Loargys

2 DOSAGE AND ADMINISTRATION • Administer LOARGYS under the supervision of a health care provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. ( 2.1 ) • Initiate LOARGYS in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. ( 2.1 ) • Consider pre‑medication with antihistamines. ( 2.1 ) • Obtain a baseline plasma arginine concentration prior to initiating treatment. ( 2.1 ) • Recommended starting dosage of LOARGYS is 0.1 mg/kg administered by intravenous infusion once weekly. ( 2.2 ) • Maximum recommended dosage is 0.2 mg/kg once weekly. ( 2.2 ) • See the Full Prescribing Information for recommended titration and maintenance dosage and recommended plasma arginine level testing during treatment. ( 2.2 ) • After eight weeks of once weekly intravenous LOARGYS, patients may be switched to once weekly subcutaneous LOARGYS at the same dosage of intravenous therapy. ( 2.4 ) • See Full Prescribing Information for dosage and administration modifications due to hypersensitivity reactions. ( 2.5 ) • See Full Prescribing Information for instructions on preparation, storage, and administration. ( 2.7 , 2.8 , 2.9 , 2.10 ) 2.1 Recommendations Prior to LOARGYS Treatment • Administer LOARGYS under the supervision of a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis [see Warnings and Precautions ( 5.1 )] . • Initiate LOARGYS in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment [see Warnings and Precautions ( 5.1 )] . • Obtain a baseline plasma arginine concentration. • Consider pre-medication with antihistamines [see Warnings and Precautions ( 5.1 )] . 2.2 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 ( 2.9 )] . 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 ( 2.4 )] . 2.3 Collect Plasma Arginine Using Specific Collection Tubes and Measure Arginine Concentration Using a Specific Assay Collect samples into Immedica Pharma’s Nor-NOHA Blood Collection Tubes, which contain Nω-hydroxy-nor-Arginine (nor-NOHA), an enzyme inhibitor used to inhibit post-sampling degradation of arginine by LOARGYS, and measure arginine concentration using Immedica Pharma’s LOARGYS Arginine Assay. LOARGYS is only available to a patient if the patient is enrolled in Study IMM-PEG-005 to obtain Immedica Pharma’s Nor-NOHA Blood Collection Tubes and LOARGYS Arginine Assay. Further information is available by contacting Immedica Pharma at 1‑844‑627‑4687. 2.4 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. 2.5 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 ( 5.1 )] . 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. 2.6 Recommendation Regarding a Missed Dose If a dose is missed, administer LOARGYS as soon as possible. Do not administer two LOARGYS doses on the same day or within four days of another dose to make up for a missed dose. Ensure there is a minimum of four days between doses. 2.7 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 ( 2.2 )] . 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. 2.8 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. 2.9 Intravenous or Subcutaneous Administration Instructions For Intravenous Administration • Administer the diluted LOARGYS infusion intravenously over at least 30 minutes. • After LOARGYS infusion, use 0.9% Sodium Chloride Injection to flush the line. • Do not mix other drugs with LOARGYS or co-administer other drugs through the same intravenous line. For Subcutaneous Administration • Administer the undiluted solution subcutaneously into the abdomen, lateral part of the thigh, or the side or back of the upper arms. If injecting into the abdomen, avoid the area directly surrounding the navel. • If more than 1 injection is needed for a single dose of LOARGYS, the injection sites should be at least 1 inch apart. • Do not inject into scar tissue or areas that are reddened, inflamed, or swollen. • Rotate injection sites between doses. 2.10 Subcutaneous Administration of LOARGYS at Home If patients tolerate maintenance subcutaneous administration of LOARGYS, they may receive subcutaneous administration at home under the supervision of a healthcare provider. When switching patients from subcutaneous administration in a supervised clinical setting to the home, initially use the same dose. Do not change the dose without supervision of a healthcare provider. In the case of a missed dose or delayed injection, contact a healthcare provider as subsequent injections may need to occur in a supervised clinical setting.

See official label

1 INDICATIONS AND USAGE LOARGYS is indicated for the treatment of hyperargininemia in adult and pediatric patients 2 years of age and older with Arginase 1 Deficiency (ARG1-D), in conjunction with dietary protein restriction.