How is BUPHENYL supplied?

• BUPHENYL is an oral product that comes in powder or tablet formulations.
• BUPHENYL Powder is available in 500 cc bottles which hold 266 grams of powder, containing 250 grams of sodium phenylbutyrate. Measurers are provided with each bottle of powder.
• BUPHENYL Tablets are available in 250 cc bottles which contain 250 tablets. Each tablet contains 500 mg of sodium phenylbutyrate.

What is BUPHENYL used for?

• BUPHENYL is indicated as adjunctive therapy in the chronic management of patients with urea cycle disorders involving deficiencies in enzymes of the urea cycle disorders involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinc acid synthetase (AS).
• BUPHENYL is indicated in all patients with neonatal-onset deficiency (complete enzymatic deficiency, presenting within the first 28 days of life)
• BUPHENYL is also indicated in patients with late-onset disease (partial enzymatic deficiency, presenting after the first month of life) who have a history of hyperammonemic encephalopathy.

How soon should treatment with BUPHENYL begin?

• It is important that a diagnosis be made early and treatment initiated immediately to improve survival.
• Any episode of acute hyperammonemia should be treated as a life-threatening emergency.
• Even on therapy, acute hyperammonemic encephalopathy recurred in the majority of patients for whom the drug is indicated.
• BUPHENYL may be required life-long unless orthotopic liver transplantation is elected.

How is BUPHENYL administered?

• The use of BUPHENYL Tablets is indicated for children weighing more than 20 kg and for adults.
• BUPHENYL Powder is indicated for oral use (via mouth, gastrostomy, or nasogastric tube) only.
• BUPHENYL Powder is to be mixed with food (solid or liquid) for immediate use; however, when dissolved in water, BUPHENYL Powder has been shown to be stable for up to one week at room temperature or refrigerated.
• When BUPHENYL Powder is added to a liquid, only sodium phenylbutyrate will dissolve, the excipients will not.
• BUPHENYL Tablets and Powder are to be taken in equally divided amounts with each meal or feeding (i.e., three to six times per day).
• The effect of food on sodium phenylbutyrate has not been determined.

How much BUPHENYL should be taken?

• The usual total daily dose for patients with urea cycle disorders is 450-600 mg/kg/day in patients weighing less than 20 kg, or 9.9 – 13.0 g/m²/day in larger patients.
• BUPHENYL Tablets and Powder are to be taken in equally divided amounts with each meal or feeding (i.e., three to six times per day).
• The safety and efficacy of doses in excess of 20 grams (40 tablets) per day has not been established.

How is BUPHENYL Powder measured?

• BUPHENYL Powder includes measurers in each bottle. Both teaspoon and tablespoon measurers are provided. A level teaspoon dispenses 3.2 grams of powder and 3.0 grams of sodium phenylbutyrate. A level tablespoon dispenses 9.1 grams of powder and 8.6 grams of sodium phenylbutyrate.

Will BUPHENYL alone manage urea cycle disorders?

• BUPHENYL must be combined with dietary protein restriction and, in some cases, essential amino acid supplementation. Thus, BUPHENYL is prescribed along with changes in diet for long-term treatment of urea cycle disorders. In addition to taking BUPHENYL, it is equally important that the prescribed diet be followed.
• Because there is great variability in the severity of urea cycle disorders, each patient’s diet should be custom designed by a physician and a nutritionist. Because the diet is so important, it is recommended that the prescribed diet be discussed with a nutritionist who is familiar with urea cycle disorders.

What are the most common side effects of BUPHENYL?

• In female patients, the most common clinical adverse event reported was amenorrhea/menstrual dysfunction, which occurred in 23% of the menstruating patients.
• Decreased appetite was reported in 4% of all people treated.
• Body odor (probably caused by the metabolite phenylacetate) and bad taste or taste aversion were reported in 3% of all patients treated.

Who should not take BUPHENYL?

• BUPHENYL is prescribed only for patients with urea cycle disorders and should not be used for any other reason.
• Because BUPHENYL is metabolized in the liver and kidney, and phenylacetylglutamine is primarily excreted by the kidney, caution must be used when administering the drug to patients with hepatic or renal insufficiency or inborn errors of beta oxidation.
• BUPHENYL should be used with great care, if at all, in patients with congestive heart failure or severe renal insufficiency, and in clinical states in which there is sodium retention with edema.
• Patients with a known hypersensitivity to sodium phenylbutyrate or any component of this preparation should not take BUPHENYL.

What is the sodium content in BUPHENYL?

• Each BUPHENYL Tablet contains 62 mg of sodium (9.2% w/w), corresponding to 124 mg of sodium per gram of sodium phenylbutyrate (12.4% w/w).
• BUPHENYL Powder contains 11.7 grams of sodium per 100 grams of powder, corresponding to 125 mg of sodium per gram of sodium phenylbutyrate (12.4% w/w).

What medications should be avoided or taken cautiously while taking BUPHENYL?

• Probenecid, a medication used to treat gout, is known to inhibit the renal transport of many organic compounds, including hippuric acid, and may affect renal excretion of the conjugated product of BUPHENYL as well as its metabolite.
• Patients with UCDs usually should not take Depakene® (valproic acid), a drug used to treat seizure disorders, and Haldol® (haloperidol), a drug used to treat certain types of psychiatric or neurological disorders. Both of these drugs have been reported to increase blood ammonia levels.
• Use of corticosteroids may cause the breakdown of body protein and increase plasma ammonia levels.

What should I do in case of an overdose?

• No adverse experiences have been reported involving overdoses of sodium phenylbutyrate in patients with urea cycle disorder.
• In the event of an overdose, discontinue the drug and institute supportive measures.
• Hemodialysis or peritoneal dialysis may be beneficial.

Are there any contraindications?

• BUPHENYL should not be used to manage acute hyperammonemia, which is a medical emergency.

How should BUPHENYL be stored?

• BUPHENYL should be stored at room temperature 15ºC-30ºC (59ºF-86ºF). After opening, keep bottle tightly closed.

How do I order BUPHENYL?

• BUPHENYL is available by prescription only.
• In the United States, BUPHENYL may be ordered through ASD Healthcare at 888-266-6685. If you are located outside of the U.S. please call Ucyclyd at 888-829-2593.
• Any questions or concerns you may have regarding BUPHENYL should be directed to Ucyclyd at 888-829-2593.

Where do I report an adverse event?

• To report an adverse event, please call PROSAR at the following numbers:
  United States: 1.800.900.6389
  Canada: 1.800.420.8941
  International: 1.651.632.6781
  

Important Safety Information for BUPHENYL

• Any episode of acute hyperammonemia should be treated as a life-threatening emergency.
• BUPHENYL must be combined with dietary protein restriction and, in some cases, essential amino acid supplementation. BUPHENYL should not be administered to patients with known hypersensitivity to sodium phenylbutyrate or any component of this preparation.
• The most common adverse reactions associated with BUPHENYL Tablets were amenorrhea/menstrual dysfunction, decreased appetite, body odor (probably caused by its metabolite, phenylacetate), and bad taste or taste aversion.
• Patients with urea cycle disorders should not take valproic acid, haloperidol, or steroids as these drugs have been reported to increase blood ammonia levels, and probenecid may affect the kidneys’ excretion.
• Use with great care, if at all, in patients with congestive heart failure or severe renal insufficiency, and in clinical states where there is sodium retention with edema.
• Use caution when administering to patients with hepatic or renal insufficiency or inborn errors of beta oxidation.
• The safety or efficacy of doses in excess of 20 grams (40 tablets) per day has not been established.

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