Glycerol phenylbutyrate

What is Glycerol phenylbutyrate?

• Glycerol phenylbutyrate (RAVICTI) is a nitrogen-binding agent used for management of patients with urea cycle disorders (UCDs).

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What are the uses of this medicine?

• This medicine is used for long-term management of high blood levels of ammonia (hyperammonemia) caused by a condition called a urea cycle disorder (UCD).
• RAVICTI should be used if the UCD cannot be managed with a low protein diet and dietary supplements alone.
• RAVICTI must be used along with a low protein diet and in some cases dietary supplements.

Limitations of Use:

• RAVICTI is not used for the acute treatment of hyperammonemia in people with UCD.
• It is not known if RAVICTI is safe and effective for the treatment of N-acetylglutamate synthase (NAGS) deficiency.

How does this medicine work?

• UCDs are inherited deficiencies of enzymes or transporters necessary for the synthesis of urea from ammonia (NH3, NH4+).
• Absence of these enzymes or transporters results in the accumulation of toxic levels of ammonia in the blood and brain of affected patients.
• RAVICTI is a triglyceride containing 3 molecules of PBA.
• PAA, the major metabolite of PBA, is the active moiety of RAVICTI.
• PAA conjugates with glutamine (which contains 2 molecules of nitrogen) via acetylation in the liver and kidneys to form PAGN, which is excreted by the kidneys .
• On a molar basis, PAGN, like urea, contains 2 moles of nitrogen and provides an alternate vehicle for waste nitrogen excretion.

Who Should Not Use this medicine ?

This medicine cannot be used:

• with known hypersensitivity to phenylbutyrate

What drug interactions can this medicine cause?

• Monitor ammonia levels closely when corticosteroids and RAVICTI are used concomitantly.
• Probenecid may inhibit the renal excretion of metabolites of RAVICTI including PAGN and PAA.
• Concomitant use of RAVICTI may decrease the systemic exposure to drugs that are substrates of CYP3A4.
• Concomitant use of RAVICTI decreased the systemic exposure of midazolam.

Is this medicine FDA approved?

• FDA approved this drug in the year of 2013.

How should this medicine be used?

Recommended Dosage: Switching From Sodium Phenylbutyrate Tablets or Powder to RAVICTI: Patients should receive the dosage of RAVICTI that contains the same amount of phenylbutyric acid.

Initial Dosage in Phenylbutyrate-Naïve Patients:

• Recommended dosage range is 4.5 to 11.2 mL/m2/day (5 to 12.4 g/m2/day).
• For patients with some residual enzyme activity not adequately controlled with dietary restriction, the recommended starting dose is 4.5 mL/m2/day.
• Take into account patient's estimated urea synthetic capacity, dietary protein intake, and diet adherence.

Dosage Adjustment and Monitoring:

• During treatment with RAVICTI, patients should be followed clinically and with plasma ammonia levels to determine the need for dosage titration.
• Closely monitor plasma ammonia levels during treatment with RAVICTI and when changing the dosage of RAVICTI.

Dosage Modifications in Patients with Hepatic Impairment:

• For patients with moderate to severe hepatic impairment, the recommended starting dosage is at the lower end of the recommended dosing range (4.5 mL/m2/day).

Administration

• Take RAVICTI exactly as your doctor tells you.
• Your doctor will tell you how much RAVICTI to take and when to take it.
• Your doctor may change your dose if needed.
• Take RAVICTI with food or formula.
• In an infant who is breastfeeding, give RAVICTI just before breastfeeding.
• RAVICTI is an oral liquid that is taken by mouth using an oral syringe.
• Ask your pharmacist for oral syringes and a reclosable bottle cap adapter for each bottle you receive if you do not have them.
• Use the RAVICTI bottle and oral syringe as follows:
• 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.
• Use a new dry oral syringe to remove each prescribed dose of RAVICTI.
• Throw away (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 throw it away.
• Throw away the bottle and any unused RAVICTI 28 days after opening.
• If you have a nasogastric or gastrostomy tube in place and can swallow, you should take RAVICTI by mouth.
• Stay on the diet that your doctor gives you.
• If you take too much RAVICTI, call your doctor or your poison control center at 1-800-222-1222 or go to the nearest hospital emergency room right away.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form: As Oral liquid: 1.1 g/mL

This medicine is available in fallowing brand namesː

• RAVICTI

What side effects can this medication cause?

The most common side effects of RAVICTI in adults include:

• diarrhea
• gas
• headache
• abdomen (stomach) pain
• vomiting
• tiredness
• decreased appetite
• indigestion or heartburn

The most common side effects of RAVICTI in children 2 years to 17 years of age include:

• upper abdomen (stomach) pain
• rash
• nausea
• vomiting
• diarrhea
• decreased appetite
• headache

The most common side effects of RAVICTI in children 2 months to less than 2 years of age include:

• low white blood cell count (neutropenia)
• vomiting
• constipation
• diarrhea
• fever
• reduced food intake
• cough
• stuffy nose
• runny nose
• skin rash
• small round bumps on the skin

The most common side effects of RAVICTI in children less than 2 months of age include:

• vomiting
• rash
• gastroesophageal reflux
• increased levels of liver enzymes in the blood
• decreased appetite and reduced food intake
• low red blood cell count (anemia)
• cough
• loss of too much body fluid (dehydration)
• too much acid in the blood (acidosis)
• high blood platelet count (thrombocytosis)
• low blood platelet count (thrombocytopenia)
• low blood neutrophil count (type of white blood cell) (neutropenia)
• high blood white blood cell count (lymphocytosis)
• diarrhea
• gas
• constipation
• fever
• drowsiness (lethargy)
• irritability
• agitation

RAVICTI may cause serious side effects, including:

• Nervous system problems (Neurotoxicity)

What special precautions should I follow?

• Neurotoxicity may occur. Phenylacetate (PAA), the active moiety of RAVICTI, may be toxic; reduce dosage for symptoms of neurotoxicity.
• Monitor ammonia levels closely in patients with pancreatic insufficiency or intestinal malabsorption.

What to do in case of emergency/overdose?

• There is no experience with overdosage in human clinical trials.
• RAVICTI, can accumulate in patients who receive an overdose.

Management for overdosage:

• If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.

Can this medicine be used in pregnancy?

• Limited available data with RAVICTI use in pregnant women are insufficient to inform a drug-associated risk of major birth defects and miscarriage.

Can this medicine be used in children?

Patients 2 Years to 17 Years of Age

• The safety and effectiveness of RAVICTI in patients 2 years to less than 18 years of age have been established.

Patients Less Than 2 Years of Age

• The safety and effectiveness of RAVICTI in patients with UCDs less than 2 years of age have been established.

What are the active and inactive ingredients in this medicine?

• Active ingredient: glycerol phenylbutyrate

Who manufactures and distributes this medicine?

Distributed by:

• Horizon Therapeutics USA

What should I know about storage and disposal of this medication?

• Store RAVICTI between 68°F to 77°F (20°C to 25°C).
• Keep RAVICTI and all medicines out of the reach of children.

• Dailymed label info on Glycerol phenylbutyrate
• FDA Glycerol phenylbutyrate

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