CARBAGLU Dispersible tablet Ref.[6534] Active ingredients: Carglumic acid

Carbaglu treatment should be initiated under the supervision of a physician experienced in the treatment of metabolic disorders.

Posology

For N-acetylglutamate synthase deficiency: Based on clinical experience, the treatment may be started as early as the first day of life. The initial daily dose should be 100 mg/kg, up to 250 mg/kg if necessary.

It should then be adjusted individually in order to maintain normal ammonia plasma levels (see section 4.4).

In the long term, it may not be necessary to increase the dose according to body weight as long as adequate metabolic control is achieved; daily doses range from 10 mg/kg to 100 mg/kg.

Carglumic acid responsiveness test

It is recommended to test individual responsiveness to carglumic acid before initiating any long term treatment. As examples:

• In a comatose child, start with a dose of 100 to 250 mg/kg/day and measure ammonia plasma concentration at least before each administration; it should normalise within a few hours after starting Carbaglu.
• In a patient with moderate hyperammonaemia, administer a test dose of 100 to 200 mg/kg/day for 3 days with a constant protein intake and perform repeated determinations of ammonia plasma concentration (before and 1 hour after a meal); adjust the dose in order to maintain normal ammonia plasma levels.

For isovaleric acidaemia, methylmalonic acidaemia and propionic acidaemia: The treatment should start upon hyperammonaemia in organic acidaemia patients. The initial daily dose should be 100 mg/kg, up to 250 mg/kg if necessary.

It should then be individually adjusted in order to maintain normal ammonia plasma levels (see section 4.4).

Renal impairment

Caution is advised when administering Carbaglu to patients with impaired renal function.

Dosage adjustment is required according to GFR.

• Patients with moderate renal impairment (GFR 30-59 mL/min)
  • the recommended initial dose is 50 mg/kg/day to 125 mg/kg/day for patients presenting an hyperammonemia due to NAGS deficiency or organic acidaemia,
  • In the long term use the daily dose will be in the range of 5 mg/kg/day to 50 mg/kg/day and should be adjusted individually in order to maintain normal ammonia plasma levels
• Patients with severe renal impairment (GFR ≤ 29 mL/min)
  • the recommended initial dose is 15 mg/kg/day to 40 mg/kg/day for patients presenting an hyperammonaemia due to NAGS deficiency or organic acidaemia,
  • In the long term use the daily dose will be in the range of 2 mg/kg/day to 20 mg/kg/day and should be adjusted individually in order to maintain normal ammonia plasma levels

Paediatric population

The safety and effectiveness of Carbaglu for the treatment of pediatric patients (birth to 17 years of age) with acute or chronic hyperammonemia due to NAGS deficiency and acute hyperammonemia due to IVA, PA or MMA have been established, and based on these data, posology adjustments in neonates are not deemed necessary.

Method of administration

This medicine is for oral use ONLY (ingestion or via a nasogastric tube using a syringe, if necessary). Based on pharmacokinetic data and clinical experience, it is recommended to divide the total daily dose into two to four doses to be given before meals or feedings. The breaking of the tablets in halves allows most of the required posology adjustments. Occasionally, the use of quarter tablets may also be useful to adjust the posology prescribed by the physician. The tablets must be dispersed in a minimum of 5-10 ml of water and ingested immediately or administered by fast push through a syringe via a nasogastric tube.

The suspension has a slightly acidic taste.

In one patient treated with carglumic acid, where the dose was increased up to 750 mg/kg/day, symptoms of intoxication occurred which can be characterised as a sympathomimetic reaction: tachycardia, profuse sweating, increased bronchial secretion, increased body temperature and restlessness. These symptoms resolved once the dose was reduced.

36 months.

After first opening of the tablet container: 3 months.

Store in a refrigerator (2°C–8°C)

After first opening of the tablet container:

Do not refrigerate.

Do not store above 30°C.

Keep the container tightly closed in order to protect from moisture.

5-, 15- or 60- high density polyethylene tablet containers closed by a child resistant polypropylene cap with a desiccant unit.

Not all pack sizes may be marketed.

No special requirements.