• Chronic treatment of urea cycle disorders that cannot be managed by dietary protein restriction and/or amino acid supplementation, which must be continued.

Contraindicated in:

• Known hypersensitivity to phenylbutyrate (wheezing, dyspnea, coughing, hypotension, flushing, nausea, rash)
• Acute hyperammonemia
• Lactation: Lactation.

Use Cautiously in:

• Moderate to severe hepatic impairment (initiate treatment at low end of dose range)
• Pancreatic insufficiency/ intestinal malabsorption (may ↓ absorption of phenylbutyrate)
• Renal impairment (monitor ammonia levels carefully)
• OB: Safety not established in pregnancy
• Geri: Consider age-related ↓ in renal/hepatic/cardiac function, concurrent disease states and medications in older adults.

Derm: rash (↑ in children).

GI: ↓ appetite, abdominal pain (↑ in children), diarrhea, flatulence, nausea, dyspepsia, vomiting.

Metab: hyperammonemia.

Neuro: fatigue (↑ in adults), headache, neurotoxicity.

Drug-Drug:

• Ammonia levels may be ↑ by corticosteroids,.haloperidol or valproic acid, monitor carefully.
• Probenecid↓ renal excretion of metabolites PAGN and PAA.
• May ↓ levels and effects of CYP3A4 substrates, including cyclosporine, midazolam, and quinidine.

• Oral liquid: 1.1 g/mL;

• PO (Adults and Children): Switching from sodium phenylbutyrate: total daily dose of glycerol phenylbutyrate (mL) = daily dose of sodium phenylbutyrate tablets (g) x 0.86; total daily dose of glycerol phenylbutyrate (mL) = daily dose of sodium phenylbutyrate powder (g) x 0.81; Initial dose in phenylbutyrate nave patients: 4.5–11.2 mL/m²/day (5–12.4 g/m²/day). For patients ≥2 yr, total daily dose is divided into 3 equal doses, rounded up to the nearest 0.5 mL. For patients <2 yr, total daily dose is divided into 3 equal doses, rounded up to the nearest 0.1 mL. Maximum daily dose = 19 g (17.5 mL).

Ravicti

• Binds nitrogen.

• Decreased ammonia levels with decreased sequelae of hyperammonemia.

Therapeutic Classification:

Pharmacologic Classification: nitrogen-binding agents

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Protein Binding: PBA: 80.6–98%.

Metabolism/Excretion: Glycerol phenylbutyrate is a triglyceride prodrug that releases phenylbutyrate (PBA) following the action of lipases in the GI tract. Further metabolism results in conversion to phenylacetate (PAA), the active moiety. PAA binds glutamine in the liver and kidneys forming phenylacetylglutamine (PAGN), which is then renally eliminated (68.9%). Women form a higher percentage of metabolites.

Half-life: Unknown.

(PAA levels)

• Instruct patient to take glycerol phenylbutyrate as directed along with dietary protein restriction and, if prescribed, dietary supplements (essential amino acids, arginine, citrulline, protein-free calorie supplements). Advise patient to read Medication Guide before starting and with each Rx refill in case of changes.
• Advise patient to notify health care professional promptly if signs and symptoms of neurotoxicity (sleepiness, worsening neuropathy, weakness, numbness, tingling, lightheadedness, burning in hands or feet, change in taste, problems with hearing, headache, confusion, problems with memory) occur.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding..

GLI-ser-ol fen-il-BUE-ti-rate