Ucedane (Carglumic Acid)
Treatment for hyperammonaemia in N-acetylglutamate synthase deficiency and organic acidaemias
Quick facts about Ucedane
Key takeaways about Ucedane
- Treats dangerously high ammonia: Ucedane is used to lower life-threatening ammonia levels caused by NAGS deficiency and organic acidaemias
- Lifelong treatment for NAGS deficiency: Patients with this rare inherited disorder require continuous treatment to prevent ammonia build-up
- Specialist supervision required: Treatment must be initiated and monitored by a physician experienced in metabolic diseases
- Dose adjusted individually: Dosing is based on body weight and tailored to maintain normal ammonia levels in each patient
- Cannot breastfeed: Breastfeeding must be avoided during treatment as the drug passes into breast milk
What Is Ucedane and What Is It Used For?
Ucedane (carglumic acid) is a prescription medicine used to treat hyperammonaemia – dangerously elevated ammonia levels in the blood. It is the primary treatment for N-acetylglutamate synthase (NAGS) deficiency and is also used during hyperammonaemic crises in isovaleric acidaemia, methylmalonic acidaemia, and propionic acidaemia.
Ammonia is a toxic by-product of protein metabolism that is normally converted to urea by the urea cycle in the liver and then excreted by the kidneys. When the urea cycle does not function properly, ammonia accumulates in the blood to dangerous levels – a condition known as hyperammonaemia. Elevated ammonia is particularly harmful to the brain and, in severe cases, can lead to reduced consciousness, seizures, brain damage, and even coma or death.
Ucedane contains carglumic acid, which is a structural analogue of N-acetylglutamate (NAG). NAG is the natural activator of carbamoyl phosphate synthetase 1 (CPS 1), the first enzyme in the urea cycle. By replacing the function of the missing or deficient NAG, carglumic acid restores urea cycle activity and allows the body to convert ammonia into urea safely. This mechanism makes Ucedane uniquely effective in conditions where NAG production is impaired.
NAGS deficiency
N-acetylglutamate synthase (NAGS) deficiency is an extremely rare autosomal recessive metabolic disorder in which the body cannot produce enough N-acetylglutamate to activate the urea cycle. Without treatment, affected patients – most commonly diagnosed in the neonatal period – develop severe hyperammonaemia that can be fatal. Ucedane provides exogenous replacement for the missing NAG, effectively restoring the urea cycle. Treatment for NAGS deficiency is lifelong, as the underlying genetic defect is permanent.
NAGS deficiency is estimated to affect fewer than 1 in 2,000,000 live births worldwide, making it one of the rarest urea cycle disorders. Despite its rarity, early recognition and prompt initiation of carglumic acid therapy can be life-saving and dramatically improve long-term neurological outcomes. Affected patients who are treated early often achieve normal cognitive development and quality of life.
Organic acidaemias
Ucedane is also indicated for the acute treatment of hyperammonaemia during metabolic crises in patients with certain organic acidaemias, specifically:
- Isovaleric acidaemia (IVA): A disorder of leucine metabolism caused by isovaleryl-CoA dehydrogenase deficiency
- Methylmalonic acidaemia (MMA): Caused by deficiency of methylmalonyl-CoA mutase or related cofactor deficiencies
- Propionic acidaemia (PA): Caused by propionyl-CoA carboxylase deficiency
In these conditions, the accumulation of organic acids inhibits the production of N-acetylglutamate by NAGS, effectively causing a secondary functional impairment of the urea cycle. By providing a synthetic NAG analogue, Ucedane bypasses this inhibition and restores ammonia detoxification during acute crises. Unlike in NAGS deficiency, treatment in organic acidaemias is typically administered only during acute hyperammonaemic episodes rather than as continuous long-term therapy.
The urea cycle is a series of six enzymatic reactions in the liver that converts toxic ammonia into urea, which is then safely excreted by the kidneys in urine. The cycle requires the activation of its first enzyme, CPS 1, by N-acetylglutamate. When NAG is absent or insufficient – either because NAGS itself is deficient or because organic acids inhibit NAGS activity – the entire urea cycle stalls and ammonia accumulates. Ucedane solves this problem by acting as a synthetic replacement for NAG.
What Should You Know Before Taking Ucedane?
Do not take Ucedane if you are allergic to carglumic acid or any of the other ingredients. Breastfeeding must be stopped during treatment. Treatment should only be started under the supervision of a physician experienced in metabolic diseases, and regular monitoring of liver, kidney, cardiac, and haematological parameters is required.
Contraindications
Ucedane must not be used in the following situations:
- Allergy to carglumic acid or any of the other ingredients in the tablets (microcrystalline cellulose, colloidal anhydrous silica, sodium stearyl fumarate, mannitol, copovidone K28, crospovidone type B)
- Breastfeeding: You must not breastfeed while taking Ucedane, as carglumic acid has been shown to pass into breast milk in animal studies with potential toxic effects on nursing offspring
It is essential to inform your doctor about all known allergies before starting treatment. Although allergic reactions to carglumic acid are very rare given the small patient population, any signs of hypersensitivity such as rash, swelling, or difficulty breathing should be reported immediately.
Warnings and precautions
There are several important precautions to be aware of before and during treatment with Ucedane:
- Specialist supervision: Treatment must be initiated under the supervision of a physician experienced in the management of metabolic diseases. This ensures correct diagnosis, appropriate dosing, and adequate monitoring
- Treatment evaluation: Your doctor will evaluate your individual response to carglumic acid before committing to long-term treatment. Not all patients respond equally, and dose adjustments may be needed
- Individual dose adjustment: The dose must be adjusted individually to maintain normal plasma ammonia levels. Too low a dose may result in inadequate ammonia control, while excessively high doses may increase the risk of side effects
- Dietary management: Your doctor may prescribe arginine supplementation or recommend restricting your protein intake as part of a comprehensive management plan alongside Ucedane treatment
- Regular monitoring: To track your condition and treatment response, your doctor will need to perform regular assessments of liver function, kidney function, cardiac function, and blood parameters
Plasma ammonia levels must be monitored regularly during treatment. Elevated ammonia can cause irreversible brain damage if not promptly treated. If you notice signs of worsening hyperammonaemia – such as unusual drowsiness, confusion, vomiting, or difficulty staying alert – contact your healthcare provider immediately or seek emergency medical attention.
Pregnancy and breastfeeding
The effects of Ucedane on pregnancy and the developing foetus are not known. No clinical studies have been conducted in pregnant women, and the available preclinical data are limited. If you are pregnant, think you may be pregnant, or are planning to become pregnant, you should consult your doctor or pharmacist before using this medicine. Your physician will carefully weigh the potential benefits against the unknown risks before recommending treatment during pregnancy.
Breastfeeding is contraindicated during Ucedane treatment. Studies in lactating rats demonstrated that carglumic acid passes into breast milk and may cause harmful effects in nursing offspring. Since it has not been studied in human breast milk, the precautionary principle applies, and women taking Ucedane must use alternative feeding methods for their infants.
Driving and using machines
The effects of Ucedane on the ability to drive and use machines are not known. However, it is important to note that the underlying condition being treated – hyperammonaemia – can itself cause drowsiness, confusion, and impaired consciousness. Patients should be aware of their own ammonia status and neurological condition before engaging in activities that require full alertness.
Sodium content
Ucedane contains less than 1 mmol sodium (23 mg) per maximum daily dose, meaning it is essentially sodium-free. This is relevant for patients who are on a controlled sodium diet, as they can be reassured that Ucedane will not contribute significantly to their sodium intake.
How Does Ucedane Interact with Other Drugs?
No specific drug interactions with Ucedane have been identified in clinical studies. However, as with all medicines, you should inform your doctor about all medications you are currently taking, have recently taken, or plan to take, including over-the-counter medicines and supplements.
Because Ucedane is used to treat very rare metabolic disorders, the patient population studied in clinical trials has been small. This means that rare or uncommon drug interactions may not yet have been identified. The mechanism of action of carglumic acid – acting as a structural analogue of N-acetylglutamate to activate CPS 1 – is highly specific to the urea cycle and does not involve the cytochrome P450 enzyme system that mediates most common drug interactions.
Patients with NAGS deficiency or organic acidaemias often receive multiple other treatments as part of their overall metabolic management plan. These may include:
| Medication | Purpose | Interaction Status |
|---|---|---|
| Arginine | Urea cycle substrate supplementation | No known interaction; often co-prescribed |
| Sodium benzoate | Alternative ammonia scavenging pathway | No known interaction; may be used in acute crises |
| Sodium phenylbutyrate | Alternative ammonia scavenging pathway | No known interaction; may be used in combination |
| L-carnitine | Supports mitochondrial fatty acid oxidation | No known interaction; commonly used in organic acidaemias |
| Glycine (in IVA) | Conjugates with isovaleryl-CoA for excretion | No known interaction; specific to isovaleric acidaemia |
Although no specific interactions have been formally identified, patients should always keep their metabolic specialist informed of any changes to their medication regimen, including herbal supplements, vitamins, or over-the-counter medicines. Some dietary supplements that alter protein metabolism or nitrogen balance could theoretically interact with the overall management strategy for hyperammonaemia.
Carglumic acid acts through a highly specific mechanism (CPS 1 activation) that does not involve hepatic cytochrome P450 enzymes. Nevertheless, given the severity of hyperammonaemia and the vulnerability of the patient population, any new concomitant medication should be introduced with caution, and ammonia levels should be monitored closely during the transition period.
What Is the Correct Dosage of Ucedane?
The usual initial dose of Ucedane is 100 mg per kg of body weight per day, with a maximum of 250 mg/kg/day. For long-term use in NAGS deficiency, the maintenance dose typically ranges from 10 to 100 mg/kg/day, individually adjusted based on plasma ammonia levels. Always take this medicine exactly as your doctor prescribes.
Ucedane dosing is highly individualised and depends on several factors, including the patient's body weight, the severity of hyperammonaemia, the underlying condition, and the individual response to treatment. Your doctor will determine the appropriate dose for you and may adjust it over time based on regular monitoring of plasma ammonia levels.
NAGS deficiency – initial and maintenance dosing
Initial treatment
The recommended initial daily dose is 100 mg per kg of body weight, up to a maximum of 250 mg/kg/day. For example, a patient weighing 10 kg would receive 1,000 mg (1 g) per day, equivalent to 5 dispersible tablets.
Long-term maintenance
Once ammonia levels are stabilised, the maintenance dose typically ranges between 10 mg and 100 mg per kg of body weight per day. The dose is carefully titrated to maintain normal plasma ammonia levels while minimising the potential for side effects.
Organic acidaemias – acute crisis dosing
During hyperammonaemic crisis
For patients with isovaleric acidaemia, methylmalonic acidaemia, or propionic acidaemia who develop hyperammonaemia during acute metabolic crises, the dose is determined by the treating physician based on the severity of ammonia elevation and the patient's clinical status. Treatment is typically continued until ammonia levels return to normal.
| Patient Group | Condition | Initial Dose | Maintenance Dose |
|---|---|---|---|
| Neonates / Infants | NAGS deficiency | 100 mg/kg/day | 10–100 mg/kg/day |
| Children | NAGS deficiency | 100 mg/kg/day | 10–100 mg/kg/day |
| Adults | NAGS deficiency | 100 mg/kg/day (max 250 mg/kg/day) | 10–100 mg/kg/day |
| All ages | Organic acidaemias (acute crisis) | As determined by specialist | Until ammonia normalises |
How to take Ucedane
Ucedane dispersible tablets should be taken before meals or feedings. The tablets must be dissolved in at least 5 to 10 ml of water and taken immediately. The resulting suspension has a slightly acidic taste. The tablets are designed to be easily split into four equal doses thanks to the scoring on both sides.
For patients who cannot take medicine by mouth – particularly neonates or patients in hyperammonaemic coma – the dissolved tablet suspension can be administered via a nasogastric tube using a syringe. In emergency situations involving hyperammonaemic coma, the dose can be rapidly delivered through the nasogastric tube to begin lowering ammonia levels as quickly as possible.
Renal impairment
If you have impaired kidney function, your doctor should reduce your daily dose accordingly. Since carglumic acid and its metabolites are primarily excreted by the kidneys, reduced renal function can lead to accumulation and potentially increased side effects. Your doctor will use your kidney function parameters to determine the appropriate dose reduction.
Missed dose
If you forget to take a dose of Ucedane, do not take a double dose to make up for the missed one. Simply take your next dose at the usual scheduled time and continue with your normal dosing regimen. Missing doses can lead to a rise in ammonia levels, so it is important to maintain a consistent dosing schedule. If you frequently forget doses, speak with your doctor or pharmacist about strategies to help you remember.
Overdose
If you take more Ucedane than prescribed, contact your doctor or pharmacist immediately. While specific information about overdose effects is limited due to the rarity of the condition and the small patient population, medical supervision is recommended to monitor for any unexpected effects and to check ammonia and other metabolic parameters.
Never stop taking Ucedane without consulting your doctor first. In patients with NAGS deficiency, abrupt discontinuation can lead to a rapid and dangerous rise in blood ammonia levels, which may result in hyperammonaemic crisis, brain damage, coma, or death. If you are experiencing side effects, discuss them with your doctor who can adjust your dose rather than stopping treatment entirely.
What Are the Side Effects of Ucedane?
Like all medicines, Ucedane can cause side effects, although not everyone experiences them. Common side effects include increased sweating. Uncommon side effects include bradycardia (decreased heart rate), diarrhoea, fever, elevated liver enzymes (transaminases), and vomiting. Rash has also been reported.
Clinical experience with Ucedane is limited by the rarity of the conditions it treats, so the full spectrum of potential side effects may not yet be completely characterised. The side effects reported to date have generally been manageable and should be discussed with your healthcare provider if they occur or become bothersome.
It is important to distinguish between side effects of the medicine itself and symptoms of the underlying metabolic condition. Patients with urea cycle disorders and organic acidaemias can experience a range of symptoms related to their disease, including neurological changes, gastrointestinal problems, and metabolic instability, which may overlap with potential drug side effects.
Common
May affect up to 1 in 10 patients
- Increased sweating (hyperhidrosis)
Uncommon
May affect up to 1 in 100 patients
- Bradycardia (decreased heart rate)
- Diarrhoea
- Fever (pyrexia)
- Elevated transaminases (liver enzymes)
- Vomiting
Frequency not known
Cannot be estimated from available data
- Rash (skin eruption)
When to seek medical attention for side effects
You should contact your doctor or pharmacist if any of the side effects listed above become severe or troublesome. Additionally, if you experience any side effects not mentioned in this information, report them to your healthcare provider. Post-marketing surveillance and patient reporting play a crucial role in expanding our understanding of the safety profile of rare disease treatments like Ucedane.
Particular attention should be paid to bradycardia (decreased heart rate), as this can occasionally be clinically significant. If you notice symptoms such as unusual tiredness, dizziness, fainting episodes, or a very slow pulse, seek medical advice promptly. Your doctor may wish to perform an electrocardiogram (ECG) to assess your cardiac rhythm.
Elevated transaminases (liver enzymes) detected on blood tests should also be monitored closely. While mild, transient elevations may not require dose adjustment, persistent or significantly elevated levels may prompt your doctor to reassess the treatment plan. Regular blood tests as part of routine monitoring will help detect this early.
It is important to report suspected side effects after a medicine has been authorised. This allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare professionals and patients are encouraged to report suspected adverse reactions to their national medicines regulatory authority (e.g., the EMA in Europe, the FDA in the United States, the MHRA in the United Kingdom).
How Should You Store Ucedane?
Store Ucedane out of the sight and reach of children. No special storage conditions are required. Do not use this medicine after the expiry date stated on the blister and carton. Dispose of unused medicine through your pharmacy, not in household waste or drains.
Ucedane dispersible tablets do not require any special storage conditions. They should be kept in their original aluminium/aluminium blister packaging to protect them from moisture and light until ready for use. There is no need for refrigeration.
The expiry date refers to the last day of the stated month. For example, if the packaging states "EXP 09/2027," the tablets should not be used after 30 September 2027. Always check the expiry date before taking a dose, and dispose of any expired tablets appropriately.
Proper disposal of unused or expired medicines is important for both safety and environmental protection. Do not throw medicines away via household waste or flush them down drains. Instead, return them to your pharmacy for proper disposal. Many pharmacies and healthcare facilities offer take-back programmes for unused medicines.
Tablet appearance and packaging
Ucedane dispersible tablets are rod-shaped, white, biconvex tablets with three score lines on both sides and engraved with "L/L/L/L" on one side. Each tablet is approximately 17 mm long and 6 mm wide. The score lines allow the tablet to be divided into four equal 50 mg doses, providing flexibility in dosing for patients of different weights.
The tablets are supplied in aluminium/aluminium blister packs contained within a cardboard carton. Available pack sizes include 12 and 60 dispersible tablets per carton, although not all pack sizes may be marketed in all countries.
What Does Ucedane Contain?
Each Ucedane dispersible tablet contains 200 mg of carglumic acid as the active substance. The other ingredients are microcrystalline cellulose, colloidal anhydrous silica, sodium stearyl fumarate, mannitol, copovidone K28, and crospovidone type B. The medicine is essentially sodium-free.
Active ingredient
The active substance in Ucedane is carglumic acid (also known as N-carbamyl-L-glutamic acid). Each dispersible tablet contains 200 mg of carglumic acid. Carglumic acid is a synthetic structural analogue of N-acetylglutamate (NAG), which is the obligate activator of carbamoyl phosphate synthetase 1 (CPS 1), the first enzyme of the urea cycle in hepatic mitochondria.
Inactive ingredients (excipients)
The other ingredients in Ucedane tablets are:
- Microcrystalline cellulose: A commonly used pharmaceutical excipient that serves as a filler and binder
- Colloidal anhydrous silica: Acts as a glidant to improve powder flow during manufacturing
- Sodium stearyl fumarate: A lubricant that prevents tablets from sticking to manufacturing equipment. This is the source of the trace sodium content
- Mannitol: A sugar alcohol used as a sweetener and filler, contributing to the slightly sweet taste of the dispersed tablet
- Copovidone K28: A binder that helps maintain tablet integrity
- Crospovidone type B: A disintegrant that helps the tablet disperse rapidly in water
The total sodium content per maximum daily dose is less than 1 mmol (23 mg), making Ucedane essentially sodium-free. This is important information for patients following sodium-restricted diets, such as those with certain cardiac or renal conditions.
Frequently Asked Questions About Ucedane
Ucedane (carglumic acid) is used to treat hyperammonaemia (dangerously elevated ammonia levels in the blood) caused by N-acetylglutamate synthase (NAGS) deficiency, a rare inherited metabolic disorder. It is also used during hyperammonaemic crises in patients with isovaleric acidaemia, methylmalonic acidaemia, and propionic acidaemia. In NAGS deficiency, treatment is lifelong because the underlying enzyme deficiency cannot be corrected.
Carglumic acid is a structural analogue of N-acetylglutamate (NAG), the natural activator of carbamoyl phosphate synthetase (CPS 1), the first enzyme of the urea cycle. By replacing the missing or insufficient NAG, Ucedane restores urea cycle function in the liver, enabling the body to convert toxic ammonia into urea, which is then safely excreted by the kidneys. This targeted mechanism is what makes Ucedane specifically effective for NAGS-related hyperammonaemia.
The most common side effect is increased sweating (hyperhidrosis), which may affect up to 1 in 10 patients. Less common side effects include bradycardia (decreased heart rate), diarrhoea, fever, elevated transaminases (liver enzymes), vomiting, and rash. Most side effects are manageable, but you should report any concerns to your healthcare provider for appropriate management.
The effects of Ucedane on pregnancy are not known, so you should consult your doctor if you are pregnant or planning to become pregnant. Breastfeeding must be avoided while taking Ucedane because animal studies have shown that carglumic acid passes into breast milk and may cause harmful effects in nursing offspring. Alternative feeding methods should be used for infants whose mothers require Ucedane treatment.
For patients with NAGS deficiency, yes – Ucedane treatment is lifelong because the underlying genetic enzyme deficiency is permanent. The body cannot produce N-acetylglutamate without the NAGS enzyme, so ongoing carglumic acid supplementation is needed to maintain urea cycle function and keep ammonia levels normal. For patients with organic acidaemias, Ucedane is typically used only during acute hyperammonaemic crises rather than as continuous long-term therapy.
Ucedane dispersible tablets should be dissolved in at least 5 to 10 ml of water and taken immediately before meals or feedings. The resulting suspension has a slightly acidic taste. For patients who cannot swallow, the dissolved medication can be administered through a nasogastric tube using a syringe. Each tablet has score lines allowing it to be divided into four equal 50 mg doses for flexible dosing.
References
- European Medicines Agency (EMA). Ucedane – Summary of Product Characteristics. Last updated 2024. Available at: www.ema.europa.eu
- Ah Mew N, Simpson KL, Gropman AL, et al. Urea Cycle Disorders Overview. In: Adam MP, et al., editors. GeneReviews. Seattle (WA): University of Washington; 2003 [Updated 2023].
- Haberle J, Burlina A, Chakrapani A, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision. J Inherit Metab Dis. 2019;42(6):1192-1230.
- Daniotti M, la Marca G, Fiorini P, Filippi L. New developments in the treatment of hyperammonemia: emerging use of carglumic acid. Int J Gen Med. 2011;4:21-28.
- Ah Mew N, McCarter R, Daikhin Y, et al. N-carbamylglutamate augments ureagenesis and reduces ammonia and glutamine in propionic acidemia. Pediatrics. 2010;126(1):e208-e214.
- Levrat V, Forest I, Fouilhoux A, et al. Carglumic acid: an additional therapy in the treatment of organic acidurias with hyperammonemia? Orphanet J Rare Dis. 2008;3:2.
- World Health Organization (WHO). WHO Model List of Essential Medicines for Children. 9th List, 2023.
- Valayannopoulos V, Baruteau J, Barber A, et al. Carglumic acid enhances rapid ammonia detoxification in classical organic acidurias with a favourable risk-benefit profile. Orphanet J Rare Dis. 2016;11:32.
About Our Medical Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, comprising licensed physicians and pharmacologists with expertise in clinical pharmacology, metabolic medicine, and paediatrics. Our team follows international guidelines from the EMA, FDA, WHO, and ACMG, and adheres to the GRADE evidence framework.
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