Prospect: information for the user

Qarziba 4.5 mg/ml concentrate for solution for infusion

dinutuximab beta

This medicine is subject to additional monitoring, which will speed up the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor.
• If you experience adverse effects, consult your doctor, even if they are not listed in this prospect. See section 4.

1. Possible adverse effects
2. Storage of Qarziba
3. Contents of the container and additional information

Qarziba contains dinutuximab beta, which belongs to a group of medications known as «monoclonal antibodies». It is a protein that specifically recognizes and binds to other unique proteins in the body. Dinutuximab beta binds to the molecule called disialogangliósido 2 (GD2), which is present in cancer cells, and activates the body's immune system, causing it to attack cancer cells.

Qarziba is used to treat neuroblastomawith a high risk of recurring after a series of treatments, including a stem cell transplant to restore the immune system. It is also used to treat neuroblastoma that has recurred (relapsed) or that has not been completely treated with previous treatments.

Before treating relapsed neuroblastoma, the treating doctor will stabilize the disease, if it is active, through appropriate measures.

Your doctor will also decide if it is necessary or not to administer a second medication, interleucina-2, concomitantly for cancer treatment.

Neuroblastoma is a type ofcancerthat grows from abnormal nerve cells in the body, particularly in glands located above the kidneys. It is one of the most common cancers in childhood.

It is used for patients 12 months of age or older.

No use Qarziba:

• if he isallergicto dinutuximab beta or to any of the other components of this medication (listed in section 6)

• if he has a grade 3 or 4 acute or chronic graft-versus-host disease. This is a reaction in whichthe cells from the transplanted tissue attack thecells of the recipient.

Warnings and precautions

Before receiving Qarziba, blood tests will be performed to check his liver, lung, kidney, and bone marrow functions.

He may experience the following effects when receiving Qarziba for the first time and during the course of treatment:

• Pain

Pain is one of the most common side effects of Qarziba. It usually occurs at the beginning of the infusion. Therefore, his doctor will give him appropriate pain treatment from 3 days before the use of Qarziba and during its use.

• Allergic reactions or other reactions related to the infusion

Inform his doctor or nurse if he experiences any type of reaction during or after the infusion, such as:

He will receive appropriate treatment to prevent these reactions and will be closely monitored for these symptoms during the infusion of Qarziba.

• Bleeding from small blood vessels (capillary leak syndrome)

Bleeding from small blood vessels can cause rapid swelling of the arms, legs, and other parts of the body. Other signs are a rapid drop in blood pressure, dizziness, and difficulty breathing.

• Eye problems

He may notice changes in vision.

• Nervous system problems

He may notice numbness, tingling, or burning in the hands, feet, legs, or arms, a decrease in sensitivity, or weakness with movement.

• Problems with the spinal cord and brain (central nervous system, CNS)

Inform his doctor or nurse if he experiences any type of CNS symptom, such as: significant and prolonged neurological deficit without apparent reason, for example, muscle weakness or loss of muscle strength in the legs (or arms), or problems with mobility or unusual sensations and numbness. Persistent or sudden headache, or progressive loss of memory and cognitive ability, subtle changes in personality, inability to concentrate, lethargy, and progressive loss of knowledge.

Inform his doctor immediately if he experiences any of these problems.

If he experiences any of the mentioned problems, his doctor may decide to interrupt treatment. In some cases, treatment may be resumed after a break or at a slower pace, but sometimes it may be necessary to suspend it definitively.

His doctor will perform blood tests and, perhaps, eye tests while he is receiving this medication.

Children

This medication should not be administered to children under 12 months of age due to insufficient experience in this age group.

Other medications and Qarziba

Inform his doctor if he is using, has used recently, or may need to use any other medication.

Do not useimmunosuppressive medicationsfrom 2 weeks before the first dose of Qarziba to 1 week after the last treatment cycle, unless prescribed by his doctor. Some examples of immunosuppressive medications are corticosteroids used to reduce inflammation or prevent organ transplant rejection.

Avoidvaccinationsduring treatment with Qarziba and for 10 weeks after.

Pregnancy, breastfeeding, and fertility

If he is pregnant or breastfeeding, thinks he may be pregnant, or intends to become pregnant, consult his doctor before taking this medication.

Inform his doctor before receiving Qarziba if he is fertile. It is recommended to use contraceptive methods for 6 months after stopping treatment with Qarziba. He can only use Qarziba if his doctor considers that the benefits outweigh the risks for the fetus.

Inform his doctor if he is breastfeeding. Do not breastfeed during treatment with Qarziba and for 6 months after the last dose. It is not known if the medication can pass into breast milk.

Driving and operating machinery

Qarziba has several side effects that can affect his ability to drive and operate machinery. Do not perform these activities if his ability to concentrate and react is affected.

Your treatment will be monitored by a doctor with experience in using medications to treat cancer. You will be administered by a doctor or nurse in the hospital. It is administered through a vein (intravenous infusion), usually using special tubes (catheters) and a pump.

You will be monitored regularly during and after the infusion regarding any adverse effects related to the infusion.

You will be administered Qarziba in 5 treatment cycles of 35 days, and the infusion will have a duration of 5 or 10 days at the beginning of each cycle. The recommended dose is100 mgof dinutuximab betapersquare meter of body surface per treatment cycle.The doctor will calculate the body surface area from your weight and height.

If your doctor considers the concurrent administration of interleukin-2, you will be administered twice, by subcutaneous injection, over 5 consecutive days each time (before and during treatment with Qarziba).

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

Inform your doctor or nurse immediatelyif you experience any of the following side effects:

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

• rapid swelling of the arms, legs, and other parts of the body, rapid drop in blood pressure, feeling of dizziness, and difficulty breathing (capillary leak syndrome)

• stomach pain, throat pain, chest pain, face pain, hand pain, foot pain, leg pain, arm pain, back pain, neck pain, joint pain, or muscle pain

• allergic reactions and cytokine release syndrome with symptoms such as swelling of the face or throat, difficulty breathing, dizziness, hives, rapid or palpable heart rate, low blood pressure, skin rash, fever, or nausea

Other side effects and their frequencies are:

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

• fever, chills
• vomiting, diarrhea, constipation
• inflammation of the mouth and lips (stomatitis)
• cough
• itching, skin rash
• low blood pressure, increased heart rate
• oxygen deficiency
• swelling of tissues (in the face, lips, around the eyes, in the lower extremities)

• weight gain
• infection, particularly catheter-associated infection
• headache
• pupil dilation or abnormal pupil reactions
• abnormal results in blood or urine tests (blood cells and other components, liver function, kidney function)

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

• potentially life-threatening infection (sepsis)
• seizures
• agitation, anxiety
• nerve disorder in the arms and/or legs (with abnormal sensitivity or weakness), feeling of dizziness, tremor, muscle spasms

• paralysis of eye muscles, blurred vision, sensitivity to light, swelling in the retina

• high blood pressure
• heart failure, presence of fluid around the heart
• respiratory failure, presence of fluid in the lungs
• sudden constriction of airways (bronchospasm, laryngospasm), rapid breathing
• loss of appetite, nausea, abdominal distension, accumulation of fluid in the abdominal cavity

• reactions at the injection site, skin problems such as redness, dryness, eczema, excessive sweating, light sensitivity
• difficulty urinating or reduced urine output
• weight loss, dehydration

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

• shock due to decreased fluid volume
• formation of blood clots in small blood vessels (disseminated intravascular coagulation)
• a type of allergy (serum sickness) with fever, skin rash, joint inflammation
• a brain disorder characterized by headache, confusion, seizures, and loss of vision (reversible posterior encephalopathy syndrome)
• inflammatory bowel disease, liver damage
• kidney insufficiency
• a disorder in which some of the small liver veins become blocked (veno-occlusive disease)

Reporting of side effects

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

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

Do not use this medication after the expiration date that appears on the label and the box after CAD. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2 °C and 8 °C). Store the vial in the outer packaging to protect it from light.

Once opened, Qarziba must be used immediately.

Composition of Qarziba

• The active principle is dinutuximab beta.

One milliliter of concentrate contains 4.5 mg of dinutuximab beta. Each vial contains 20 mg of dinutuximab beta in 4.5 ml.

• The other components are histidine, sucrose, polisorbate 20, water for injectable preparations, hydrochloric acid (for pH adjustment).

Aspect of the product and contents of the package

Qarziba is a colorlessto slightly yellowliquid that is supplied in a transparent glass vial with a rubber stopper and a metal cap.

Each box contains 1 vial.

• Holder of the marketing authorization

RecordatiNetherlands B.V..

Beechavenue 54,

1119PW Schiphol-Rijk

Netherlands

• Responsible for manufacturing

Millmount Healthcare Ltd

Block 7, City North Business Campus

Stamullen, Co. Meath

K32 YD60

Ireland

Patheon Italia S.P.A.

Via Morolense,

5 – 03013 Ferentino

Italy

Last review date of this leaflet: 07/2023.

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu.There are also links to other websites on rare diseases and orphan drugs.

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This information is intended solely for healthcare professionals:

Qarziba is limited to hospital use only and should be administered under the supervision of a doctor experienced in the use of oncological treatments. It should be administered by a healthcare professional prepared to treat severe allergic reactions such as anaphylaxis in an environment where immediate access to complete resuscitation services is available.

Dosage

The treatment with dinutuximab beta consists of 5 consecutive cycles, each lasting 35 days. The individual dose is determined based on the body surface area and should be a total of 100 mg/m2per cycle.

There are two possible administration modes:

• continuous infusion over the first 10 days of each cycle (a total of 240 hours) with a daily dose of 10 mg/m2

• or 5 daily infusions of 20 mg/m2administered over 8 hours on the first 5 days of each cycle.

If IL-2 is combined with dinutuximab beta, it should be administered as subcutaneous injections over 5 consecutive days twice during each cycle. The first treatment of 5 days should start 7 days before the first infusion of dinutuximab beta. The second treatment of 5 days with IL-2 should start concomitantly with the infusion of dinutuximab beta (days 1 to 5 of each cycle). IL-2 is administered at a dose of 6 × 106IU/m2per day, for a total dose of 60 × 106IU/m2per cycle.

Preparation of the infusion

The infusion solution should be prepared in aseptic conditions. It should not be exposed to direct sunlight or heat.

The patient's specific Qarziba dose should be calculated based on the body surface area. Qarziba should be diluted in aseptic conditions to the patient's specific concentration/dose with a 9 mg/ml sodium chloride solution (0.9 %) containing human albumin at 1 % (e.g. 5 ml of human albumin at 20 % per 100 ml of sodium chloride solution).

• For continuous infusions, the infusion solution can be prepared fresh daily or in sufficient quantity for a maximum of 5 days of continuous infusion. The maximum dose is 10 mg/m2. The amount of solution to be infused per day (in a 10-day consecutive treatment cycle) should be 48 ml, for a total of 240 ml for a 5-day dose. It is recommended to prepare 50 ml of solution in a 50 ml syringe, or 250 ml in a suitable infusion bag for the infusion pump used, i.e. an additional 2 ml (syringe) or 10 ml (infusion bag) to account for the residual volumes of the infusion systems.

• For repeated daily infusions, the daily dose is 20 mg/m2, and the calculated dose should be diluted in 100 ml of a 9 mg/ml sodium chloride solution (0.9 %) containing human albumin at 1 %.

Administration of the infusion

The infusion solution should be administered through a peripheral or central intravenous route. If other medications are administered concomitantly by intravenous route, they should be administered through a different infusion route. The container should be visually inspected to rule out the presence of solid particles before administration. It is recommended to use a 0.22 µm in-line filter during infusion.

For continuous infusions, any suitable medical device for infusion at a rate of 2 ml/h, such as infusion pumps or electronic ambulatory infusion pumps, can be used. It should be noted that elastomeric pumps are not considered suitable in combination with in-line filters.

Storage of the diluted solution

Chemical and physical stability has been demonstrated for use over 48 hours at 25 °C (50 ml syringe) and over 7 days at 37 °C (250 ml infusion bag), after storage accumulated in a refrigerator (between 2 °C and 8 °C) for 72 hours.

From a microbiological point of view, the product should be used immediately. If not used immediately, the user will be responsible for the storage periods and conditions during use, which should not normally exceed 24 hours at 2 °C to 8 °C, unless the dilution was prepared in controlled and validated aseptic conditions.

Disposal

The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.