Sodium Phenylbutyrate Tablets (Ammonaps)
Essential guide to Ammonaps for managing urea cycle disorders and controlling ammonia levels effectively.
Sodium phenylbutyrate, marketed as Ammonaps, is an essential medication for the chronic management of urea cycle disorders (UCDs). These rare genetic conditions impair the body’s ability to remove ammonia, a toxic waste product from protein breakdown, leading to potentially life-threatening hyperammonaemia.
About urea cycle disorders
Urea cycle disorders are inherited metabolic conditions caused by deficiencies in enzymes responsible for converting toxic ammonia into urea for excretion via the kidneys. Key affected enzymes include carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), and argininosuccinate synthetase (ASS).
When protein is consumed, nitrogen enters the body and converts to ammonia. In UCD patients, ammonia accumulates, causing hyperammonaemic encephalopathy—symptoms range from lethargy and vomiting in mild cases to coma, brain damage, or death in severe ones, especially neonates.
There are two main presentations:
- Neonatal-onset: Complete enzyme deficiencies appearing within the first 28 days of life, often with rapid deterioration.
- Late-onset: Partial deficiencies after the first month, typically in patients with a history of hyperammonaemic crises.
Ammonaps serves as adjunctive therapy alongside dietary protein restriction, arginine supplementation, and ammonia scavengers to maintain normal ammonia levels and prevent crises.
How sodium phenylbutyrate works
Sodium phenylbutyrate is a nitrogen scavenger. In the liver, it converts to phenylacetate, which conjugates with glutamine (a major ammonia storage form) to produce phenylacetylglutamine. This water-soluble compound is excreted in urine, effectively removing excess nitrogen and lowering plasma ammonia and glutamine levels.
Unlike acute therapies like sodium benzoate, Ammonaps is designed for long-term control, not emergency use. It does not replace the defective urea cycle but bypasses it, reducing reliance on hepatic function.[10]
Therapeutic monitoring is crucial: maintain plasma ammonia, glutamine (<1,000 µmol/L), arginine, branched-chain amino acids, carnitine, and proteins within normal limits.
How to take sodium phenylbutyrate
Before starting, read the patient information leaflet (PIL) for full details on usage, side effects, and storage. Dosing is individualized by a UCD specialist and must be followed precisely.
Administration:
- Swallow tablets whole with water, during meals or feeds to enhance absorption and reduce GI upset. Do not crush or chew due to oesophageal ulceration risk, especially in dysphagia patients—tablets are contraindicated here.
- Divide doses 3-6 times daily with food for better tolerance.
- Available as 500 mg tablets; granules for those unable to swallow tablets.
Dosing by body surface area (BSA, m²):
| Patient Group | Dose (g/m²/day) | Max Daily Dose |
|---|---|---|
| Infants <20 kg | 0.45 g/kg/day (8.1-11.4) | 20 g (40 tablets) |
| >20 kg, adolescents, adults | 9.9-13.0 | 20 g |
Safety/efficacy beyond 20 g/day unestablished. Adjust based on ammonia/glutamine levels; safety in excess doses not proven.
Dosage in special populations
Children: Use BSA or weight-based dosing; monitor closely as neonates may require haemodialysis acutely.
Renal/Hepatic impairment: Use caution—metabolism/excretion relies on liver/kidneys. Monitor potassium (risk of hypokalaemia from phenylacetylglutamine excretion).
Elderly/Pregnancy/Breastfeeding: Contraindicated in pregnancy/breastfeeding; limited data in elderly.
Getting the most from your treatment
Success requires multidisciplinary care:
- Regular monitoring: Blood tests for ammonia, glutamine, amino acids, carnitine. Keep appointments with your doctor/dietitian.
- Diet: Strict low-protein diet (essential amino acids supplemented). Account for tablet sodium (62 mg/tablet, 3% WHO daily max; max dose = 124% max intake).
- Lifestyle: Avoid high-protein foods, infections, fasting, or stressors triggering decompensation. Report acute symptoms (vomiting, lethargy) immediately—Ammonaps not for acute hyperammonaemia.
- Sodium awareness: High sodium content; caution in heart failure, renal issues, oedema, low-salt diets.
Side effects
Most are mild-moderate; report persistent/severe issues. Acute encephalopathy possible despite therapy.
| Common (≥1/100) | Uncommon (≥1/1,000) | Rare |
|---|---|---|
| Metabolic acidosis/alkalosis, decreased appetite, depression, irritability, headache, syncope, oedema, abdominal pain, nausea/vomiting, constipation, dysgeusia | Aplastic anaemia, ecchymosis, arrhythmia, pancreatitis, peptic ulcer, rectal haemorrhage, gastritis | – |
Patient tips:
| Side Effect | What to do |
|---|---|
| Nausea/vomiting, stomach discomfort | Simple foods; smaller, frequent doses. Consult doctor. |
| Fainting | Sit down; rise slowly. |
| Headache | Hydrate; suitable painkiller. Persistent? See doctor. |
| Irregular periods, appetite loss, body odour, taste changes, swollen ankles, mood changes, rash, weight gain | Speak to doctor if troublesome. |
Cautions
- Contraindications: Hypersensitivity, pregnancy, breastfeeding, severe dysphagia.
- Warnings: High sodium (monitor in cardiac/renal patients); hypokalaemia risk; not for acute crises.
- Overdose: May cause acidosis, hypernatraemia, cerebral oedema—seek emergency care.
Important information about all medicines
Never share medicines. Inform doctors/pharmacists/dentists of all treatments. Some drugs interact (e.g., corticosteroids, valproate may worsen hyperammonaemia).
Frequently Asked Questions
Q: Who should take Ammonaps?
A: Patients with CPS, OTC, or ASS deficiency UCDs—neonatal-onset or late-onset with encephalopathy history.
Q: Can Ammonaps be used for acute hyperammonaemia?
A: No, it’s for chronic management only. Acute cases need emergency interventions like dialysis.
Q: What if I miss a dose?
A: Take as soon as remembered unless near next dose. Never double up; consult your doctor.
Q: Is Ammonaps safe in kidney/liver disease?
A: Use with caution and monitoring due to sodium load and excretion pathways.
Q: How does diet fit in?
A: Essential low-protein diet mandatory; dietitian guidance required.
References
- Ammonaps EPAR Product Information — European Medicines Agency (EMA). 2023-05-15. https://www.ema.europa.eu/en/documents/product-information/ammonaps-epar-product-information_en.pdf
- Ammonaps 500 mg tablets SmPC — electronic Medicines Compendium (emc). 2024-01-10. https://www.medicines.org.uk/emc/product/10986/smpc
- Sodium phenylbutyrate – Patient.info — Patient.info. 2023-11-20. https://patient.info/medicine/sodium-phenylbutyrate-tablets-ammonaps
- Ammonaps EPAR Summary — European Medicines Agency (EMA). 2024-02-05. https://www.ema.europa.eu/en/medicines/human/EPAR/ammonaps
- Ammonaps Patient Information Leaflet — electronic Medicines Compendium (emc). 2023-12-01. https://www.medicines.org.uk/emc/files/pil.10986.pdf
- Sodium phenylbutyrate for urea cycle disorders — Medicines for Children. 2023-08-15. https://medicinesforchildren.org.uk/medicines/sodium-phenylbutyrate-for-urea-cycle-disorders/
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