"The U.S. Food and Drug Administration today approved Tretten, Coagulation Factor XIII A-Subunit (Recombinant), the first recombinant product for use in the routine prevention of bleeding in adults and children who have a rare clotting disorder, k"...
RAVICTI is indicated for use as a nitrogen-binding agent for chronic management of adult and pediatric patients ≥ 2 years of age with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. RAVICTI must be used with dietary protein restriction and, in some cases, dietary supplements (eg, 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.
The use of RAVICTI in patients < 2 months of age is contraindicated [see CONTRAINDICATIONS].
DOSAGE AND ADMINISTRATION
RAVICTI should be prescribed by a physician experienced in the management of UCDs. Instruct patients to take RAVICTI with food and to administer directly into the mouth via oral syringe or dosing cup. See the instructions on the use of RAVICTI by nasogastric tube or g-tube [see Preparation for Nasogastric Tube or Gastrostomy Tube Administration].
The recommended dosages for patients switching from sodium phenylbutyrate to RAVICTI and patients na´ve to phenylbutyric acid are different [see below]. For both subpopulations:
Give RAVICTI in 3 equally divided dosages, each rounded up to the nearest 0.5 mL.
The maximum total daily dosage is 17.5 mL (19 g).
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).
Switching From Sodium Phenylbutyrate to RAVICTI
Patients switching from sodium phenylbutyrate to RAVICTI should receive the dosage of RAVICTI that contains the same amount of phenylbutyric acid. The conversion is as follows:
Total daily dosage of RAVICTI (mL) = total daily dosage of sodium phenylbutyrate (g) x 0.8
Initial Dosage in Phenylbutyrate-Na´ve Patients
The recommended dosage range, based upon body surface area, in patients na´ve to phenylbutyrate (PBA) is 4.5 to 11.2 mL/m² /day (5 to 12.4 g/m² /day). For patients with some residual enzyme activity who are not adequately controlled with protein restriction, the recommended starting dosage is 4.5 mL/m² /day.
In determining the starting dosage of RAVICTI in treatment-na´ve patients, consider the patient's residual urea synthetic capacity, dietary protein requirements, and diet adherence. Dietary protein is approximately 16% nitrogen by weight. Given that approximately 47% of dietary nitrogen is excreted as waste and approximately 70% of an administered PBA dose will be converted to urinary phenylacetylglutamine (U-PAGN), an initial estimated RAVICTI dose for a 24-hour period is 0.6 mL RAVICTI per gram of dietary protein ingested per 24 hour period. The total daily dosage should not exceed 17.5 mL.
Dosage Adjustment and Monitoring
Adjustment based on Plasma Ammonia
Adjust the RAVICTI dosage to produce a fasting plasma ammonia level that is less than half the upper limit of normal (ULN) according to age.
Adjustment Based on Urinary Phenylacetylglutamine
If available, U-PAGN measurements may be used to help guide RAVICTI dose adjustment. Each gram of U-PAGN excreted over 24 hours covers waste nitrogen generated from 1.4 grams of dietary protein. If U-PAGN excretion is insufficient to cover daily dietary protein intake and the fasting ammonia is greater than half the ULN, the RAVICTI dose should be adjusted upward. The amount of dose adjustment should factor in the amount of dietary protein that has not been covered, as indicated by the 24-h U-PAGN level and the estimated RAVICTI dose needed per gram of dietary protein ingested and the maximum total daily dosage i.e. 17.5 mL.
Consider a patient's use of concomitant medications, such as probenecid, when making dosage adjustment decisions based on U-PAGN. Probenecid may result in a decrease of the urinary excretion of PAGN [see DRUG INTERACTIONS].
Adjustment Based on Plasma Phenylacetate
If available, measurements of the plasma PAA levels may be useful to guide dosing if symptoms of vomiting, nausea, headache, somnolence, confusion, or sleepiness are present in the absence of high ammonia or intercurrent illness. Ammonia levels must be monitored closely when changing the dose of RAVICTI. The ratio of PAA to PAGN in plasma may provide additional information to assist in dose adjustment decisions. In patients with a high PAA to PAGN ratio, a further increase in RAVICTI dose may not increase PAGN formation, even if plasma PAA concentrations are increased, due to saturation of the conjugation reaction. The PAA to PAGN ratio has been observed to be generally less than 1 in patients without significant PAA accumulation. [see WARNINGS AND PRECAUTIONS].
Dosage Modifications in Patients with Hepatic Impairment
Preparation for Nasogastric Tube or Gastrostomy Tube Administration
- Utilize an oral syringe to withdraw the prescribed dosage of RAVICTI from the bottle.
- Place the tip of the syringe into to the tip of the gastrostomy/nasogastric tube.
- Utilizing the plunger of the syringe, administer RAVICTI into the tube.
- Flush once with 30 mL of water and allow the flush to drain.
- Flush a second time with an additional 30 mL of water to clear the tube.
Dosage Forms And Strengths
Oral liquid: colorless to pale yellow, 1.1 g/mL of glycerol phenylbutyrate (delivers 1.02 g/mL of phenylbutyrate).
Storage And Handling
RAVICTI (glycerol phenylbutyrate) oral liquid 1.1 g/mL is supplied in multi-use, 25-mL glass bottles. The bottles are supplied in the following configurations:
NDC 76325-100-25: Single 25-mL bottle per carton
NDC 76325-100-04: Four 25-mL bottles per carton
Store at 20°-25°C (68°-77°F) with excursions permitted to 15°-30°C (59°-86°F).
Manufactured by: Lyne Laboratories, Inc., Brockton, MA 02301. Manufactured for: Hyperion Therapeutics Inc., 601 Gateway Boulevard, Suite 200. Issued: January 2013
Last reviewed on RxList: 2/15/2013
This monograph has been modified to include the generic and brand name in many instances.
Additional Ravicti Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.