glycerol phenylbutyrate(gli-ser-ol fen-il-bue-ti-rate) ,
Pregnancy Category: C
Pharmacologic: temporary class
ClassificationTherapeutic: orphan drugs
Pharmacologic: temporary class
Chronic treatment of hyperammonemia associated with urea cycle disorders (UCDs) that cannot be managed by dietary protein restriction and/or amino acid supplementation, which must be continued.Not to be use for acute treatment of hyperammonemia.
Decreased ammonia levels with decreased sequelae of hyperammonemia.
Absorption: Well absorbed following oral administration
Protein Binding: PBA—80.6–98%
Metabolism and 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.
Time/action profile (PAA levels)
|PO||unknown||4 hr||8 hr|
Contraindicated in: Known hypersensitivity to phenylbutyrate (wheezing, dyspnea, coughing, hypotension, flushing, nausea, rash) Lactation: Avoid breastfeeding Pediatric: Age <2 mos
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) Geriatric: Consider age-related decrease in renal/hepatic/cardiac function, concurrent disease states and medications. Obstetric: Use only if maternal benefit justifies potential fetal risk.
Adverse Reactions/Side Effects
Central nervous system
- headache (most frequent)
- fatigue (↑ in adults) (most frequent)
- abdominal pain (↑ in children) (most frequent)
- ↓ appetite (most frequent)
- diarrhea (most frequent)
- flatulence (most frequent)
- nausea (most frequent)
- rash (↑ in children) (most frequent)
- hyerammonemia (most frequent)
Drug-Drug interactionAmmonia levels may be↑ by corticosteroids,.haloperidol or valproic acid, monitor carefully.Probenecid ↓ renal excretion of metabolites PAGN and PAA.
Route/DosageTotal daily dose is given in three equally divided doses, adjustments based on plasma ammonia, urinary phenylacetylglutamine or plasma phenylacetate. Consider estimated ability to synthesize urea, dietary protein intake and adherence to dietary recommendations.
Oral (Adults and Children ≥2 yr) Swtiching from sodium phenylbutyrate—total daily dose of glycerol phenylbutyrate = daily dose of sodium phenylbutyrate (g) x 0.86; initial dose in phenylbutyrate naïve patients—4.5–11.2 mL/m2/day (5–12.4 g/m2/day). Total daily dose is divided into three equal doses, rounded up to the nearest 0.5 mL.
Hepatic ImpairmentOral (Adults and Children ≥2 yr) Initiate therapy at lower end of dose range.
Oral liquid: 1.1 g/mL
- Monitor for signs and symptoms of high blood ammonia (headache, feeling tired, lightheadedness, confusion) periodically during therapy.
- Monitor for signs and symptoms of neurotoxicity (somnolence, fatigue, lightheadedness, headache, dysgeusia, partial hearing loss, disorientation, impaired memory, exacerbation of preexisting neuropathy). May be seen with plasma PAA concentrations ≥500 mcg/mL.
- Lab Test Considerations: Monitor fasting plasma ammonia levels frequently during dose changes. less than half the upper limit of normal according to age.
- Urinary phenylacetylglutamine (U-PAGN) may be used to help guide dosing. Each gram of U-PAGN excreted over 24 hr covers waste nitrogen generated from 1.4 grams of dietary protein. If U-PAGN excretion is insufficient to cover daily dietary protein intake and fasting ammonia is > half upper limit of normal, adjust dose of glycerol phenylbutyrate upward. Factor in amount of dietary protein not covered in dose adjustment indicated by 24-h U-PAGN level.
- Monitoring plasma PAA levels can assist with dosing if side effect occur. Ratio of PAA to PAGN in plasma may also assist in dose adjustment.
Potential Nursing DiagnosesDeficient knowledge, related to diet and medication regimen (Patient/Family Teaching)
- Glycerol phenylbutyrate should only be prescribed by clinicians with experience treating patients with urea cycle disorders.
- Oral: Administer with food and directly into mouth via oral syringe or dosing cup. Store at room temperature.
- For administration via nasogastric or gastrostomy tube, use oral syringe to withdraw dose, place tip of syringe into tip of gastrostomy/nasogastric tube. Use plunger of syringe to administer medication into tube. Flush once with 30 mL of water and allow flush to drain. Flush a second time with an additional 30 mL of water to clear tube.
- 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 female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
- Encourage patients to enroll in a UCD registry to collect information about people with UCD to improve care. Contact registry by calling 1-855-823-2595 or visit www.ucdregistry.com.
- Decreased ammonia levels for a fasting plasma ammonia level less than half the upper limit of normal according to age with decreased sequelae of hyperammonemia. If symptoms of vomiting, nausea, headache, somnolence, confusion, or sleepiness are present in the absence of high ammonia or other illnesses, reduce dose of glycerol phenylbutyrate.