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Please see Important Safety Information and Full Prescribing Information for BUPHENYL.

RAVICTI: The only FDA-approved oral liquid treatment for UCDs1,2

RAVICTI® (glycerol phenylbutyrate) Oral Liquid

RAVICTI is indicated for the chronic management of adult and pediatric patients ≥2 years of age with UCDs who cannot be managed by dietary protein restriction and/or amino acid supplementation alone.

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
  • The use of RAVICTI in patients <2 months of age is contraindicated

RAVICTI is the only FDA-approved oral liquid medicine that

  • Has been clinically studied over 12 months1
  • Is nearly tasteless and odorless3
  • Requires no pill or powder preparation1


Please see Important Safety Information for BUPHENYL.

Prescribing RAVICTI to your patients

Along with dietary protein restriction, RAVICTI may be prescribed for patients diagnosed with a UCD or for patients switching from BUPHENYL, as indicated. In some cases, dietary supplements must also be used for UCD management.1

Please see Important Safety Information and Full Prescribing Information for BUPHENYL.

For use in patients with a nasogastric or gastrostomy feeding tube

  • See Dosing RAVICTI for more information about dosing and administration for your patients who have a nasogastric or gastrostomy feeding tube in place.

RAVICTI can be prescribed to treat a variety of UCD subtypes1,4,a:

aThe safety and efficacy of RAVICTI for the treatment of N-acetylglutamate synthase (NAGS) deficiency has not been established.

UCD DEFICIENCIES TREATED BY RAVICTI
image description Ornithine transcarbamylase (OTC)
image description Argininosuccinate synthetase (ASS) or citrullinemia I
image description Argininosuccinate lyase (ASL) or argininosuccinic aciduria
image description Carbamyl phosphate synthase (CPS1)
image description Arginase (ARG) or hyperargininemia
image description Ornithine translocase (0RNT1); also called hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome
image description Citrin (aspartate glutamate transporter)

Contraindications

RAVICTI is contraindicated in patients:

  • Less than 2 months of age. Children <2 months of age may have immature pancreatic exocrine function, which could impair hydrolysis of RAVICTI, leading to impaired absorption of phenylbutyrate and hyperammonemia.1
  • With known hypersensitivity to phenylbutyrate. Signs of hypersensitivity include wheezing, dyspnea, coughing, hypotension, flushing, nausea, and rash.1

Efficacy

Consider redefining treatment goals with RAVICTI—the only UCD therapy studied in a 12-month controlled clinical trial.1

As the only FDA-approved oral therapy that has been clinically studied over the long term (greater than one year) in both adult and pediatric patients ≥2 years of age with UCDs who cannot be managed by dietary protein restriction and/or amino acid supplementation alone, RAVICTI offers established ammonia control for UCD patients over a 24-hour period and 12-month period.

Managing ammonia levels

Mildly elevated ammonia for a prolonged period of time may result in serious medical consequences.5-8

Of 51 adult patients in the 12-month study of RAVICTI, 7 patients (14%) reported a total of 10 hyperammonemic crises. Of the 26 pediatric patients 6 to 17 years of age in the two 12-month studies of RAVICTI, 5 patients (19%) reported a total of 5 hyperammonemic crises. 

Targeting fasting ammonia levels below half the upper limit of normal (ULN) helps control ammonia levels in patients with UCDs.
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Safety of RAVICTI® (glycerol phenylbutyrate) Oral Liquid

Adverse reactions reported in 2 adult patients1

System organ class preferred term Number (%) of patients
Sodium phenylbutyrate (N=45) RAVICTI (N=44)
Gastrointestinal disorders    
Abdominal discomfort 3 (7) 0
Abdominal pain 2 (4) 3 (7)
Diarrhea 3 (7) 7 (16)
Dyspepsia 3 (7) 2 (5)
Flatulence 1 (2) 6 (14)
Nausea 3 (7) 1 (2)
Vomiting 2 (4) 3 (7)
General disorders and administration
site conditions
   
Fatigue 1 (2) 3 (7)
Investigations    
Ammonia increased 1 (2) 2 (5)
Metabolism and nutrition disorders    
Decreased appetite 2 (4) 3 (7)
Nervous system disorders    
Dizziness 4 (9) 0
Headache 4 (9) 6 (14)

Study design

  • Assessment of adverse reactions in a randomized, double-blind, active-controlled, crossover study of 45 patients >18 years of age being treated with either RAVICTI or sodium phenylbutyrate for 2 weeks1

Adults and pediatrics: adverse reactions during 12 months of treatment

  • Adverse reactions occurring in >10% of adult patients during 12 months of treatment were nausea, vomiting, diarrhea, decreased appetite, hyperammonemia, dizziness, headache, and fatigue1
  • Of the 51 adult patients, 7 patients (14%) reported a total of 10 hyperammonemic crises1
  • Adverse reactions occurring in >10% of pediatric patients during 12 months of treatment were upper abdominal pain, rash, nausea, vomiting, diarrhea, decreased appetite, hyperammonemia, and headache1
  • Of the 26 pediatric patients 6 to 17 years of age, 5 patients (19%) reported a total of 5 hyperammonemic crises1

PAA-associated adverse events

The major metabolite of RAVICTI, PAA, is associated with neurotoxicity. In a study of cancer patients who were administered IV PAA, signs and symptoms of PAA neurotoxicity were observed at plasma PAA concentrations >500 μg/mL. These included somnolence, fatigue, lightheadedness, headache, dysgeusia, hypoacusis, disorientation, impaired memory, and exacerbation of preexisting neuropathy. In this study, adverse events were reversible.1

If symptoms of vomiting, nausea, headache, somnolence, confusion, or sleepiness are present in the absence of high ammonia or other intercurrent illnesses, reduce the RAVICTI dosage.1

Please see RAVICTI Full Prescribing Information for more information.

Mechanism of action

RAVICTI exhibits slow-release characteristics1

Unlike other nitrogen-scavenging treatments, RAVICTI is a pro-drug of phenylbutyrate (PBA).1 The active moiety of RAVICTI is phenylacetate—a metabolically active compound that combines with glutamine to form phenylacetylglutamine (PAGN), which is then excreted by the kidneys.1

phenylacetylglutamine

On a molar basis PAGN, like urea, contains 2 moles of nitrogen and provides an alternate vehicle for waste nitrogen excretion.1 The release of phenylbutyrate occurs mostly in the small intestine, rather than in the stomach. Phenylbutyrate is then converted to phenylacetate in the blood and combined with glutamine and then excreted as phenylacetylglutamine.1,2

image description

The absorption of PBA is approximately 70% to 75% slower when administered as RAVICTI vs sodium phenylbutyrate.1,12 The release and absorption of phenylbutyric acid (PBA) leads to urinary phenylacetylglutamine (U-PAG n) excretion.1,11,12

Dosing

For patients switching from sodium phenylbutyrate

Patients switching from sodium phenylbutyrate to RAVICTI should receive the dosage of RAVICTI that contains the same amount of phenylbutyric acid.1 Use the table in the Dosing Conversion Tool below to see standard conversion results.

Under certain circumstances, adjustments may need to be made or your patients may have other limitations. Click here for complete Dosing and Administration.

DOSING CONVERSION TOOL1

TOTAL DAILY DOSE OF SODIUM PHENYLBUTYRATE (g) ROUND EACH DOSE OF RAVICTI UP TO THE NEAREST 0.5 mL
(TO BE GIVEN TID)
2 1
3 1
4 1.5
5 1.5
6 2
7 2.5
8 2.5
9 3
10 3
11 3.5
12 3.5
13 4
14 4.5
15 4.5
16 5
17 5
18 5.5
19 5.5
20 6

Total daily dose of sodium phenylbutyrate (g) x 0.86 = Total daily dose of RAVICTI (mL). Divide total daily dose by 3 doses/day. Round each dose up to the nearest 0.5 mL (to be given TID).1







For patients naïve to phenylbutyrate (PBA)

Patients new to PBA treatment and on concurrent dietary protein restriction and/or dietary supplements1








Dosing adjustments (PBA)

Your patients’ plasma ammonia levels will help guide how you adjust their RAVICTI dosages. RAVICTI should be dosed to produce a fasting ammonia level that is less than half the upper limit of normal according to age.1

MAKING ADJUSTMENTS BASED ON U-PAGN PLASMA PHENYLACETATE (PAA) LEVELS

Your patients may still experience symptoms that are similar to hyperammonemia, despite not having elevated ammonia levels. There are alternative tests based on U-PAGN and PAA levels to help guide RAVICTI dosing.1

You can order these tests by contacting Horizon UCD Support Services.
Get the tests today >>

Administering RAVICTI orally

Administering RAVICTI with nasogastric or gastrostomy feeding tube

Administration

Three oral liquid doses per day can help control ammonia1,b

Choosing a therapy that requires minimal preparation may make your patient's UCD treatment easy.1  

Please see Important Safety Information and Full Prescribing Information for BUPHENYL.

dosing administration

bOf 51 adult patients in the 12-month study of RAVICTI, 7 patients (14%) reported a total of 10 hyperammonemic crises. Of the 26 pediatric patients 6 to 17 years of age in the two 12-month studies of RAVICTI, 5 patients (19%) reported a total of 5 hyperammonemic crises.1

NEXT: PRESCRIBING RAVICTI