Ravicti binds with other substances in the liver and kidneys to help eliminate nitrogen from the body. Excess nitrogen can cause hyperammonemi, 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.

Ravicti helps prevent a build-up of ammonia in the blood in adults and children with urea cycle disorder. This medicine will not treat hyperammonemia.

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

Ravicti 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.

Take Ravicti exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

Ravicti is usually taken 3 times per day. Take with food or infant formula. If you are breastfeeding a baby who is taking this medicine, give each dose right before nursing.

Measure Ravicti liquid carefully. Use the dosing syringe provided, or use a medicine dose-measuring device (not a kitchen spoon).

Ravicti may be given through a nasogastric (NG) or gastric feeding tube as follows: Measure the correct dose in the oral syringe, attach it to the feeding tube and push the plunger down to empty the syringe into the tube. Flush the tube with 10 milliliters (mL) of water and allow the tube to drain. Follow this with 10 mL more of water to wash the contents down.

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

Glycerol phenylbutyrate doses are based on body surface area (height and weight). Your dose needs may change if you gain or lose weight or if you are still growing.

You may need to follow a special diet while using Ravicti. Follow all instructions of your doctor or dietitian. Learn about the foods to eat or avoid to help control your condition.

A buildup of ammonia in the blood can quickly cause brain injury or death. You will need frequent 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 Ravicti at room temperature away from moisture and heat.

Usual Adult Dose of Ravicti for Urea Cycle Disorders:

Initial Doses:
Administer orally in 3 equally divided dosages rounded up to the nearest 0.5 mL:
-Phenylbutyrate-Naive Patients: 4.5 to 11.2 mL/m2/day (5 to 12.4 g/m2/day)
-Phenylbutyrate-Naive Patients with Some Residual Enzyme Activity: 4.5 mL/m2/day
-Patients Switching from sodium phenylbutyrate, use the following conversion:
--Tablets: Total daily dose of glycerol phenylbutyrate (mL)=total daily dose of sodium phenylbutyrate tablets (g) x 0.86
--Powder: Total daily dose of glycerol phenylbutyrate (mL)=total daily dose of sodium phenylbutyrate powder (g) x 0.81

MAINTENANCE DOSES: Follow clinically and with plasma ammonia levels, especially with changing doses; for elevated plasma ammonia, increase dose to maintain fasting plasma ammonia to less than half the upper limit of normal; if the phenylacetate (PAA) to phenylacetylglutamine (PAGN) ratio and urinary phenylacetylglutamine (U-PAGN) measurement are available, this will help guide dosing; product labeling may be consulted for additional information

MAXIMUM DOSE: 17.5 mL (19 g) per day

Usual Pediatric Dose of Ravicti for Urea Cycle Disorders:

Initial Doses:
-Patients less than 2 years: Administer in 3 or more equally divided dosages, rounded up to the nearest 0.1 mL
-Patients 2 years or older: Administer in 3 equally divided dosages, rounded up to the nearest 0.5 mL
Phenylbutyrate-Naive Patients: 4.5 to 11.2 mL/m2/day (5 to 12.4 g/m2/day)
Phenylbutyrate-Naive Patients with Some Residual Enzyme Activity: 4.5 mL/m2/day
Patients Switching from sodium phenylbutyrate, use the following conversion:
--Tablets: Total daily dose of glycerol phenylbutyrate (mL)=total daily dose of sodium phenylbutyrate tablets (g) x 0.86
--Powder: Total daily dose of glycerol phenylbutyrate (mL)=total daily dose of sodium phenylbutyrate powder (g) x 0.81

MAINTENANCE DOSES:
-Patients 6 years or older: Follow clinically and with plasma ammonia levels, especially with changing doses; for elevated plasma ammonia, increase dose to maintain fasting plasma ammonia to less than half the upper limit of normal; if the phenylacetate (PAA) to phenylacetylglutamine (PAGN) ratio and urinary phenylacetylglutamine (U-PAGN) measurement are available, this will help guide dosing; product labeling may be consulted for additional information
-Patients less than 6 years: Follow above guidance, however, if obtaining fasting ammonia is problematic due to frequent feedings, adjust the dose to keep the first ammonia of the morning below the upper limit for age

MAXIMUM DOSE: 17.5 mL (19 g) per day

Comments:
-When 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.
-Must use with dietary protein restriction and in some cases, with dietary supplements (e.g., essential amino acids, arginine, citrulline, protein-free calorie 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.

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

To make sure Ravicti is safe for you, tell your doctor if you have ever had:

• liver or kidney disease;

• a pancreas disorder;

• stomach or intestinal disorder,

• a condition called NAGS (N-acetylglutamate synthase) deficiency; or

• if you use other medicines.

It is not known whether glycerol phenylbutyrate will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

If you become pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of glycerol phenylbutyrate on the baby.

You should not breastfeed while using Ravicti.

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

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

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Get emergency medical help if you have signs of an allergic reaction to Ravicti: hives; cough, wheezing, difficult breathing; feeling like you might pass out; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any signs of high blood levels of ammonia (hyperammonemia):

• weakness, lack of energy;

• thinking problems, changes in behavior, feeling irritable;

• breathing problems;

• feeding problems; or

• seizure (convulsions).

Ravicti can affect your nervous system. Call your doctor at once if you have:

• drowsiness, unusual tiredness;

• memory problems;

• a light-headed feeling, like you might pass out;

• confusion, ongoing headache, vomiting;

• numbness, tingling, or burning pain in your hands or feet;

• altered sense of taste; or

• hearing problems.

Common Ravicti side effects may include:

• occasional headache;

• nausea, vomiting, diarrhea;

• loss of appetite, gas, stomach pain;

• dizziness, tiredness;

• rash; or

• (in children younger than 2 years) fever, cold or flu symptoms, cough, small bumps on the skin.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Sometimes it is not safe to use certain medications at the same time. Certain other drugs can affect your blood levels of ammonia, making Ravicti less effective or causing hyperammonemia.

Many drugs can interact with glycerol phenylbutyrate. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed here. Tell your doctor about all your current medicines and any medicine you start or stop using.