Loargys

Treatment should be initiated and supervised by a physician experienced in the management of patients with inherited metabolic diseases. Posology 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. 1). 1 mg/kg once weekly. 05 mg/kg increments to achieve therapeutic goals. 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.

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. 4).

Missed dose 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. Special population Elderly population The safety and efficacy of Loargys in patients older than 65 years have not been established.

No data are available. 2). Renal impairment The safety and efficacy of Loargys in patients with renal impairment have not been established. No data are available. 2). Paediatric population 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. Method of administration Loargys is intended for intravenous infusion or subcutaneous injection and should be administered by a healthcare professional.

5%). Tabulated list of adverse reactions Assessment of adverse reactions was based on exposure in 48 ARG1-D patients (8 adults and 40 children between the ages of 2 and 31 years at enrolment) with treatment duration of up to approximately 5 years across 3 clinical trials.

Adverse reactions are listed by MedDRA system organ class and by frequency in Table 1 below. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Due to the small size of the medicinal product safety ARG1-D population database (N=48), the adverse reaction frequency for uncommon, rare and very rare could not be reliably estimated.

Table 1. Adverse reactions System organ class Very common Immune system disorders Hypersensitivity General disorders and administration site conditions Injection site reactions Description of selected adverse reactions Hypersensitivity Hypersensitivity reactions with symptoms including facial swelling, rash, flushing and dyspnoea have been reported.

5%) Loargys-treated patients, experienced signs and symptoms either consistent with, or that may be related to a hypersensitivity reaction. The reactions generally occurred with the first few doses. The reactions were mild or moderate and resolved spontaneously, or rapidly after treatment with standard medical care.

None of the reactions led to discontinuation of treatment. 4). Post-marketing, hypersensitivity reactions were reported, even involving patients treated by subcutaneous administration who were pre-medicated with antihistamines. 6% (6/44) of Loargys-treated patients after subcutaneous administration.

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Hypersensitivity reactions Hypersensitivity reactions (such as facial swelling, rash, flushing, dyspnoea) have occurred in Loargys treated subjects with intravenous and subcutaneous administration.

8 for additional details. The initial administrations of Loargys should be performed under medical observation. If a hypersensitivity reaction occurs, appropriate medical treatment should be provided and the patient monitored until signs and symptoms are resolved.

The management of hypersensitivity reactions may include temporarily interrupting the administration or lowering the infusion rate and/or treatment with 5 antihistamines and/or corticosteroids. In severe cases stopping the administration and adrenaline treatment may be necessary.

Pre-medication with an antihistamine and/or corticosteroid should be considered in patients who previously have developed a hypersensitivity reaction in connection with pegzilarginase treatment. , hives, generalised urticaria, tightness of the chest, wheezing and hypotension.

Prescription of medication for treatment of a potential severe hypersensitivity reaction should be considered. Patients should also be advised what to do if symptoms of severe hypersensitivity occur which includes seeking immediate medical support.

Monitoring of plasma arginine Pegzilarginase will interfere with routine arginine laboratory analysis, resulting in erroneous low measurements due to post-collection degradation of arginine. The testing laboratory should be informed that the patient is treated with a medicinal product that metabolises and reduces arginine levels.

Alternative validated sampling procedures to measure arginine must be used in patients treated with Loargys. This includes CE-marked blood collection tubes containing the enzyme-blocker nor-NOHA. Populations not studied in clinical trials No data from clinical trials are available in middle-age and elderly patients with long-existing motoric impairment, or in patients with arginine levels near 200 μM on dietary protein restriction alone.

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