PIASKY Solution for injection Ref.[110563] Active ingredients: Crovalimab

2.1 Recommended Vaccination and Prophylaxis for Meningococcal Infection

Vaccinate patients for meningococcal infection (serogroups A, C, W, Y and B) according to current ACIP recommendations at least 2 weeks prior to initiation of PIASKY [see Warnings and Precautions (5.1)].

If urgent PIASKY therapy is indicated in a patient who is not up to date with meningococcal vaccines according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible.

Healthcare providers who prescribe PIASKY must enroll in the PIASKY REMS [see Warnings and Precautions (5.2)].

2.2 Recommended Dosage Regimen

The recommended dosage regimen consists of one loading dose administered by intravenous (IV) infusion (on Day 1), followed by four additional weekly loading doses administered by subcutaneous (SUBQ) 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. Administer doses based on the patient’s actual body weight, as shown in Table 1.

Table 1. PIASKY Dosage Regimen Based on Body Weight:

IV = intravenous, SUBQ = subcutaneous
^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.

Modification of the maintenance dose is required if the patient’s body weight changes to become consistently greater than or lower than 100 kg during the course of therapy.

2.3 Recommended Timing for Switching to PIASKY from Another C5 Inhibitor

Healthcare providers should consider the benefits of the timing of switching C5 inhibitors vs. the risks of Type III hypersensitivity reactions [see Warnings and Precautions (5.3)]. For patients switching from another C5 inhibitor (e.g., eculizumab or ravulizumab), the first intravenous loading dose of PIASKY should be administered no sooner than the time of the next scheduled complement inhibitor administration. The administration of the additional subcutaneous loading doses and maintenance doses of PIASKY should follow as per the schedule shown in Table 1.

2.4 Delayed or Missed Dose

If an entire planned dose or part of a planned dose of PIASKY is missed, administer the missed dose or remainder of the missed dose as soon as possible before the day of the next scheduled dose. Then administer the next dose on the regularly scheduled dosing day. Do not administer two doses or more than the prescribed dose on the same day to make up for a missed dose.

2.5 Preparation and Administration

Each vial of PIASKY is for one-time use in only one patient.

PIASKY is administered as an intravenous infusion (first dose) and as a subcutaneous injection (subsequent doses). Only healthcare providers should administer PIASKY.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. PIASKY is clear to opalescent, and an almost colorless to brownish-yellow solution. PIASKY should be discarded if the medicine looks cloudy, discolored, or has particles in it.

Preparation of Intravenous Infusion:

• Use aseptic technique to prepare PIASKY for intravenous administration. PIASKY must be diluted and administered as an intravenous infusion over 60 minutes ± 10 minutes (1,000 mg) or 90 minutes ± 10 minutes (1,500 mg).
• PIASKY solution must be diluted in 0.9% Sodium Chloride Injection prior to administration. A 0.2 micron in-line filter must be used with the infusion set during administration. A dedicated infusion line must be used during intravenous administration.
• Only dilute PIASKY in 0.9% Sodium Chloride Injection.

Dilution of Intravenous Infusion:

• Withdraw the required volume of PIASKY from the vial (see Table 2) using a sterile syringe and dilute into the infusion bag. Use multiple vials 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 0.9% Sodium Chloride Injection must be in the range of 4-15 mg/mL (final concentration after dilution) (see Table 2).

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

Table 2. Dose Example Volume Determination:

• Gently mix the infusion bag by slowly inverting the bag. Do not shake.
• Inspect the infusion bag for particles and discard if present.
• Flushing of infusion line is required to ensure complete administration of the entire dose.

Storage of Diluted Solution for Infusion:

The diluted solution for intravenous infusion should be used immediately because PIASKY does not contain any antimicrobial preservative. If immediate use is not possible, see Table 3 for detailed storage conditions of the prepared solution for infusion, which depends on the type of infusion bags used.

Table 3. Storage Conditions for the Prepared Solution for Infusion:

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

No incompatibilities have been observed between PIASKY and intravenous infusion bags with productcontacting materials made of polyvinyl chloride, or polyolefins such as polyethylene and polypropylene. In addition, no incompatibilities have been observed with infusion sets or infusion aids with productcontacting materials made of polyvinyl chloride, polyethylene, polyurethane, polybutadiene, acrylonitrile butadiene styrene, polycarbonate, or polytetrafluorethylene.

The infusion of PIASKY 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 Warnings and Precautions (5.5)].

Preparation of the Subcutaneous Injection:

For subcutaneous injection, PIASKY must be used undiluted.

• Remove the vial cap and clean the vial rubber stopper.
• Attach the transfer needle on the syringe.
• Withdraw all the medicine from the vial.
  • Remove air bubbles if any.
• Remove the transfer needle from the vial.
  • Recap the transfer needle using a one-handed scoop technique.
  • Detach the transfer needle.
• Attach the injection needle on the syringe.
• Clean the injection site with an alcohol pad and let air dry.
• Inject the medicine subcutaneously.
  If the dose requires multiple injections, perform a new injection using a new PIASKY vial.
  A syringe, a transfer needle and an injection needle are needed to withdraw PIASKY solution from the vial and inject it subcutaneously.
  • A 2 mL or 3 mL syringe fulfilling the following criteria are recommended: Transparent polypropylene or polycarbonate syringe with Luer-Lock tip (if not available, a syringe with Luer Slip tip can be used), sterile, single-use, latex-free and non-pyrogenic, and commercially available in the US.
  • A transfer needle without a filter fulfilling the following criteria may be used: 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, and commercially available in the US.
  • An injection needle fulfilling the following criteria may be used: Hypodermic needle, stainless steel, sterile, gauge 25 G, 26 G or 27 G, length 3/8'‘ to 1/2’', single-use, latex-free and non-pyrogenic, preferably including safety needle shield, and commercially available in the US.
• Each injection is a volume of 2 mL PIASKY, corresponding to 340 mg. A 2 mL-size or 3 mLsize 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 1020 mg is achieved by performing three consecutive subcutaneous injections of 340 mg.
• Inject PIASKY subcutaneously in the abdomen region and rotate abdominal injection sites with every injection. Consecutive injections must be at least 2 inches apart. No data are available on injection at other sites of the body. Injections should never be given into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact.

Storage of Solution for Injection:

Once transferred from the vial to the syringe, PIASKY should be injected immediately because PIASKY does not contain any antimicrobial-preservative. If immediate use is not possible, the capped syringe can be refrigerated at 2°C to 8°C (36°F to 46°F) for up to 64 hours protected from light and stored at room temperature up to 30°C (86°F) for up to 5 hours under ambient light conditions. Protect from direct sunlight.

• Store refrigerated at 2°C to 8°C (36°F to 46°F) in the outer carton to protect from light. Do not freeze. Do not shake.
• Once removed from the refrigerator, the unopened vial can be kept at room temperature up to 30°C (86°F) in its outer carton for no longer than 7 days.
• Prior to administration, unopened vials of PIASKY may be stored out of the refrigerator at room temperature if needed and then returned to refrigeration. The total combined time out of refrigeration should not exceed 7 days and the temperature should not exceed 30°C (86°F). Discard if stored out of the refrigerator at room temperature for longer than 7 days.