Nitrogen-binding agent Pregnancy: US label: limited available data in pregnant women are insufficient to inform a drug-associated risk of major birth defects or miscarriage. In animal reproduction studies, maternal toxicity occurred in rabbits without effects on embryo-foetal development; in rats, maternal toxicity, reduced foetal weights and skeletal development variations were seen at higher multiples of the adult clinical dose.

Glycerol phenylbutyrate

Brand names: Ravicti

Glycerol phenylbutyrate is a nitrogen-scavenging agent used as adjunctive long-term therapy in the management of urea cycle disorders that cannot be controlled by dietary protein restriction alone.

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: Phenylbutyrate-naive patients: 4.5 to 11.2 mL/m2/day (5 to 12.4 g/m2/day) of oral liquid (1.1 g/mL)

Route: Oral — administered directly into the mouth via oral syringe, with food or formula; may be given via nasogastric or gastrostomy tube

Frequency: In 3 equally divided doses daily (patients 2 years of age and older), each rounded up to the nearest 0.5 mL

Max: Maximum total daily dosage 17.5 mL (19 g)

US labelling (no UK SPC retrieved). Should be prescribed by a physician experienced in the management of urea cycle disorders (UCDs). For patients with some residual enzyme activity who are not adequately controlled with dietary protein restriction, the recommended starting dosage is 4.5 mL/m2/day; take into account the patient's estimated urea synthetic capacity, dietary protein intake and diet adherence. An initial estimated dose for a 24-hour period is 0.6 mL per gram of dietary protein ingested per 24-hour period. Switching from sodium phenylbutyrate: total daily dosage (mL) = total daily dosage of sodium phenylbutyrate TABLETS (g) x 0.86, or of sodium phenylbutyrate POWDER (g) x 0.81. Titrate against plasma ammonia levels — monitor closely during treatment and whenever the dosage is changed. Hepatic impairment: start dosage at the lower end of the range. Elderly: start at the low end of the dosing range. Must be used with dietary protein restriction and, in some cases, dietary supplements (e.g. essential amino acids, arginine, citrulline, protein-free calorie supplements). Paediatric: patients less than 2 years of age should be given the daily dosage in 3 or more equally divided doses, each rounded up to the nearest 0.1 mL; for patients requiring less than 1 mL per dose via nasogastric or gastrostomy tube the delivered dose may be less than anticipated — monitor ammonia closely. Administer just prior to breastfeeding in infants who are breastfeeding. Reduce dosage for symptoms of neurotoxicity. Discard the bottle and any remaining contents 28 days after opening; do not use if the contents appear cloudy.

Dose auto-extracted from 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.

Contraindications

Known hypersensitivity to phenylbutyrate (signs include wheezing, dyspnoea, coughing, hypotension, flushing, nausea and rash)

Side effects

Diarrhoea (most common, >=10% in adults)
Flatulence (most common, >=10% in adults)
Headache (most common, >=10% in adults)
Neurotoxicity related to phenylacetate (PAA) — somnolence, fatigue, lightheadedness, dysgeusia, hypoacusis, disorientation, impaired memory, exacerbation of pre-existing neuropathy
Hypersensitivity reactions (wheezing, dyspnoea, coughing, hypotension, flushing, nausea, rash)

Interactions

Corticosteroids — may cause breakdown of body protein and increase plasma ammonia; monitor ammonia levels closely
Valproic acid and haloperidol — may induce hyperammonaemia; monitor ammonia levels closely
Probenecid — may inhibit renal excretion of glycerol phenylbutyrate metabolites (PAGN and PAA)
CYP3A4 substrates with a narrow therapeutic index (e.g. alfentanil, quinidine, ciclosporin) — exposure may be decreased; monitor for reduced efficacy
Midazolam — decreased exposure; monitor for suboptimal effect

Clinical monograph

How it works

It is hydrolysed to phenylbutyrate and then phenylacetate, which conjugates with glutamine to form phenylacetylglutamine; this is excreted renally, providing an alternative route for waste nitrogen elimination that bypasses the deficient urea cycle.

Prescribing in practice

It does not treat acute hyperammonaemic crises, which require emergency management; it is a long-term measure to maintain control alongside dietary protein restriction.
It is used as part of a specialist regimen including a low-protein diet and, where appropriate, amino acid supplementation under metabolic medicine supervision.
Reduced exposure can occur in hepatic impairment, and gastrointestinal symptoms are commonly reported.

Monitoring

Monitor plasma ammonia together with the metabolic and nutritional parameters guided by the specialist metabolic team to confirm adequate nitrogen control.

Counselling the patient

This medicine helps control your condition long term and must be taken alongside the prescribed diet; it is not a treatment for sudden episodes.
Do not stop or change the dose without advice from your metabolic team.

Evidence & guidelines

Nitrogen-scavenging therapy is an established component of chronic urea cycle disorder management used under specialist supervision.

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.

Pathways