Ammonia scavenger (alternative pathway) Pregnancy: Contraindicated during pregnancy and during lactation. Animal studies showed reproductive toxicity (effects on embryo/foetal development). Effective contraceptive measures must be taken by women of child-bearing potential.

Sodium phenylbutyrate

Brand names: Ammonaps, Pheburane

Sodium phenylbutyrate is a nitrogen-scavenging agent used as adjunctive therapy in the chronic management of urea cycle disorders.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Urea cycle disorders: usual total daily dose 9.9 to 13.0 g/m2/day in adolescents and adults (and in children weighing more than 20 kg)

Route: Oral — tablets, for adults and children able to swallow tablets, taken with a large volume of water; granules are available for infants, for children unable to swallow tablets and for patients with dysphagia

Frequency: Total daily dose divided into equal amounts and given with each meal (e.g. three times per day)

Max: The safety and efficacy of doses in excess of 20 g/day (40 tablets) have not been established

eMC SPC for Ammonaps 500 mg tablets. Treatment should be supervised by a physician experienced in the treatment of urea cycle disorders. The daily dose should be individually adjusted according to the patient's protein tolerance and the daily dietary protein intake needed to promote growth and development. Therapeutic monitoring: plasma ammonia, arginine, essential amino acids (especially branched chain amino acids), carnitine and serum proteins should be maintained within normal limits, and plasma glutamine below 1,000 micromol/l. Must be combined with dietary protein restriction and, in some cases, essential amino acid and carnitine supplementation; if caloric supplementation is indicated a protein-free product is recommended. Citrulline or arginine supplementation is required for patients with the neonatal-onset form of carbamyl phosphate synthetase or ornithine transcarbamylase deficiency at 0.17 g/kg/day or 3.8 g/m2/day; arginine supplementation is required for argininosuccinate synthetase deficiency at 0.4 to 0.7 g/kg/day or 8.8 to 15.4 g/m2/day. Tablets should not be used in patients with dysphagia (risk of oesophageal ulceration). Not recommended for the management of acute hyperammonaemia, which is a medical emergency. High sodium content: 62 mg sodium per tablet; the maximum recommended daily dose contains 2.5 g sodium (124% of the WHO recommended maximum daily intake) — use with caution in congestive heart failure, severe renal insufficiency and conditions with sodium retention and oedema. Monitor serum potassium during therapy.

Paediatric dose

Dose: 450 mg/kg

Route: Oral — granules should be used in infants and in children unable to swallow tablets; the tablets are indicated only for children able to swallow tablets

Frequency: 450 to 600 mg/kg/day total daily dose, divided into equal amounts and given with each meal (e.g. three times per day)

Max: The safety and efficacy of doses in excess of 20 g/day (40 tablets) have not been established

The 450 to 600 mg/kg/day range applies to children weighing less than 20 kg. Children weighing more than 20 kg are dosed as adolescents and adults, at 9.9 to 13.0 g/m2/day. The daily dose should be individually adjusted according to protein tolerance and the daily dietary protein intake needed to promote growth and development, combined with dietary protein restriction. The US label additionally states that use of the tablets for neonates, infants and children up to 20 kg is not recommended. Clinician to verify against a children's formulary.

Dose adjustments

Renal

Since the metabolism and excretion of sodium phenylbutyrate involves the liver and kidneys, it should be used with caution in patients with hepatic or renal insufficiency, and with caution in severe renal insufficiency because of the high sodium content. No numeric dose adjustment is stated.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Paediatric weight-based calculator

Patient weight (kg)

Verify in a children's formulary

Contraindications

Pregnancy
Breast-feeding
Hypersensitivity to the active substance or to any of the excipients

Side effects

Amenorrhoea and irregular menstruation (very common)
Anaemia, thrombocytopenia, leukopenia, leukocytosis, thrombocytosis (common)
Abdominal pain, vomiting, nausea, constipation, dysgeusia (common)
Metabolic acidosis, alkalosis, decreased appetite (common)
Renal tubular acidosis (common); also depression and irritability, syncope and headache, oedema, rash and abnormal skin odour (common)

Interactions

Probenecid — concurrent administration may affect renal excretion of the conjugation product of sodium phenylbutyrate
Haloperidol — published reports of induced hyperammonaemia; more frequent monitoring of plasma ammonia advised
Valproate — published reports of induced hyperammonaemia; more frequent monitoring of plasma ammonia advised
Corticosteroids — may cause breakdown of body protein and thus increase plasma ammonia levels

Clinical monograph

How it works

It is metabolised to phenylacetate, which conjugates with glutamine to form phenylacetylglutamine that is excreted renally, providing an alternative route for waste nitrogen elimination.

Prescribing in practice

It is used alongside dietary protein restriction and must not replace emergency management of acute hyperammonaemia, which requires urgent specialist treatment.
It carries a substantial sodium load, requiring caution in heart failure, hypertension, renal impairment and other states where sodium retention is harmful.
Monitor for and manage potential metabolic and electrolyte disturbances; refer to the SPC for guidance.

Monitoring

Plasma ammonia, amino acids, electrolytes and nutritional status are monitored regularly to guide therapy.

Counselling the patient

Take this medicine with meals as directed and continue your prescribed low-protein diet.
Seek urgent help for vomiting, drowsiness or confusion, which may signal high ammonia.
Do not stop treatment suddenly without specialist advice.

Evidence & guidelines

Sodium phenylbutyrate is an established component of urea cycle disorder management supported by long-term clinical experience.

Reference: SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways