Important information
- Of the 16 pediatric patients less than 2 months of age in a 24-month, uncontrolled, open-label study, 5 patients (31%) reported a total of 7 hyperammonemic crises.1
- Of the 17 pediatric patients 2 months to less than 2 years of age in 3 open-label studies, 7 patients (41%) reported a total of 11 hyperammonemic crises.1
- Of the 26 pediatric patients 6 to 17 years of age in two 12-month studies of RAVICTI, 5 patients (19%) reported a total of 5 hyperammonemic crises.1
- Of 51 adult patients in a 12-month study of RAVICTI, 7 patients (14%) reported a total of 10 hyperammonemic crises.1
aThe safety and efficacy of RAVICTI for the treatment of N-acetylglutamate synthase (NAGS) deficiency have not been established.1
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Clinical data for patients less than 2 months of age
Stay up-to-date with RAVICTI
Dosing and administration instructions for patients who are breastfed
Stay up-to-date with RAVICTI
Information on using phenylbutyrate metabolite testing for targeted ammonia control
The lifelong, chronic nature of UCDs means patients are constantly living on the edge2,3
Ammonia elevations: it’s not a matter of if, but when
- The inherited risk of UCDs can result in elevated ammonia levels (greater than or equal to 35 μmol/L) for a prolonged period of time, leading to serious medical consequences.4,5
Metabolic stressors can occur anytime, anywhere
- Everyday risks include excessive protein intake, stress, major life milestones, and illness.6,7
Despite UCD treatment, adherence may affect ammonia control
- 67% of physicians reported poor adherence to treatment to be a barrier or unmet need in the care of patients with UCDs.4
One moment can change everything for patients with UCDsb—now is the time for RAVICTI
Unique mechanism of action designed for slow release of phenylbutyrate (PBA)
- Absorption of PBA is slower when administered as RAVICTI vs sodium phenylbutyrate, resulting in more sustained levels of active downstream metabolites.1,8
Established long-term ammonia control and safety profile for patients of all ages
- Long-term safety data exist for patients on RAVICTI and RAVICTI is the only UCD treatment that has been shown to provide ammonia control in both the short term (2 or 4 weeks) and long term (at least 12 months) in clinical studies.1,5
Easy administration and convenient dosing
- RAVICTI is nearly tasteless and odorless with no pills or powder to prepare.1,9
RAVICTI is contraindicated in patients with known hypersensitivity to phenylbutyrate.1
bThe safety and efficacy of RAVICTI for the treatment of NAGS deficiency have not been established.1
Get more information about RAVICTI dosing
Calculate the appropriate starting dose for treatment-naïve patients, quickly convert the dosage from NaPBA to RAVICTI, and optimize the RAVICTI dosage.
Optimize the RAVICTI dosage with a metabolite testing kit at no cost
With this test, you can determine your patient's plasma PAA:PAGN ratio and urinary PAGN level.
References: 1. RAVICTI (glycerol phenylbutyrate) Oral Liquid [prescribing information] Horizon. 2. Lichter-Konecki U, Diaz GA, Merritt JL II, et al. Ammonia control in children with urea cycle disorders (UCDs); phase 2 comparison of sodium phenylbutyrate and glycerol phenylbutyrate. Mol Genet Metab. 2011;103(4):323-329. doi:10.1016/j.ymgme.2011.04.013. 3. Lee B, Diaz GA, Rhead W, et al. Blood ammonia and glutamine as predictors of hyperammonemic crises in patients with urea cycle disorder. Genet Med. 2015;17(7):561-568. doi:10.1038/gim.2014.148. 4. Enns GM, Porter MH, Francis-Sedlak M, Burdett A, Vockley J. Perspectives on urea cycle disorder management: results of a clinician survey. Mol Genet Metab. 2019;128(1-2):102-108. doi:10.1016/j.ymgme.2019.07.009. 5. Diaz GA, Schulze A, Longo N, et al. Long-term safety and efficacy of glycerol phenylbutyrate for the management of urea cycle disorder patients. Mol Genet Metab. 2019;127(4):336-345. doi:10.1016/j.ymgme.2019.07.004. 6. Summar ML, Dobbelaere D, Brusilow S, Lee B. Diagnosis, symptoms, frequency and mortality of 260 patients with urea cycle disorders from a 21-year, multicentre study of acute hyperammonaemic episodes. Acta Paediatr. 2008;97(10):1420-1425. doi:10.1111/j.1651-2227.2008.00952.x. 7. Häberle J, Boddaert N, Burlina A, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Dis. 2012;7:32. doi:10.1186/1750-1172-7-32. 8. Monteleone JPR, Mokhtarani M, Diaz GA, et al. Population pharmacokinetic modeling and dosing simulations of nitrogen-scavenging compounds: disposition of glycerol phenylbutyrate and sodium phenylbutyrate in adult and pediatric patients with urea cycle disorders. J Clin Pharmacol. 2013;53(7):699-710. doi:10.1002/jcph.92. 9. Diaz GA, Krivitzky LS, Mokhtarani M, et al. Ammonia control and neurocognitive outcome among urea cycle disorder patients treated with glycerol phenylbutyrate. Hepatology. 2013;57(6):2171-2179. doi:10.1002/hep.26058.
INDICATION and IMPORTANT SAFETY INFORMATION
INDICATION
RAVICTI is indicated for the chronic management of patients with UCDs who cannot be managed by diet and supplementation alone. It must be used with dietary protein restriction. RAVICTI is not indicated for the treatment of acute hyperammonemia or for NAGS deficiency.1
RAVICTI (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 supplementation alone. RAVICTI must be used with dietary protein restriction and, in some cases, dietary supplements (e.g. essential amino acids, arginine, citrulline, protein-free calorie supplements).
LIMITATIONS OF USE
- RAVICTI 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.
- The safety and efficacy of RAVICTI for the treatment of N-acetylglutamate synthase (NAGS) deficiency has not been established.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
- Patients with known hypersensitivity to phenylbutyrate: Reactions include wheezing, dyspnea, coughing, hypotension, flushing, nausea, and rash.
WARNINGS AND PRECAUTIONS
- Neurotoxicity: Phenylacetate (PAA), the major metabolite of RAVICTI, may be toxic at levels of 500 micrograms/mL or greater. 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 RAVICTI dosage.
- Pancreatic Insufficiency or Intestinal Malabsorption: Low or absent pancreatic enzymes or intestinal disease resulting in fat malabsorption may result in reduced or absent digestion of RAVICTI and/or absorption of phenylbutyrate and reduced control of plasma ammonia. Monitor ammonia levels closely.
ADVERSE REACTIONS
The most common adverse reactions reported in clinical trials (at least 10% of patients) were:
- Adult patients: diarrhea, flatulence, and headache occurred during 4-week treatment (n=45) with RAVICTI; nausea, vomiting, diarrhea, decreased appetite, dizziness, headache, and fatigue occurred during 12-month treatment (n=51) with RAVICTI.
- Pediatric patients ages 2 to 17 years: upper abdominal pain, rash, nausea, vomiting, diarrhea, decreased appetite, and headache occurred during 12-month treatment (n=26) with RAVICTI.
- Pediatric patients ages 2 months to less than 2 years: neutropenia, vomiting, constipation, diarrhea, pyrexia, hypophagia, cough, nasal congestion, rhinorrhea, rash, and papule occurred during 12-month treatment (n=17) with RAVICTI.
- Pediatric patients less than 2 months of age: 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 occurred during 24-month treatment (n=16) with RAVICTI.
DRUG INTERACTIONS
- Corticosteroids, valproic acid, or haloperidol may increase plasma ammonia level. Monitor ammonia levels closely.
- Probenecid may affect renal excretion of metabolites of RAVICTI, including phenylacetylglutamine (PAGN) and PAA.
- CYP3A4 substrates with narrow therapeutic index (eg, alfentanil, quinidine, cyclosporine): RAVICTI may decrease exposure to the concomitant drug.
- Midazolam: Use of RAVICTI decreased exposure of midazolam with concomitant use.
USE IN SPECIFIC POPULATIONS
- Pregnancy: RAVICTI should be used with caution in patients who are pregnant or planning to become pregnant. Based on animal data, RAVICTI may cause fetal harm. Report pregnancies to Horizon at 1‐866‐479‐6742.
- Lactation: breastfeeding is not recommended during treatment with RAVICTI. There are no data on the presence of RAVICTI in human milk, the effects on the breastfed infant, nor the effects on milk production.
Please see Full Prescribing Information.
INDICATION and IMPORTANT SAFETY INFORMATION
INDICATION
RAVICTI is indicated for the chronic management of patients with UCDs who cannot be managed by diet and supplementation alone. It must be used with dietary protein restriction. RAVICTI is not indicated for the treatment of acute hyperammonemia or for NAGS deficiency.1
RAVICTI (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 supplementation alone. RAVICTI must be used with dietary protein restriction and, in some cases, dietary supplements (e.g. essential amino acids, arginine, citrulline, protein-free calorie supplements).
LIMITATIONS OF USE
- RAVICTI 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.
- The safety and efficacy of RAVICTI for the treatment of N-acetylglutamate synthase (NAGS) deficiency has not been established.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
- Patients with known hypersensitivity to phenylbutyrate: Reactions include wheezing, dyspnea, coughing, hypotension, flushing, nausea, and rash.
WARNINGS AND PRECAUTIONS
- Neurotoxicity: Phenylacetate (PAA), the major metabolite of RAVICTI, may be toxic at levels of 500 micrograms/mL or greater. 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 RAVICTI dosage.
- Pancreatic Insufficiency or Intestinal Malabsorption: Low or absent pancreatic enzymes or intestinal disease resulting in fat malabsorption may result in reduced or absent digestion of RAVICTI and/or absorption of phenylbutyrate and reduced control of plasma ammonia. Monitor ammonia levels closely.
ADVERSE REACTIONS
The most common adverse reactions reported in clinical trials (at least 10% of patients) were:
- Adult patients: diarrhea, flatulence, and headache occurred during 4-week treatment (n=45) with RAVICTI; nausea, vomiting, diarrhea, decreased appetite, dizziness, headache, and fatigue occurred during 12-month treatment (n=51) with RAVICTI.
- Pediatric patients ages 2 to 17 years: upper abdominal pain, rash, nausea, vomiting, diarrhea, decreased appetite, and headache occurred during 12-month treatment (n=26) with RAVICTI.
- Pediatric patients ages 2 months to less than 2 years: neutropenia, vomiting, constipation, diarrhea, pyrexia, hypophagia, cough, nasal congestion, rhinorrhea, rash, and papule occurred during 12-month treatment (n=17) with RAVICTI.
- Pediatric patients less than 2 months of age: 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 occurred during 24-month treatment (n=16) with RAVICTI.
DRUG INTERACTIONS
- Corticosteroids, valproic acid, or haloperidol may increase plasma ammonia level. Monitor ammonia levels closely.
- Probenecid may affect renal excretion of metabolites of RAVICTI, including phenylacetylglutamine (PAGN) and PAA.
- CYP3A4 substrates with narrow therapeutic index (eg, alfentanil, quinidine, cyclosporine): RAVICTI may decrease exposure to the concomitant drug.
- Midazolam: Use of RAVICTI decreased exposure of midazolam with concomitant use.
USE IN SPECIFIC POPULATIONS
- Pregnancy: RAVICTI should be used with caution in patients who are pregnant or planning to become pregnant. Based on animal data, RAVICTI may cause fetal harm. Report pregnancies to Horizon at 1‐866‐479‐6742.
- Lactation: breastfeeding is not recommended during treatment with RAVICTI. There are no data on the presence of RAVICTI in human milk, the effects on the breastfed infant, nor the effects on milk production.
Please see Full Prescribing Information.