(kar GLU mik AS id)
- N-Carbamoyl-L-Glutamic Acid
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Carbaglu: 200 mg [scored]
Brand Names: U.S.
- Metabolic Alkalosis Agent
- Urea Cycle Disorder (UCD) Treatment Agent
N-acetylglutamate synthase (NAGS) is a mitochondrial enzyme which produces N-acetylglutamate (NAG). NAG is a required allosteric activator of the hepatic mitochondrial enzyme, carbamoyl phosphate synthetase 1 (CPS 1), which converts ammonia into urea in the first step of the urea cycle. In NAGS-deficient patients, carglumic acid serves as a replacement for NAG.
Vd: ~2657 L
Via intestinal flora to carbon dioxide
Feces (≤60% as unchanged drug); urine (9% as unchanged drug)
Time to Peak
Median: 3 hours
Median: 5.6 hours (range: 4.3 to 9.5 hours)
Use: Labeled Indications
Hyperammonemia: Adjunctive treatment of acute hyperammonemia and maintenance therapy of chronic hyperammonemia due to the deficiency of the hepatic enzyme N-acetylglutamate synthase (NAGS) in adult and pediatric patients
There are no contraindications listed in the US labeling.
Canadian labeling: Hypersensitivity to carglumic acid or any component of the formulation; breast-feeding
Acute hyperammonemia: Infants, Children, Adolescents, and Adults: Oral: 100 to 250 mg/kg/day given in 2 or 4 divided doses (rounded to the nearest 100 mg for adults); titrate to age-appropriate plasma ammonia levels. Concomitant adjunctive ammonia-lowering therapy recommended.
Note: Prior to initiating long-term therapy the Canadian labeling recommends a test dose to determine responsiveness; examples of test dosing include:
Comatose child: 100 to 250 mg/kg/day in 2 to 4 divided doses; measure plasma ammonia levels at least prior to each administration; ammonia levels should normalize within a few hours of therapy initiation
Moderate hyperammonemia: 100 to 200 mg/kg/day in 2 to 4 divided doses for 3 days with a consistent protein intake; measure plasma ammonia levels before and 1 hour after a meal; dose should be adjusted to maintain normal ammonia levels
Chronic hyperammonemia: Infants, Children, Adolescents, and Adults: Oral:
US labeling: Usual dose (based on limited data): <100 mg/kg/day given in 2 or 4 divided doses; titrate to age-appropriate normal plasma ammonia levels
Canadian labeling: Dosing range: 10 mg/kg to 100 mg/kg/day in 2 to 4 divided doses; titrate to age-appropriate normal plasma ammonia levels.
Dosage adjustment in renal impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Dosage adjustment in hepatic impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Oral: Each 200 mg tablet should be dispersed in at least 2.5 mL of water (no other foods/liquids) and administered immediately.
Oral syringe: Disperse each 200 mg tablet in 2.5 mL of water to yield a concentration of 80 mg/mL (shake gently in container). Appropriate volume of dispersion should be drawn up in an oral syringe and administered immediately (discard unused dispersion).
Nasogastric tube: Disperse each 200 mg tablet in water (2.5 mL per tablet for pediatric patients; ≥2.5 mL per tablet for adults) and shake gently; administer immediately.
Administer immediately prior to meals or feedings. Disperse in water prior to administration; should not be mixed with any other foods or liquids other than water .
Oral: Tablets should not be crushed or swallowed whole. After dispersion in water, administer immediately. Tablets do not dissolve completely, and some particles may remain; rinse container with water and administer rinse immediately.
Oral syringe: After dispersion of tablets in water, draw up appropriate volume and administer immediately (discard unused dispersion). After initial administration, refill oral syringe with a minimum of 1 to 2 mL of water and administer immediately.
Nasogastric tube: After dispersion of tablets in water, immediately administer through a nasogastric tube (tablets do not dissolve completely; some particles may remain). Follow with a flush with additional water to clear the tube.
Take immediately prior to meals or feedings.
Before opening, store refrigerated at 2°C to 8°C (36°F to 46°F). After opening, do not refrigerate or store above 30°C (86°F). Protect from moisture. Discard 1 month after opening.
There are no known significant interactions.
Central nervous system: Fever (17%), headache (13%)
Gastrointestinal: Vomiting (26%), abdominal pain (17%), diarrhea (13%)
Hematologic: Anemia (13%)
Otic: Ear infection (13%)
Respiratory: Tonsillitis (17%), nasopharyngitis (13%)
Miscellaneous: Infections (13%)
1% to 10%:
Central nervous system: Somnolence (9%)
Dermatologic: Hyperhidrosis (9%), rash (9%)
Gastrointestinal: Anorexia (9%), dysgeusia (9%), weight loss (9%)
Neuromuscular & skeletal: Weakness (9%)
Respiratory: Pneumonia (9%)
Miscellaneous: Influenza (9%)
• Experienced physician: Acute symptomatic hyperammonemia is a life-threatening emergency; management of hyperammonemia due to N-acetylglutamate synthase (NAGS) deficiency should be done in coordination with those experienced in the management of metabolic disorders.
• Nutritional management: Since hyperammonemia is the result of protein catabolism, complete protein restriction is recommended to be maintained for 24-48 hours and caloric supplementation should be maximized to reverse catabolism and nitrogen turnover.
Plasma ammonia; monitor for physical signs/symptoms of hyperammonemia (eg, lethargy, ataxia, confusion, vomiting, seizures, and memory impairment). Canadian labeling also recommends hepatic, renal, hematologic, and cardiac monitoring (limited safety data).
Pregnancy Risk Factor
Adverse events have been observed in animal reproduction studies. There are no adequate and well-controlled studies in pregnant women. However, due to the potential for irreversible fetal neurologic damage for untreated NAGS deficiency, women with this condition must remain on treatment throughout pregnancy.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache, diarrhea, dyspepsia, pharyngitis, or nausea. Have patient report immediately to prescriber signs of infection, illogical thinking, significant change in balance, hyperhidrosis, lack of appetite, or severe asthenia (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
More about carglumic acid
- Other brands: Carbaglu