Important Administration Instructions

RAVICTI should be prescribed by a physician experienced in the management of UCDs.

• ​Instruct patients to take RAVICTI with food or formula and to administer directly into the mouth via oral syringe.
• ​Instruct patients to use the RAVICTI bottle and oral syringe as follows:
  • Use a new reclosable bottle cap adapter with each new bottle that is opened.
  • Open the RAVICTI bottle and twist on the new reclosable bottle cap adapter.
  • Use a new and dry oral syringe to withdraw each prescribed dose of RAVICTI.
  • 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.
  • Discard bottle and any remaining contents 28 days after opening.
  • If water or moisture enters the RAVICTI bottle, the contents will become cloudy in appearance. If the contents of the bottle appear cloudy at any time, do not use the remaining RAVICTI in the bottle and return it to the pharmacy to be discarded.
• Instruct that RAVICTI should be administered just prior to breastfeeding in infants who are breastfeeding.
• For patients who cannot swallow, see the instructions on administration of RAVICTI by nasogastric tube or gastrostomy tube [see Dosage and Administration (2.6)].
• For patients who require a volume of less than 1 mL per dose via nasogastric or gastrostomy tube, the delivered dose may be less than anticipated. Closely monitor these patients using ammonia levels [see Dosage and Administration (2.6)].
• The recommended dosages for patients switching from sodium phenylbutyrate to RAVICTI and patients naïve to phenylbutyric acid are different [see Dosage and Administration (2.2, 2.3)]. For both subpopulations:
  • Patients 2 years of age and older: Give RAVICTI in 3 equally divided dosages, each rounded up to the nearest 0.5 mL
  • Patients less than 2 years: Give RAVICTI in 3 or more equally divided dosages, each rounded up to the nearest 0.1 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 tablets (g) × 0.86

Total daily dosage of RAVICTI (mL) = total daily dosage of sodium phenylbutyrate powder (g) × 0.81

Initial Dosage in Phenylbutyrate-Naïve Patients

The recommended dosage range, based upon body surface area, in patients naïve 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-naïve 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

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.

The methods used for measuring plasma ammonia levels vary among individual laboratories and values obtained using different assay methods may not be interchangeable. Normal ranges and therapeutic target levels for plasma ammonia depend upon the assay method used by the individual laboratory. During treatment with RAVICTI, refer to the assay-specific normal ranges and to the therapeutic target ranges for plasma ammonia.

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) and the dosage should be kept at the lowest necessary to control the patient's plasma ammonia [see Use in Specific Populations (8.7)].

Preparation for Nasogastric Tube or Gastrostomy Tube Administration

It is recommended that all patients who can swallow take RAVICTI orally, even those with nasogastric and/or gastrostomy tubes. For patients who cannot swallow, a nasogastric tube or gastrostomy tube may be used to administer RAVICTI as follows:

• ​Utilize a new dry oral syringe to withdraw each prescribed dosage of RAVICTI from the bottle.
• ​Place the tip of the syringe into the nasogastric/gastrostomy tube.
• ​Utilizing the plunger of the syringe, administer RAVICTI into the tube.
• ​Use a separate syringe to flush the nasogastric/gastrostomy tube. Flush once with 10 mL of water or formula and allow the flush to drain.
• If needed, flush a second time with an additional 10 mL of water or formula to clear the tube.

For patients who require a volume of less than 1 mL per dose via nasogastric or gastrostomy tube, the delivered dosage may be less than anticipated due to adherence of RAVICTI to the plastic tubing. Therefore, these patients should be closely monitored using ammonia levels following initiation of RAVICTI dosing or dosage adjustments.