Glycerol Phenylbutyrate

UCDs are inherited deficiencies of enzymes or transporters necessary for the synthesis of urea from ammonia (NH 3 , NH 4 + ). Absence of these enzymes or transporters results in the accumulation of toxic levels of ammonia in the blood and brain of affected patients.

• Glycerol phenylbutyrate oral liquid is indicated for use as a nitrogen-binding agent for chronic management of patients with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. Glycerol phenylbutyrate oral liquid must be used with dietary protein restriction and, in some cases, dietary supplements (e.g., essential amino acids, arginine, citrulline, protein-free calorie supplements).

• Glycerol phenylbutyrate oral liquid is contraindicated in patients with known hypersensitivity to phenylbutyrate. Signs of hypersensitivity include wheezing, dyspnea, coughing, hypotension, flushing, nausea, and rash.contraindicated

Glycerol phenylbutyrate oral liquid should be prescribed by a physician experienced in management of UCDs. For administration and preparation, see full prescribing information. ( 2.1 , 2.6 ) Switching From Sodium Phenylbutyrate Tablets or Powder to Glycerol Phenylbutyrate Oral Liquid : Patients should receive the dosage of glycerol phenylbutyrate oral liquid that contains the same amount of phenylbutyric acid, see full prescribing information for conversion. ( 2.2 ) Initial Dosage in Phenylbutyrate-Naïve Patients ( 2.3 ): Recommended dosage range is 4.5 to 11.2 mL/m 2 /day (5 to 12.4 g/m 2 /day). For patients with some residual enzyme activity not adequately controlled with dietary restriction, the recommended starting dose is 4.5 mL/m 2 /day. Take into account patient's estimated urea synthetic capacity, dietary protein intake, and diet adherence. Dosage Adjustment and Monitoring : Follow plasma ammonia levels to determine the need for dosage titration. ( 2.4 ) Dosage Modifications in Patients with Hepatic Impairment : Start dosage at lower end of range. ( 2.5 , 8.7 ) 2.1 Important Administration Instructions Glycerol phenylbutyrate oral liquid should be prescribed by a physician experienced in the management of UCDs. Instruct patients to take glycerol phenylbutyrate oral liquid with food or formula and to administer directly into the mouth via oral syringe. Instruct patients to use the glycerol phenylbutyrate oral liquid bottle and oral syringe as follows: Use a new reclosable bottle cap adapter with each new bottle that is opened.

Neurotoxicity : Phenylacetate (PAA), the active moiety of glycerol phenylbutyrate, may be toxic; reduce dosage for symptoms of neurotoxicity. ( 5.1 ) Pancreatic Insufficiency or Intestinal Malabsorption: Monitor ammonia levels closely. ( 5.2 ) 5.1 Neurotoxicity Increased exposure to PAA, the major metabolite of glycerol phenylbutyrate, may be associated with neurotoxicity in patients with UCDs. In a study of adult cancer patients, subjects received sodium phenylacetate administered as a 1-hour infusion twice daily at two dose levels of 125 and 150 mg/kg for a 2-week period. Of 18 subjects enrolled, 7 had a history of primary central nervous system tumor. Signs and symptoms of potential PAA neurotoxicity, which were reversible, were reported at plasma PAA concentrations above 500 micrograms/mL and included somnolence, fatigue, lightheadedness, headache, dysgeusia, hypoacusis, disorientation, impaired memory, and exacerbation of preexisting neuropathy. PAA concentrations were not measured when symptoms resolved. In healthy subjects, after administration of 4 mL and 6 mL glycerol phenylbutyrate 3 times daily (13.2 g/day and 19.8 g/day, respectively) for 3 days, a dose-dependent increase in non-serious nervous system adverse reactions were observed. In subjects who had nervous system adverse reactions, plasma PAA concentrations, which were measured on Day 3 per protocol and not always at onset of symptoms, ranged from 8 to 56 micrograms/mL with 4 mL glycerol phenylbutyrate 3 times daily and from 31 to 242 micrograms/mL with 6 mL glycerol phenylbutyrate 3 times daily.

The following clinically significant adverse reactions are described elsewhere in the labeling: Neurotoxicity [see Warnings and Precautions (5.1) ] Pancreatic insufficiency or Intestinal Malabsorption [see Warnings and Precautions (5.2) ] Most common adverse reactions (≥10%) in adults are: diarrhea, flatulence, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Assessment of adverse reactions was based on exposure of 45 adult patients (31 female and 14 male) with UCD subtype deficiencies of ornithine transcarbamylase (OTC, n=40), carbamoyl phosphate synthetase (CPS, n=2), and argininosuccinate synthetase (ASS, n=1) in a randomized, double-blind, active-controlled (glycerol phenylbutyrate vs sodium phenylbutyrate), crossover, 4-week study (Study 1) that enrolled patients 18 years of age and older [see Clinical Studies (14.1) ]. One of the 45 patients received only sodium phenylbutyrate prior to withdrawing on day 1 of the study due to an adverse reaction. The most common adverse reactions (occurring in at least 10% of patients) reported during short-term treatment with glycerol phenylbutyrate were diarrhea, flatulence, and headache.

Lactation : Breastfeeding is not recommended. ( 8.2 ) 8.1 Pregnancy Risk Summary Limited available data with glycerol phenylbutyrate use in pregnant women are insufficient to inform a drug-associated risk of major birth defects and miscarriage. In an animal reproduction study, administration of oral glycerol phenylbutyrate to pregnant rabbits during organogenesis at doses up to 2.7–times the dose of 6.87 mL/m 2 /day in adult patients resulted in maternal toxicity, but had no effects on embryo-fetal development. In addition, there were no adverse developmental effects with administration of oral glycerol phenylbutyrate to pregnant rats during organogenesis at 1.9 times the dose of 6.87 mL/m 2 /day in adult patients; however, maternal toxicity, reduced fetal weights, and variations in skeletal development were observed in pregnant rats administered oral glycerol phenylbutyrate during organogenesis at doses greater than or equal to 5.7 times the dose of 6.87 mL/m 2 /day in adult patients [ see Data] . Report pregnancies to Aurobindo Pharma USA, Inc.at 1-866-850-2876. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S.

Metabolism

Absorption Glycerol phenylbutyrate is a pro-drug of PBA. Upon oral ingestion, PBA is released from the glycerol backbone in the gastrointestinal tract by lipases.

While there is no experience with overdosage in human clinical trials, PAA, a toxic metabolite of glycerol phenylbutyrate, can accumulate in patients who receive an overdose [see Warnings and Precautions (5.1) ] . If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.

• Feb 1, 2013NDANDA203284Horizon Therap Us
• Dec 2, 2021ANDAANDA205742Ph Health
• Apr 15, 2026ANDAANDA218738Teva Pharms Inc
• Apr 15, 2026ANDAANDA220313Aurobindo Pharma
• Apr 15, 2026ANDAANDA219540Msn
• Apr 23, 2026ANDAANDA220568Navinta Llc

1. 1Ammonia Increased18914%
2. 2Vomiting16312%
3. 3Hyperammonaemia15212%
4. 4Decreased Appetite1017.7%
5. 5Nausea735.6%
6. 6Headache665.0%
7. 7Hyperammonaemic Crisis634.8%
8. 8Off Label Use614.6%
9. 9Diarrhoea584.4%
10. 10Fatigue524.0%
11. 11Somnolence493.7%
12. 12Weight Decreased473.6%
13. 13Malaise463.5%
14. 14Seizure443.3%
15. 15Lethargy393.0%

Recent PubMed references pinned to Glycerol 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
• [Clinical characteristics and efficacy of glyceryl phenylbutyrate treatment in 20 pediatric patients with urea cycle disorder].
  Zhonghua er ke za zhi = Chinese journal of pediatrics · 2025 · Qiu WJ, Sun CK, Xiao Y, et al.
  PMID 40835254DOI 10.3760/cma.j.cn112140-20250310-00193
• 4-Phenylbutyrate restored GABA uptake, mitigated seizures in SLC6A1 and SLC6A11 microdeletions/3p- syndrome: From cellular models to human patients.
  Epilepsy research · 2025 · DeLeeuw MB, Shen W, Tian X, et al.
  PMID 39923323DOI 10.1016/j.eplepsyres.2025.107514
• [Treatment of ornithine transcarbamylase deficiency in a child with glyceryl phenylbutyrate].
  Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2024 · Yang F, Wang LR, Li X, et al.
  PMID 38802913DOI 10.7499/j.issn.1008-8830.2310050
• Glycerol Phenylbutyrate Treatment of 2 Patients With Monocarboxylate Transporter 8 Deficiency.
  The Journal of clinical endocrinology and metabolism · 2024 · Zung A, Sonntag N, Schweizer U, et al.
  PMID 38469646DOI 10.1210/clinem/dgae146
• Monitoring the treatment of urea cycle disorders using phenylbutyrate metabolite analyses: Still many lessons to learn.
  Molecular genetics and metabolism · 2023 · Glinton KE, Minard CG, Liu N, et al.
  PMID 37717413DOI 10.1016/j.ymgme.2023.107699
• Glycerol phenylbutyrate efficacy and safety from an open label study in pediatric patients under 2 months of age with urea cycle disorders.
  Molecular genetics and metabolism · 2021 · Longo N, Diaz GA, Lichter-Konecki U, et al.
  PMID 33388234DOI 10.1016/j.ymgme.2020.12.002
• Long-term safety and efficacy of glycerol phenylbutyrate for the management of urea cycle disorder patients.
  Molecular genetics and metabolism · 2019 · Diaz GA, Schulze A, Longo N, et al.
  PMID 31326288DOI 10.1016/j.ymgme.2019.07.004

The 10 most recently updated of 24 ClinicalTrials.gov registrations naming Glycerol Phenylbutyrate as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• 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
• 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
• Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy
  Active not recruiting · Early phase 1 · Interventional · 50 enrolled · Weill Medical College of Cornell University
  NCT04937062updated 2026-01-22
• PBA Use for Treatment of ATF6-/- Patients
  Suspended · Early phase 1 · Interventional · 2 enrolled · Columbia University
  NCT04041232updated 2025-09-12
• To Evaluate the Safety of Long-term Use of HPN-100 in the Management of Urea Cycle Disorders (UCDs)
  Completed · Phase 4 · Interventional · 88 enrolled · Amgen
  NCT01257737updated 2024-08-22
• Study of the Safety, Pharmacokinetics and Efficacy of HPN-100, in Pediatric Subjects With Urea Cycle Disorders (UCDs)
  Completed · Phase 3 · Interventional · 23 enrolled · Amgen
  NCT01347073updated 2024-07-11
• Study of the Safety and Tolerability of HPN-100 Compared to Sodium Phenylbutyrate in Children With Urea Cycle Disorders
  Completed · Phase 2 · Interventional · 17 enrolled · Amgen
  NCT00947544updated 2024-07-11
• Study of the Safety of HPN (Hyperion)-100 for the Long-Term Treatment of Urea Cycle Disorders (Treat UCD)
  Completed · Phase 3 · Interventional · 60 enrolled · Amgen
  NCT00947297updated 2024-07-10

Frequently asked questions

How does Glycerol Phenylbutyrate work?

UCDs are inherited deficiencies of enzymes or transporters necessary for the synthesis of urea from ammonia (NH 3 , NH 4 + ). Absence of these enzymes or transporters results in the accumulation of toxic levels of ammonia in the blood and brain of affected patients.

What is Glycerol Phenylbutyrate used for?

According to FDA labeling, Glycerol Phenylbutyrate carries indications including: Glycerol phenylbutyrate oral liquid is indicated for use as a nitrogen-binding agent for chronic management of patients with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. Glycerol phenylbutyrate oral liquid must be used with dietary protein restriction and, in some cases, dietary supplements (e.g., essential amino acids, arginine, citrulline, protein-free calorie supplements).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Glycerol Phenylbutyrate?

Glycerol Phenylbutyrate is classified as Various alimentary tract and metabolism products.

What are the brand names for Glycerol Phenylbutyrate?

Glycerol Phenylbutyrate is marketed under brand names including Ravicti.

What are the contraindications for Glycerol Phenylbutyrate?

Glycerol Phenylbutyrate labeling lists contraindications including: Glycerol phenylbutyrate oral liquid is contraindicated in patients with known hypersensitivity to phenylbutyrate. Signs of hypersensitivity include wheezing, dyspnea, coughing, hypotension, flushing, nausea, and rash.. Always consult the full prescribing information and a clinician.