Pegzilarginase

Recommended Dosage and Administration The recommended starting dosage of LOARGYS is 0.1 mg/kg administered via intravenous infusion once weekly [see Dosage and Administration] . For the recommended dosage use actual body weight. Recommended Adjustment, Maximum Dosage, and Monitoring To maximize the time within the normal range of 40 to 115 micromolar, dose adjustments should be aimed at achieving a pre-dose level of plasma arginine near the upper limit of normal (ULN).

After four weeks of LOARGYS administration, measure pre-dose plasma arginine (168 hours after prior dose) to determine the need for dosage adjustment. If two consecutive weekly pre-dose plasma arginine measurements are not in the desired therapeutic range, increase or decrease the weekly LOARGYS dosage as follows:

Below 50 micromolar, reduce the weekly LOARGYS dosage by 0.05 mg/kg.

Above 150 micromolar, increase the weekly LOARGYS dosage by 0.05 mg/kg. The maximum recommended LOARGYS dosage is 0.2 mg/kg once weekly. Monitor plasma arginine levels (prior to LOARGYS dosing) weekly for 2 weeks after any LOARGYS dosage adjustment and as clinically indicated. Patients may be switched from intravenous administration of LOARGYS to subcutaneous administration [see Dosage and Administration] .

Switching Patients from Intravenous to Subcutaneous LOARGYS Administration After eight weeks of once weekly intravenous LOARGYS, patients may be switched to once weekly subcutaneous LOARGYS at the same dosage of intravenous therapy.

Dosage and Administration Modifications Due to Hypersensitivity Reactions In the event of a severe hypersensitivity reaction (e.g., anaphylaxis), discontinue LOARGYS and immediately initiate appropriate medical treatment, including use of epinephrine. For additional recommendations in the event of a severe hypersensitivity reaction, [see Warnings and Precautions] .

In the event of a mild or moderate hypersensitivity reaction, consider treatment with antihistamines and/or corticosteroids. For intravenous administration, consider temporarily holding the infusion or slowing the infusion rate.

Preparation Instructions for Subcutaneous or Intravenous Administration Use aseptic technique when preparing and administering LOARGYS for subcutaneous or intravenous administration. 1. Determine the number of LOARGYS vials needed based on actual body weight in kg and the recommended dose [see Dosage and Administration] .

Round the calculated volume of LOARGYS to nearest 0.1 mL. 2. Remove the vial(s) from the refrigerator and allow the vial(s) to reach room temperature. 3. Visually inspect the solution in the vials for particulate matter and discoloration. The solution should be clear to slightly opalescent, colorless to slightly yellow or slightly pink.

Discard the vial(s) if the solution is not consistent with this appearance or if visible particulate matter is present. 4. Use a syringe to withdraw the calculated volume from the vial(s). 5. Discard unused portion. Do not dilute the withdrawn volume of LOARGYS solution for subcutaneous administration. However, dilute the withdrawn volume of LOARGYS solution for intravenous administration.

Dilution Instructions for Intravenous Administration 1. Dilute the withdrawn volume of LOARGYS solution in 0.9% Sodium Chloride Injection to a maximum concentration of 0.5 mg/mL. 2. Gently invert the infusion bag to mix the solution. Avoid vigorous shaking or agitation.

Storage of the Diluted LOARGYS Solution for Intravenous Use and the Undiluted LOARGYS Solution for Subcutaneous Use Use LOARGYS immediately after preparation. If not used immediately, store the diluted solution for intravenous use in the infusion container, and the undiluted solution for subcutaneous use in the syringe for up to:

2 hours at room temperature at 20°C to 25°C (68°F to 77°F) or

4 hours if stored refrigerated at 2°C to 8°C (36°F to 46°F). Discard LOARGYS if not administered within these time frames, including total infusion time if administered intravenously.