Carglumic acid

What is Carglumic acid?

• Carglumic acid (Carbaglu) is a carbamoyl phosphate synthetase 1 (CPS 1) activator used used for the treatment of hyperammonaemia.

Carglumic acid

What are the uses of this medicine?

This medicine is used in pediatric and adult patients as:

• Adjunctive therapy to standard of care for the treatment of acute hyperammonemia due to N-acetylglutamate synthase (NAGS) deficiency.
• Maintenance therapy for the treatment of chronic hyperammonemia due to NAGS deficiency.
• Adjunctive therapy to standard of care for the treatment of acute hyperammonemia due to propionic acidemia (PA) or methylmalonic acidemia (MMA).

How does this medicine work?

• Carglumic (kar gloo' mik) acid is a small molecule that resembles N-acetylglutamate, a normal occurring metabolite that activates the enzyme carbamoyl phosphate synthetase I (CPS-1), the first step in the urea cycle which is responsible for removal and detoxification of ammonia.
• Carglumic acid is used to treat the severe hyperammonemia that occurs in the urea cycle disorder caused by deficiency of hepatic N-acetylglutamate synthase (NAGS) which normally produces N-acetylglutamate.
• Carglumic acid was shown to decrease ammonia levels during acute exacerbation of NAGS deficiency as well as decreasing levels chronically between acute episodes.

Who Should Not Use this medicine ?

• This medicine have no usage limitations.

What drug interactions can this medicine cause?

• No formal drug interaction studies have been conducted with Carbaglu.

Is this medicine FDA approved?

• Carglumic acid was approved as oral therapy of NAGS deficiency in the United States in 2010.
• It has been used experimentally and off-label to treat other genetic as well as acquired causes of severe hyperammonemia including idiopathic cases due to valproate and cancer chemotherapy and secondary genetic cases due to organic acidurias such as isovaleric, methylmalonic and propionic aciduria.
• Carglumic acid is available in tablets of 200 mg under the brand name Carbaglu.

How should this medicine be used?

Recommended dosage: Acute Hyperammonemia due to NAGS deficiency:

• The recommended pediatric and adult dosage is 100 mg/kg/day to 250 mg/kg/day divided into 2 to 4 doses and rounded to the nearest 100 mg.

Chronic Hyperammonemia due to NAGS deficiency:

• The recommended pediatric and adult dosage is 10 mg/kg/day to 100 mg/kg/day divided into 2 to 4 doses and rounded to the nearest 100 mg.

Therapeutic Monitoring for NAGS Deficiency:

• Closely monitor plasma ammonia and titrate dosage to maintain the ammonia level within normal range for the patient's age, taking into consideration their clinical condition.

Acute Hyperammonemia due to propionic acidemia (PA) or methylmalonic acidemia (MMA): The recommended pediatric and adult dosage is:

• 150 mg/kg/day for patients less than or equal to 15 kg
• 3.3 g/m2/day for patients greater than 15 kg
• Divide the daily dosage into two equal doses and round up to the nearest 50 mg; administer each dose 12 hours apart.
• Continue treatment until ammonia level is less than 50 micromol/L and for a maximum duration of 7 days.

Administration:

• Carbaglu tablets for oral suspension (Carbaglu tablet) must be mixed in water before taking. Carbaglu tablets should not be mixed in any other food or liquid.
• Do not swallow Carbaglu tablets whole.
• Do not crush Carbaglu tablets.
• Take Carbaglu right before meals or feedings.
• The Carbaglu tablet and water mixture has a slightly sour taste.
• Carbaglu tablets dispersed in water can be administered orally or via a nasogastric tube or gastrostomy tube.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form: As Tablets for oral suspension: 200 mg, functionally scored

This medicine is available in fallowing brand namesː

• Carbaglu

What side effects can this medication cause?

The most common side effects of this medicine include: In NAGS deficiency:

• vomiting
• abdominal pain
• pyrexia
• tonsillitis
• anemia
• diarrhea
• ear infection
• infections
• nasopharyngitis
• hemoglobin decreased
• headache

In Acute hyperammonemia due to propionic acidemia (PA) or methylmalonic acidemia (MMA):

• neutropenia
• anemia
• vomiting
• electrolyte imbalance
• decreased appetite
• hypoglycemia
• lethargy/stupor
• encephalopathy
• pancreatitis/lipase increased

What special precautions should I follow?

• Monitor plasma ammonia levels during treatment. Prolonged exposure to elevated plasma ammonia levels can rapidly result in injury to the brain or death. Prompt use of all therapies necessary to reduce plasma ammonia levels is essential.
• Plasma ammonia levels should be maintained within normal range for age via individual dose adjustment.
• 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 increased with the goal of unrestricted protein intake.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• tachycardia
• profuse sweating
• increased bronchial secretions
• increased body temperature
• restlessness

Treatment of overdosage:

• All symptoms resolves upon reduction of the dose.

Can this medicine be used in pregnancy?

• Carbaglu use in pregnant women are insufficient to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
• Untreated NAGS deficiency, PA and MMA can result in irreversible neurologic damage and death in pregnant women.
• If Carbaglu is administered during pregnancy, health care providers should report Carbaglu exposure by calling 1-888-575-8344.

Can this medicine be used in children?

• The safety and effectiveness of Carbaglu for the treatment of pediatric patients (birth to 17 years of age) with acute or chronic hyperammonemia due to NAGS deficiency and acute hyperammonemia due to PA or MMA have been established.

What are the active and inactive ingredients in this medicine?

Active ingredient: CARGLUMIC ACID

Inactive ingredients: MICROCRYSTALLINE CELLULOSE SODIUM LAURYL SULFATE HYPROMELLOSE, UNSPECIFIED CROSCARMELLOSE SODIUM SILICON DIOXIDE SODIUM STEARYL FUMARATE

Who manufactures and distributes this medicine?

Distributed by: Recordati Rare Diseases Inc. Lebanon, NJ Carbaglu® is a licensed trademark of Recordati Rare Diseases.

What should I know about storage and disposal of this medication?

• Before opening, store Carbaglu in a refrigerator between 36°F to 46°F (2°C to 8°C) in the container it comes in.
• After opening, store Carbaglu at room temperature between 59°F to 86°F (15°C to 30°C). Do not store Carbaglu in a refrigerator after opening.
• Keep Carbaglu tablets in a tightly closed container to protect the tablets from moisture.
• Write the date the Carbaglu tablet container is opened on the container label. Throw away any unused tablets one month after opening the tablet container.
• Do not use Carbaglu tablets after the expiration date on the tablet container.
• Keep Carbaglu and all medicines out of the reach of children.

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• Dailymed label info on Carglumic acid
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