breathing, fast heartbeat, chest discomfort, mild swelling of the eyelids, red eyes, runny nose, hot flushes, hives, itching, diarrhoea, paleness, wheezing, low oxygen levels in the blood, skin redness and irritability. If
you or your child experience symptoms such as these, seek immediate medical attention. If you or your child experience an infusion reaction, you may be given additional medicines to treat or prevent future reactions. If the infusion reaction is severe, your doctor may decide to stop the intravenous infusion of KANUMA and initiate appropriate medical treatment.

Very common side effects (may affect more than 1 in 10) reported in neonates (from birth to 6 months of age) are:
Hypersensitivity (irritability, restlessness, vomiting, hives, eczema, itching, paleness and drug hypersensitivity), severe allergic reactions (anaphylactic reactions)
Swelling of the eyelids
Fast heartbeat
Breathing difficulties
Diarrhoea, vomiting
Skin rash, raised skin rash
Fever
Reduced oxygen in the blood, increased blood pressure, rapid breathing, development of proteins in the blood

Very common side effects (may affect 1 or more in 10) reported in children and adolescents (aged 4 to 18 years) and adults are:
Hypersensitivity (chills, eczema, laryngeal oedema, nausea, itching and hives)
Dizziness
Stomach discomfort, diarrhoea
Fatigue, fever

Common side effects (may affect up to 1 in 10) reported in children and adolescents (aged 4 to 18 years) and adults are:
Severe allergic reaction (anaphylactic reaction)
Fast heartbeat
Skin redness, low blood pressure
Shortness of breath
Stomach swelling
Skin rash, red and swollen skin
Chest discomfort, reaction at the infusion site

The frequency, type and severity of adverse reactions in children are similar to those in adults.

Reporting of side effects
If you or your child experience any side effects, including those not listed in this leaflet, please inform your doctor. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store KANUMA

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton after EXP/Exp. The expiry date refers to the last day of that month.
Store in the refrigerator (2 °C–8 °C). Do not freeze. Do not shake. Keep in the original packaging to protect the medicine from light.
For diluted solutions, immediate use is recommended. If not used immediately, the diluted solution can be stored for up to 24 hours at a temperature of 2–8 °C or up to 12 hours at a temperature below 25 °C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What KANUMA contains

• The active substance is sebelipase alfa. Each mL of concentrate contains 2 mg of sebelipase alfa. Each vial contains 20 mg of sebelipase alfa in 10 mL.
• The other components are sodium citrate (see section 2, “KANUMA contains sodium”), citric acid monohydrate, human serum albumin, and water for injections.

Description of the appearance of KANUMA and contents of the pack
KANUMA is supplied as a concentrate for solution for infusion (sterile concentrate). It is a solution that ranges from clear to slightly opalescent and from colourless to slightly coloured.
Pack: 1 vial containing 10 mL of concentrate.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Alexion Europe SAS
103-105 rue Anatole France
92300 Levallois-Perret
France

Manufacturers:
Almac Pharma Services
Seagoe Industrial Estate
Craigavon BT63 5UA
United Kingdom

Alexion Pharma International Operations Limited
College Business and Technology Park
Blanchardstown Road North
Dublin 15
D15 R925
Ireland

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Alexion Pharma Belgium UAB AstraZeneca Lietuva
Tél/Tel: +32 0 800 200 31 Tel: +370 5 2660550

България Luxembourg/Luxemburg
АстраЗенека България ЕООД Alexion Pharma Belgium
Teл.: +359 24455000 Tél/Tel: +32 0 800 200 31

Česká republika Magyarország
AstraZeneca Czech Republic s.r.o. AstraZeneca Kft.
Tel: +420 222 807 111 Tel.: +36 1 883 6500

Danmark Malta
Alexion Pharma Nordics AB Alexion Europe SAS
Tlf: +46 0 8 557 727 50 Tel: +353 1 800 882 840

Deutschland Nederland
Alexion Pharma Germany GmbH Alexion Pharma Netherlands B.V.
Tel: +49 (0) 89 45 70 91 300 Tel: +32 (0)2 548 36 67

Eesti Norge
AstraZeneca Alexion Pharma Nordics AB
Tel: +372 6549 600 Tlf: +46 (0)8 557 727 50

Ελλάδα Österreich
AstraZeneca A.E. Alexion Pharma Austria GmbH
Τηλ: +30 210 6871500 Tel: +41 44 457 40 00

España Polska
Alexion Pharma Spain, S.L. AstraZeneca Pharma Poland Sp. z o.o.
Tel: +34 93 272 30 05 Tel.: +48 22 245 73 00

France Portugal
Alexion Pharma France SAS Alexion Pharma Spain, S.L. - Sucursal em Portugal
Tél: +33 1 47 32 36 21 Tel: +34 93 272 30 05

Hrvatska România
AstraZeneca d.o.o. AstraZeneca Pharma SRL
Tel: +385 1 4628 000 Tel: +40 21 317 60 41

Ireland Slovenija
Alexion Europe SAS AstraZeneca UK Limited
Tel: +353 1 800 882 840 Tel: +386 1 51 35 600

Ísland Slovenská republika
Alexion Pharma Nordics AB AstraZeneca AB, o.z.
Sími: +46 0 8 557 727 50 Tel: +421 2 5737 7777

Italia Suomi/Finland
Alexion Pharma Italy srl Alexion Pharma Nordics AB
Tel: +39 02 7767 9211 Puh/Tel: +46 0 8 557 727 50

Κύπρος Sverige
Alexion Europe SAS Alexion Pharma Nordics AB
Τηλ: +357 22490305 Tel: +46 0 8 557 727 50

Latvija United Kingdom (Northern Ireland)
SIA AstraZeneca Latvija Alexion Europe SAS
Tel: +371 67377100 Tel: +44 (0) 800 028 4394

Further sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu. In addition, links to other websites on rare diseases and their therapeutic treatments are provided.

The following information is intended exclusively for healthcare professionals:

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Each vial of KANUMA is for single use only. KANUMA must be diluted with
sodium chloride 9 mg/mL (0.9%) infusion solution using aseptic technique.
The diluted solution should be administered to patients using an infusion set with low protein binding, equipped with a low protein binding in-line filter of 0.2 μm pore size and a filter surface area greater than 4.5 cm², if available, to minimize the risk of filter occlusion.

Preparation of sebelipase alfa infusion
KANUMA must be prepared and used according to the instructions outlined below. Aseptic technique must be used.
a. Determine the number of vials to be diluted based on the patient's body weight and prescribed dose.
b. It is recommended to allow KANUMA vials to warm to a temperature between 15 and 25 °C prior to dilution to minimize the potential for protein particle formation of sebelipase alfa in the solution. Vials must not be left outside the refrigerator for more than 24 hours before dilution for infusion. The vials must not be frozen, heated, or placed in a microwave, and must be protected from light.
c. The vials must not be shaken. Prior to dilution, the concentrate in the vials should be inspected visually; the concentrate should appear from clear to slightly opalescent and from colorless to slightly colored (yellow). Due to the protein nature of the medicinal product, slight flocculation (fine translucent fibers) in the vial may be observed, which is acceptable for use.
d. Do not use the concentrate if it appears cloudy or if foreign particulate matter is observed.
e. Withdraw slowly up to 10 mL of concentrate from each vial and dilute in sodium chloride 9 mg/mL (0.9%) infusion solution. For recommended total infusion volumes by weight range, see Table 1. The solution should be gently mixed and must not be shaken.

Table 1. Recommended infusion volumes*

* The infusion volume must be based on the prescribed dose and should be prepared so as to obtain a final sebelipase alfa concentration of 0.1–1.5 mg/mL.
**For patients with LAL deficiency presenting within the first 6 months of life who do not achieve an optimal clinical response with a dose of 3 mg/kg.
Any unused medicinal product and waste material derived from this medicinal product must be disposed of in accordance with local applicable regulations.