Sodium Phenylbutyrate

Sodium Phenylbutyrate is a prescription medicine indicated as an adjunct to dietary protein restriction and essential amino acid supplementation for chronic management of urea cycle disorders (UCD) with deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). 

Buphenyl/Pheburane is used for all patients, including neonatal-onset (first 28 days) and late-onset disease with a history of hyperammonemic encephalopathy, while Olpruva is indicated for patients aged 1 year and older and weighing 7 kg and greater.

• Sodium Phenylbutyrate is available under the following different brand names: Buphenyl, Olpruva, Pheburane

Common side effects of Sodium Phenylbutyrate include:

• menstrual dysfunction
• decreased appetite
• body odor 
• taste aversion

Serious side effects of Sodium Phenylbutyrate include:

• neurotoxicity
• hypokalemia 
• edema

Rare side effects of Sodium Phenylbutyrate include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and Pediatric dosage

Tablet (Buphenyl)

• 500 mg

Powder for oral suspension (Buphenyl)

• 3 g/level teaspoon (measuring device included)
• 8.6 g/level tablespoon (measuring device included)

Oral pellets for suspension (Olpruva)

• 2 g/packet
• 3 g/packet
• 4 g/packet
• 5 g/packet
• 6 g/packet
• 6.67 g/packet

Oral pellets (Pheburane)

1. 84 g/bottle

Urea Cycle Disorders 

Adult dosage

• 9.9-13 g/m²/day orally divided in 3-6 doses; not to exceed 20 g/day 

Pediatric dosage

• Children weighing 20 kg and more
  • Buphenyl tablets, Olpruva, Pheburane
  • 9.9-13 g/m²/day orally divided in 3-6 doses; not to exceed 20 g/day
• Children weighing less than 20 kg
  • Buphenyl tablets, Buphenyl powder for suspension, Pheburane
  • 450-600 mg/kg/day orally divided in 3-6 doses 
• Children weighing 7 kg to less than 20 kg

Olpruva

• 450 to 600 mg/kg/day of sodium phenylbutyrate in 3-6 doses

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

Drug interaction overview

• Corticosteroids
  • Use of corticosteroids may cause the breakdown of body protein and increase plasma ammonia levels.
  • Valproic Acid, Haloperidol, or Corticosteroids
  • May increase plasma ammonia level; monitor ammonia levels closely.
• Probenecid
  • May inhibit renal excretion of metabolites of sodium phenylbutyrate, including phenylacetate and phenylacetylglutamine; monitor for potential neurotoxicity.
  • What Are Warnings and Precautions for Sodium Phenylbutyrate?

Contraindications

• Hypersensitivity
• Acute hyperammonemia

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Sodium Phenylbutyrate?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Sodium Phenylbutyrate?”

Cautions

• Renal insufficiency, hepatic insufficiency, and congestive heart failure
• Patients on restricted sodium intake (contains 125 mg sodium/g)
• Powder should not be mixed with acidic liquids
• May cause sodium and fluid retention; caution in patients who poorly tolerate fluid retention, like those with heart failure
• Hyperammonemia and hyperammonemic encephalopathy may occur while on therapy (manage hyperammonemia as a medical emergency
• Will not reverse existing hyperammonemia-inflicted neurologic damage
• Low-protein diet recommended with possible amino acid substitution
• Neurotoxicity of Phenylacetate 
  • Increased exposure to phenylacetate, the major metabolite of sodium phenylbutyrate, may be associated with neurotoxicity in patients with UCDs
  • Not approved for intravenous use or for the treatment of patients with cancer
  • If symptoms of vomiting, nausea, headache, somnolence, or confusion are present in the absence of high ammonia levels or other intercurrent illnesses, consider reducing the dose
• 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
  • To decide if administration of sodium phenylbutyrate is appropriate in patients with diseases that involve edema, such as heart failure, cirrhosis, or nephrosis, calculate the total amount of sodium patients will be exposed to based on their body surface areas (BSAs)
  • If a patient develops new-onset edema or worsening edema while on treatment, discontinue administration of the drug and initiate appropriate therapy
• Diabetes Mellitus, Hereditary Fructose Intolerance, Glucose-Galactose Malabsorption or Sucrase-Isomaltase Insufficiency (pheburane)
  • Avoid use of sodium phenylbutyrate in patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency

Pregnancy and Lactation

Pregnancy

• Available data on sodium phenylbutyrate use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with sodium phenylbutyrate.
• Disease-Associated Maternal and/or Embryo/Fetal Risk 
  • Pregnancy is a time of increased metabolic demand, which increases the risk for hyperammonemic episodes when metabolic demands are not met. Hyperammonemic episodes in pregnancy are associated with impaired cognition in the mother and an increased risk of maternal and fetal death.  

Lactation

• There are no data on the presence of sodium phenylbutyrate and its metabolite in either human or animal milk, its effects on the breastfed infant, or milk production. 
• The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for sodium phenylbutyrate and any potential adverse effects on the breastfed infant from sodium phenylbutyrate or from the underlying maternal condition.