Crovalimab

Type III hypersensitivity reactions can also cause renal abnormalities. Healthcare providers should consider the benefits of the timing of switching C5 inhibitors vs. the risks of Type III hypersensitivity reactions. Patients are expected to no longer be at risk of Type III hypersensitivity reactions if the prior C5 inhibitor has been cleared from the body prior to starting PIASKY or if PIASKY has been cleared from the body prior to starting another C5 inhibitor.

PIASKY is contraindicated in patients with a known serious hypersensitivity reaction to crovalimab or any of the excipients. 5.6 Monitoring PNH Manifestations after Discontinuation of PIASKY In case of PIASKY discontinuation, patients who do not switch to another treatment for PNH, must be closely monitored for at least 20 weeks for signs and symptoms of serious hemolysis, identified by elevated lactate dehydrogenase (LDH) levels, along with a sudden decrease in hemoglobin, or re-appearance of symptoms such as fatigue, hemoglobinuria, abdominal pain, dyspnea, major adverse vascular events (including thrombosis), dysphagia, erectile dysfunction or renal impairment.

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. [See table below.] 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. [See table below.] PVC Refrigerate at 2°C to 8°C (36°F to 46°F) for up to 12 hours protected from light, and store at room temperature up to 30°C (86°F) for up to 6 hours including infusion time under ambient light conditions.

Protect from direct sunlight. No incompatibilities have been observed between PIASKY and intravenous infusion bags with product-contacting 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 product-contacting 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 ] . 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 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 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.