Carglumic Acid (carglumic acid)
Urea Cycle Disorder Agents Oral Tablet, Dispersible
Last reviewed · Source: First Databank (FDB) drug data
Overview
Carglumic acid, a synthetic structural analog of N-acetylglutamate (NAG), activates carbamoyl phosphate synthetase 1 (CPS 1), the first enzyme in the urea cycle.
Carglumic acid is a synthetic structural analog of N-acetylglutamate (NAG). N-Acetylglutamate synthase (NAGS) is a mitochondrial enzyme that produces NAG, which activates carbamoyl phosphate synthetase 1 (CPS 1), the first enzyme in the urea cycle. Activation of the urea cycle requires the binding of NAG to CPS 1.
Carglumic acid acts as a replacement for NAG in patients with NAGS deficiency by activating CPS 1.
The urea cycle (which resides exclusively in periportal hepatocytes) is an essential biochemical pathway for waste nitrogen excretion. Toxic ammonia is converted by metabolic transformation to nontoxic water-soluble urea and, as such, is eliminated in the urine. Because there is no effective secondary pathway for clearance of ammonia, disruption of the main pathway (associated with decreased activity of NAGS or core enzymes in the urea cycle) may result in accumulation of precursor metabolites (e.g., ammonia) in the urea cycle.
The rapid accumulation of ammonia and other precursor metabolites results in acute cerebral edema with severe neurologic compromise. Thus, fast and effective treatment (usually, dialysis and pharmacologic therapy) is essential for a satisfactory clinical outcome.
Carglumic acid restores activity of the urea cycle and rapidly reduces plasma ammonia concentrations to normal levels in patients with NAGS deficiency. Reductions in plasma ammonia concentrations are maintained with continued use of the drug. Normal neurologic development may be possible if therapy is started early (before irreversible brain damage occurs).
USES: This medication is used to help treat certain inherited disorders that cause high levels of a certain substance (ammonia) to build up in your body. Carglumic acid works by helping your body remove ammonia. Too much ammonia in the body can cause brain damage and sometimes death.
Generic name: carglumic acid
Pronunciation: (kar-GLOO-mik AS-id)
Drug class: Urea Cycle Disorder Agents
Therapeutic class: Metabolic Modifiers
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Carglumic Acid
Indications
The following indications are listed for Carglumic Acid:
- Hyperammonemia Associated With N-Acetylglutamate Synthase Deficiency
- Hyperammonemia Due To Methylmalonic Acidemia
- Hyperammonemia Due To Propionic Acidemia
Also known as: Hyperammonemia Due To Mma, Hyperammonemia Due To Pa, Hyperammonemia In Nags Deficiency, Type Iii Hyperammonemia.
Dosing
No dosing information is available for this tab.
Carglumic acid is administered orally in 2-4 divided doses daily. The drug should be given immediately prior to meals or feedings.
Carglumic acid tablets should be dispersed in an appropriate volume of water prior to administration. The tablets should not be crushed or swallowed whole, nor should the tablets be dispersed in food or mixed with any liquids other than water. The carglumic acid dispersion should be used immediately following preparation.
For administration in adults, each 200-mg tablet should be placed in a cup containing at least 2.5 mL of water. The water should be stirred or the cup shaken gently until the tablet is dispersed (the tablet will not completely dissolve). Following administration, any residue in the cup should be resuspended in additional volumes of water and swallowed. The dispersion also may be administered through a nasogastric tube.
For administration in pediatric patients, each 200-mg tablet should be placed in a cup containing 2.5 mL of water to provide a suspension containing 80 mg/mL. The water should be stirred or the cup shaken gently until the tablet is dispersed (the tablet will not completely dissolve). For administration in infants and children, the appropriate dose of the dispersion should be withdrawn from the cup and administered using an oral syringe. Following administration, the oral syringe should be refilled with a small volume of water (1-2 mL) and the rinsing administered immediately. The dispersion also may be administered through a nasogastric tube. Any unused portion of the dispersion should be discarded.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Carglumic Acid 200 Mg Tab Susp | Maintenance | Take 50 mg/kg (dissolving each 200 mg tablet in at least 2.5 mL of water) by oral route 2 times per day immediately before meals. |
| Drug label | Dosing type | Instructions |
|---|---|---|
| Carglumic Acid 200 Mg Tab Susp | Maintenance | Take 50 mg/kg (dissolving each 200 mg tablet in at least 2.5 mL of water) by oral route 2 times per day immediately before meals. |
Drug interactions
Formal drug interaction studies have not been performed to date.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
The manufacturer states that there are no known contraindications to the use of carglumic acid.
There are no contraindication contraindications for this drug.
- Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
- Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
- Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
- Chronic kidney disease stage 5 (failure) GFr<15 ml/min
- Kidney disease with likely reduction in glomerular filtration rate (GFr)
Adverse reactions
Adverse effects reported in 13% or more of patients receiving carglumic acid include infection, vomiting, abdominal pain, pyrexia, tonsilitis, anemia, ear infection, diarrhea, nasopharyngitis, and headache.
Less Frequent
- Influenza
Rare or Very Rare
- Bradycardia
- Maculopapular rash
- Manic disorder
More Frequent
- Acute abdominal pain
- Anemia
- Diarrhea
- Dysgeusia
- Fever
- Headache disorder
- Infection
- Otitis
- Pharyngitis
- Tonsillitis
- Vomiting
Less Frequent
- Anorexia
- Drowsy
- General weakness
- Hyperhidrosis
- Pneumonia
- Skin rash
- Weight loss
Rare or Very Rare
- Erythema
- Pruritus of skin
Precautions
No enhanced messaging available.
Efficacy of carglumic acid has been evaluated in neonates, infants, and children with hyperammonemia associated with N-acetylglutamate synthase (NAGS) deficiency. (See Uses: Hyperammonemia.) No substantial differences in response have been observed relative to adults; however, data are limited.
Category C. (See Users Guide.)
Carglumic acid is distributed into milk in rats. Increased mortality and impaired weight gain have been observed in nursing offspring of lactating rats receiving the drug. It is not known whether carglumic acid is distributed into human milk. Because of the potential for serious adverse reactions from carglumic acid in nursing infants, women receiving the drug should be advised not to breast-feed infants.
Safety and efficacy of carglumic acid have not been established in geriatric patients.
ICD codes
| Code | Type | Description |
|---|---|---|
| Hyperammonemia associated with n-acetylglutamate synthase deficiency | ||
| E72.29 | ICD10CM | Other disorders of urea cycle metabolism |
| Hyperammonemia due to methylmalonic acidemia | ||
| E71.120 | ICD10CM | Methylmalonic acidemia |
| Hyperammonemia due to propionic acidemia | ||
| E71.121 | ICD10CM | Propionic acidemia |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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