Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: Immedica Pharma AB, 113 63 Stockholm, Sweden
Loargys is indicated for the treatment of arginase 1 deficiency (ARG1-D), also known as hyperargininemia, in adults, adolescents and children aged 2 years and older.
Treatment should be initiated and supervised by a physician experienced in the management of patients with inherited metabolic diseases.
Loargys is intended for chronic management of patients with ARG1-D in conjunction with individualised disease management such as dietary protein restriction, amino acid supplements and pharmacological treatment including nitrogen scavengers.
Loargys should be administered by intravenous infusion or subcutaneous injection, using the same dose. In clinical trials, treatment was initiated as intravenous administration with subsequent transition to subcutaneous administration after 8 weeks, at the earliest (see section 5.1).
The recommended initial dose of Loargys is 0.1 mg/kg per week. The dose may be increased or decreased in 0.05 mg/kg increments to achieve therapeutic goals. Doses above 0.2 mg/kg per week have not been studied in clinical trials in ARG1-D.
Prior to initiating treatment, a baseline plasma arginine concentration should be obtained. After initiating treatment, the weekly dose should be adjusted based on pre-dose plasma arginine concentrations to maintain plasma arginine within the normal range. To maximise the time within the normal range, dose adjustments should be aimed at achieving a pre-dose level of plasma arginine near the upper limit of normal (ULN) (see section 5.1). The dose adjustment should typically be based on two consecutive measurements, and first such assessment performed after 4 weeks of administration. It is recommended to monitor plasma arginine levels weekly for 2 weeks after any dose adjustment to assess impact of the dose change.
Once the individualised dose level has been established, monitoring of plasma arginine concentration is recommended to be performed in accordance with standard clinical monitoring visits, with no longer intervals than 3-6 months.
Validated methods to monitor arginine levels are to be used in patients treated with Loargys, as standard methods are not adequate to control residual enzyme activity of pegzilarginase after sampling, and may lead to artificially low arginine levels, and incorrect dose adjustments (see section 4.4).
If a dose is missed, administer Loargys as soon as possible. Patients should not be administered 2 doses to make up for the missed dose and should have a minimum of 4 days between doses.
The safety and efficacy of Loargys in patients older than 65 years have not been established. No data are available.
Hepatic impairment is not expected to impact the recommended Loargys dosing regimen (see section 5.2).
The safety and efficacy of Loargys in patients with renal impairment have not been established. No data are available. Renal impairment is not expected to impact the recommended Loargys dosing regimen (see section 5.2).
The posology in the paediatric population aged 2 years and older is the same as in adults.
The safety and efficacy of Loargys in children below 2 years of age have not yet been established. No data are available.
Loargys is intended for intravenous infusion or subcutaneous injection and should be administered by a healthcare professional.
If appropriate, subcutaneous home administration by the patient or caregiver may be considered after at least 8 weeks of treatment, once a stable maintenance dose has been established and the risk for hypersensitivity reactions is assessed as low (see section 4.4). Before self-administration, the patient or caregiver should be adequately trained.
Loargys vial is for single use only.
Determine the total dose and volume of Loargys to be administered (and the number of vials needed) based on the patient’s weight (kg) and dose level (mg/kg).
Total dose (mg) = Patient weight (kg) x Dose level (mg/kg)
Volume of Loargys (ml) = Total dose (mg) / Solution strength (5 mg/ml)
For intravenous administration:
For subcutaneous administration:
Potential effects from an overdose would likely be an exaggerated pharmacologic effect of pegzilarginase resulting in abnormally low plasma arginine levels (see section 5.3).
In an oncology Phase 1 trial in subjects with advanced solid tumours, 1 subject inadvertently received 1.6 mg/kg of pegzilarginase (16 × the recommended initial dose of 0.1 mg/kg in ARG1-D patients). The subject developed nausea, vomiting, diarrhoea, and fatigue, and was successfully treated with intravenous supportive care without sequelae.
Patients suspected of receiving an overdose should be closely monitored and general supportive measures should be initiated.
Unopened vial:
2 years.
Once removed from the refrigerator, Loargys can be stored for 2 hours at room temperature up to 25°C.
After preparation:
Chemical and physical stability has been demonstrated for 2 hours when stored at room temperature up to 25°C or up to 4 hours if stored refrigerated at 2°C to 8°C. If the product is not used within these time frames, it must be discarded. From a microbiological point of view, the product should be used immediately after preparation.
Store in a refrigerator (2°C–8°C).
Do not freeze.
Store in the original carton in order to protect from light.
For storage conditions after preparation/dilution of the medicinal product, see section 6.3.
Each pack contains 1 vial with 0.4 ml or 1 ml solution for injection/infusion.
0.4 ml solution for injection/infusion in a 3 ml type 1 glass vial with a Fluorotec coated chlorobutyl rubber stopper, aluminium seal and a blue flip-off cap.
1 ml solution for injection/infusion in a 5 ml type 1 glass vial with a Teflon coated chlorobutyl rubber stopper, aluminium seal and a white flip-off cap.
Pack size of 1 vial.
Not all pack sizes may be marketed.
Do not shake.
Loargys is intended for intravenous infusion or subcutaneous injection and should be administered by a healthcare professional. If appropriate, subcutaneous home administration by the patient or caregiver may be considered (see section 4.2).
Use aseptic technique when preparing and administering Loargys.
Instruction for preparation:
For intravenous administration:
For subcutaneous administration:
Discard unused portion of the medicinal product.
No special requirements for disposal.
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