Glycerol phenylbutyrate

>10%

Diarrhea (16%)

Flatulence (14%)

Headache (14%)

1-10%

Abdominal pain (7%)

Vomiting (7%)

Decreased appetite (7%)

Fatigue (7%)

Ammonia increased (5%)

Dyspepsia (5%)

Nausea (2%)

Postmarketing Reports

Abnormal body odor, including from skin, hair, and urine

Retching and gagging

Dysgeusia or burning sensation in mouth

Neutropenia

Pyrexia

Hypophagia

Cough

Nasal congestion

Rhinorrhea

Rash and papule

Glycerol phenylbutyrate binds with other substances in the liver and kidneys to help eliminate nitrogen from the body. Excess nitrogen can cause hyperammonemia (HYE-per-AM-moe-NEE-mee-a), a build-up of ammonia in the blood. Ammonia is very toxic when it circulates in blood and tissues and can cause permanent brain damage, coma, or death.

Glycerol phenylbutyrate helps prevent a build-up of ammonia in the blood in people with urea cycle disorder. This medicine is used in adults and children who are at least 2 years old. Glycerol phenylbutyrate will not treat hyperammonemia.

Glycerol phenylbutyrate is usually given together with a low-protein diet and sometimes dietary supplements.

Glycerol phenylbutyrate may also be used for purposes not listed in this medication guide.

Glycerol phenylbutyrate should not be given to a child under 2 months old.

You should not use glycerol phenylbutyrate if you are allergic to it.

Glycerol phenylbutyrate should not be given to a child under 2 months old. Do not give this medicine to a child younger than 2 years old without medical advice.

To make sure glycerol phenylbutyrate is safe for you, tell your doctor if you have:

• liver or kidney disease;
• pancreas disorder;
• stomach or intestinal disorder,
• a condition called NAGS (N-acetylglutamate synthase) deficiency; or
• if you take haloperidol or probenecid, or if you use a steroid medicine (beclomethasone, dexamethasone, fluticasone, prednisone, and others).

FDA pregnancy category C. It is not known whether glycerol phenylbutyrate will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine.

It is not known whether glycerol phenylbutyrate passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Glycerol phenylbutyrate is usually taken 3 times per day. Take with food.

Measure liquid medicine with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

Glycerol phenylbutyrate can also be given through a nasogastric (NG) or gastric feeding tube as follows: After measuring the correct dose in the syringe, attach it to the feeding tube and push the plunger down to empty the syringe into the tube. Then flush the tube with 2 tablespoons of water and allow it to drain. Follow this with 2 more tablespoons of water to wash the contents down.

If you switch from sodium phenylbutyrate to glycerol phenylbutyrate, your dose will not be the same. Follow your doctor's dosing instructions very carefully.

Glycerol phenylbutyrate is only part of a complete program of treatment that may also include a special diet and other medications. It is very important to follow the diet plan created for you by your doctor or nutrition counselor. You should become very familiar with the list of foods you should eat or avoid to help control your condition.

To be sure this medicine is helping your condition and is not causing harmful effects, your blood will need to be tested often. A buildup of ammonia in the blood can quickly cause brain injury or death. Do not miss any follow up visits to your doctor for blood tests. Every person with a urea cycle disorder should remain under the care of a doctor.

Your name may be listed on a Urea Cycle Disorder registry. This is to collect information about people with these disorders and to evaluate the effects of treatment.

Store at room temperature away from moisture and heat.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• corticosteroid medications such as beclomethasone, budesonide, medrol, prednisolone, prednisone, fluticasone and others
• valproic acid (Depakote, Depakene, Stavzor)
• haloperidol (Haldol)
• probenecid (Benemid, Probalan, in Colbenemid, and Proben-C)

This is not a complete list of glycerol phenylbutyrate drug interactions. Ask your doctor or pharmacist for more information. 

Glycerol phenylbutyrate may cause serious side effects, including:

Nervous system problems (Neurotoxicity). Phenylacetate, a breakdown product of glycerol phenylbutyrate, may cause nervous system side effects. Call your doctor or get medical help right away if you get any of these symptoms while taking glycerol phenylbutyrate:

• sleepiness
• weakness
• lightheadedness
• change in taste
• problems with hearing
• confusion
• problems with memory
• worsening neuropathy (numbness, tingling, or burning in your hands or feet)
• headache

Do not take glycerol phenylbutyrate if you are:

• less than 2 months of age because it may not be digested in babies less than 2 months of age.
• allergic to phenylbutyrate. Call your doctor or go to the nearest hospital emergency room if you get wheezing, shortness of breath, cough, low blood pressure, flushing, nausea or a rash while taking glycerol phenylbutyrate.

This medicine can affect your nervous system. Call your doctor right away if you have: confusion, headaches, memory problems, hearing problems, vomiting, an altered sense of taste, numbness or tingling in your hands or feet, or if you feel unusually sleepy or light-headed.

Glycerol phenylbutyrate should not be given to a child under 2 months old.

Usual Adult Dose for Urea Cycle Disorders:

Phenylbutyrate-Naive Patients:
-Initial dose: 4.5 to 11.2 mL/m2/day (5 to 12.4 g/m2/day) orally in 3 equally divided dosages
-Initial dose when residual enzyme activity is not adequately controlled with dietary restriction: 4.5 mL/m2/day
-Maintenance dose: Adjust dose to produce a fasting plasma ammonia level less than half the upper limit of normal according to age
-Maximum dose: 17.5 mL (19.5 g)

Comments:
-Doses should be rounded up to the nearest 0.5 mL.
- In determining the starting dose, consider the patient's residual urea synthetic capacity, dietary protein requirements, and diet adherence; may consider an initial estimated daily dose of 0.6 mL per gram of dietary protein ingested per 24 hour period.

Patients switching from Sodium Phenylbutyrate should use the following conversion:
-Total daily dose of glycerol phenylbutyrate (mL) should equal the total daily dose of sodium phenylbutyrate (g) x 0.86
Maximum dose: 17.5 mL (19.5 g)

Comments:
-Must use with dietary protein restriction and in some cases, with dietary supplements.
-Not indicated for the treatment of acute hyperammonemia as more rapid interventions should be used.
-Safety and efficacy for treatment of N-acetylglutamate synthase (NAGS) deficiency has not been established.

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 amino acid supplementation alone.

Usual Pediatric Dose for Urea Cycle Disorders:

Aged 2 years or older:
Phenylbutyrate-Naive Patients:
-Initial dose: 4.5 to 11.2 mL/m2/day (5 to 12.4 g/m2/day) orally in 3 equally divided dosages
-Initial dose when residual enzyme activity is not adequately controlled with dietary restriction: 4.5 mL/m2/day
-Maintenance dose: Adjust dose to produce a fasting plasma ammonia level less than half the upper limit of normal according to age
-Maximum dose: 17.5 mL (19.5 g)

Comments:
-Doses should be rounded up to the nearest 0.5 mL.
- In determining the starting dose, consider the patient's residual urea synthetic capacity, dietary protein requirements, and diet adherence; may consider an initial estimated daily dose of 0.6 mL per gram of dietary protein ingested per 24 hour period.

Patients switching from Sodium Phenylbutyrate should use the following conversion:
-Total daily dose of glycerol phenylbutyrate (mL) should equal the total daily dose of sodium phenylbutyrate (g) x 0.86
Maximum dose: 17.5 mL (19.5 g)

Comments:
-Must use with dietary protein restriction and in some cases, with dietary supplements.
-Not indicated for the treatment of acute hyperammonemia as more rapid interventions should be used.
-Safety and efficacy for treatment of N-acetylglutamate synthase (NAGS) deficiency has not been established.

Use: As a nitrogen-binding agent for chronic management of pediatric patients 2 years or older with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone.

In the U.S.

• Ravicti

Available Dosage Forms:

• Solution

Therapeutic Class: Hyperammonemia Agent

Take glycerol phenylbutyrate exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

glycerol phenylbutyrate comes with a Medication Guide. Read and follow the instructions carefully. Ask your doctor if you have any questions.

It is important that you or your child follow any special diet instructions from your doctor, such as using a low-protein diet. If you have any questions about this, check with your doctor.

Use an oral syringe or dosing cup to measure your dose. You may also give glycerol phenylbutyrate with a nasogastric tube or gastrostomy tube (g-tube).

To use the oral liquid with a nasogastric tube or g-tube:

• Use an oral syringe to measure your dose and place it on the tip of the nasogastric tube or g-tube.
• Inject the medicine into the tube.
• Flush the tube with 10 mL of water to rinse all of the medicine into the stomach.
• Rinse the tube again with additional 10 mL of water to clear the tube.

Dosing

The dose of glycerol phenylbutyrate will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of glycerol phenylbutyrate. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (liquid):
  • For treatment of urea cycle disorders:
    • For patients not on phenylbutyrate treatment:
      • Adults and children 2 years of age and older—Dose is based on body size and must be determined by your doctor. The dose is 4.5 to 11.2 milliliters (mL) per square meter (m[2]) per day and divided into 3 equal doses, each rounded up to the nearest 0.5 mL. Your doctor may adjust your dose as needed. However, the dose is usually not more than 17.5 mL per day.
      • Children 2 months up to 2 years of age—Dose is based on body size and must be determined by your doctor. The dose is 4.5 to 11.2 milliliters (mL) per square meter (m[2]) per day and divided into 3 or more equal doses, each rounded up to the nearest 0.1 mL. Your doctor may adjust your dose as needed. However, the dose is usually not more than 17.5 mL per day.
      • Children younger than 2 months of age—Use is not recommended.
    • For patients switching from sodium phenylbutyrate powder to Ravicti®:
      • Adults and children 2 years of age and older—The dose is the total daily dose of sodium phenylbutyrate that you are already taking multiplied by 0.81 and divided into 3 equal doses, each rounded up to the nearest 0.5 mL. Your doctor may adjust your dose as needed. However, the dose is usually not more than 17.5 milliliters (mL) per day.
      • Children 2 months up to 2 years of age—The dose is the total daily dose of sodium phenylbutyrate that you are already taking multiplied by 0.81 and divided into 3 or more equal doses, each rounded up to the nearest 0.1 mL. Your doctor may adjust your dose as needed. However, the dose is usually not more than 17.5 milliliters (mL) per day.
      • Children younger than 2 months of age—Use is not recommended.
    • For patients switching from sodium phenylbutyrate tablets to Ravicti®:
      • Adults and children 2 years of age and older—The dose is the total daily dose of sodium phenylbutyrate that you are already taking multiplied by 0.86 and divided into 3 equal doses, each rounded up to the nearest 0.5 mL. Your doctor may adjust your dose as needed. However, the dose is usually not more than 17.5 milliliters (mL) per day.
      • Children 2 months up to 2 years of age—The dose is the total daily dose of sodium phenylbutyrate that you are already taking multiplied by 0.86 and divided into 3 or more equal doses, each rounded up to the nearest 0.1 mL. Your doctor may adjust your dose as needed. However, the dose is usually not more than 17.5 milliliters (mL) per day.
      • Children younger than 2 months of age—Use is not recommended.

Missed Dose

If you miss a dose of glycerol phenylbutyrate, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

• It is used to treat urea cycle problems.

For all patients taking glycerol phenylbutyrate:

• If you have an allergy to glycerol phenylbutyrate or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are breast-feeding. Do not breast-feed while you take glycerol phenylbutyrate.

Children:

• If your child is younger than 2 months of age. Do not give this medicine to an infant younger than 2 months of age.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take glycerol phenylbutyrate with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Aged 2 years or older:
Phenylbutyrate-Naive Patients:
-Initial dose: 4.5 to 11.2 mL/m2/day (5 to 12.4 g/m2/day) orally in 3 equally divided dosages
-Initial dose when residual enzyme activity is not adequately controlled with dietary restriction: 4.5 mL/m2/day
-Maintenance dose: Adjust dose to produce a fasting plasma ammonia level less than half the upper limit of normal according to age
-Maximum dose: 17.5 mL (19.5 g)

Comments:
-Doses should be rounded up to the nearest 0.5 mL.
- In determining the starting dose, consider the patient's residual urea synthetic capacity, dietary protein requirements, and diet adherence; may consider an initial estimated daily dose of 0.6 mL per gram of dietary protein ingested per 24 hour period.

Patients switching from Sodium Phenylbutyrate should use the following conversion:
-Total daily dose of glycerol phenylbutyrate (mL) should equal the total daily dose of sodium phenylbutyrate (g) x 0.86
Maximum dose: 17.5 mL (19.5 g)

Comments:
-Must use with dietary protein restriction and in some cases, with dietary supplements.
-Not indicated for the treatment of acute hyperammonemia as more rapid interventions should be used.
-Safety and efficacy for treatment of N-acetylglutamate synthase (NAGS) deficiency has not been established.

Use: As a nitrogen-binding agent for chronic management of pediatric patients 2 years or older with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone.