PIASKY Solution for injection/infusion Ref.[111488] Active ingredients: Crovalimab

Treatment should be initiated under the supervision of a physician experienced in the treatment of haematological disorders.

Posology

The recommended dosing regimen consists of one loading dose administered by intravenous infusion (on Day 1), followed by four additional weekly loading doses administered by subcutaneous injection (on Days 2, 8, 15, and 22). The maintenance dose starts on Day 29 and is then administered every 4 weeks by subcutaneous injection. The doses to be administered are based on the patient’s body weight, as shown in Table 1.

For patients switching from treatment with another complement inhibitor, the first intravenous loading dose of Piasky should be administered at the time of the next scheduled complement inhibitor administration (see section 4.4 for additional information related to switching between complement component 5 [C5] inhibitor treatments). The administration of the additional subcutaneous loading doses and maintenance doses of Piasky will follow as per the schedule shown in Table 1.

Table 1. Piasky dosing regimen based on body weight:

^a Q4W=every 4 weeks

The dosing schedule is allowed to occasionally vary within 2 days of the scheduled administration day (except at Day 1 and Day 2). If this occurs, the subsequent dose should be administered according to the regular schedule.

Duration of treatment

Piasky is intended for long-term treatment unless the discontinuation of this medicinal product is clinically indicated (see section 4.4).

Delayed or missed doses

If an entire planned dose or part of a planned dose of Piasky is missed, the missing dose or remainder of the planned dose should be administered as soon as possible before the day of the next scheduled dose. The next dose should then be administered on the regular scheduled dosing day. Do not take two doses or administer more than the prescribed dose on the same day to make up for a missed dose.

Dose modifications

Modification of the maintenance dose is required if the patient’s body weight changes by 10% or more to become consistently greater than or lower than 100 kg during the course of treatment (see Table 1 for recommended dose). Accordingly, the patient’s body weight should be monitored periodically and on an ongoing basis, as appropriate.

Special populations

Elderly

No dose adjustment is required in patients ≥65 years of age, although experience with crovalimab in elderly patients in clinical studies is limited (see section 5.2).

Renal impairment

No dose adjustment is recommended for patients with mild, moderate or severe renal impairment (see section 5.2).

Hepatic impairment

No dose adjustment is recommended for patients with mild hepatic impairment. Crovalimab has not been studied in patients with moderate to severe hepatic impairment and no recommendation on posology can be provided (see section 5.2).

Paediatric population

No dose adjustment of crovalimab is required in paediatric patients 12 years of age or older with body weight ≥40 kg. The safety and efficacy of crovalimab in children less than 12 years of age and children with body weight <40 kg have not yet been established. No data are available.

Method of administration

Piasky is administered as an intravenous infusion (first dose) and as a subcutaneous injection (subsequent doses).

Intravenous administration

Piasky should be prepared for intravenous administration using appropriate aseptic technique. Piasky must be diluted and administered by a healthcare professional as an intravenous infusion over 60 minutes ± 10 minutes (1 000 mg) or 90 minutes ± 10 minutes (1 500 mg). Piasky should not be administered as an intravenous push or bolus.

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

The infusion of crovalimab may be slowed or interrupted if the patient develops an infusion related reaction. The infusion should be discontinued immediately if the patient experiences a serious hypersensitivity reaction (see section 4.4).

Subcutaneous administration

Piasky must be used undiluted and should be prepared using appropriate aseptic technique. It is recommended to inject Piasky into the abdomen. Within the abdomen, injection sites should be rotated with every injection. Injections should never be given into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact.

Administration by the patient and/or caregiver

After proper training in subcutaneous injection technique, the patient may self-administer Piasky or the caregiver may administer Piasky without healthcare professional (HCP) supervision if the treating physician determines that it is appropriate.

Comprehensive instructions for the administration of Piasky are given at the end of the Package Leaflet.

In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted.

Unopened vial

3 years.

Once removed from the refrigerator, the unopened vial can be kept at room temperature (up to 30°C) in its outer carton for no longer than 7 days.

Diluted solution for intravenous infusion

From a microbiological point of view, unless the method of dilution precludes the risk of microbial contamination, the diluted solution for intravenous infusion should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

If the diluted solution is prepared under controlled and validated aseptic conditions, the medicinal product can be stored in the refrigerator at 2°C to 8°C and at room temperature (up to 30℃). Detailed storage conditions of the prepared solution for infusion depending on the type of infusion bags used are provided in Table 4.

Table 4. Storage conditions for the solution for infusion prepared using aseptic conditions:

polyolefins (PO), polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC)

Undiluted solution for subcutaneous injection

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 normally not be longer than 24 hours at 2-8°C, unless preparation has taken place in controlled and validated aseptic conditions.

If Piasky is transferred from the vial to the syringe under controlled and validated aseptic conditions, the medicinal product in the capped syringe can be stored in the refrigerator at 2°C to 8°C for up to 14 days protected from light and at room temperature (up to 30°C) for up to 24 hours at ambient light.

Piasky solution must be protected from direct sunlight.

Unopened vial:

Store in a refrigerator (2°C–8°C).

Do not freeze.

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

For storage conditions of the diluted solution for intravenous infusion and the undiluted solution for subcutaneous injection, see section 6.3.

Solution for injection/infusion in a 2 mL single-use vial (Type I glass) with a stopper (rubber) and a seal (aluminium).

Each carton contains one vial.

Piasky vial is for single use only.

Piasky is used diluted for intravenous infusion or undiluted for subcutaneous injection.

Piasky should be inspected visually to ensure there is no particulate matter or discolouration prior to administration. Piasky is clear to strongly opalescent, and almost colourless to brownish-yellow solution. Piasky should be discarded if the medicinal product looks cloudy, discoloured or has particles in it.

Intravenous administration

Piasky must be prepared by a healthcare professional under aseptic technique. Piasky solution must be diluted in sodium chloride 9 mg/mL (0.9%) solution for infusion prior to administration. A 0.2 μm in-line filter must be used with the infusion set during administration.

A dedicated infusion line must be used during intravenous administration.

Dilution:

1. Withdraw the required volume of Piasky from the vial (see Table 5) using a sterile syringe and dilute into the infusion bag. Multiple vials need to be used to meet the required volume of Piasky to be added to the infusion bag. Discard any unused portion left in the vial.

Dilution of Piasky in infusion bags containing sodium chloride 9 mg/mL (0.9%) solution for infusion must be in the range of 4-15 mg/mL (final concentration after dilution).

Intravenous infusion bags of a volume of 100 mL or 250 mL can be used.

Table 5. Dose example volume determination:

^* Each 340 mg vial contains a nominal fill volume of 2.0 mL

2. Gently mix the infusion bag by slowly inverting the bag. Do not shake.

3. Inspect the infusion bag for particles and discard if present.

4. Flushing of infusion line is required in order to ensure complete administration of the entire dose.

No incompatibilities have been observed between Piasky and intravenous infusion bags with product-contacting materials made of polyvinyl chloride (PVC), or polyolefins (PO) such as polyethylene (PE) and polypropylene (PP). In addition, no incompatibilities have been observed with infusion sets or infusion aids with product-contacting materials made of PVC, PE, polyurethane (PU), polybutadiene (PBD), acrylonitrile butadiene styrene (ABS), polycarbonate (PC), or polytetrafluorethylene (PTFE).

For storage conditions of the infusion bags, see section 6.3.

Subcutaneous administration

Piasky should be used undiluted and should be prepared using aseptic technique. A syringe, a transfer needle and an injection needle are needed to withdraw Piasky solution from the vial and inject it subcutaneously.

Each injection is of a volume of 2 mL, corresponding to 340 mg. A 2 mL-size or 3 mL-size syringe should be used for each injection. A dose of 680 mg is achieved by performing two consecutive subcutaneous injections of 340 mg. A dose of 1 020 mg is achieved by performing three consecutive subcutaneous injections of 340 mg.

2 mL or 3 mL syringe:

Criteria: Transparent polypropylene or polycarbonate syringe with Luer-Lock tip (in case not locally available, a syringe with Luer Slip tip can be used), sterile, single-use, latex-free and non-pyrogenic.

Transfer needle:

Criteria: Stainless steel, sterile, preferably gauge 18 G with single bevel at approximately 45 degrees to reduce risk of needle stick injury, or gauge 21 G standard needle as an alternative, single use, latex free and non-pyrogenic. A transfer needle without filter is recommended.

Injection needle:

Criteria: Hypodermic needle, stainless steel, sterile, gauge 25 G, 26 G or 27 G, length from 9 to 13 mm, single use, latex free and non-pyrogenic, preferably including safety needle shield.

Please see section 4.2 for additional information on administration.

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

The following points should be strictly adhered to regarding the use and disposal of syringes and other medicinal sharps:

• Needles and syringes should never be reused or shared with others.
• Place all used needles and syringes into a sharp container (puncture-proof disposable container).