carglumic acid

(car-gloo-mik as-id) carglumicacid,

Carbaglu

(trade name)

Classification

Therapeutic: hyperammonemia treatments
Pharmacologic: enzyme activators
Pregnancy Category: C

Indications

Treatment (acute/maintenance) of hyperammonemia due to deficiency of hepatic enzyme N-acetylglutamate synthase (NAGS). During acute hyperammonemia, additional treatments should be used including alternate pathway medications, hemodialysis, and protein restriction.

Action

Serves as an analogue of N-acetyl glutamate (NAG), the natural activator of cabamoyl phosphate synthetase 1 (CPS 1) in the liver. CPS 1 helps to convert ammonia into urea. Carglumic acid replaces NAG in NAGS deficiency patients by activating CPS 1.

Therapeutic effects

↓ ammonia levels.

Pharmacokinetics

Absorption: Some absorption follows oral administration; bioavailability unknown.Distribution: .Metabolism and Excretion: Some metabolism by intestinal bacteria; 9% excreted unchanged in urine, 60% excreted unchanged in feces. Metabolic end product (CO₂) eliminated via lungs.Half-life: 5.6 hr.

Time/action profile (↓ ammonia levels)

ROUTE	ONSET	PEAK	DURATION
PO	within 24 hr	3 days	unknown

Contraindications/Precautions

Contraindicated in: Lactation: Breastfeeding not recommended.Use Cautiously in: Obstetric: Due to risk of neurologic complications in NAGS patients, carglumic acid must be used throughout pregnancy.

Adverse Reactions/Side Effects

Central nervous system

headache (most frequent)
drowsiness
weakness

Ear, Eye, Nose, Throat

nasopharyngitis (most frequent)

Gastrointestinal

abdominal pain (most frequent)
diarrhea (most frequent)
vomiting (most frequent)
abnormal taste

Dermatologic

rash

Hematologic

anemia (most frequent)

Metabolic

↓ weight

Miscellaneous

infections (most frequent)
fever (most frequent)

Interactions

Drug-Drug interaction

None noted.

Route/Dosage

Oral (Adults) 100–250 mg/kg/day initially, given in 2–4 divided doses immediately before meals/feedings, adjusted to maintain normal plasma ammonia levels based on age. Dose should be rounded to the nearest 100 mg.Oral (Children) 100–250 mg/kg/day initially, given in 2–4 divided doses immediately before meals/feedings.

Availability

Tablets: 200 mg

Nursing implications

Nursing assessment

Assess for hyperammonemia (neurological status, plasma ammonia levels) during therapy.
Lab Test Considerations: Monitor plasma ammonia levels periodically during therapy. Maintain within normal range for age via individual dose adjustment.
- May cause ↓ hemoglobin.

Potential Nursing Diagnoses

Activity intolerance

Implementation

Concommitant administration of other ammonia-lowering therapies is recommended.
Oral: Disperse each 250 mg tablet in at least 2.5 mL of water immediately before use and take immediately; do not crush or swallow whole. Tablets may not dissolve completely in water; undissolved particles may remain in mixing container. Rinse mixing container with additional volumes of water to ensure complete delivery of dose; swallow immediately. Administer via oral syringe or nasogastric tube.
- Refrigerate before opening. After first opening of container, do not refrigerate. Keep container tightly closed to protect from moisture. Write date of opening on tablet container; discard 1 mo after first opening. Do not use after expiration date stated on container.

Patient/Family Teaching

Instruct patient to take carglumic acid as directed.
Advise patient that during acute hyperammonemic episodes, protein restriction and hypercaloric intake is recommended to block ammonia generating catabolic pathways. When plasma ammonia levels have normalized, protein intake can usually be ↑ with goal of unrestricted protein intake.
Advise female patients to notify health care professional if pregnancy is planned or suspected or if breastfeeding Due to risk of neurologic complications in NAGS patients, carglumic acid must be used throughout pregnancy.

Evaluation/Desired Outcomes

Normalization of plasma ammonia levels.