Endo Launches First and Only Generic Version of RAVICTI® (glycerol phenylbutyrate) Oral Liquid in the United States

• Endo announces the U.S. launch of a generic version of RAVICTI^® (glycerol phenylbutyrate), marking a significant milestone as a new generic treatment option for patients with urea cycle disorders.
• The generic formulation offers a new option for both adult and pediatric patients managing rare metabolic conditions.
• This launch represents a key first-to-market generic entry for Endo, reinforcing a focus on complex generics.

MALVERN, Pa., Oct. 20, 2025 /PRNewswire/ -- Endo, a wholly-owned subsidiary of Mallinckrodt plc, announced today the launch of a generic version of Amgen's RAVICTI^® (glycerol phenylbutyrate), 1.1 gm/mL oral liquid, following final approval from the U.S. Food and Drug Administration for its Abbreviated New Drug Application.

Endo's glycerol phenylbutyrate is the first and currently the only FDA-approved generic version of RAVICTI^® available in the U.S.

"This first-to-market launch of generic RAVICTI^® oral liquid is a meaningful milestone for Endo and important for our Generics business as we near the planned spin-off of Par Health," said Scott Sims, Senior Vice President and General Manager, Endo Injectable Solutions and Generics. "It expands access for patients and providers, and reinforces our commitment to quality, reliability, and leadership in complex generics."

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).

RAVICTI^® is a registered trademark of Amgen, Inc.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

• 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.

WARNINGS AND PRECAUTIONS

• Neurotoxicity - Increased exposure to phenylacetate (PAA), the major metabolite of glycerol phenylbutyrate, may be associated with neurotoxicity in patients with UCDs. Signs and symptoms of potential PAA neurotoxicity 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. 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.
• Pancreatic Insufficiency or Intestinal Malabsorption - Exocrine pancreatic enzymes hydrolyze glycerol phenylbutyrate in the small intestine, separating the active moiety, phenylbutyrate, from glycerol. 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. Monitor ammonia levels closely in patients with pancreatic insufficiency or intestinal malabsorption.

ADVERSE REACTIONS

• Adult patients: The most common adverse reactions (occurring in at least 10% of patients) reported during short-term treatment (4-week study, n=45) with glycerol phenylbutyrate were diarrhea, flatulence, and headache. Other adverse reactions reported in at least 10% of adult patients (12-months of treatment, n=51) were nausea, vomiting, diarrhea, decreased appetite, dizziness, headache, and fatigue.
• Pediatric patients ages 2–17 years: Adverse reactions reported in at least 10% of pediatric patients ages 2 years to 17 years (n=26) were upper abdominal pain, rash, nausea, vomiting, diarrhea, decreased appetite, and headache.
• Pediatric patients ages 2 months to less than 2 years: Adverse reactions reported in at least 10% of pediatric patients aged 2 months to less than 2 years (n=17) were neutropenia, vomiting, constipation, diarrhea, pyrexia, hypophagia, cough, nasal congestion, rhinorrhea, rash, and papule.
• Pediatric patients less than 2 months of age: Adverse reactions reported in at least 10% of pediatric patients aged less than 2 months (n=16) were vomiting, rash, gastroesophageal reflux, increased hepatic enzymes, feeding disorder (decreased appetite, hypophagia), anemia, cough, dehydration, metabolic acidosis, thrombocytosis, thrombocytopenia, neutropenia, lymphocytosis, diarrhea, flatulence, constipation, pyrexia, lethargy, and irritability/agitation.

Postmarketing Experience:

The following adverse reactions have been identified during post-approval use of glycerol phenylbutyrate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

• • Abnormal body odor, including from skin, hair, and urine
  • Retching and gagging
  • Dysgeusia or burning sensation in mouth

DRUG INTERACTIONS 
Potential for Other Drugs to Affect Ammonia Levels:

• Corticosteroids - May cause the breakdown of body protein and increase plasma ammonia levels. Monitor ammonia levels closely when used concomitantly with glycerol phenylbutyrate.
• Valproic Acid and Haloperidol - These drugs may induce hyperammonemia. If used in UCD patients receiving glycerol phenylbutyrate, close monitoring of plasma ammonia levels is advised.

Potential for Other Drugs to Affect Glycerol Phenylbutyrate:

• Probenecid - May inhibit renal excretion of glycerol phenylbutyrate metabolites including phenylacetylglutamine (PAGN) and PAA.

Potential for Glycerol Phenylbutyrate to Affect Other Drugs:

• Drugs with a Narrow Therapeutic Index (CYP3A4 Substrates) - Glycerol phenylbutyrate is a weak CYP3A4 inducer. Concomitant use of glycerol phenylbutyrate may decrease the systemic exposure to drugs that are substrates of CYP3A4. Monitor for decreased efficacy of drugs with a narrow therapeutic index (e.g., alfentanil, quinidine, cyclosporine).
• Midazolam - Systemic exposure to midazolam may be reduced when used with glycerol phenylbutyrate. Monitor for suboptimal clinical effects of midazolam in patients who are being treated with glycerol phenylbutyrate.

USE IN SPECIFIC POPULATIONS

Pediatric Use - Safety and efficacy have been established in pediatric patients.
Geriatric Use - Clinical studies did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently. Dose selection 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.
Pregnancy - The limited available data for the use of glycerol phenylbutyrate in pregnant women is insufficient to inform a drug-associated risk of major birth defects and miscarriage.
Lactation - 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. 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.
Hepatic Impairment - 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. 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.
Renal Impairment - The efficacy and safety of glycerol phenylbutyrate in patients with renal impairment are unknown. Monitor ammonia levels closely when starting patients with impaired renal function on glycerol phenylbutyrate.

Click for Full Prescribing Information.

About Endo
Endo, a wholly owned subsidiary of Mallinckrodt plc, is a diversified therapeutics manufacturer boldly transforming insights into life-enhancing therapies. Our passionate team members collaborate to develop and deliver these essential medicines. Together, we are committed to helping everyone we serve live their best life. Learn more at www.endo.com or connect with us on LinkedIn.

Cautionary Note Regarding Forward-Looking Statements
This release contains forward-looking statements, including with regard to product efficacy, potential treatments or indications, therapeutic outcomes or treatment responses, and any statements that refer to expected, estimated or anticipated future results or that do not relate solely to historical facts. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: the effects of each of Endo's and Mallinckrodt's recent emergences from bankruptcy; satisfaction of, and compliance with, regulatory and other requirements; actions of regulatory bodies and other governmental authorities; changes in laws and regulations; changes in market demand; issues with product quality, manufacturing or supply, or patient safety issues or adverse side effects or adverse reactions associated with our products; and other risks identified and described in more detail in the "Risk Factors" and the "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of Endo's and Mallinckrodt's most recent Annual Reports on Form 10-K, Mallinckrodt's Registration Statement on Form S-4, as amended, and other filings with the Securities and Exchange Commission (SEC), all of which are available from the SEC's website (www.sec.gov) and Mallinckrodt's website (www.mallinckrodt.com). The forward-looking statements made herein speak only as of the date hereof and we do not assume any obligation to update or revise any forward-looking statement, whether as a result of new information, future events and developments or otherwise, except as required by law. 

SOURCE Endo USA, Inc.