Ravicti (glycerol phenylbutyrate)

It isessential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Glycerol phenylbutyrate should be prescribed by a physician experienced in management of UCDs.

Administer glycerol phenylbutyrate with food or formula and administer directly into the mouth via oral syringe.

Instruct patients to use the glycerol phenylbutyrate bottle and oral syringe as follows: use a new reclosable bottle cap adapter with each new bottle that is opened; open the glycerol phenylbutyrate bottle and twist on the new reclosable bottle cap adapter; use a new and dry oral syringe to withdraw each prescribed dose of glycerol phenylbutyrate; 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 glycerol phenylbutyrate bottle, the contents will become cloudy in appearance; if the contents of the bottle appear cloudy at any time, do not use the remaining glycerol phenylbutyrate in the bottle and return it to the pharmacy to be discarded.

For patients who cannot swallow and who have a nasogastric tube or gastrostomy tube in place, instruct patients/caregivers to administer glycerol phenylbutyrate as follows: utilize a new dry oral syringe to withdraw the prescribed dosage of glycerol phenylbutyrate from the bottle; place the tip of the syringe into the gastrostomy/nasogastric tube; utilizing the plunger of the syringe, administer glycerol phenylbutyrate 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.

Switching From Sodium Phenylbutyrate Tablets or Powder to Glycerol Phenylbutyrate: Patients should receive the dosage of glycerol phenylbutyrate that contains the same amount of phenylbutyric acid. See full prescribing information for conversion.

Initial Dosage in Phenylbutyrate-Naive Patients: The recommended dosage range in phenylbutyrate-naive patients 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 dietary restriction, the recommended starting dose is 4.5 mL/m2/day. In determining the starting dosage of glycerol phenylbutyrate in treatment-naive patients, consider the patient's residual urea synthetic capacity, dietary protein requirements, and diet adherence.

Dosage Adjustment and Monitoring: Monitor patients clinically and with plasma ammonia levels to determine the need for dosage titration.

Dosage Modifications in Patients with Hepatic Impairment: Start dosage at lower end of the recommended dosage range in patients with moderate to severe hepatic impairment.

See Full Prescribing Information for additional details on preparation, administration, and recommendations for dosage modifications.

No dosing information is available for this tab.

No dosing information is available for this tab.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

Known hypersensitivity to phenylbutyrate.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

Most common adverse reactions (>=10%) in adults are: diarrhea, flatulence, and headache.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

The safety and effectiveness of glycerol phenylbutyrate in patients 2 years to less than 18 years of age have been established in 3 clinical studies: 2 open-label, fixed-sequence, switchover clinical studies from sodium phenylbutyrate to glycerol phenylbutyrate, and 1 long-term, open label safety study.

The safety and effectiveness of glycerol phenylbutyrate in patients with UCDs less than 2 years of age have been established in 3 open-label studies. Pharmacokinetics and pharmacodynamics (plasma ammonia), and safety were studied in 17 patients 2 months to less than 2 years of age and in 16 patients less than 2 months of age.

In a juvenile rat study with daily oral dosing performed on postpartum day 2 through mating and pregnancy after maturation, terminal body weight was dose-dependently reduced by up to 16% in males and 12% in females at 900 mg/kg/day or higher (3 times the dose of 6.87 mL/m2/day in adult patients, based on combined AUCs for PBA and PAA). Learning, memory, and motor activity endpoints were not affected. However, fertility (number of pregnant rats) was decreased by up to 25% at 650 mg/kg/day or higher (2.6 times the dose of 6.87 mL/m2/day in adult patients, based on combined AUCs for PBA and PAA).

Limited available data with glycerol phenylbutyrate use in pregnant women are insufficient to inform a drug-associated risk of major birth defects and miscarriage. In an animal reproduction study, administration of oral glycerol phenylbutyrate to pregnant rabbits during organogenesis at doses up to 2.7-times the dose of 6.87 mL/m2/day in adult patients resulted in maternal toxicity, but had no effects on embryo-fetal development. In addition, there were no adverse developmental effects with administration of oral glycerol phenylbutyrate to pregnant rats during organogenesis at 1.9 times the dose of 6.87 mL/m2/day in adult patients; however, maternal toxicity, reduced fetal weights, and variations in skeletal development were observed in pregnant rats administered oral glycerol phenylbutyrate during organogenesis at doses greater than or equal to 5.7 times the dose of 6.87 mL/m2/day in adult patients. Report pregnancies to Horizon at 1-866-479-6742.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

There are no data on the presence of glycerol phenylbutyrate in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions, including neurotoxicity and tumorigenicity in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with glycerol phenylbutyrate.

Clinical studies of glycerol phenylbutyrate did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.