IMPORTANT SAFETY INFORMATION

INDICATION

Pheburane® is indicated as adjunctive therapy to standard of care, which includes dietary management, for the chronic management of adult and pediatric patients with urea cycle disorders (UCDs), involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC) or argininosuccinic acid synthetase (AS).

 

Limitations of Use

Episodes of acute hyperammonemia may occur in patients while on Pheburane®. Pheburane® is not indicated for the treatment of acute hyperammonemia, which can be a life-threatening medical emergency that requires rapid acting interventions to reduce plasma ammonia levels.

WARNINGS AND PRECAUTIONS

 

Neurotoxicity of Phenylacetate

Increased exposure to phenylacetate, the major metabolite of Pheburane®, may be associated with neurotoxicity in patients with UCDs.  If symptoms of vomiting, nausea, headache, somnolence or confusion are present in the absence of high ammonia levels, consider reducing the dose of Pheburane®.

 

Hypokalemia

Renal excretion of phenylacetylglutamine may induce urinary loss of potassium. Monitor serum potassium during therapy, and initiate appropriate treatment when necessary.

 

Conditions Associated with Edema

In order to decide if administration of Pheburane® is appropriate in patients with diseases that involve edema, calculate the total amount of sodium patients will be exposed to, based on their weight or body surface area.

 

If a patient develops new-onset edema or worsening edema while on treatment, discontinue administration of Pheburane® and initiate appropriate therapy.

 

Diabetes Mellitus, Hereditary Fructose Intolerance, Glucose-Galactose Malabsorption or Sucrase-Isomaltase Insufficiency

Avoid use of Pheburane® in patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency.

ADVERSE REACTIONS

The most common adverse reactions (incidence > 3%) are menstrual dysfunction, decreased appetite, body odor and bad taste or taste aversion.

DRUG INTERACTIONS

  • Valproic acid, Haloperidol, or Corticosteroids: May increase plasma ammonia levels. Monitor ammonia levels closely.
  • Probenicid: May inhibit renal excretion of metabolites of Pheburane® including phenylacetate and phenylacetylglutamine. Monitor patients for potential neurotoxicity.

OVERDOSAGE

Overdoses of Pheburane® exceeding ten-fold the maximum recommended dosage may produce emesis, CNS depression, metabolic acidosis with or without respiratory alkalosis, hypernatremia, hypokalemia, and hypophosphatemia. Symptoms of overdose overlap with those of acute hyperammonemia. If overdose occurs, discontinue Pheburane®, monitor plasma phenylacetate and ammonia levels closely, and institute appropriate emergency management.

To report suspected adverse reactions, contact Medunik USA at 1-844-884-5520 or medicalinfo@medunikusa.com.

Please read the Full Prescribing Information.

Important Safety Information

INDICATION

Pheburane® is indicated as adjunctive therapy to standard of care, which includes dietary management, for the chronic management of adult and pediatric patients with urea cycle disorders (UCDs), involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC) or argininosuccinic acid synthetase (AS).

 

Limitations of Use

Episodes of acute hyperammonemia may occur in patients while on Pheburane®. Pheburane® is not indicated for the treatment of acute hyperammonemia, which can be a life-threatening medical emergency that requires rapid acting interventions to reduce plasma ammonia levels.

WARNINGS AND PRECAUTIONS

 

Neurotoxicity of Phenylacetate

Increased exposure to phenylacetate, the major metabolite of Pheburane®, may be associated with neurotoxicity in patients with UCDs. If symptoms of vomiting, nausea, headache, somnolence or confusion are present in the absence of high ammonia levels, consider reducing the dose of Pheburane®.

 

Hypokalemia

Renal excretion of phenylacetylglutamine may induce urinary loss of potassium. Monitor serum potassium during therapy, and initiate appropriate treatment when necessary.

 

Conditions Associated with Edema

In order to decide if administration of Pheburane® is appropriate in patients with diseases that involve edema, calculate the total amount of sodium patients will be exposed to, based on their weight or body surface area.

 

If a patient develops new-onset edema or worsening edema while on treatment, discontinue administration of Pheburane® and initiate appropriate therapy.

 

Diabetes Mellitus, Hereditary Fructose Intolerance, Glucose-Galactose Malabsorption or Sucrase-Isomaltase Insufficiency

Avoid use of Pheburane® in patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency.

ADVERSE REACTIONS

The most common adverse reactions (incidence > 3%) are menstrual dysfunction, decreased appetite, body odor and bad taste or taste aversion.

DRUG INTERACTIONS

  • Valproic acid, Haloperidol, or Corticosteroids: May increase plasma ammonia levels. Monitor ammonia levels closely.
  • Probenicid: May inhibit renal excretion of metabolites of Pheburane® including phenylacetate and phenylacetylglutamine. Monitor patients for potential neurotoxicity.

OVERDOSAGE

Overdoses of Pheburane® exceeding ten-fold the maximum recommended dosage may produce emesis, CNS depression, metabolic acidosis with or without respiratory alkalosis, hypernatremia, hypokalemia, and hypophosphatemia. Symptoms of overdose overlap with those of acute hyperammonemia. If overdose occurs, discontinue Pheburane®, monitor plasma phenylacetate and ammonia levels closely, and institute appropriate emergency management.

To report suspected adverse reactions, contact Medunik USA at 1-844-884-5520 or medicalinfo@medunikusa.com.

Please read the Full Prescribing Information.

References:

  1. Pheburane® (sodium phenylbutyrate) oral pellets [Prescribing Information]. Medunik USA, Inc.
  2. Kibleur Y, Dobbelaere D, Barth M, Brassier A, Guffon N. Results from a Nationwide Cohort Temporary Utilization Authorization (ATU) survey of patients in france treated with Pheburane® (Sodium Phenylbutyrate) taste-masked granules. Paediatr Drugs. 2014.
  3. Kibleur Y, Guffon N. Long-Term Follow-Up on a Cohort Temporary Utilization Authorization (ATU) Survey of Patients Treated with Pheburane (Sodium Phenylbutyrate) Taste-Masked Granules. Paediatr Drugs. 2016 Apr;18(2):139-44. doi: 10.1007/s40272-015-0159-8. PMID: 26747635.
  4. Guffon N, Kibleur Y, Copalu W, Tissen C, Breitkreutz J. Developing a new formulation of sodium phenylbutyrate. Arch Dis Child. 2012 Dec;97(12):1081-5. doi: 10.1136/archdischild-2012-302398. Epub 2012 Aug 31. PMID: 22941860.
  5. Peña-Quintana L, Llarena M, Reyes-Suárez D, Aldámiz-Echevarria L. Profile of sodium phenylbutyrate granules for the treatment of urea-cycle disorders: patient perspectives. Patient Prefer Adherence. 2017 Sep 6;11:1489-1496. doi: 10.2147/PPA.S136754. PMID: 28919721; PMCID: PMC5593420.