Dosing and Administration

Dosing and Administration

Dosing & Administration

Recommended LOARGYS dosing and administration

Prior to LOARGYS treatment

Administer LOARGYS under the supervision of a healthcare provider knowledgeable in the management of hypersensitivity reactions, including anaphylaxis
Initiate LOARGYS in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment
Consider pre-medication with antihistamines
Obtain a baseline plasma arginine concentration

How to initiate LOARGYS

LOARGYS is supplied in 2 mg/0.4 mL single-dose vials
The recommended starting dosage of LOARGYS is 0.1 mg/kg (actual body weight) administered via intravenous infusion once weekly
Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not shake

Please see full Prescribing Information for more directions on proper dosing and administration.

Monitoring of plasma arginine for patients treated with LOARGYS

For patients treated with LOARGYS, plasma arginine samples must be collected 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
Plasma arginine concentration is then measured using Immedica Pharma’s LOARGYS Arginine Assay

LOARGYS is available only to patients who are enrolled in Study IMM-PEG-005 for purposes of obtaining Immedica Pharma’s Nor-NOHA Blood Collection Tubes and the LOARGYS Arginine Assay. For additional information, please contact Immedica Pharma at 1-(844)-627-4687 and dial 1 to speak to a Medical Information representative.

Recommended dosage adjustment and monitoring

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

If the pre-dose plasma arginine concentration is below 50 micromolar, reduce the weekly LOARGYS dosage by 0.05 mg/kg
If the pre-dose plasma arginine concentration is 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. 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 4 days between doses.

The table below provides examples to determine how many vials of LOARGYS are needed for 3 different patient cases

Determine the number of LOARGYS vials needed based on actual body weight in kg and the recommended dose. Round the calculated volume of LOARGYS to nearest 0.1 mL.

LOARGYS preparation instructions

Use aseptic technique when preparing and administering LOARGYS

Remove the vial(s) from the refrigerator and allow the vial(s) to reach room temperature
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
Use a syringe to withdraw the calculated volume from the vial(s) and round the calculated volume of LOARGYS to nearest 0.1 mL
Discard unused portion

For intravenous administration

Dilute the withdrawn volume of LOARGYS solution in 0.9% Sodium Chloride Injection to a maximum concentration of 0.5 mg/mL
Gently invert the infusion bag to mix the solution. Avoid vigorous shaking or agitation
Administer the intravenous infusion over at least 30 minutes
After LOARGYS infusion, use 0.9% Sodium Chloride to flush the line
1. Do not mix other medications with LOARGYS or co-administer other drugs through the same intravenous line
After 8 weeks of once weekly intravenous LOARGYS, patients may be switched to once weekly subcutaneous LOARGYS at the same dosage of intravenous therapy

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 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. If injecting into the abdomen, avoid the area directly surrounding the navel
Rotate injection sites between doses

Patients treated subcutaneously may experience shorter periods of hypoargininemia than patients treated with LOARGYS intravenously
If patients tolerate maintenance subcutaneous administration of LOARGYS, they may receive subcutaneous administration at home under the supervision of a healthcare provider

Home Administration

When switching patients from subcutaneous administration in a supervised clinical setting to at home administration under the supervision of a healthcare provider, initially use the same dose

Storage of the Solution After Preparation

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

Find Helpful Resources

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Complete the Patient Enrollment Form for your patients starting LOARGYS.

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Reference: LOARGYS (pegzilarginase-nbln) Prescribing Information. Immedica Pharma.

IMPORTANT SAFETY INFORMATION

WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS
See full prescribing information for complete boxed warning

Initiate LOARGYS in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue LOARGYS, and immediately initiate appropriate medical treatment, including use of epinephrine.

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions Including Anaphylaxis: Life-threatening hypersensitivity reactions, including anaphylaxis, have occurred in patients treated with enzyme replacement therapies, including LOARGYS. Hypersensitivity reactions that were mild to moderate in severity occurred in 13% (6/48) of LOARGYS-treated subjects in clinical trials. Hypersensitivity reactions have included facial swelling, rash, flushing and dyspnea. The reactions generally occurred with the first few doses but may occur later in treatment.

Administration of LOARGYS should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis in a healthcare setting with appropriate medical monitoring and support measures. Premedication with an antihistamine and/or corticosteroid should be considered in patients who previously have developed a hypersensitivity reaction. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue LOARGYS and immediately initiate appropriate medical treatment, including use of epinephrine. Consider the risks and benefits of re-administering LOARGYS in patients who have experienced a severe hypersensitivity reaction. Caution should be exercised upon rechallenge. Inform patients of the symptoms of life-threatening hypersensitivity reactions and to seek immediate medical attention should symptoms occur. If a mild or moderate reaction occurs, consider treatment with antihistamines and/or corticosteroids.

ADVERSE REACTIONS

The most common adverse reactions are vomiting, pyrexia, infusion associated reactions and constipation.

USE IN SPECIFIC POPULATIONS

Pregnancy: There are no available data on LOARGYS use in pregnant females to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.

Lactation: There is no data on the presence of LOARGYS in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LOARGYS and any potential adverse effects on the breast-fed infant from LOARGYS or from the underlying maternal condition.

Pediatric: The safety and effectiveness of LOARGYS have been established for the reduction of plasma arginine in pediatric patients 2 years and older with ARG-1 D, in conjunction with dietary protein restriction. The safety and effectiveness of LOARGYS have not been established for the reduction of plasma arginine in pediatric patients aged less than 2 years with ARG-1 D.

Geriatric: Clinical studies of LOARGYS did not include subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.

Indication

LOARGYS is an arginine specific enzyme 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.

This indication is approved under accelerated approval based on reduction of plasma arginine. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.