Phenylbutyrate

• Sodium phenylbutyrate tablets are indicated as adjunctive therapy in the chronic management of patients with urea cycle disorders involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). It is indicated in all patients with neonatal-onset deficiency (complete enzymatic deficiency, presenting within the first 28 days of life).

• Sodium phenylbutyrate tablets should not be used to manage acute hyperammonemia, which is a medical emergency.contraindicated

For oral use only. The use of sodium phenylbutyrate tablets is indicated for children weighing more than 20 kg and for adults. The usual total daily dose of sodium phenylbutyrate tablets for patients with urea cycle disorders is 450 to 600 mg/kg/day in patients weighing less than 20 kg, or 9.9 to 13.0 g/m 2 /day in larger patients. The tablets is to be taken in equally divided amounts with each meal or feeding (i.e., three to six times per day). The safety or efficacy of doses in excess of 20 grams (40 tablets) per day has not been established.

Each sodium phenylbutyrate tablet contains 62 mg of sodium (9.2% w/w) (corresponding to 124 mg of sodium per gram of sodium phenylbutyrate [12.4% w/w]). Sodium phenylbutyrate should be used with great care, if at all, in patients with congestive heart failure or severe renal insufficiency, and in clinical states in which there is sodium retention with edema. Because sodium phenylbutyrate is metabolized in the liver and kidney, and phenylacetylglutamine is primarily excreted by the kidney, use caution when administering the drug to patients with hepatic or renal insufficiency or inborn errors of beta oxidation. Probenecid is known to inhibit the renal transport of many organic compounds, including hippuric acid, and may affect renal excretion of the conjugated product of sodium phenylbutyrate as well as its metabolite. Use of corticosteroids may cause the breakdown of body protein and increase plasma ammonia levels.

The assessment of clinical adverse events came from 206 patients treated with sodium phenylbutyrate. Adverse events (both clinical and laboratory) were not collected systematically in these patients, but were obtained from patient visit reports by the 65 co-investigators. Causality of adverse effects is sometimes difficult to determine in this patient population because they may result from either the underlying disease, the patient’s restricted diet, intercurrent illness, or sodium phenylbutyrate. Furthermore, the rates may be underestimated because they were reported primarily by parent or guardian and not the patient. Clinical Adverse Events In female patients, the most common clinical adverse event reported was amenorrhea/menstrual dysfunction (irregular menstrual cycles), which occurred in 23% of the menstruating patients. Decreased appetite occurred in 4% of all patients. Body odor (probably caused by the metabolite, phenylacetate) and bad taste or taste aversion were each reported in 3% of patients. Other adverse events reported in 2% or fewer patients were: Gastrointestinal : abdominal pain, gastritis, nausea and vomiting; constipation, rectal bleeding, peptic ulcer disease, and pancreatitis each occurred in one patient. Hematologic : aplastic anemia and ecchymoses each occurred in one patient. Cardiovascular : arrhythmia and edema each occurred in one patient.

Pregnancy: Animal reproduction studies have not been conducted with sodium phenylbutyrate. It is also not known whether sodium phenylbutyrate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Sodium phenylbutyrate should be given to a pregnant woman only if clearly needed.

Metabolism

General: Pharmacokinetic studies have not been conducted in the primary patient population (neonates, infants, and children), but pharmacokinetic data were obtained from normal adult subjects. Absorption: Peak plasma levels of phenylbutyrate occur within 1 hour after a single dose of 5 grams of sodium phenylbutyrate tablet with a C max of 218 mcg/mL under fasting conditions.

Overdoses of sodium phenylbutyrate exceeding ten-fold the maximum recommended dosage may produce emesis, CNS depression, metabolic acidosis with or without respiratory alkalosis, hypernatremia, hypokalemia, and hypophosphatemia. Symptoms of overdose overlap with those of acute hyperammonemia. If overdose occurs, discontinue sodium phenylbutyrate, monitor plasma phenylacetate and ammonia levels closely, and institute appropriate emergency management, which may include hemodialysis, continuous veno-venous hemofiltration (CVVH), or extracorporeal membrane oxygenation (ECMO).

• Apr 30, 1996NDANDA020573Horizon Therap Us
• May 13, 1996NDANDA020572Horizon Therap Us
• Feb 1, 2013NDANDA203284Horizon Therap Us
• Mar 22, 2013ANDAANDA202819Sigmapharm Labs Llc
• Apr 15, 2016ANDAANDA204395Ph Health
• Jun 15, 2016ANDAANDA203918Ph Health
• Dec 2, 2021ANDAANDA205742Ph Health
• Jun 17, 2022NDANDA216513Medunik

1. 1Ammonia Increased21113%
2. 2Hyperammonaemia20212%
3. 3Vomiting19612%
4. 4Decreased Appetite1197.1%
5. 5Off Label Use1056.3%
6. 6Nausea925.5%
7. 7Diarrhoea824.9%
8. 8Hyperammonaemic Crisis754.5%
9. 9Headache744.4%
10. 10Fatigue674.0%
11. 11Death593.5%
12. 12Seizure543.2%
13. 13Somnolence533.2%
14. 14Weight Decreased533.2%
15. 15Malaise523.1%

Recent PubMed references pinned to Phenylbutyrate as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Synthesis and preliminary enzymatic evaluation of polyol-based 4-phenylbutyrate derivatives.
  Bioorganic & medicinal chemistry letters · 2026 · Suchetti L, Tempesti TC, Ferrayoli C, et al.
  PMID 42167552DOI 10.1016/j.bmcl.2026.130689
• Phase II trial of sodium phenylbutyrate and taurursodiol in Wolfram syndrome.
  The Journal of clinical investigation · 2026 · Urano F, Marshall BA, Hurst S, et al.
  PMID 42138079DOI 10.1172/JCI198519
• Substrate specificity engineering of leucine dehydrogenase for efficient synthesis of aromatic L-homophenylalanine.
  International journal of biological macromolecules · 2026 · Zhao L, Xing W, Zhang W, et al.
  PMID 42009150DOI 10.1016/j.ijbiomac.2026.152104
• Pharmacological Correction of Aberrant DSCAML1 Localization by 4-Phenylbutyrate Ameliorates Epileptic Phenotypes in a Mouse Model Harboring the Patient-Specific A2105T Mutation.
  Genes to cells : devoted to molecular & cellular mechanisms · 2026 · Hayase Y, Owa T, Hashizume K, et al.
  PMID 42003794DOI 10.1111/gtc.70115
• OMICS Profiling Identifies Signatures of Senescence in Osteogenesis Imperfecta Osteoblasts Counteracted by 4-PBA.
  Journal of cellular and molecular medicine · 2026 · Besio R, Maffioli E, Palladino E, et al.
  PMID 41937492DOI 10.1111/jcmm.71120
• Endoplasmic reticulum stress inhibitor 4-PBA alleviates immune damage in mice with enteroviral encephalitis by inhibiting ferroptosis.
  Virology journal · 2026 · He S, Chen X, Luo J, et al.
  PMID 41862947DOI 10.1186/s12985-026-03103-7
• QbD-based, greenness and whiteness-assessed LC-MS/MS method for simultaneous determination of sodium phenylbutyrate and Taurursodiol with pharmacokinetic application.
  Journal of pharmacological and toxicological methods · 2026 · Palla T, Maddala VKS, Gandla K, et al.
  PMID 41730326DOI 10.1016/j.vascn.2026.108417
• 4-Phenylbutyrate Induces Functional Elongation of the Microglial Process Through Activation of Akt.
  Neurochemical research · 2026 · Dai T, Dai Q, Ding Y, et al.
  PMID 41653373DOI 10.1007/s11064-026-04688-9

The 10 most recently updated of 80 ClinicalTrials.gov registrations naming Phenylbutyrate as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Study of Sodium Phenylbutyrate (ACER-001) for the Treatment of Pediatric and Adults Patients With Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)
  Recruiting · Phase 2 · Interventional · 24 enrolled · Jerry Vockley, MD, PhD
  NCT06773026updated 2026-06-08
• An Individual Patient, Open Label Study to Use ACER-001 to Treat Combined D,L-2 Hydroxyglutaric Aciduria (C-2HGA)
  Enrolling by invitation · Phase 1 · Interventional · 1 enrolled · Jerry Vockley, MD, PhD
  NCT07125066updated 2026-06-08
• AMX0035 and Progressive Supranuclear Palsy
  Completed · Phase 2 · Phase 3 · Interventional · 139 enrolled · Amylyx Pharmaceuticals Inc.
  NCT06122662updated 2026-04-30
• The Effects of Sodium Phenylbutyrate on Circulating Branched Chain Amino Acids
  Completed · Interventional · 8 enrolled · University of Nottingham
  NCT05028803updated 2026-04-28
• A Clinical Study of Glycerol Phenylbutyrate in Chinese Patients With Urea Cycle Disorders
  Recruiting · Observational · 40 enrolled · Tongji Hospital
  NCT06904027updated 2026-04-27
• Glycerol Phenylbutyrate Corrector Therapy For CF (Cystic Fibrosis)
  Terminated · Phase 1 · Phase 2 · Interventional · 16 enrolled · National Jewish Health
  NCT02323100updated 2026-04-17
• AMX0035 in Adult Patients With Wolfram Syndrome
  Active not recruiting · Phase 2 · Interventional · 12 enrolled · Amylyx Pharmaceuticals Inc.
  NCT05676034updated 2026-04-14
• Efficacy and Safety of the Treatment of Pyruvate Dehydrogenase Deficiency Patients With Glycerol Phenylbutyrate (RAVICTI)
  Recruiting · Phase 2 · Interventional · 15 enrolled · Assistance Publique - Hôpitaux de Paris
  NCT06887777updated 2026-03-31
• PROFIL Study to Investigate the Effect of GPB on NfL Levels in Patients With Corticobasal Syndrome (CBS)
  Active not recruiting · Phase 2 · Interventional · 32 enrolled · Technical University of Munich
  NCT05983588updated 2026-03-18
• Na-Phenylbutyrate VAscular Trial
  Not yet recruiting · Early phase 1 · Interventional · 30 enrolled · University of Pennsylvania
  NCT06645769updated 2026-03-12

Frequently asked questions

What is Phenylbutyrate used for?

According to FDA labeling, Phenylbutyrate carries indications including: Sodium phenylbutyrate tablets are indicated as adjunctive therapy in the chronic management of patients with urea cycle disorders involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). It is indicated in all patients with neonatal-onset deficiency (complete enzymatic deficiency, presenting within the first 28 days of life).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What are the brand names for Phenylbutyrate?

Phenylbutyrate is marketed under brand names including Buphenyl, Olpruva, Pheburane, Relyvrio.

What are the contraindications for Phenylbutyrate?

Phenylbutyrate labeling lists contraindications including: Sodium phenylbutyrate tablets should not be used to manage acute hyperammonemia, which is a medical emergency.. Always consult the full prescribing information and a clinician.