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Glycerol Phenylbutyrate is a brand name for Glycerol Phenylbutyrate. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 1 INDICATIONS AND USAGE Glycerol phenylbutyrate oral liquid is indicated for use as a nitrogen-binding agent for chronic management of patients with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. Glycerol phenylbutyrate oral liquid must be used…
Verbatim from this product's FDA label. Tap a section to expand.
2 DOSAGE AND ADMINISTRATION Glycerol phenylbutyrate oral liquid should be prescribed by a physician experienced in management of UCDs. For administration and preparation, see full prescribing information. 6 ) Switching From Sodium Phenylbutyrate Tablets or Powder to Glycerol Phenylbutyrate Oral Liquid : Patients should receive the dosage of glycerol phenylbutyrate oral liquid that contains the same amount of phenylbutyric acid, see full prescribing information for conversion.
4 g/m 2 /day). 5 mL/m 2 /day. Take into account patient's estimated urea synthetic capacity, dietary protein intake, and diet adherence.
Dosage Adjustment and Monitoring :
Follow plasma ammonia levels to determine the need for dosage titration. 4 ) Dosage Modifications in Patients with Hepatic Impairment : Start dosage at lower end of range. 1 Important Administration Instructions Glycerol phenylbutyrate oral liquid should be prescribed by a physician experienced in the management of UCDs.
Instruct patients to take glycerol phenylbutyrate oral liquid with food or formula and to administer directly into the mouth via oral syringe. Instruct patients to use the glycerol phenylbutyrate oral liquid bottle and oral syringe as follows: Use a new reclosable bottle cap adapter with each new bottle that is opened.
Open the glycerol phenylbutyrate oral liquid 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 oral liquid. 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 oral liquid 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 oral liquid in the bottle and return it to the pharmacy to be discarded. Instruct that glycerol phenylbutyrate oral liquid should be administered just prior to breastfeeding in infants who are breastfeeding.
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. 6) ] . 3 )]. 1 mL. 5 mL (19 g). , essential amino acids, arginine, citrulline, protein-free calorie supplements).
2) ] Most common adverse reactions (≥10%) in adults are: diarrhea, flatulence, and headache. 1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. gov/medwatch . 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
1) ]. One of the 45 patients received only sodium phenylbutyrate prior to withdrawing on day 1 of the study due to an adverse reaction. The most common adverse reactions (occurring in at least 10% of patients) reported during short-term treatment with glycerol phenylbutyrate were diarrhea, flatulence, and headache.
Table 1 summarizes adverse reactions occurring in 2 or more patients treated with glycerol phenylbutyrate or sodium phenylbutyrate (incidence of at least 4% in either treatment arm).
Table 1:
Adverse Reactions Reported in 2 or More Adult Patients with UCDs (at least 4% in Either Treatment Arm) in Study 1 Number (%) of Patients in Study 1 Sodium Phenylbutyrate (N = 45) Glycerol Phenylbutyrate (N = 44) Diarrhea 3 (7) 7 (16) Headache 4 (9) 6 (14) Flatulence 1 (2) 6 (14) Abdominal pain 2 (4) 3 (7) Vomiting 2 (4) 3 (7) Decreased appetite 2 (4) 3 (7) Fatigue 1 (2) 3 (7) Dyspepsia 3 (7) 2 (5) Nausea 3 (7) 1 (2) Dizziness 4 (9) 0 Abdominal discomfort 3 (7) 0 Other Adverse Reactions Glycerol phenylbutyrate has been evaluated in 77 patients with UCDs (51 adult and 26 pediatric patients ages 2 years to 17 years) in 2 open-label long-term studies, in which 69 patients completed 12 months of treatment with glycerol phenylbutyrate (median exposure = 51 weeks).
During these studies there were no deaths. Adverse reactions reported in at least 10% of adult patients were nausea, vomiting, diarrhea, decreased appetite, dizziness, headache, and fatigue. Adverse reactions reported in at least 10% of pediatric patients ages 2 years to 17 years were upper abdominal pain, rash, nausea, vomiting, diarrhea, decreased appetite, and headache.
5 WARNINGS AND PRECAUTIONS Neurotoxicity : Phenylacetate (PAA), the active moiety of glycerol phenylbutyrate, may be toxic; reduce dosage for symptoms of neurotoxicity. 1 ) Pancreatic Insufficiency or Intestinal Malabsorption: Monitor ammonia levels closely.
1 Neurotoxicity Increased exposure to PAA, the major metabolite of glycerol phenylbutyrate, may be associated with neurotoxicity in patients with UCDs. In a study of adult cancer patients, subjects received sodium phenylacetate administered as a 1-hour infusion twice daily at two dose levels of 125 and 150 mg/kg for a 2-week period.
Of 18 subjects enrolled, 7 had a history of primary central nervous system tumor. Signs and symptoms of potential PAA neurotoxicity, which were reversible, were reported at plasma PAA concentrations above 500 micrograms/mL and included somnolence, fatigue, lightheadedness, headache, dysgeusia, hypoacusis, disorientation, impaired memory, and exacerbation of preexisting neuropathy.
PAA concentrations were not measured when symptoms resolved. 8 g/day, respectively) for 3 days, a dose-dependent increase in non-serious nervous system adverse reactions were observed. In subjects who had nervous system adverse reactions, plasma PAA concentrations, which were measured on Day 3 per protocol and not always at onset of symptoms, ranged from 8 to 56 micrograms/mL with 4 mL glycerol phenylbutyrate 3 times daily and from 31 to 242 micrograms/mL with 6 mL glycerol phenylbutyrate 3 times daily.
In clinical trials in patients with UCDs who had been on sodium phenylbutyrate prior to administration of glycerol phenylbutyrate, adverse reactions of headache, fatigue, symptoms of peripheral neuropathy, seizures, tremor and/or dizziness were reported.
3) ] . 4) ] . 2 Pancreatic Insufficiency or Intestinal Malabsorption Exocrine pancreatic enzymes hydrolyze glycerol phenylbutyrate in the small intestine, separating the active moiety, phenylbutyrate, from glycerol. This process allows phenylbutyrate to be absorbed into the circulation.
4 CONTRAINDICATIONS Glycerol phenylbutyrate oral liquid is contraindicated in patients with known hypersensitivity to phenylbutyrate. Signs of hypersensitivity include wheezing, dyspnea, coughing, hypotension, flushing, nausea, and rash.
Known hypersensitivity to phenylbutyrate. ( 4 )
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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2 Switching From Sodium Phenylbutyrate to Glycerol Phenylbutyrate Oral Liquid Patients switching from sodium phenylbutyrate to glycerol phenylbutyrate oral liquid should receive the dosage of glycerol phenylbutyrate oral liquid that contains the same amount of phenylbutyric acid.
4 g/m 2 /day). 5 mL/m 2 /day. In determining the starting dosage of glycerol phenylbutyrate oral liquid 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. 6 mL glycerol phenylbutyrate oral liquid per gram of dietary protein ingested per 24-hour period. 5 mL. 4 Dosage Adjustment and Monitoring During treatment with glycerol phenylbutyrate oral liquid, 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 glycerol phenylbutyrate oral liquid and when changing the dosage of glycerol phenylbutyrate oral liquid. 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 glycerol phenylbutyrate oral liquid, refer to the assay-specific normal ranges and to the therapeutic target ranges for plasma ammonia.
g. nausea, vomiting, headache, somnolence or confusion) in the absence of high plasma ammonia or other intercurrent illness to explain these symptoms, consider reducing the glycerol phenylbutyrate oral liquid dosage and clinically monitor patients for potential neurotoxicity from high phenylacetate (PAA) concentrations.
If available, obtain measurements of plasma PAA concentrations and plasma phenylacetylglutamine (PAGN) to calculate the ratio of plasma PAA to PAGN which may help to guide glycerol phenylbutyrate oral liquid dosing. The PAA to PAGN ratio has generally been less than 1 in patients with UCDs who did not have significant plasma PAA accumulation.
3) ]. Elevated Plasma Ammonia In patients 6 years and older, when plasma ammonia is elevated, increase the glycerol phenylbutyrate oral liquid dosage to maintain fasting plasma ammonia to less than half the upper limit of normal (ULN).
In infants and pediatric patients below 6 years of age, if obtaining fasting ammonia is problematic due to frequent feedings, adjust the glycerol phenylbutyrate oral liquid dosage to keep the first ammonia of the morning below the ULN for age.
3) ]. Dietary Protein Intake If available, urinary phenylacetylglutamine (U-PAGN) measurements may be used to help guide glycerol phenylbutyrate oral liquid dosage adjustment. 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 glycerol phenylbutyrate oral liquid dosage should be increased.
5 mL). Consider a patient’s use of concomitant medications, such as probenecid, when making dosage adjustment decisions based on U-PAGN. 2) ]. 7) ] . 6 Preparation for Nasogastric Tube or Gastrostomy Tube Administration It is recommended that all patients who can swallow take glycerol phenylbutyrate oral liquid 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 glycerol phenylbutyrate oral liquid as follows: Utilize a new dry oral syringe to withdraw each prescribed dosage of glycerol phenylbutyrate oral liquid from the bottle.
Place the tip of the syringe into the nasogastric/gastrostomy tube. Utilizing the plunger of the syringe, administer glycerol phenylbutyrate oral liquid 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 glycerol phenylbutyrate oral liquid to the plastic tubing.
Therefore, these patients should be closely monitored using ammonia levels following initiation of glycerol phenylbutyrate oral liquid dosing or dosage adjustments.
Glycerol phenylbutyrate has been evaluated in 17 patients with UCDs ages 2 months to less than 2 years in 3 open-label studies. 2 to 20 months). Adverse reactions reported in at least 10% of pediatric patients aged 2 months to less than 2 years were neutropenia, vomiting, constipation, diarrhea, pyrexia, hypophagia, cough, nasal congestion, rhinorrhea, rash, and papule.
5 months) in a single, open-label study. The median exposure was 10 months (range 2 to 20 months). Adverse reactions reported in at least 10% of pediatric patients aged less than 2 months were vomiting, rash, gastroesophageal reflux, increased hepatic enzymes, feeding disorder (decreased appetite, hypophagia), anemia, cough, dehydration, metabolic acidosis, thrombocytosis, thrombocytopenia, neutropenia, lymphocytosis, diarrhea, flatulence, constipation, pyrexia, lethargy, and irritability/agitation.
2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of glycerol phenylbutyrate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Abnormal body odor, including from skin, hair and urine Retching and gagging Dysgeusia or burning sensation in mouth
Low or absent pancreatic enzymes or intestinal disease resulting in fat malabsorption may result in reduced or absent digestion of glycerol phenylbutyrate and/or absorption of phenylbutyrate and reduced control of plasma ammonia. Monitor ammonia levels closely in patients with pancreatic insufficiency or intestinal malabsorption.