Carglumic Acid

Pronunciation: kar-GLOO-mik AS-id
Class: Metabolic agent

Trade Names

Carbaglu
- Tablets, dispersible, oral 200 mg

Pharmacology

Carglumic acid is a synthetic structural analogue of N-acetylglutamate, which is an essential allosteric activator of carbamoyl phosphate synthetase 1 in liver mitochondria, which converts ammonia into urea.

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Pharmacokinetics

Absorption

T max is 3 h.

Distribution

Vd is 2,657 L.

Metabolism

Metabolized by intestinal bacterial flora, resulting in carbon dioxide eliminated through the lungs.

Elimination

Terminal half-life is 5.6 h. Total Cl is 5.7 L/min and renal Cl is 290 mL/min. Approximately 9% of the dose is excreted unchanged in the urine and up to 60% is excreted unchanged in the feces.

Indications and Usage

Adjunctive therapy in the treatment of acute hyperammonemia and maintenance therapy of chronic hyperammonemia caused by deficiency of the hepatic enzyme N-acetylglutamate synthase.

Contraindications

None well documented.

Dosage and Administration

Adults and Children

PO 100 to 250 mg/kg/day initially divided into 2 to 4 doses for acute hyperammonemia. Maintenance dosage is usually less than 100 mg/kg/day. Titrate to a target normal plasma ammonia level for age. Coadministration of other ammonia-lowering therapies is recommended.

General Advice

  • Tablets should not be swallowed whole or crushed. Disperse tablets in water (minimum of 2.5 mL) immediately before use.
  • Tablets may be administered orally or through a nasogastric (NG) tube.
  • Divide the total daily dose into 2 to 4 doses and administer immediately before meals or feedings.
  • Each divided dose should be rounded to the nearest 100 mg.
NG tube
  • Mix each 200 mg tablet in at least 2.5 mL of water for adults, and in 2.5 mL of water for children to yield a concentration of 80 mg/mL.
  • Shake gently for quick dispersal and administer the dispersion immediately through the NG tube. Flush with additional water to clear the NG tube.
Oral administration
  • Disperse each 200 mg tablet in at least 2.5 mL of water for adults, and in 2.5 mL of water for children to yield a concentration of 80 mg/mL.
  • To ensure complete delivery of the dose, the container should be rinsed with additional volumes of water and the contents swallowed immediately.
  • For children, draw up the appropriate volume of dispersion in syringe and administer immediately. Refill the syringe with a minimum of 1 to 2 mL of water and administer immediately.

Storage/Stability

Before opening tablets, store refrigerated between 36° and 46°F. After opening the container, do not refrigerate or store above 86°F. Protect from moisture. Write the date of opening on the container and discard 1 mo after first opening.

Drug Interactions

None well documented.

Adverse Reactions

CNS

Asthenia, headache, somnolence.

Dermatologic

Hyperhidrosis, rash.

GI

Abdominal pain, diarrhea, dysgeusia, vomiting.

Hematologic

Anemia, decreased hemoglobin.

Metabolic-Nutritional

Anorexia, decreased weight.

Respiratory

Nasopharyngitis, pneumonia, tonsillitis.

Miscellaneous

Ear infection, infection, influenza, pyrexia.

Precautions

Monitor

To assess patient response to treatment, ongoing monitoring of plasma ammonia levels, neurological status, laboratory tests, and clinical response in patients is recommended. Maintain plasma ammonia levels within the normal range for age via individual dosage adjustment.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy have been established.

Hyperammonemia

Treatment may require dialysis, preferably hemodialysis, to remove a large burden of ammonia. Uncontrolled hyperammonemia can rapidly result in brain injury/damage or death, and prompt use of all therapies necessary to reduce plasma ammonia levels is essential.

Nutritional management

Protein restriction and hypercaloric intake is recommended to block ammonia-generating catabolic pathways during acute hyperammonemic episodes. When plasma ammonia levels have normalized, protein intake can usually be increased with the goal of unrestricted protein intake.

Overdosage

Symptoms

Increased body temperature, increased bronchial secretion, profuse sweating, restlessness, tachycardia.

Patient Information

  • Advise patients to administer the tablets immediately before meals or feedings.
  • Instruct patients that the tablets should not be swallowed whole or crushed and that each tablet should be dispersed in a minimum of 2.5 mL of water.
  • Inform patients that not all of the tablet will dissolve completely in water and undissolved particles of the tablet may remain in the mixing container. The mixing container should be rinsed with additional volumes of water and the contents swallowed immediately.
  • Instruct patients on the proper storage of the tablets. Before opening the tablets, they should be stored in a refrigerator and kept in a tightly closed container to protect from moisture. After the first opening of the container, do not refrigerate the tablets or store above 86°F. Write the date of opening on the tablet container and discard 1 mo after the first opening.
  • Inform patients that when plasma ammonia levels have normalized, dietary protein intake can usually be increased with the goal of unrestricted protein intake.
  • Advise patients that breast-feeding is not recommended.
  • Inform patients that the most common adverse reactions are abdominal pain, anemia, diarrhea, ear infection, headache, nasopharyngitis, pyrexia, tonsillitis and vomiting.

Copyright © 2009 Wolters Kluwer Health.

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