BUPHENYL ®(sodium phenyl butyrate) Tablets
`BUPHENYL ®(sodium phenyl butyrate) Powder
`
`[bu'fen-el]
`(sodium phenylbutyrate)
`
`RxOnly
`
`DESCRIPTION
`BUPHENYL ®(sodium phenylbutyrate) Tablets for oral administration and BUPHENYL ®(sodium
`phenylbutyrate) Powder for oral, nasogastric, or gastrostomy tube administration contain sodium
`phenylbutyrate. Sodium phenylbutyrate is an off-white crystalline substance which is soluble in water and has
`a strong salty taste. Sodium phenylbutyrate also is freely soluble in methanol and practically insoluble in
`acetone and diethyl ether. It is known chemically as 4-phenylbutyric acid, sodium salt with a molecular weight
`of 186 and the molecular formula C1oH1102Na.
`
`Chemical Structure:
`
`g - -CH,CH,CH,COON'
`
`Each tablet of BUPHENYL contains 500 mg of sodium phenylbutyrate and the inactive ingredients
`microcrystalline cellulose NF, magnesium stearate NF, and colloidal silicon dioxide NF.
`
`Each gram of BUPHENYL Powder contains 0.94 grams of sodium phenylbutyrate and the inactive ingredients
`calcium stearate NF, and colloidal silicon dioxide NF.
`
`CLINICAL PHARMACOLOGY
`Sodium phenylbutyrate is a pro-drug and is rapidly metabolized to phenylacetate. Phenylacetate is a
`metabolically-active compound that conjugates with glutamine via acetylation to form phenylacetylglutamine.
`Phenylacetylglutamine then is excreted by the kidneys . On a molar basis, it is comparable to urea (each
`containing two moles of nitrogen). Therefore, phenylacetylglutamine provides an alternate vehicle for waste
`nitrogen excretion.
`
`PHARMACOKINETICS
`General:
`Pharmacokinetic studies have not been conducted in the primary patient population (neonates, infants, and
`children), but pharmacokinetic data were obtained from normal adult subjects.
`
`Absorption:
`Peak plasma levels of phenyl butyrate occur within 1 hour after a single dose of 5 grams of sodium
`phenylbutyrate tablet with a Cmax of 218 IJg/mL under fasting conditions; peak plasma levels of phenyl butyrate
`occur within 1 hour after a single dose of 5 grams of sodium phenylbutyrate powder with a Cmax of 195 IJg/mL
`under fasting conditions. The effect of food on phenylbutyrate's absorption is unknown.
`
`Disposition:
`The overall disposition of sodium phenylbutyrate and its metabolites has not been characterized fully.
`However, the drug is known to be metabolized to phenylacetate and subsequently to phenylacetylglutamine.
`Following oral administration of 5 grams (tablets), measurable plasma levels of phenylbutyrate and
`phenylacetate were detected 15 and 30 minutes after dosing, respectively, and phenylacetylglutamine was
`detected shortly thereafter. The pharmacokinetic parameters for phenylbutyrate for Cmax (IJg/mL), T max (hours),
`and elimination half-life (hours) were 218, 1.35, and 0.77, respectively, and for phenylacetate were 48.5, 3.74,
`and 1.15, respectively.
`
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`Following oral administration of 5 grams of the powder, measurable plasma levels of phenyl butyrate and
`phenylacetate were detected 15 and 30 minutes after dosing, respectively, and phenylacetylglutamine was
`detected shortly thereafter. The pharmacokinetic parameters for phenylbutyrate for Cmax (IJg/mL), T max (hours),
`and elimination half-life (hours) were 195, 1.00, and 0.76, respectively, and for phenylacetate were 45.3, 3.55,
`and 1.29, respectively.
`
`The major sites for metabolism of sodium phenyl butyrate are the liver and kidney.
`
`Excretion:
`A majority of the administered compound (approximately 80-1 00%) was excreted by the kidneys within 24
`hours as the conjugation product, phenylacetylglutamine . For each gram of sodium phenylbutyrate
`administered, it is estimated that between 0.12-0.15 grams of phenylacetylglutamine nitrogen are produced.
`
`Pharmacodynamics:
`In patients with urea cycle disorders, BUPHENYL ®decreased elevated plasma ammonia glutamine levels. It
`increases waste nitrogen excretion in the form of phenylacetylglutamine.
`
`Special Populations
`Gender:
`Significant gender differences were found in the pharmacokinetics of phenylbutyrate and phenylacetate, but
`not for phenylacetylglutamine. The pharmacokinetic parameters (AUC and Cmax), for both plasma
`phenylbutyrate and phenylacetate were about 30 to 50 percent greater in females than in males.
`
`Hepatic insufficiency:
`In patients who did not have urea cycle disorders but had impaired hepatic function, the metabolism and
`excretion of sodium phenylbutyrate were not affected. However, this information was obtained from
`unvalidated, uncontrolled case studies.
`
`INDICATIONS AND USAGE
`BUPHENYL ®is indicated as adjunctive therapy in the chronic management of patients with urea cycle
`disorders involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC),
`or argininosuccinic acid synthetase (AS). It is indicated in all patients with neonatal-onset deficiency (complete
`enzymatic deficiency, presenting within the first 28 days of life). It 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. It is important that the diagnosis be made early and treatment initiated
`immediately to improve survival. Any episode of acute hyperammonemia should be treated as a life(cid:173)
`threatening emergency.
`
`BUPHENYL must be combined with dietary protein restriction and, in some cases, essential amino acid
`supplementation. (See Nutritional Supplementation subsection of the DOSAGE AND ADMINISTRATION
`section.)
`
`Previously, neonatal-onset disease was almost universally fatal within the first year of life, even when treated
`with peritoneal dialysis and essential amino acids or their nitrogen-free analogs. However, with hemodialysis,
`use of alternative waste nitrogen excretion pathways (sodium phenylbutyrate, sodium benzoate, and sodium
`phenylacetate), dietary protein restriction, and, in some cases, essential amino acid supplementation, the
`survival rate in newborns diagnosed after birth but within the first month of life is almost 80%. Most deaths
`have occurred during an episode of acute hyperammonemic encephalopathy. Patients with neonatal-onset
`disease have a high incidence of mental retardation. Those who had IQ tests administered had an incidence
`of mental retardation as follows: ornithine transcarbamylase deficiency, 100% (14/14 patients tested);
`argininosuccinic acid synthetase deficiency, 88% (15/17 patients tested); and carbamylphosphate synthetase
`deficiency, 57% (4/7 patients tested). Retardation was severe in the majority of the retarded patients.
`
`In patients diagnosed during gestation and treated prior to any episode of hyperammonemic encephalopathy,
`survival is 100%, but even in these patients, most subsequently demonstrate cognitive impairment or other
`neurologic deficits.
`
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`In late-onset deficiency patients, including females heterozygous for ornithine transcarbamylase deficiency,
`who recover from hyperammonemic encephalopathy and are then treated chronically with sodium
`phenylbutyrate and dietary protein restriction, the survival rate is 98%. The two deaths in this group of patients
`occurred during episodes of hyperammonemic encephalopathy. However, compliance with the therapeutic
`regimen has not been adequately documented to allow evaluation of the potential for BUPHENYL and dietary
`protein restriction to prevent mental deterioration and recurrence of hyperammonemic encephalopathy if
`carefully adhered to. The majority of these patients tested (30/46 or 65%) have IQ's in the average to low
`average/borderline mentally retarded range. Reversal of pre-existing neurologic impairment is not likely to
`occur with treatment and neurologic deterioration may continue in some patients.
`
`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 .
`
`(See CLINICAL PHARMACOLOGY, Pharmacodynamics subsection for the biochemical effects of
`BUPHENYL) .
`
`CONTRAINDICATIONS
`BUPHENYL ®should not be used to manage acute hyperammonemia, which is a medical emergency.
`
`WARNINGS
`Each BUPHENYL ®Tablet contains 62 mg of sodium (9 .2% w/w) (corresponding to 124 mg of sodium per gram
`of sodium phenyl butyrate [12 .4% w/w]) and 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) .
`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.
`
`Because BUPHENYL is metabolized in the liver and kidney, and phenylacetylglutamine is primarily excreted
`by the kidney, use caution when administering the drug to patients with hepatic or renal insufficiency or inborn
`errors of beta oxidation. Probenecid 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.
`
`Use of corticosteroids may cause the breakdown of body protein and increase plasma ammonia levels.
`
`PRECAUTIONS
`General:
`BUPHENYL ®should not be administered to patients with known hypersensitivity to sodium phenylbutyrate or
`any component of this preparation.
`
`There have been published reports of hyperammonemia being induced by haloperidol and by valproic acid.
`
`Neurotoxicity of phenylacetate in animals:
`When given subcutaneously to rat pups, 190-4 7 4 mg/kg phenylacetate caused decreased proliferation and
`increased loss of neurons, and it reduced CNS myelin. Cerebral synapse maturation was retarded, and the
`number of functioning nerve terminals in the cerebrum was reduced, which resulted in impaired brain growth.
`Prenatal exposure of rat pups to phenylacetate produced lesions in layer 5 of the cortical pyramidal cells;
`dendritic spines were longer and thinner than normal and reduced in number.
`
`Information for Patients:
`The full text of the separate insert of information for patients is reprinted at the end of the labeling.
`
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`Laboratory Tests:
`Plasma levels of ammonia, arginine, branched-chain amino acids, and serum proteins should be maintained
`within normal limits, and plasma glutamine should be maintained at levels less than 1 ,000 IJmoi!L. Serum drug
`levels of phenylbutyrate and its metabolites, phenylacetate and phenylacetylglutamine, should be monitored
`periodically.
`
`Carcinogenesis, Mutagenesis, Impairment of Fertility:
`Carcinogenicity, mutagenicity, and fertility studies of sodium phenylbutyrate have not been conducted.
`
`Pregnancy:
`Pregnancy Category C. Animal reproduction studies have not been conducted with BUPHENYL ®. It is also
`not known whether BUPHENYL can cause fetal harm when administered to a pregnant woman or can affect
`reproduction capacity.
`
`BUPHENYL should be given to a pregnant woman only if clearly needed.
`
`Nursing Mothers:
`It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk,
`caution should be exercised when BUPHENYL ®is administered to a nursing woman.
`
`Pediatric Use:
`The use of tablets for neonates, infants and children to the weight of 20 kg is not recommended . (See Dosage
`and Administration.)
`
`ADVERSE REACTIONS
`The assessment of clinical adverse events came from 206 patients treated with sodium phenylbutyrate.
`Adverse events (both clinical and laboratory) were not collected systematically in these patients, but were
`obtained from patient-visit reports by the 65 co-investigators. Causality of adverse effects is sometimes
`difficult to determine in this patient population because they may result from either the underlying disease, the
`patient's restricted diet, intercurrent illness, or BUPHENYL ®. Furthermore, the rates may be under-estimated
`because they were reported primarily by parent or guardian and not the patient.
`
`CLINICAL ADVERSE EVENTS
`In female patients, the most common clinical adverse event reported was amenorrhea/menstrual dysfunction
`(irregular menstrual cycles), which occurred in 23% of the menstruating patients.
`
`Decreased appetite occurred in 4% of all patients. Body odor (probably caused by the metabolite,
`phenylacetate) and bad taste or taste aversion were each reported in 3% of patients.
`
`Other adverse events reported in 2% or fewer patients were :
`
`Gastrointestinal: abdominal pain, gastritis, nausea and vomiting; constipation, rectal bleeding, peptic ulcer
`disease, and pancreatitis each occurred in one patient.
`Hematologic: aplastic anemia and ecchymoses each occurred in one patient.
`Cardiovascular: arrhythmia and edema each occurred in one patient.
`Renal: renal tubular acidosis
`Psychiatric: depression
`Skin : rash
`Miscellaneous: headache, syncope, and weight gain
`
`Neurotoxicity was reported in cancer patients receiving intravenous phenylacetate, 250-300 mg/kg/day for 14
`days, repeated at 4-week intervals. Manifestations were predominately somnolence, fatigue, and
`lightheadedness; with less frequent headache, dysgeusia, hypoacusis, disorientation, impaired memory, and
`exacerbation of a pre-existing neuropathy. These adverse events were mainly mild in severity. The acute
`onset and reversibility when the phenylacetate infusion was discontinued suggest a drug effect.
`
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`LABORATORY ADVERSE EVENTS:
`In patients with urea cycle disorders, the frequency of laboratory adverse events by body system were:
`
`Metabolic: acidosis (14%), alkalosis and hyperchloremia (each 7%), hypophosphatemia (6%), hyperuricemia
`and hyperphosphatemia (each 2%), and hypernatremia and hypokalemia (each 1 %) .
`Nutritional: hypoalbuminemia (11 %) and decreased total protein (3%) .
`Hepatic: increased alkaline phosphatase (6%), increased liver transaminases (4%), and hyperbilirubinemia
`(1%).
`Hematologic: anemia (9%), leukopenia and leukocytosis (each 4%), thrombocytopenia (3%), and
`thrombocytosis (1 %).
`
`The clinician is advised to routinely perform urinalysis, blood chemistry profiles, and hematologic tests.
`
`OVERDOSAGE
`No adverse experiences have been reported involving overdoses of sodium phenyl butyrate in patients with
`urea cycle disorders.
`
`In the event of an overdose, discontinue the drug and institute supportive measures.
`
`Hemodialysis or peritoneal dialysis may be beneficial.
`
`DOSAGE AND ADMINISTRATION
`For oral use only.
`
`The use of BUPHENYL ®Tablets is indicated for children weighing more than 20 kg and for adults.
`
`The usual total daily dose of BUPHENYL Tablets and Powder 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. The tablets and
`powder are to be taken in equally divided amounts with each meal or feeding (i.e., three to six times per day).
`
`BUPHENYL ®Powder is indicated for oral use (via mouth, gastrostomy, or nasogastric tube) only. The 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. Sodium
`phenylbutyrate is very soluble in water (5 grams per 10 ml). When BUPHENYL Powder is added to a liquid,
`only sodium phenyl butyrate will dissolve, the excipients will not. The effect of food on sodium phenyl butyrate
`has not been determined.
`
`Each level teaspoon (enclosed) dispenses 3.2 grams of powder and 3.0 grams of sodium phenylbutyrate.
`Each level tablespoon (enclosed) dispenses 9.1 grams of powder and 8.6 grams of sodium phenylbutyrate.
`
`Shake lightly before use .
`
`The safety or efficacy of doses in excess of 20 grams (40 tablets) per day has not been established .
`
`NUTRITIONAL MANAGEMENT
`To promote growth and development, plasma levels of ammonia, arginine, branched-chain amino acids, and
`serum protein should be maintained within normal limits while plasma glutamine is maintained at levels less
`than 1 ,000 !Jmoi/L. Minimum daily protein intake for a patient of a particular age should be taken from, for
`example, "Recommended Dietary Allowances", 1Oth ed ., Food and Nutrition Board, National Academy of
`Sciences, 1989. The allocation of dietary nitrogen into natural protein and essential amino acids is a function
`of age, residual urea-cycle enzyme activity, and the dose of sodium phenylbutyrate.
`
`At the recommended dose of sodium phenylbutyrate, it is suggested that infants with neonatal-onset CPS and
`OTC deficiencies initially receive a daily dietary protein intake limited to approximately 1.6 g/kg/day for the first
`4 months of life. If tolerated, the daily protein intake may be increased to 1.9 g/kg/day during this period.
`
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`Protein tolerance will decrease as the growth rate decreases, requiring a reduction in dietary nitrogen intake.
`From 4 months to 1 year of age, it is recommended that the infant receive at least 1.4 g/kg/day, but 1.7
`g/kg/day is advisable. From 1 to 3 years of age, the protein intake should not be less than 1.2 g/kg/day; 1.4
`g/kg/day is advisable during this period. For neonatal-onset patients with carbamylphosphate synthetase
`deficiency or ornithine transcarbamylase deficiency who are at least 6 months of age, it is recommended that
`the daily protein intake be equally divided between natural protein and supplemental essential amino acids.
`
`Patients with argininosuccinic acid synthetase deficiency and those with late-onset disease (partial
`deficiencies, including females heterozygous for ornithine transcarbamylase), initially may receive a diet
`containing the age-determined minimal daily natural protein allowance. The protein intake may be increased
`as tolerated and determined by plasma glutamine and other amino acid levels. However, many patients with
`partial deficiencies avoid dietary protein.
`
`Citrulline supplementation is required and recommended for patients diagnosed with neonatal-onset deficiency
`of carbamylphosphate synthetase or ornithine transcarbamylase; citrulline daily intake is recommended at 0.17
`g/kg/day or 3.8 g/m2/day.
`
`The free-base form of arginine may be used instead of citrulline in patients with milder forms of
`carbamylphosphate synthetase and ornithine transcarbamylase deficiency (daily intake is recommended at
`0.17 g/kg/day or 3.8 g/m2/day).
`
`Arginine supplementation is needed for patients diagnosed with deficiency of argininosuccinic acid synthetase;
`arginine (free base) daily intake is recommended at 0.4-0.7 g/kg/day or
`8.8-15 .4 g/m2/day.
`
`If caloric supplementation is indicated, a protein-free product is recommended . Caloric intake should be based
`upon the "Recommended Dietary Allowances", 1Oth ed ., Food and Nutrition Board, National Research
`Council, National Academy of Sciences, 1989.
`
`HOW SUPPLIED
`BUPHENYL ®Tablets are available in 250 cc bottles which contain 250 sodium phenylbutyrate tablets (NDC
`62592-496-03). The bottles are equipped with child-resistant caps . Each tablet is off-white, oval, and
`embossed with "UCY 500". Each tablet contains 500 mg of sodium phenylbutyrate. STORE AT ROOM
`TEMPERATURE 15°C-30°C (59°F-86°F). AFTER OPENING, KEEP BOTTLE TIGHTLY CLOSED.
`
`BUPHENYL ®Powder is available in 500 cc bottles, which hold 266 grams of powder, containing 250 grams of
`sodium phenylbutyrate (NDC 62592-188-64). The bottles are equipped with child-resistant caps. Measurers
`are provided. Each level teaspoon (enclosed) dispenses 3.2 grams of powder and 3.0 grams of sodium
`phenylbutyrate. Each level tablespoon (enclosed) dispenses 9.1 grams of powder and 8.6 grams of sodium
`phenylbutyrate. STORE AT ROOM TEMPERATURE 15°C-30°C (59°F-86°F). AFTER OPENING, KEEP
`BOTTLE TIGHTLY CLOSED.
`
`All marks are the property of their respective owners.
`
`Manufactured for: Ucyclyd Pharma, Inc., Scottsdale, AZ 85256
`By: Pharmaceutics International, Inc., Hunt Valley, MD 21031
`
`NDC 62592-496-03 bottle contains 250 tablets of 500 mg.
`NDC 62592-188-64 bottle containing 250 g of sodium phenylbutyrate powder.
`
`Prescribing Information as of April 2008.
`
`49603-08C
`
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`49603-08C
`
`PATIENT PACKAGE INSERT:
`BUPHENYL ® (sodium phenylbutyrate) Tablets
`BUPHENYL ® (sodium phenylbutyrate) Powder
`
`What is the most important information I should know about BUPHENYL ®?
`BUPHENYL ®is prescribed along with changes in diet for long-term treatment of urea cycle disorders.
`BUPHENYL can only be obtained with a prescription from your doctor.
`
`BUPHENYL must be taken exactly as the doctor prescribes; do not increase or decrease the dose of this
`medication without the doctor's approval.
`
`What are urea cycle disorders?
`Urea cycle disorders include a group of diseases, each having a specific liver enzyme deficiency. Because
`they are inherited, other family members may be affected . These disorders vary in severity and may be first
`detected at various ages, from newborn infants to adults. They lead to increased amounts of ammonia in the
`blood, which may cause disturbed brain function and severe brain damage. Typical signs of the disease are
`decreased mental awareness, vomiting, combativeness, slurred speech, unstable gait, and
`unconsciousness. The diagnosis of urea cycle disorders requires special laboratory tests. These typical
`signs of the disease may recur after the diagnosis is made if the condition is not under control. If they
`do, the doctor should be notified immediately because this is a medical emergency. An infection can
`cause the condition to go out of control. Therefore, if a fever develops, the doctor should be seen
`immediately.
`
`A patient or carrier of these disorders should wear a Medic Alert tag stating the diagnosis. In the event
`that the patient has a sudden, rapid, accumulation of ammonia in the blood, and, therefore, in the
`brain, leading to unconsciousness, the doctor will be alerted to treat the disease properly.
`
`Periodically, depending upon the severity of a particular patient's urea cycle disorder, it will be necessary to
`perform blood tests. These include plasma ammonia, plasma amino acid levels, and other more routine blood
`tests to evaluate nutritional status.
`
`What is BUPHENYL ®?
`BUPHENYL ®is a drug that helps to prevent ammonia from accumulating in the blood. BUPHENYL aids the
`body in eliminating substances that produce ammonia. However, despite drug treatment, blood ammonia
`levels may become elevated periodically and there may be episodes of altered brain function in association
`with these ammonia elevations. Patients who have disease onset as newborns have a high incidence of
`mental retardation. Medical attention should be obtained as soon as signs appear (see above under "What
`are urea cycle disorders?") . BUPHENYL may be used as life-long therapy or as a temporary measure until
`liver transplantation is performed.
`
`What diet should I or my child follow?
`In addition to taking BUPHENYL ®, it is equally important that a 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.
`
`Who should not take BUPHENYL ®?
`BUPHENYL ®is prescribed only for patients with urea cycle disorders. It is not to be used for any other reason.
`Keep the medication in a safe place where children cannot reach it.
`
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`What other medical conditions may also be present that could increase the risk of taking
`BUPHENYL®?
`Heart failure or decreased kidney function may lead to retention of the sodium content of BUPHENYL ®with
`potentially serious consequences such as worsening heart failure, high blood pressure, and swelling. If these
`medical conditions are present, the doctor will determine if your child should take BUPHENYL.
`
`How should I or my child take BUPHENYL ®?
`The dose of BUPHENYL ®prescribed for adults and children is based upon the patient's weight or size. It is
`very important that the full amount prescribed for any 24-hour period be taken. If a dose is missed it should be
`administered as soon as possible that same day. The total daily dose should be administered in equally
`divided amounts with meals.
`
`What medications should I or my child avoid or be cautious of taking while on BUPHENYL ®?
`Patients with urea cycle disorders usually should not take Depakene® (valproic acid), a drug sometimes
`prescribed for seizure disorders, or Haldol® (haloperidol), a drug used to treat certain types of psychiatric or
`neurologic disorders. Both of these drugs have been reported to increase blood ammonia levels. Steroids
`may break down body protein, thereby increasing blood ammonia levels. The doctor should be consulted
`before administering medications containing steroids.
`
`What medications may affect the way the body breaks down the drug?
`Probenecid, a medication used to treat gout, may affect the way the kidneys excrete BUPHENYL ®(consult the
`doctor for details).
`
`What are most common side effects of BUPHENYL ®?
`The most common side effect reported in premenopausal women taking BUPHENYL ®was absent or irregular
`menstrual periods. Decreased appetite was reported in 4% of all people treated. Body odor and bad taste
`were each reported in 3% of all patients treated.
`
`A breakdown product of BUPHENYL has been associated mainly with sleepiness and light-headedness.
`Because these symptoms may also be due to the urea cycle going out of control, a doctor should see the
`patient immediately if these symptoms occur, so the cause can be determined. Blood tests should be
`performed periodically for adverse effects and for levels of medication and its breakdown products.
`
`How should BUPHENYL ® be stored?
`BUPHENYL ®should be stored in a tightly closed bottle at room temperature.
`
`This leaflet provides a brief summary of the information available on BUPHENYL ®. The information here is
`incomplete and is not designed to take the place of your doctor's instructions. For more complete information,
`consult your physician or call or write Ucyclyd Pharma, Inc. at 7720 N. Dobson Road, Scottsdale, AZ 85256.
`(888) 829-2593.
`
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