Evaluating RAVICTI® (glycerol phenylbutyrate) Oral Liquid for phenylbutyrate-naïve patients

Look over the patient treatment profile and administration features of RAVICTI

Sarah, a 22-year-old patient with ornithine transcarbamylase (OTC) deficiency.Sarah, a 22-year-old patient with ornithine transcarbamylase (OTC) deficiency.

RAVICTI effectively controls ammonia with oral administration1

For patients with urea cycle disorders (UCDs), controlling ammonia is a process that typically includes dietary modifications, supplements, and sometimes nitrogen scavenger therapies. As the only oral liquid treatment for patients with UCDs with no pills or powders to prepare, RAVICTI is made to fit today’s busy lives.1,2

RAVICTI bottle with childproof cap being opened.

Getting started: all it takes is 1 twist off and 1 twist on

Remove the childproof cap on the RAVICTI bottle by pushing down on the cap while twisting it to the left. Then, attach the reclosable bottle cap adapter onto the bottle by twisting right.

Syringe inserted in RAVICTI bottle.

Fill the syringe: it’s as easy as “hold, flip, pull”

  • Use a new and dry oral syringe to withdraw each prescribed dose of RAVICTI.
  • Use a new reclosable bottle cap adapter with each new RAVICTI bottle that is opened.
  • Open the RAVICTI bottle and twist on the new reclosable bottle cap adapter.
  • Hold the RAVICTI bottle securely as you place the tip of the oral syringe into a new reclosable bottle cap adapter.
  • Flip the bottle upside down with the new dry oral syringe still inserted.
  • Pull the plunger of the oral syringe back slowly to draw up the amount of RAVICTI prescribed by your doctor. Don’t forget to turn the bottle upright again. (Tip: Pulling slowly will help avoid large air bubbles from forming in the medicine.)
Young child receiving RAVICTI orally by syringe.

Squirt RAVICTI directly into mouth

Once the oral syringe is ready, place it into the mouth. Push the plunger to squirt all of the medicine directly into the mouth.

Important Information on taking RAVICTI by Mouth

  • 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.
  • If water or moisture enters the RAVICTI bottle, the contents will become cloudy in appearance. If the contents appear cloudy at any time, do not use the remaining RAVICTI and return the bottle to your pharmacy to be discarded.
  • Throw away the bottle and any unused RAVICTI 28 days after opening.
Young child washing RAVICTI down with a glass of water.

Wash RAVICTI down with water or food

Ensure the full dose of RAVICTI is swallowed completely by drinking liquid or eating some food. Breakfast, lunch, or dinner, RAVICTI can work with the timing of your patients’ meals.1

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References: 1. RAVICTI (glycerol phenylbutyrate) Oral Liquid [prescribing information] Horizon. 2. 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.

INDICATION and IMPORTANT SAFETY INFORMATION

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INDICATION

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

true

INDICATION

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.