QARZIBA Concentrate for solution for infusion Ref.[27962] Active ingredients: Dinutuximab

Qarziba is restricted to hospital-use only and must be administered under the supervision of a physician experienced in the use of oncological therapies. It must be administered by a healthcare professional prepared to manage severe allergic reactions including anaphylaxis in an environment where full resuscitation services are immediately available.

Posology

Treatment with Qarziba consists of 5 consecutive courses, each course comprising 35 days. The individual dose is determined based on the body surface area and should be a total of 100 mg/m² per course.

Two modes of administration are possible:

• a continuous infusion over the first 10 days of each course (a total of 240 hours) at the daily dose of 10 mg/m²
• or five daily infusions of 20 mg/m² administered over 8 hours, on the first 5 days of each course

When IL-2 is combined with Qarziba, it should be administered as subcutaneous injections of 6×10⁶ IU/m²/day, for 2 periods of 5 consecutive days, resulting in an overall dose of 60×10⁶ IU/m² per course. The first 5-day course should start 7 days prior to the first infusion of dinutuximab beta and the second 5-day course should start concurrently with dinutuximab beta infusion (days 1 to 5 of each dinutuximab beta course).

Prior to starting each treatment course, the following clinical parameters should be evaluated and treatment should be delayed until these values are reached:

• pulse oximetry >94% on room air
• adequate bone marrow function: absolute neutrophil count ≥500/µL, platelet count ≥20,000/µL, haemoglobin >8.0 g/dL
• adequate liver function: alanine aminotransferase (ALT)/aspartate aminotransferase (AST) <5 times upper limit of normal (ULN)
• adequate renal function: creatinine clearance or glomerular filtration rate (GRF) >60 mL/min/1.73 m²

Dose modification of dinutuximab beta

Based on the physician’s evaluation of the severity of adverse drug reactions to dinutuximab beta, patients may undergo a dose reduction of 50% or a temporary interruption of the infusion. As a consequence, either the infusion period is prolonged or, if tolerated by the patient, the infusion rate may be increased up to 3 mL/h (continuous infusion), in order to administer the total dose.

Recommended dose modifications for dinutuximab beta:

Treatment with dinutuximab beta should be permanently discontinued if the following toxicities occur:

• grade 3 or 4 anaphylaxis
• prolonged grade 2 peripheral motor neuropathy
• grade 3 peripheral neuropathy
• grade 3 vision eye toxicity
• grade 4 hyponatremia (<120 mEq/L) despite appropriate fluid management
• recurrent or grade 4 capillary leak syndrome (requires ventilator support)

Renal and hepatic impairment

There are no data in patients with renal and hepatic impairment (see section 5.2).

Paediatric population

The safety and efficacy of Qarziba in children aged less than 12 months have not yet been established. No data are available.

Method of administration

Qarziba is for intravenous infusion. The solution should be administered via a peripheral or central intravenous line. Other intravenously co-administered agents should be delivered via a separate infusion line (see section 6.6).

For continuous infusions, the solution is administered at a rate of 2 mL per hour (48 mL per day) using an infusion pump.

For 8-hour daily infusions, the solution is administered at a rate of approximately 13 mL per hour.

Pre-medication should always be considered before starting each infusion (see section 4.4).

For instructions on dilution of the medicinal product before administration, see section 6.6.

No cases of dinutuximab beta overdose have been reported.

In the case of overdose, patients should be carefully observed for signs or symptoms of adverse reactions and supportive care administered, as appropriate.

Unopened vial: 3 years.

Diluted solution (solution for infusion): Chemical and physical in-use stability has been demonstrated for up to 48 hours at 25°C (50 mL syringe) and for up to 7 days at 37°C (250 mL infusion bag), after cumulative storage in a refrigerator (2°C-8°C) for 72 hours (see section 6.6).

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would not normally be longer than 24 hours at 2 to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

Store in a refrigerator (2°C-8°C).

Keep the vial in the outer carton in order to protect from light.

For storage conditions after dilution of the medicinal product, see section 6.3.

Clear Type I glass vial (6 mL) with a halobutyl rubber stopper and aluminium flip-off cap, containing a minimum extractable volume of 4.5 mL concentrate for solution for infusion.

Each carton contains 1 vial.

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

The patient specific daily dose of Qarziba is calculated based on body surface area (see section 4.2).

Qarziba should be diluted aseptically to the patient specific concentration/dose with sodium chloride 9 mg/mL (0.9%) solution for infusion containing 1% human albumin (e.g. 5 mL of human albumin 20% per 100 mL sodium chloride solution).

For continuous infusions, the solution for infusion can be prepared freshly on a daily basis, or sufficient for up to 5 days of continuous infusion. The daily dose is 10 mg/m². The amount of solution to be infused per day (within a treatment course of 10 consecutive days) should be 48 mL; with 240 mL for a 5-day dose. It is recommended to prepare 50 mL solution in a 50 mL syringe, or 250 mL in an infusion bag suitable for the employed infusion pump, i.e. an overfill of 2 mL (syringe) or 10 mL (infusion bag) to allow for dead volumes of the infusion systems.

For repeated daily 8-hour infusions, the daily dose is 20 mg/m² and the calculated dose should be diluted in 100 mL sodium chloride 9 mg/mL (0.9%) containing 1% human albumin.

The solution for infusion should be administered via a peripheral or central intravenous line. Other intravenously co-administered agents should be delivered via a separate infusion line. The container should be inspected visually for particulates prior to administration. It is recommended that a 0.22 micrometre in-line filter is used during infusion.

For continuous infusions, any medical device suitable for infusion at a rate of 2 mL per hour can be used, e.g. syringe infusion pumps/infusors, electronic ambulatory infusion pumps. Note that elastomeric pumps are not considered suitable in combination with in-line filters.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.