Drug Description
Each tablet contains 200 mg of carglumic acid.

Presentation
Dispersible tabletThe tablets are white and elongated with three score marks.The tablet can be divided into equal halves.

Indications
Treatment of hyperammonaemia due to N-acetylglutamate synthase deficiency.

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

Contra Indications
Hypersensitivity to the active substance or to any of the excipients.Breast-feeding during the use of carglumic acid is contraindicated.

Special Precautions
Therapeutic monitoringPlasma levels of ammonia and amino acids should be maintained within normal limits.As very few data on the safety of carglumic acid are available, systematic surveillance of liver, renal, cardiac functions and haematological parameters is recommended.Nutritional managementProtein restriction and arginine supplementation may be indicated in case of low protein tolerance.

Interactions
No specific interaction studies have been performed.

Adverse Reactions
Clinical experience has been collected in about 170 patient-years.Reported adverse reactions are listed below, by system organ class and by frequency. Frequencies are defined as: very common ( 1/10), common (1/100 to <1/10) and uncommon (1/1,000 to <1/100).Within each frequency grouping, undesirable effects are presented in order of decreasing seriousnessInvestigationsUncommon: increased transaminasesSkin and subcutaneous tissue disordersCommon: increased sweating

Manufacturer
Orphan Europe (UK) Limited

Drug Availability
POM

Updated
15 September 2009