Ravicti®
Glycerol phenylbutyrate is a nitrogen-binding agent.1
Glycerol phenylbutyrate has the following uses:
Glycerol phenylbutyrate is indicated for chronic management of patients with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone.1 Glycerol phenylbutyrate must be used with dietary protein restriction and, in some cases, dietary supplements (e.g., essential amino acids, arginine, citrulline, protein-free calorie supplements).1
Glycerol phenylbutyrate is not indicated for the treatment of acute hyperammonemia in patients with UCDs because more rapidly acting interventions are essential to reduce plasma ammonia levels.1
The safety and efficacy of glycerol phenylbutyrate for the treatment of N-acetylglutamate synthase (NAGS) deficiency has not been established.1
Glycerol phenylbutyrate is available in the following dosage form(s) and strength(s):
Oral liquid: 1.1 g/mL.1
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
Glycerol phenylbutyrate should be prescribed by a physician experienced in management of UCDs.1
Administer glycerol phenylbutyrate with food or formula and administer directly into the mouth via oral syringe.1
Instruct patients to use the glycerol phenylbutyrate bottle and oral syringe as follows: use a new reclosable bottle cap adapter with each new bottle that is opened; open the glycerol phenylbutyrate bottle and twist on the new reclosable bottle cap adapter; use a new and dry oral syringe to withdraw each prescribed dose of glycerol phenylbutyrate; discard the oral syringe after each dose; tightly close the tethered tab on the reclosable bottle cap adapter after each use; do not rinse the reclosable bottle cap adapter; discard bottle and any remaining contents 28 days after opening; if water or moisture enters the glycerol phenylbutyrate bottle, the contents will become cloudy in appearance; if the contents of the bottle appear cloudy at any time, do not use the remaining glycerol phenylbutyrate in the bottle and return it to the pharmacy to be discarded.1
For patients who cannot swallow and who have a nasogastric tube or gastrostomy tube in place, instruct patients/caregivers to administer glycerol phenylbutyrate as follows: utilize a new dry oral syringe to withdraw the prescribed dosage of glycerol phenylbutyrate from the bottle; place the tip of the syringe into the gastrostomy/nasogastric tube; utilizing the plunger of the syringe, administer glycerol phenylbutyrate into the tube; use a separate syringe to flush the nasogastric/gastrostomy tube; flush once with 10 mL of water or formula and allow the flush to drain; if needed, flush a second time with an additional 10 mL of water or formula to clear the tube.1
Switching From Sodium Phenylbutyrate Tablets or Powder to Glycerol Phenylbutyrate: Patients should receive the dosage of glycerol phenylbutyrate that contains the same amount of phenylbutyric acid.1 See full prescribing information for conversion.1
Initial Dosage in Phenylbutyrate-Naïve Patients: The recommended dosage range in phenylbutyrate-naïve patients is 4.5 to 11.2 mL/m2/day (5 to 12.4 g/m2/day).1 For patients with some residual enzyme activity who are not adequately controlled with dietary restriction, the recommended starting dose is 4.5 mL/m2/day.1 In determining the starting dosage of glycerol phenylbutyrate in treatment-naïve patients, consider the patient's residual urea synthetic capacity, dietary protein requirements, and diet adherence.1
Dosage Adjustment and Monitoring: Monitor patients clinically and with plasma ammonia levels to determine the need for dosage titration.1
Dosage Modifications in Patients with Hepatic Impairment: Start dosage at lower end of the recommended dosage range in patients with moderate to severe hepatic impairment.1
See Full Prescribing Information for additional details on preparation, administration, and recommendations for dosage modifications.1
Known hypersensitivity to phenylbutyrate.1
Increased exposure to PAA, the major metabolite of glycerol phenylbutyrate, may be associated with neurotoxicity in patients with UCDs.1 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.1 Of 18 subjects enrolled, 7 had a history of primary central nervous system tumor.1 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.1 PAA concentrations were not measured when symptoms resolved. 1
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.1 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. 1
In clinical trials in patients with UCDs who had been on sodium phenylbutyrate prior to administration of glycerol phenylbutyrate, adverse reactions of headache, fatigue, symptoms of peripheral neuropathy, seizures, tremor and/or dizziness were reported.1 No correlation between plasma PAA concentration and neurologic symptoms was identified but plasma PAA concentrations were generally not consistently measured at the time of neurologic symptom occurrence. 1
If symptoms of vomiting, nausea, headache, somnolence or confusion are present in the absence of high ammonia or other intercurrent illness which explains these symptoms, consider the potential for PAA neurotoxicity which may need reduction in the glycerol phenylbutyrate dosage. 1
Pancreatic Insufficiency or Intestinal Malabsorption
Exocrine pancreatic enzymes hydrolyze glycerol phenylbutyrate in the small intestine, separating the active moiety, phenylbutyrate, from glycerol.1 This process allows phenylbutyrate to be absorbed into the circulation.1 Low or absent pancreatic enzymes or intestinal disease resulting in fat malabsorption may result in reduced or absent digestion of glycerol phenylbutyrate and/or absorption of phenylbutyrate and reduced control of plasma ammonia.1 Monitor ammonia levels closely in patients with pancreatic insufficiency or intestinal malabsorption.1
Limited available data with glycerol phenylbutyrate use in pregnant women are insufficient to inform a drug-associated risk of major birth defects and miscarriage.1 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/m2/day in adult patients resulted in maternal toxicity, but had no effects on embryo-fetal development.1 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/m2/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/m2/day in adult patients.1 Report pregnancies to Horizon at 1-866-479-6742.1
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.1 All pregnancies have a background risk of birth defect, loss or other adverse outcomes.1 In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.1
There are no data on the presence of glycerol phenylbutyrate in human milk, the effects on the breastfed infant, or the effects on milk production.1 Because of the potential for serious adverse reactions, including neurotoxicity and tumorigenicity in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with glycerol phenylbutyrate.1
The safety and effectiveness of glycerol phenylbutyrate in patients 2 years to less than 18 years of age have been established in 3 clinical studies: 2 open-label, fixed-sequence, switchover clinical studies from sodium phenylbutyrate to glycerol phenylbutyrate, and 1 long-term, open label safety study.1
The safety and effectiveness of glycerol phenylbutyrate in patients with UCDs less than 2 years of age have been established in 3 open-label studies.1 Pharmacokinetics and pharmacodynamics (plasma ammonia), and safety were studied in 17 patients 2 months to less than 2 years of age and in 16 patients less than 2 months of age.1
In a juvenile rat study with daily oral dosing performed on postpartum day 2 through mating and pregnancy after maturation, terminal body weight was dose-dependently reduced by up to 16% in males and 12% in females at 900 mg/kg/day or higher (3 times the dose of 6.87 mL/m2/day in adult patients, based on combined AUCs for PBA and PAA).1 Learning, memory, and motor activity endpoints were not affected.1 However, fertility (number of pregnant rats) was decreased by up to 25% at 650 mg/kg/day or higher (2.6 times the dose of 6.87 mL/m2/day in adult patients, based on combined AUCs for PBA and PAA).1
Clinical studies of glycerol phenylbutyrate did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently than younger subjects.1 Other reported clinical experience has not identified differences in responses between the elderly and younger patients.1 In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.1
The efficacy and safety of glycerol phenylbutyrate in patients with renal impairment are unknown.1 Monitor ammonia levels closely when starting patients with impaired renal function on glycerol phenylbutyrate.1
No studies were conducted in patients with UCDs and hepatic impairment.1 Because conversion of PAA to PAGN occurs in the liver, patients with hepatic impairment may have reduced conversion capability and higher plasma PAA and PAA to PAGN ratio.1 Therefore, dosage for patients with moderate to severe hepatic impairment should be started at the lower end of the recommended dosing range and should be kept on the lowest dose necessary to control their ammonia levels.1
Most common adverse reactions (≥10%) in adults are: diarrhea, flatulence, and headache.1
It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:
UCDs are inherited deficiencies of enzymes or transporters necessary for the synthesis of urea from ammonia (NH3, NH4 + ).1 Absence of these enzymes or transporters results in the accumulation of toxic levels of ammonia in the blood and brain of affected patients.1 Glycerol phenylbutyrate is a triglyceride containing 3 molecules of phenylbutyrate (PBA).1 Phenylacetate (PAA), the major metabolite of PBA, is the active moiety of glycerol phenylbutyrate.1 PAA conjugates with glutamine (which contains 2 molecules of nitrogen) via acetylation in the liver and kidneys to form PAGN, which is excreted by the kidneys.1 On a molar basis, PAGN, like urea, contains 2 moles of nitrogen and provides an alternate vehicle for waste nitrogen excretion.1
Additional Information
AHFS first Release™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Liquid | 1.1 g/mL (delivers 1.02 g/mL of phenylbutyrate) | Ravicti® | Horizon Therapeutics USA |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions December 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Horizon Therapeutics USA, Inc. Ravicti® (glycerol phenylbutyrate) ORAL prescribing information. 2021 Sep. [Web]