Carglumic Acid
Hyperammonemia
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Drug Status
Government Approvals
US(FDA), UK(BNF)
WHO Essential Medicine
NO
Known Teratogen
No
Pharmaceutical Class
Carbamoyl Phosphate Synthetase 1 Activator
Controlled Drug Substance
No
Carglumic Acid
Summary
Carglumic Acid is used to treat acute and chronic hyperammonemia caused by N-acetylglutamate synthase (NAGS) deficiency. It's also used for acute hyperammonemia due to propionic acidemia (PA) or methylmalonic acidemia (MMA).
Carglumic Acid activates an enzyme in the urea cycle called carbamoyl phosphate synthetase 1. This helps convert ammonia into urea, which is then excreted from the body, reducing ammonia levels and preventing toxic accumulation.
For acute hyperammonemia due to NAGS deficiency, the daily dose is 100-250 mg/kg divided into 2-4 doses. For chronic hyperammonemia, the dose is 10-100 mg/kg divided into 2-4 doses. For acute hyperammonemia due to PA or MMA, the dose is 150 mg/kg for patients weighing 15 kg or less, or 3.3 gm for those weighing more than 15 kg, divided into 2 doses.
Common side effects of Carglumic Acid include vomiting (26% of patients), abdominal pain (17%), headache (13%), and decreased appetite (5%).
Carglumic Acid may be present in human milk, so breastfeeding mothers should weigh the benefits against potential risks. Pregnant women with NAGS deficiency should be closely monitored. Patients should inform their healthcare provider of all medications and supplements they are taking to avoid potential interactions. Side effects should be reported to a healthcare provider, who can adjust the dosage or treatment as necessary.
Indications and Purpose
How does Carglumic Acid work?
Carglumic Acid acts as an activator of carbamoyl phosphate synthetase 1, a key enzyme in the urea cycle. This activation helps convert ammonia, a toxic byproduct of protein metabolism, into urea, which is then excreted in the urine. This process reduces ammonia levels in the blood, preventing potential neurological damage.
Is Carglumic Acid effective?
Carglumic Acid's effectiveness is supported by clinical studies and retrospective case series. In patients with NAGS deficiency, it rapidly normalizes plasma ammonia levels, usually within 24 hours. In a clinical trial for PA and MMA, it reduced the time to reach normal ammonia levels compared to placebo, demonstrating its efficacy in managing hyperammonemia.
What is Carglumic Acid?
Carglumic Acid is used to treat hyperammonemia due to NAGS deficiency, PA, and MMA. It works by activating carbamoyl phosphate synthetase 1, a liver enzyme crucial for the urea cycle, which helps convert ammonia into urea for excretion. This process reduces toxic ammonia levels in the blood, preventing neurological damage.
Directions for Use
For how long do I take Carglumic Acid?
The duration of use for Carglumic Acid depends on the condition being treated. For acute hyperammonemia, treatment continues until ammonia levels are normalized, typically within a few days. For chronic conditions, Carglumic Acid may be used long-term to maintain normal ammonia levels, with treatment duration potentially spanning years under medical supervision.
How do I take Carglumic Acid?
Carglumic Acid should be taken immediately before meals or feedings. The tablets must be dispersed in water and should not be swallowed whole or crushed. There are no specific food restrictions, but it is important to follow any dietary advice given by your healthcare provider, especially regarding protein intake.
How long does it take for Carglumic Acid to start working?
Carglumic Acid typically starts working within 24 hours to reduce plasma ammonia levels when administered for hyperammonemia. The exact time may vary depending on the individual's condition and response to treatment.
How should I store Carglumic Acid?
Store unopened Carglumic Acid bottles in a refrigerator at 2°C to 8°C (36°F to 46°F). After opening, store at room temperature between 15°C and 30°C (59°F and 86°F) and keep the bottle tightly closed to protect from moisture. Discard the bottle one month after opening and do not use it past the expiration date.
What is the usual dose of Carglumic Acid?
The usual daily dose of Carglumic Acid for both adults and children varies based on the condition being treated. For acute hyperammonemia due to NAGS deficiency, the dose ranges from 100 mg/kg to 250 mg/kg daily, divided into 2 to 4 doses. For chronic hyperammonemia, the dose ranges from 10 mg/kg to 100 mg/kg daily, also divided into 2 to 4 doses. For acute hyperammonemia due to PA or MMA, the dose is 150 mg/kg daily for patients weighing 15 kg or less, and 3.3 g/m² daily for those over 15 kg, divided into 2 doses.
Warnings and Precautions
Can Carglumic Acid be taken safely while breastfeeding?
It is not known if Carglumic Acid is present in human milk, but it is found in the milk of treated rats. The potential effects on a breastfed infant are unknown. Mothers should consider the benefits of breastfeeding along with their need for the medication and consult their healthcare provider for guidance.
Can Carglumic Acid be taken safely while pregnant?
There is limited data on the use of Carglumic Acid during pregnancy. Untreated NAGS deficiency, PA, and MMA can cause serious harm to both mother and fetus. Pregnant women should consult their healthcare provider to weigh the benefits and risks. A pregnancy exposure registry is available to monitor outcomes.
Is Carglumic Acid safe for the elderly?
Clinical studies of Carglumic Acid did not include patients 65 years and older, so it is unclear if they respond differently from younger patients. Elderly patients should use this medication under close medical supervision, considering potential age-related health issues and the need for dosage adjustments.
Who should avoid taking Carglumic Acid?
Carglumic Acid has no specific contraindications listed, but it should be used with caution in patients with renal impairment, requiring dosage adjustments. Regular monitoring of plasma ammonia levels is essential to ensure safety and effectiveness. Patients should also be aware of potential side effects and consult their healthcare provider if they experience any adverse reactions.
