Starting

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

Look over the patient treatment profile and administration features of RAVICTI

RAVICTI effectively controls ammonia with easy 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

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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 blue AdaptaCap® Bottle Adapter on to the bottle by twisting it to the right.

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

  • Hold the RAVICTI bottle securely as you place the tip of the oral dosing syringe into the AdaptaCap® Bottle Adapter.
  • Flip the bottle upside down with the oral dosing syringe still inserted.
  • Pull the plunger of the oral dosing 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.)
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Squirt RAVICTI right into mouth

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

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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

If you’re ready to prescribe RAVICTI to your patients, it’s important that you and your patients understand how to administer RAVICTI properly. Watch the videos below to review the complete directions for taking RAVICTI.

Ready to start your patients on RAVICTI?

Review dosage guidelines for phenylbutyrate-naïve patients.

View Dosage Guide

Switching

Consider RAVICTI as an alternative to sodium phenylbutyrate (NaPBA)

Look over the patient treatment profile, see how RAVICTI works, and get helpful forms and tools for switching.

Patients switching from NaPBA to RAVICTI should receive the dosage of RAVICTI that contains the same amount of phenylbutyric acid.1

Patient profile jonas Patient profile jonas

RAVICTI offers convenient dosing, easy administration, and requires minimal preparation1

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Nearly tasteless and odorless liquid3

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No pill or powder preparation and minimal dosing steps required1

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Taken with meals or feedings via oral dosing syringe1

  • RAVICTI is the only FDA-approved oral liquid for the treatment of patients with UCDs.1
  • The total daily dosage of RAVICTI should be divided into equally divided doses according to age range.1
    • Patients 2 years of age and older: Give RAVICTI in 3 equally divided doses, each rounded up to the nearest 0.5 mL.1
    • Patients less than 2 years of age: Give RAVICTI in 3 or more equally divided doses, each rounded up to the nearest 0.1 mL.1
    • RAVICTI should be administered just prior to breastfeeding in infants who are breastfed.1
  • RAVICTI can be taken orally, even in patients with a nasogastric tube or g-tube.1
    • For patients who require a volume of less than 1 mL per dose via nasogastric or gastrostomy tube, the delivered dose may be less than anticipated. Closely monitor these patients using ammonia levels.1
  • The maximum daily dosage of RAVICTI (17.5 mL) is equivalent to 40 tablets of sodium phenylbutyrate.1,3

Download this form to initiate switching

If your patients are ready to make the switch, complete the Patient Enrollment Form.

Ready to start your patients on RAVICTI?

Review dosage guidelines and calculate the dose for patients currently taking NaPBA.

View Dosage Guide

Optimizing

Knowing when to modify the dose of RAVICTI

Look over the patient treatment profile and important biomarkers, and order a metabolite testing kit

Patient profile miranda Patient profile miranda

Order phenylbutyrate metabolite testing at no cost

With this test, you can determine your patient’s plasma PAA:PAGN ratio and urinary PAGN level.

Order Kit

Using key biomarkers, RAVICTI dosing may be modified for targeted ammonia control1,4,5

Plasma ammonia

  • Elevated ammonia levels: Increase the RAVICTI dosage to reduce the fasting plasma ammonia level to less than half the upper limit of normal (ULN) in patients 6 years of age and older. In infants and pediatric patients (generally less than 6 years of age) in whom obtaining fasting ammonia is problematic due to frequent feedings, adjust the dosage to keep the first ammonia of the morning below the ULN.1,b

Phenylbutyrate (PBA) metabolites

  • Plasma PAA:PAGN ratio and urinary PAGN: Use these biomarkers, along with plasma ammonia and glutamine levels, to help guide dosing decisions.1,4,5
Website Table PBA Metabolism
  • Phenylbutyrate metabolite analysis testing is available through Baylor Genetics and sponsored by Horizon. Order your test kits free of charge at bmgl.com/testing/order-kits

Assess how your patients are doing on RAVICTI

This assessment tool can help you evaluate treatment of your patients and ensure that they are staying on track with their UCD management.

Should you modify the RAVICTI dosage?

Learn more about optimizing RAVICTI dosage and how changes in body surface area may impact the appropriate dosage.

View Dosage Guide

aHypothetical case study.

bInstruct patients to abstain from eating or drinking any foods or liquids 4 to 6 hours before plasma ammonia levels are to be measured.6

References:    1. RAVICTI (glycerol phenylbutyrate) [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.   3. 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.   4. Mokhtarani M, Diaz GA, Rhead W, et al. Elevated phenylacetic acid levels do not correlate with adverse events in patients with urea cycle disorders or hepatic encephalopathy and can be predicted based on the plasma PAA to PAGN ratio. Mol Genet Metab. 2013;110(4):446-453. doi:10.1016/j.ymgme.2013.09.017.   5. Mokhtarani M, Diaz GA, Rhead W, et al. Urinary phenylacetylglutamine as dosing biomarker for patients with urea cycle disorders. Mol Genet Metab. 2012;107(3):308-314. doi:10.1016/j.ymgme.2012.08.006.   6. Häberle J. Clinical practice: the management of hyperammonemia. Eur J Pediatr. 2011;170(1):21-34. doi:10.1007/s00431-010-1369-2.  

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. A voluntary patient registry monitors pregnancy outcomes in women exposed to RAVICTI. For more information regarding the registry program, visit ucdregistry.com or call 1-855-823-2595.
  • 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. A voluntary patient registry monitors pregnancy outcomes in women exposed to RAVICTI. For more information regarding the registry program, visit ucdregistry.com or call 1-855-823-2595.
  • 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.