KANUMA Concentrate for solution for infusion Ref.[7581] Active ingredients: Sebelipase alfa

KANUMA treatment should be supervised by a healthcare professional experienced in the management of patients with LAL deficiency, other metabolic disorders, or chronic liver diseases. KANUMA should be administered by a trained healthcare professional who can manage medical emergencies.

Posology

It is important to initiate treatment as early as possible after diagnosis of LAL deficiency.

For instructions on the preventive measures and monitoring of hypersensitivity reactions, see section 4.4. Following the occurrence of a hypersensitivity reaction, appropriate pre-treatment should be considered according to the standard of care (see section 4.4).

Infants (<6 months of age)

The recommended starting dose in infants (<6 months of age) presenting with rapidly progressive LAL deficiency is 1 mg/kg administered as an intravenous infusion once weekly. Dose escalation to 3 mg/kg once weekly should be considered based on clinical response.

Children and adults

The recommended dose in children and adults who do not present with rapidly progressive LAL deficiency prior to 6 months of age is 1 mg/kg administered as an intravenous infusion once every other week.

Special populations

Renal impairment

No dosing adjustment is recommended in patients with renal impairment based on current knowledge of the pharmacokinetics and pharmacodynamics of sebelipase alfa (see section 5.2).

Hepatic impairment

No dosing adjustment is recommended in patients with hepatic impairment based on current knowledge of the pharmacokinetics and pharmacodynamics of sebelipase alfa (see section 5.2).

Elderly population (≥65 years old)

The safety and efficacy of sebelipase alfa in patients older than 65 years have not been evaluated and no alternative dose regimens can be recommended for these patients (see section 5.1).

Overweight patients

The safety and efficacy of sebelipase alfa in overweight patients have not been thoroughly evaluated and therefore no alternative dose regimens can be recommended for these patients at this time.

Paediatric population

Administration of sebelipase alfa to infants with confirmed multiple-organ failure should be at the discretion of the treating physician.

Method of administration

KANUMA is for intravenous use only.

The total volume of the infusion should be administered over approximately 2 hours. A 1-hour infusion may be considered after patient tolerability is established. The infusion period may be extended in the event of dose escalation.

KANUMA should be administered through a 0.2 μm filter (see section 6.6).

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

In clinical studies, doses of sebelipase alfa were explored up to 5 mg/kg once weekly and no specific signs or symptoms were identified following the higher doses. For management of adverse reactions, see sections 4.4 and 4.8.

Unopened vials: 2 years.

After dilution: Chemical and physical in-use stability has been demonstrated for up to 24 hours at 2°C to 8°C, or up to 12 hours below 25°C.

From a microbiological point of view, the diluted solution 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 normally not be longer than 24 hours at 2°C to 8°C, or up to 12 hours below 25°C, unless dilution has taken place in controlled and validated aseptic conditions.

Store in a refrigerator (2°C to 8°C).

Do not freeze.

Store in the original package in order to protect from light.

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

Clear glass vial (Type I) with a siliconised butyl rubber stopper, and an aluminium seal with a plastic flipoff cap, containing 10 ml of concentrate.

Pack size: 1 vial.

Each vial of KANUMA is intended for single use only. KANUMA has to be diluted with sodium chloride 9 mg/ml (0.9%) solution for infusion using aseptic technique. The diluted solution should be administered to patients using a low-protein binding infusion set equipped with an in-line, low-protein binding 0.2 μm filter, with a surface area of greater than 4.5 cm² as available in order to avoid filter occlusion.

Preparation of the sebelipase alfa infusion

KANUMA should be prepared and used according to the following steps. Aseptic technique should be used.

• The number of vials to be diluted for infusion should be determined based on the patient’s weight and prescribed dose.
• It is recommended to allow KANUMA vials to reach a temperature between 15°C and 25°C prior to dilution to minimise the potential for the formation of sebelipase alfa protein particles in solution. The vials should not be left outside the refrigerator longer than 24 hours prior to dilution for infusion. The vials should not be frozen, heated or microwaved and should be protected from light.
• The vials should not be shaken. Prior to dilution, the concentrate in the vials should be inspected visually; the concentrate should be clear to slightly opalescent, colourless to slightly coloured (yellow). Due to the proteinaceous nature of the medicinal product, slight flocculation (e.g., thin translucent fibres) may be present in the vial concentrate and is acceptable for use.
• Do not use if the concentrate is cloudy, or if foreign particulate matter is present.
• Up to 10 ml of concentrate should be slowly withdrawn from each vial and diluted with sodium chloride 9 mg/ml (0.9%) solution for infusion. See table 5 for recommended total infusion volumes by weight range. The solution should be mixed gently, and not be shaken.

Table 5. Recommended infusion volumes (1 mg/kg dose)*:

* The infusion volume should be based on the prescribed dose and should be prepared to a final sebelipase alfa concentration of 0.1-1.5 mg/ml.

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