QARZIBA 4.5 mg/ml CONCENTRATE FOR INFUSION SOLUTION

2. What you need to know before you use Qarziba

Do not use Qarziba:

• if you are allergicto dinutuximab beta or any of the other ingredients of this medicine (listed in section 6)

• if you have acute grade 3 or 4 graft-versus-host disease, or intense chronic graft-versus-host disease. This disease is a reaction in which the cells from the transplanted tissue attack thecells of the recipient.

Warnings and precautions

Before receiving Qarziba, you will have blood tests to check your liver, lung, kidney, and bone marrow functions.

You may notice the following effects when you first receive Qarziba and during treatment:

• Pain

Pain is one of the most common side effects of Qarziba. It usually occurs at the start of the infusion. Therefore, your doctor will give you suitable pain treatment from 3 days before using Qarziba and during use.

• Allergic reactions or other infusion-related reactions

Tell your doctor or nurse if you have any reaction during or after the infusion, such as:

• fever, chills, or low blood pressure
• difficulty breathing

• skin rash, hives.

You will receive suitable treatment to prevent these reactions and will be closely monitored for these symptoms during Qarziba infusion.

• Leakage from small blood vessels (capillary leak syndrome)

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

• Eye problems

You may notice changes in your vision.

• Nervous system problems

You may notice numbness, tingling, or burning in your hands, feet, legs, or arms, decreased sensitivity, or weakness when moving.

• Spinal and brain problems (central nervous system, CNS)

Tell your doctor or nurse if you have any CNS symptoms, 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 mobility problems or unusual sensations and numbness. Persistent or sudden headache, or progressive memory loss and cognitive impairment, subtle personality changes, inability to concentrate, lethargy, and progressive loss of knowledge.

Tell your doctor immediately if you notice any of these problems.

If you have any of these problems, your doctor may decide to stop treatment. In some cases, treatment can be restarted after a break or at a slower rate, but sometimes it may be necessary to stop it permanently.

Your doctor will perform blood tests and possibly eye tests while you are receiving this medicine.

Children

This medicine must not be given to children under 12 months because there is not enough experience with this age group.

Other medicines and Qarziba

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

Do not use medicines that suppress the immune systemfrom 2 weeks before the first dose of Qarziba to 1 week after the last treatment cycle, unless your doctor prescribes them. Some examples of medicines that suppress the immune system are corticosteroids used to reduce inflammation or prevent organ transplant rejection.

Avoid vaccinesduring treatment with Qarziba and for 10 weeks after.

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 for advice before taking this medicine.

Tell your doctor before receiving Qarziba if you are of childbearing potential. It is recommended to use contraceptive methods during 6 months after stopping treatment with Qarziba. You can only use Qarziba if your doctor considers that the benefits outweigh the risks to the fetus.

Tell your doctor if you are breastfeeding. You must not breastfeed during treatment with Qarziba and for 6 months after the last dose. It is not known whether the medicine can pass into breast milk.

Driving and using machines

Qarziba has several side effects that may affect your ability to drive and use machines. Do not perform these activities if your ability to concentrate and react is affected.

3. How to use Qarziba

Your treatment will be supervised by a doctor with experience in the use of medicines to treat cancer. You will be given Qarziba by a doctor or nurse in the hospital. It is administered into a vein (intravenous infusion), usually using special tubes (catheters) and a pump.

During and after the infusion, you will be regularly monitored for infusion-related side effects.

You will receive Qarziba in 5 treatment cycles of 35 days, and the infusion will last for 5 or 10 days at the start of each cycle. The recommended dose is 100 mgof dinutuximab beta persquare meter of body surface area per treatment cycle.Your doctor will calculate the body surface area from your weight and height.

If your doctor considers it necessary to administer interleukin-2 at the same time as Qarziba, you will receive it twice, by injection under the skin, for 5 consecutive days each time (before and during treatment with Qarziba).

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor or nurse immediatelyif you get 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, dizziness, and difficulty breathing (capillary leak syndrome)

• pain in the stomach, throat, chest, face, hands, feet, legs, arms, back, neck, joints, or muscles

• allergic reactions and cytokine release syndrome with symptoms such as swelling of the face or throat, difficulty breathing, dizziness, hives, rapid or noticeable heartbeat, 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
• lack of oxygen
• swelling of tissues (in the face, lips, around the eyes, in the lower limbs)

• weight gain
• infection, in particular, infection associated with the catheter that administers the medicine
• headache
• dilation of the pupils or abnormal pupillary reactions
• abnormal blood or urine test results (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
• nervous disorder in the arms and/or legs (with abnormal sensitivity or weakness), dizziness, tremor, muscle spasms

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

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

• reactions at the injection site, skin problems such as redness, dryness of the skin, eczema, excessive sweating, reaction to light
• inability to urinate or reduced urine output
• weight loss, fluid loss (dehydration)

Uncommon(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 (posterior reversible encephalopathy syndrome)
• intestinal inflammation, liver damage
• kidney failure
• a disorder in which some of the small veins in the liver are blocked (veno-occlusive disease)

Reporting of side effects

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Qarziba

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 label and carton after EXP. The expiry date is the last day of the month shown.

Store in a refrigerator (2 °C - 8 °C). Keep the vial in the outer packaging to protect it from light.

Once opened, Qarziba must be used immediately.

6. Container Contents and Additional Information

Composition of Qarziba

• The active substance 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, polysorbate 20, water for injections, hydrochloric acid (for pH adjustment).

Appearance and Container Contents of the Product

Qarziba is a colorless to slightly yellow liquid supplied in a transparent glass vial with a rubber stopper and a metal cap.

Each box contains 1 vial.

• Marketing Authorization Holder

Recordati Netherlands B.V.

Beechavenue 54,

1119PW Schiphol-Rijk

Netherlands

• Manufacturer

Patheon Italia S.P.A.

Via Morolense,

5 – 03013 Ferentino

Italy

Date of Last Revision of this Leaflet: 04/2025.

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu. There are also links to other websites on rare diseases and orphan medicines.

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This Information is Intended Exclusively for Healthcare Professionals:

Qarziba is restricted exclusively to hospital use and must be administered under the supervision of a physician experienced in the use of oncologic treatments. It should be administered by a healthcare professional prepared to treat severe allergic reactions such as anaphylaxis in an environment where full resuscitation services are immediately available.

Dosage

Treatment with dinutuximab beta consists of 5 consecutive cycles, each lasting 35 days. The individual dose is determined based on body surface area and should be a total of 100 mg/m2 per cycle.

There are two possible modes of administration:

• 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/m2 administered 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 5-day treatment should start 7 days before the first dinutuximab beta infusion. The second 5-day treatment with IL-2 should be initiated concomitantly with the dinutuximab beta infusion (days 1 to 5 of each cycle). IL-2 is administered at a dose of 6 × 10^6 IU/m2 per day, for a total dose of 60 × 10^6 IU/m2 per cycle.

Preparation of the Infusion

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

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

• For continuous infusions, the infusion solution can be prepared fresh daily or in sufficient quantity for up to 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 pump used, i.e., an excess of 2 ml (syringe) or 10 ml (infusion bag) to account for residual volumes of 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 sodium chloride solution for infusion of 9 mg/ml (0.9%) containing 1% human albumin.

Administration of the Infusion

The infusion solution should be administered through a peripheral or central intravenous line. If other medicinal products are administered concomitantly by intravenous infusion, they should be administered through a separate infusion line. The container should be inspected visually for particulate matter before administration. The use of an in-line filter of 0.22 µm is recommended during infusion.

For continuous infusions, any suitable medical device for infusion at a rate of 2 ml/h can be used, e.g., syringe drivers or electronic ambulatory infusion pumps. 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 during use for up to 48 hours at 25 °C (50 ml syringe) and up to 7 days at 37 °C (250 ml infusion bag), after storage in the 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 conditions and periods during use, which normally should not exceed 24 hours at 2 °C to 8 °C, unless the dilution has been made in controlled and validated aseptic conditions.

Disposal

Disposal of unused medicinal products and all materials that have come into contact with them should be done in accordance with local regulations.