Ammonaps (Sodium Phenylbutyrate)
Nitrogen-binding agent for urea cycle disorders
Ammonaps (sodium phenylbutyrate) is a prescription medication used to manage urea cycle disorders (UCDs), a group of rare inherited metabolic conditions. By providing an alternative pathway for nitrogen excretion, Ammonaps helps reduce dangerously high ammonia levels in the blood. This medication must always be combined with a protein-restricted diet and requires lifelong use unless a successful liver transplantation is performed.
Quick Facts
Key Takeaways
- Ammonaps treats urea cycle disorders by providing an alternative pathway for nitrogen excretion, reducing toxic ammonia levels in the blood.
- It must always be combined with a specially designed protein-restricted diet tailored to each individual patient.
- Ammonaps is contraindicated during pregnancy and breastfeeding due to potential harm to the fetus or infant.
- Treatment is lifelong unless the patient undergoes a successful liver transplantation.
- Regular blood tests are essential to monitor ammonia levels and adjust dosing appropriately.
What Is Ammonaps and What Is It Used For?
Quick Answer: Ammonaps (sodium phenylbutyrate) is a nitrogen-binding medication prescribed for patients with urea cycle disorders. It helps the body eliminate nitrogen waste through an alternative metabolic pathway when the normal urea cycle is deficient, thereby preventing dangerous ammonia accumulation in the blood.
Urea cycle disorders (UCDs) are a group of rare genetic conditions that affect the body's ability to process nitrogen, a natural byproduct of protein metabolism. In healthy individuals, the liver converts nitrogen waste into urea through a series of enzymatic reactions known as the urea cycle. Urea is then safely excreted by the kidneys in urine. In patients with UCDs, one or more of these liver enzymes are absent or dysfunctional, leading to a buildup of nitrogen waste products, particularly ammonia (hyperammonemia).
Ammonia is highly toxic to the central nervous system. Even moderately elevated levels can cause neurological symptoms including confusion, lethargy, and behavioral changes. Severe hyperammonemia can lead to cerebral edema, seizures, coma, and death. The European Medicines Agency (EMA) approved Ammonaps as an orphan medicinal product specifically for the long-term management of these life-threatening conditions.
Ammonaps works by providing an alternative biochemical route for nitrogen elimination. The active substance, sodium phenylbutyrate, is metabolized in the liver through beta-oxidation to phenylacetate. Phenylacetate then conjugates with the amino acid glutamine in the liver and kidneys to form phenylacetylglutamine. Since glutamine contains two nitrogen atoms, each molecule of phenylacetylglutamine that is excreted in the urine carries away two molecules of nitrogen waste, effectively bypassing the defective urea cycle.
The medication is authorized for use in patients with confirmed diagnoses of urea cycle enzyme deficiencies, including but not limited to carbamoyl phosphate synthetase (CPS) deficiency, ornithine transcarbamylase (OTC) deficiency, argininosuccinate synthetase (ASS) deficiency (citrullinemia), and argininosuccinate lyase (ASL) deficiency (argininosuccinic aciduria). Ammonaps is intended for chronic maintenance therapy and must always be used alongside a carefully controlled protein-restricted diet prescribed by a specialist metabolic physician or dietitian.
Ammonaps does not prevent acute hyperammonemic crises from occurring and is not suitable for the emergency treatment of such episodes. Acute hyperammonemia requires immediate medical intervention with measures such as intravenous sodium benzoate, sodium phenylacetate, or hemodialysis in a hospital setting.
What Should You Know Before Taking Ammonaps?
Quick Answer: Before starting Ammonaps, your doctor must evaluate your complete medical history, including kidney and liver function, cardiac status, and any medications you are currently taking. Ammonaps is strictly contraindicated during pregnancy and breastfeeding. Patients on low-sodium diets should be aware that this medication contains significant amounts of sodium.
Contraindications
Ammonaps must not be used in certain situations due to serious safety concerns. Understanding these contraindications is essential for patient safety.
- Pregnancy: Ammonaps is contraindicated during pregnancy. Animal studies and the mechanism of action suggest potential harm to the developing fetus. Women of childbearing potential must use reliable contraception throughout the duration of treatment.
- Breastfeeding: The medication must not be used while breastfeeding, as sodium phenylbutyrate or its metabolites may pass into breast milk and potentially harm the nursing infant.
- Hypersensitivity: Patients with known allergy to sodium phenylbutyrate or any of the excipients (calcium stearate, colloidal anhydrous silica) should not take Ammonaps.
Warnings and Precautions
Several important precautions must be observed when using Ammonaps. Your healthcare provider should be informed of all existing medical conditions to ensure safe use of this medication.
Heart failure and fluid retention: Ammonaps contains a significant amount of sodium. Each gram of granules contains approximately 124 mg of sodium. Patients with congestive heart failure, severe renal impairment, or any condition where sodium retention could worsen the clinical picture should be monitored carefully. The sodium content may exacerbate fluid retention and edema in susceptible individuals.
Renal and hepatic impairment: Since sodium phenylbutyrate is metabolized in the liver and its metabolites are excreted through the kidneys, patients with impaired kidney or liver function require close monitoring. Dose adjustments may be necessary, and more frequent blood tests should be performed to ensure that ammonia levels remain within acceptable limits.
Dietary compliance: Ammonaps must always be combined with a protein-restricted diet that has been individually designed by a specialist metabolic physician or clinical dietitian. The diet must provide sufficient calories and essential amino acids while limiting total protein intake to prevent excessive nitrogen production. Failure to adhere to dietary restrictions can lead to breakthrough hyperammonemia despite adequate medication dosing.
Laboratory test interference: Sodium phenylbutyrate can affect the results of certain laboratory tests. Patients should inform all healthcare providers involved in their care that they are taking Ammonaps, particularly before any blood work is performed. This is important for accurate interpretation of test results, including serum electrolytes, amino acid profiles, and liver function panels.
Ammonaps does not prevent acute hyperammonemic episodes from occurring. If you experience symptoms such as unusual drowsiness, confusion, persistent vomiting, or changes in consciousness, seek emergency medical attention immediately. Acute hyperammonemia is a medical emergency that requires hospital-based treatment.
Pregnancy and Breastfeeding
Ammonaps is strictly contraindicated during both pregnancy and breastfeeding. The potential risks to the developing fetus and the nursing infant outweigh any potential benefit of the medication in these populations.
Women of childbearing potential who are prescribed Ammonaps must use effective contraception throughout the entire duration of treatment. If pregnancy occurs or is suspected while taking Ammonaps, the patient should contact her prescribing physician immediately to discuss the risks and potential alternatives. The management of urea cycle disorders during pregnancy is complex and requires multidisciplinary specialist input from metabolic physicians, obstetricians, and genetic counselors.
Women who are breastfeeding should not take Ammonaps, as the drug or its metabolites may be excreted in human milk. The decision to discontinue breastfeeding or to discontinue the medication should be made in consultation with the treating physician, taking into account the importance of the drug to the mother's health and the potential risk of hyperammonemia if the medication is stopped.
Sodium Content
Ammonaps granules contain a clinically significant amount of sodium, which is important for patients on sodium-restricted diets. The following sodium content applies per measuring spoon:
- Small white spoon (1.2 g granules): approximately 149 mg sodium
- Medium yellow spoon (3.3 g granules): approximately 408 mg sodium
- Large blue spoon (9.7 g granules): approximately 1,200 mg sodium
Patients who require two or more small white spoons, or one or more medium or large spoons daily on a long-term basis, should discuss sodium intake with their doctor or pharmacist, particularly if they have been advised to follow a low-sodium diet for other medical conditions such as hypertension or heart failure.
How Does Ammonaps Interact with Other Drugs?
Quick Answer: Ammonaps can interact with several medications including valproate, haloperidol, corticosteroids, and probenecid. These interactions may affect the efficacy of sodium phenylbutyrate or increase the risk of hyperammonemia, requiring more frequent monitoring of blood ammonia levels.
Drug interactions with Ammonaps are clinically important because they can affect either the metabolism of sodium phenylbutyrate itself or the underlying disease process. Some medications may increase blood ammonia levels independently, counteracting the therapeutic effect of Ammonaps. Others may alter the pharmacokinetic profile of sodium phenylbutyrate or its active metabolite phenylacetate.
It is essential that patients inform their doctor about all medications they are taking, including prescription drugs, over-the-counter medicines, herbal supplements, and vitamins. The prescribing physician should evaluate potential interactions before adding any new medication to the treatment regimen and may need to adjust monitoring schedules accordingly.
Major Interactions
| Drug | Drug Class | Effect on Ammonaps | Clinical Recommendation |
|---|---|---|---|
| Valproate (valproic acid) | Antiepileptic | May increase ammonia levels independently; can counteract the therapeutic effect of Ammonaps | Avoid if possible; monitor ammonia levels frequently if co-administration is necessary |
| Haloperidol | Antipsychotic | May alter phenylbutyrate metabolism and increase ammonia levels | Monitor closely; consider alternative antipsychotic agents |
| Corticosteroids | Anti-inflammatory / immunosuppressant | May increase protein catabolism, leading to elevated nitrogen waste and ammonia levels | Use lowest effective dose; increase frequency of ammonia monitoring |
| Probenecid | Uricosuric agent | May inhibit renal excretion of phenylacetylglutamine, reducing the nitrogen-clearing efficacy of Ammonaps | Avoid co-administration; consider alternative gout treatments |
Additional Interaction Considerations
Beyond the major interactions listed above, patients should be aware that any medication capable of increasing protein catabolism or impairing renal or hepatic function may indirectly affect the efficacy of Ammonaps. This includes certain antibiotics, chemotherapy agents, and high-dose nonsteroidal anti-inflammatory drugs (NSAIDs).
Patients should also exercise caution with dietary supplements containing amino acids or high-protein nutritional products, as these can increase the nitrogen load and potentially overwhelm the alternative excretion pathway provided by Ammonaps. Any changes in diet or supplementation should be discussed with the treating metabolic specialist.
What Is the Correct Dosage of Ammonaps?
Quick Answer: The dosage of Ammonaps is calculated individually based on the patient's protein tolerance, dietary intake, and body weight or body surface area. The usual dose is 450-600 mg/kg/day for patients weighing less than 20 kg, and 9.9-13.0 g/m²/day for those weighing over 20 kg. The daily dose is divided into equal portions taken with each meal.
Ammonaps dosing is highly individualized and requires regular monitoring through blood tests to ensure optimal ammonia control. The prescribing metabolic specialist will determine the appropriate dose based on the patient's specific enzyme deficiency, residual enzyme activity, protein tolerance, growth requirements (in children), and plasma ammonia levels.
General Dosing Principles
| Patient Group | Body Weight | Recommended Dose | Administration |
|---|---|---|---|
| Infants and young children | < 20 kg | 450–600 mg/kg/day | Divided into 4–6 equal doses with meals/feedings |
| Older children and adults | ≥ 20 kg | 9.9–13.0 g/m²/day | Divided into 3–6 equal doses with meals |
How to Take Ammonaps
Ammonaps granules must be carefully measured using the three color-coded measuring spoons provided with each bottle. Accurate dosing is critical to maintain adequate nitrogen clearance and prevent hyperammonemia.
Measuring Spoon Guide
- Small white spoon: 1.2 g of granules (contains approximately 149 mg sodium)
- Medium yellow spoon: 3.3 g of granules (contains approximately 408 mg sodium)
- Large blue spoon: 9.7 g of granules (contains approximately 1,200 mg sodium)
Shake the bottle gently before opening. Take a heaped spoonful, then level it off with a flat surface such as a knife blade to ensure an accurate measure.
Oral administration: Mix the measured dose of granules with solid food (such as mashed potatoes or applesauce) or liquid food (such as water, apple juice, orange juice, or protein-free infant formula). The mixture must be consumed immediately after preparation; do not store mixed preparations for later use.
Gastrostomy or nasogastric tube administration: Mix the granules with water and stir until no dry granules remain. When dissolved in water, the granules form a milky white solution. Administer the solution immediately after preparation through the feeding tube.
Ammonaps must be taken with every meal or feeding throughout the day. In small infants, this may mean 4 to 6 doses per day. In older children and adults, the medication is typically taken 3 to 4 times daily, always coinciding with meals.
Missed Dose
If you miss a dose of Ammonaps, take the next dose as soon as possible at the next mealtime. Ensure that at least 3 hours have elapsed between two doses. Do not take a double dose to make up for a forgotten one. Missing doses can lead to a rise in blood ammonia levels, so it is important to maintain a consistent dosing schedule. If doses are frequently missed, discuss strategies with your healthcare team to improve adherence.
Overdose
An overdose of Ammonaps can cause a range of neurological symptoms, reflecting the pharmacological effects of excessive phenylbutyrate and its metabolites on the central nervous system. Patients who have taken very high doses have experienced the following symptoms:
- Drowsiness, fatigue, and dizziness
- Confusion and disorientation (in more severe cases)
- Headache
- Taste disturbances (dysgeusia)
- Decreased hearing
- Memory impairment
- Worsening of pre-existing neurological conditions
If you suspect an overdose, contact your doctor or the nearest emergency department immediately for supportive care. There is no specific antidote for sodium phenylbutyrate overdose, and treatment is symptomatic and supportive.
What Are the Side Effects of Ammonaps?
Quick Answer: The most common side effect of Ammonaps is menstrual irregularities in women. Other common side effects include decreased appetite, headache, depression, nausea, vomiting, body odor, taste changes, and weight gain. Serious but less common side effects include bone marrow depression, cardiac arrhythmias, and pancreatitis.
Like all medications, Ammonaps can cause side effects, although not everyone will experience them. The frequency and severity of side effects may vary depending on the dose, duration of treatment, and individual patient factors. It is important to report any new or worsening symptoms to your healthcare provider promptly, as some side effects may require dose adjustment or additional treatment.
The side effects of Ammonaps are categorized below according to their frequency of occurrence, based on post-marketing surveillance data and clinical trial evidence. Understanding these categories helps patients and caregivers make informed decisions about monitoring and when to seek medical attention.
Very Common
Affects more than 1 in 10 patients
- Irregular menstrual periods or absence of menstruation (amenorrhea) — if menstruation stops completely and you are sexually active, consult your doctor as this could also indicate pregnancy
Common
Affects 1 to 10 in 100 patients
- Changes in blood cell counts (red blood cells, white blood cells, and platelets)
- Decreased appetite
- Depression and irritability
- Headache and fainting (syncope)
- Fluid retention (edema / swelling)
- Taste changes (dysgeusia)
- Abdominal pain, nausea, vomiting, and constipation
- Body odor and skin rash
- Abnormal kidney function
- Weight gain
- Altered laboratory test values
Uncommon
Affects 1 to 10 in 1,000 patients
- Red blood cell deficiency due to bone marrow depression (aplastic anemia)
- Easy bruising (ecchymosis)
- Cardiac arrhythmias (altered heart rhythm)
- Rectal bleeding
- Gastric irritation and peptic ulcer disease
- Pancreatitis (inflammation of the pancreas)
Contact your doctor immediately or go to the nearest emergency department if you experience repeated vomiting, as this may indicate accumulating ammonia levels or a serious gastrointestinal complication. Persistent vomiting can also impair the absorption of Ammonaps, leading to a dangerous rise in blood ammonia.
Reporting Side Effects
It is important to report suspected side effects after the medication has been authorized. This enables continuous monitoring of the benefit-risk balance of the medicine. Patients and healthcare professionals can report suspected adverse reactions to their national pharmacovigilance authority, such as the EMA (European Medicines Agency), the FDA (U.S. Food and Drug Administration), or the MHRA (UK Medicines and Healthcare products Regulatory Agency).
How Should You Store Ammonaps?
Quick Answer: Store Ammonaps at or below 25°C (77°F). Keep the bottle tightly closed with the child-resistant cap. Do not use the granules after the expiration date printed on the carton and bottle label. Keep out of the sight and reach of children.
Proper storage of Ammonaps is essential to maintain the stability and effectiveness of the medication. The granules should be stored at temperatures not exceeding 25°C (77°F) in their original container. Avoid exposing the medication to excessive heat, moisture, or direct sunlight, as these conditions may degrade the active substance.
The expiration date is printed on the carton and bottle label after "EXP" and refers to the last day of the indicated month. Do not use the medication after this date. Even if the granules appear unchanged in appearance, the chemical stability of the active ingredient cannot be guaranteed beyond the expiration date.
Ammonaps is packaged in plastic bottles with child-resistant caps. Each bottle contains either 266 g or 532 g of granules. Three color-coded measuring spoons are included with each bottle. Always keep the bottle tightly sealed when not in use and store it out of the sight and reach of children.
Do not dispose of unused medication by flushing it down the toilet or throwing it in household waste. Return any unused or expired medication to your pharmacist for proper disposal in accordance with local environmental regulations.
What Does Ammonaps Contain?
Quick Answer: Each gram of Ammonaps granules contains 940 mg of the active substance sodium phenylbutyrate. The inactive ingredients are calcium stearate and colloidal anhydrous silica. The granules are off-white in appearance.
Active Ingredient
The active substance in Ammonaps is sodium phenylbutyrate. Each gram of granules contains 940 mg of sodium phenylbutyrate, which is the sodium salt of 4-phenylbutyric acid. Sodium phenylbutyrate acts as a prodrug; it is metabolized in the body to its active form, phenylacetate, through beta-oxidation in the liver mitochondria.
Inactive Ingredients (Excipients)
- Calcium stearate: Used as a lubricant in the granule manufacturing process to ensure uniform granule formation and prevent adhesion to processing equipment.
- Colloidal anhydrous silica: A flow agent that prevents the granules from clumping together, ensuring consistent dosing and ease of measuring with the provided spoons.
Appearance and Packaging
Ammonaps granules are off-white in color. The granules are supplied in plastic bottles fitted with child-resistant closures. Each bottle contains either 266 g or 532 g of granules. Three measuring spoons are provided with each bottle: a small white spoon (1.2 g), a medium yellow spoon (3.3 g), and a large blue spoon (9.7 g).
The marketing authorization holder for Ammonaps is Immedica Pharma AB. The medication is manufactured by Patheon France in Bourgoin-Jallieu, France. Additional information is available from the European Medicines Agency (EMA) website.
Frequently Asked Questions About Ammonaps
Ammonaps (sodium phenylbutyrate) is used to treat urea cycle disorders (UCDs), a group of rare inherited metabolic conditions where the liver cannot properly convert nitrogen waste into urea. By providing an alternative pathway for nitrogen excretion, Ammonaps helps reduce dangerous ammonia levels in the blood (hyperammonemia), which can cause brain damage, coma, and death if left untreated. It is always used in combination with a protein-restricted diet.
Ammonaps contains sodium phenylbutyrate, which is metabolized in the liver to phenylacetate through beta-oxidation. Phenylacetate then combines with the amino acid glutamine to form phenylacetylglutamine. This compound contains nitrogen waste and is excreted by the kidneys in urine, effectively bypassing the defective urea cycle and removing excess nitrogen from the body. Each molecule of phenylacetylglutamine eliminates two nitrogen atoms.
No. Ammonaps is contraindicated during pregnancy because it may cause harm to the developing fetus. Women of childbearing potential must use reliable contraception during treatment. The medication should also not be used while breastfeeding, as it may pass into breast milk and harm the infant. If you become pregnant while taking Ammonaps, contact your prescribing physician immediately.
The most common side effect is irregular or absent menstrual periods in women (amenorrhea), affecting more than 1 in 10 patients. Common side effects (affecting 1-10 in 100 patients) include decreased appetite, depression, irritability, headache, taste changes, abdominal pain, nausea, vomiting, constipation, body odor, skin rash, abnormal kidney function, and weight gain. If you experience persistent vomiting, seek medical attention immediately.
Yes. Treatment with Ammonaps and the accompanying protein-restricted diet is typically lifelong. Urea cycle disorders are genetic conditions, and continuous management is needed to prevent dangerous accumulation of ammonia in the blood. The only exception is a successful liver transplantation, which can restore normal urea cycle function and potentially allow discontinuation of the medication under specialist supervision.
Yes. Ammonaps can interact with several medications. The most significant interactions are with valproate (an anti-epileptic drug), haloperidol (an antipsychotic), corticosteroids (anti-inflammatory agents), and probenecid (used for gout). These drugs may affect the efficacy of sodium phenylbutyrate or independently increase ammonia levels. Always inform your doctor about all medications, supplements, and herbal products you are taking.
References
This article is based on the following peer-reviewed sources and authoritative medical guidelines. All information has been verified against current evidence-based standards.
- European Medicines Agency (EMA). Ammonaps (sodium phenylbutyrate) — Summary of Product Characteristics (SmPC). Last updated 2022. Available from: EMA — Ammonaps.
- Brusilow SW, Maestri NE. Urea cycle disorders: diagnosis, pathophysiology, and therapy. Advances in Pediatrics. 1996;43:127–170.
- Häberle J, Burlina A, Chakrapani A, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders: first revision. Journal of Inherited Metabolic Disease. 2019;42(6):1192–1230. doi:10.1002/jimd.12100.
- Ah Mew N, Simpson KL, Gropman AL, et al. Urea Cycle Disorders Overview. In: Adam MP, et al., eds. GeneReviews. University of Washington, Seattle; Updated 2023.
- Enns GM, Berry SA, Berry GT, et al. Survival after treatment with phenylacetate and benzoate for urea-cycle disorders. New England Journal of Medicine. 2007;356(22):2282–2292.
- Summar ML, Koelker S, Freedenberg D, et al. The incidence of urea cycle disorders. Molecular Genetics and Metabolism. 2013;110(1–2):179–180.
- World Health Organization (WHO). WHO Model List of Essential Medicines. 23rd List, 2023.
- American College of Medical Genetics and Genomics (ACMG). Standards and guidelines for the interpretation of urea cycle disorders. Genetics in Medicine. 2020.
Editorial Team
This article has been written and reviewed by qualified medical professionals with expertise in metabolic medicine, clinical pharmacology, and rare disease management. All content follows the iMedic editorial standards and is reviewed according to the GRADE evidence framework.
iMedic Medical Editorial Team — Specialists in metabolic medicine, clinical pharmacology, and inherited metabolic disorders. Content based on EMA SmPC, published clinical evidence, and international treatment guidelines.
Independent panel of board-certified physicians specializing in metabolic medicine, pediatric metabolism, and clinical pharmacology. All content reviewed for accuracy, completeness, and adherence to current evidence-based guidelines.
All medicine information on iMedic is based on approved product information (SmPC), peer-reviewed research, and international clinical guidelines. We maintain strict independence with no pharmaceutical company funding or advertising. Content is reviewed at least annually and updated when new evidence becomes available. For more details, see our Editorial Standards.