carglumic acid (Rx)

Brand and Other Names:Carbaglu
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

dispersible tablet

  • 200mg

Hyperammonemia

Initial dose

  • 100-250 mg/kg/day PO/NG divided in 2-4 doses immediately before meals; round total daily dose to nearest 100 mg  
  • Concomitant administration of other ammonia lowering therapies is recommended

Maintenance dose

  • 10-100 mg/kg/day PO/NG divided in 2-4 doses immediately before meals; round total daily dose to nearest 100 mg

Dosing Considerations

Closely monitor plasma ammonia levels

Titrate dosage to maintain the plasma ammonia level within the normal range for the patient’s age, taking into consideration their clinical condition (eg, nutritional requirements, protein intake, growth parameters)

Dosage Forms & Strengths

dispersible tablet

  • 200mg

Hyperammonemia

Initial dose

  • 100-250 mg/kg/day PO/NG divided in 2-4 doses immediately before meals or feedings; round total daily dose to nearest 100 mg  
  • Concomitant administration of other ammonia lowering therapies is recommended

Maintenance dose

  • 10-100 mg/kg/day PO/NG divided in 2-4 doses immediately before meals or feedings; round total daily dose to nearest 100 mg

Dosing Considerations

Closely monitor plasma ammonia levels

Titrate dosage to maintain the plasma ammonia level within the normal range for the patient’s age, taking into consideration their clinical condition (eg, nutritional requirements, protein intake, growth parameters)

Next:

Adverse Effects

Note: Adverse effects are derived from retrospective case series of 23 patients

>10%

Vomiting (26%)

Abdominal pain (17%)

Pyrexia (17%)

Tonsillitis (17%)

Anemia (13%)

Ear infection (13%)

Diarrhea (13%)

Nasopharyngitis (13%)

Headache (13%)

1-10%

Asthenia (9%)

Somnolence (9%)

Dysgeusia (9%)

Hyperhidrosis (9%)

Weakness (9%)

Pneumonia (9%)

Anorexia (9%)

Weight loss (9%)

Influenza (9%)

Rash (9%)

Previous
Next:

Warnings

Contraindications

None

Cautions

Hyperammonemia

  • Monitor serum ammonia levels and adjust dose to maintain within normal range for age
  • Treat acute hyperammonemia episode as life-threatening emergency
  • Treatment of severe hyperammonemia may require dialysis, preferably hemodialysis and/or hemofiltration, to reduce plasma ammonia concentration
  • Untreated hyperammonemia can result in brain damage and death, and prompt use of all therapies necessary to reduce plasma ammonia level is essential
  • Protein restriction during an acute hyperammonemic episode is recommended for no longer than 12-36 hr while maximizing caloric supplementation to reverse catabolism; protein should be reintroduced as early as possible, following improvement of metabolic and clinical abnormalities in this setting; during long-term management, dietary protein restriction should be instituted to maintain blood ammonia level within an acceptable range for age
  • Ongoing monitoring of plasma ammonia level, neurological status, growth parameters, protein intake/nutritional status (both during acute hyperammonemic episodes and long-term), and relevant laboratory tests in patients receiving therapy should be part of evaluating clinical response to treatment
Previous
Next:

Pregnancy & Lactation

Pregnancy

Rare case reports of use in pregnant women are insufficient to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Pregnancy pharmacovigilance program for carglumic acid exposures: 1-888-575-8344

Clinical considerations

  • Pregnant women with urea cycle disorders may experience an increase in catabolic stress which can trigger a hyperammonemic crisis both in the intrapartum and in the post-partum (3-14 days post-partum) periods
  • Mternal complications related to hyperammonemic crisis can include neurological impairment, coma and in some cases death

Animal data

  • In an animal reproduction study, decreased survival and growth occurred in offspring born to rats that received carglumic acid at a dose approximately 38 times maximum reported human maintenance dose

Lactation

It is not known whether drug is excreted in human milk; it is excreted in rat milk, and an increase in mortality and impairment of body weight gain occurred in neonatal rats nursed by mothers receiving carglumic acid; because many drugs are excreted in human milk and because of potential for serious adverse reactions in nursing infants from therapy, breast-feeding is not recommended; treatment is continuous and life-long for NAGS deficiency patients

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Previous
Next:

Pharmacology

Mechanism of Action

Structural analogue of N-acetylglutamate (NAG), which is produced from glutamate and acetyl-CoA in a reaction catalyzed by N-acetylglutamate synthase (NAGS), a mitochondrial liver enzyme

NAG acts as an essential allosteric activator of carbamoyl phosphate synthetase 1 (CPS 1), a mitochondrial liver enzyme which catalyzes the first reaction of the urea cycle

Carglumic acid acts as a CPS1 activator in patients with NAGS deficiency, thereby removing the block in the urea cycle and facilitating ammonia detoxification and urea production

Pharmacokinetics

Half-Life: 5.6 hr

Bioavailability: Absolute biovailability is not known

Vd: 2657 L

Peak plasma time: 3 hr (range: 2-4 hr)

Metabolism: Portion metabolized by intestinal bacterial flora; likely end product is carbon dioxide eliminated via lungs

Renal clearance: 5.7 L/min (total); 290 mL/min (renal)

Excretion: unchanged in feces (60%) and urine (9%)

Previous
Next:

Administration

Preparation

Add ~2.5 mL of water into a small cup for each 200-mg tablet or each half tablet needed for the prescribed dose

Tablets do not dissolve completely in water and undissolved tablet particles may remain in the mixing container

Add tablet(s) to water in cup

Carefully stir the tablet and water mixture and administer immediately

Oral Administration

Do not swallow tablet whole or crush

Take immediately before meals or feedings

Suspension has a slightly acidic taste

For all preparations, use in foods or liquids, other than water, has not been studied clinically and is not recommended

Orally

  • Swallow mixture immediately after dispersing tablet
  • Pieces of tablet may remain in the cup
  • Rinse the cup with additional water and swallow the mixture immediately; repeat as needed until no tablet pieces are left in the cup

Nasogastric

  • Draw up mixture into a catheter-tip syringe
  • Administer mixture immediately through the nasogastric (NG) tube
  • Pieces of tablet may remain in the catheter-tip syringe or NG tube
  • Flush immediately with 1-2 mL of additional water to clear NG tube
  • Flush the NG tube again, as needed, until no pieces of tablet are left in syringe or NG tube

Oral syringe

  • Draw up mixture in oral syringe and administer immediately
  • Pieces of tablet may remain in oral syringe
  • Refill oral syringe with a minimum volume of water (1-2 mL) and administer immediately
  • Flush oral syringe again, as needed, until no pieces of tablet are left in syringe

Storage

Store in original unopened container at 2-8ºC (36-46ºF)

After opening container

  • Do not refrigerate, store at room temperature between 15-30ºC (59-86ºF)
  • Keep container tightly closed between openings to protect from moisture
  • Write the date of opening on the tablet container
  • Do not use after the expiration date stated on the tablet container
  • Discard 1 month after first opening
Previous
Next:

Images

Previous
Next:

Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
  • Manage and view all your plans together – even plans in different states.
  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
Additional Offers
Email to Patient

From:

To:

The recipient will receive more details and instructions to access this offer.

By clicking send, you acknowledge that you have permission to email the recipient with this information.

Email Forms to Patient

From:

To:

The recipient will receive more details and instructions to access this offer.

By clicking send, you acknowledge that you have permission to email the recipient with this information.

Previous
Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.