GOOBWIN PROCTERnase
`DEC 6 4 2005
`
`RECEIVED
`
`
`
`EDITION
`
`
` PDR
`
`
`60
`
`2006}
`PHYSICIANS
`DEK
`REFERENCE
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`Page 1 of 3
`
`LUPIN EX. 1018
`
`Page 1 of 3
`
`LUPIN EX. 1018
`
`

`

`PRODUCT INFORMATION
`
`on
`
`__
`
`Each tablet of BUPHENYL contains 500 mgof sodium phe-
`nylbuiyrate and the inactive ingredients microcrystalline
`
`cellulose, magnesium stearate, and colloidalsilicon dioxide.
`Each gram of BUPHENYL Powder contains 6.94 grams of
`sodium phenylbutyrate and the inactive ingredients cal-
`ciumstearate, and colloidalsilicon dioxide.
`CLINICAL PHARMACOLOGY
`Sodium phenylbutyrate is a pro-drug andis rapidly metab-
`olized to phenylacetate. Phenylavetate is a mietabolically-
`active compound that conjugates with glutamine via
`acetylation to form phenylacetyiglutamine. Phenylacetyl-
`
`glutamine then is excreted by the kidneys. On a-molar
`sis, it is comparable to urea (each containing two moles
`nitrogen). Therefore, phenylacetylglutamine provides an al-
`ternate vehicle for waste nitrogen excretion.
`PHARMACOKINETICS
`General:
`Pharmacokinetic studies have not been conducted in the |
`primary patient population (neonates, infants, and chil-
`dren), but pharmacokinetic data were obtained from normal
`adult subjects.
`Absorptio
`
`Peak plasma levels of phenylbutyrate occur within 1 hour
`after a single dose of5 gramsof sodiam phenylbutyrate tab-
`let with a C,,,, of 218 pg/mL underfasting conditions; peak
`plasma levels of phenylbutyrate occur within 1 hour after a
`single dose of 5 grams of sodium phenylbutyrate powder
`with a Cy... of 195 ng/mL under fasting conditions. The ef.
`feet of food on phenylbutyrato’s aksorption 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 sub-
`sequently to phenylacetylglutamine. F‘allowing oral admin-
`
`istration of 5 grams(tablets), measurable plasmalevels of
`pheny!butyrate and phenylacetate were detected 15 and 30
`
`minutes afer dosing,
`respeciively, and phenylacetyl-
`glutamine was detected shortly thereafter. The pharmaco-
`kinetic parameters for phenylbutyrate for Cras (ngimL),
`Pgs Coours), and elimination half-life (hours) were 218,
`1.85, and 0.77, respectively, and for phenylacetate were
`48.5, 3.74, and 1.15, respectively.
`Following oral administration of 5 grams of the powder,
`measurable plasmalevels of phenylbutyrate and phenylae-
`etate were detected 15 and 30 minutes after dosing, respec-
`
`tively, and phenylacetyglutamine was detected shortly
`thereafier. The pharmacokinetic parameters for phenylbu-
`tyrate for C,,., (ug/ml), Tip (hours), and elimination halt
`life Caours). were 198, 1.00, and 0.76, respectively, and for
`phenylacetate were 45.3, 3.55, end 1.29, respectively,
`The major sites for metabolism ofsodium phenylbutyrate
`are the liver and kidney,
`Excretion:
`Amajority ofthe administered compound (approximately 80
`~ 100%) was excreted bythe 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 phenylacetyiglutamine nitro-
`gen are produced.
`Pharmacodynamics:
`In pationts with urea cycle disorders, BUPHENYL de-
`ereases elevated plasma ammonia glutamine levels. It in-
`creases waste nitrogen excretion in the form of phenyl-
`acetylglutamine.
`Special Populations:
`Gender:
`
`the pharmaco-
`Significant gender differences were found in
`
`kinetics of phenylbutyrate and phenylaceiate but not for
`phenylacetylglutamine. The pharmacokinetic parameters,
`(AUC and C,,,,), for both plasma phenylbutyrate and phe-
`nylacetate were about 30 to 50 percent greater in females
`than in males.
`Hepatic insufficiency:
`In patients who did not have urea eyele disorders but had
`impaired hepatic function, the metabolism and excretion of
`
`|
`
`UCYCLYD/3327
`
`BUPHENYL®
`
`ww
`sodium phenylbutyrate were not affected, However, this in-
`lbuyen-ai}
`apse maturation was retarded, and the number of function-
`formation was obtained from unval
`Lidated, uncontrolled case
`studies.
`{sedium phenylbutyrate)
`ing nerve terminals in the cerebramwas reduced, which re-
`
`Tablets
`sulted in impaired brain growth. Prenatal exposure of rat
`INDICATIONS AND USAGE
`
`pups to phenylacetate produced lesions in layer§ of the cor-
`BUPHENYL®
`tical pyramidalcells; dendritic
`spines were longer and thin-
`BUPHENYL is indicated as adjunctive therapy in the
`
`ner than normal and reduced in number.
`(sodium phenyfbutyrate}
`chronic managementof patients with urea cycle disorders
`information for the Patients:
`
`Powder
`involving deficiencies of carbamylphosphate synthetase
`Rx Only
`The full text of the separate insert of information for pa-
`(CPS), ornithine transcarbamylase (OTC), or argininosuc-
`tients is reprinted at the end of the labeling.
`cinic acid synthetase (AS). It is indicatedin all patients with
`Laboratory Tests:
`DESCRIPTION
`
`neonatal-onset deficiency (complete cnzymatic deficiency,
`
`Plasma levels of ammonia, arginine, branched-chain andas
`presenting within the frst 28 days of life). It is also indi-
`
`
`ityrate} Tablete for oral admin-
`Buphenyl® (sodiumphe
`acids, and seram proteins should he maintained within nor.
`cated in patients with late-onset disease (partial enzymatic
`
`istration and Buphenyl@ (sodium phenylbutyrale) Powder
`mal limits, and plasma glutamine should be maintained at
`deficiency, presenting afier the first month of hfe) who have
`for oral, nasugasiric, or gastrostamy tube admini
`levels less than 1,000 pmol/L. Seram drug levels of phenyl-
`
`a history of hyperammonemie encephalopathy, It is impor-
`contain sodium phenylbutyrate. Sodium phenylbutyrate is
`
`tant that the diagn
`be made early and treatmonit initi-
`butyrate and its metabolites, phenylacetate a.
`r
`
`au offhite crystalline substance which is soluble in water
`
`ylacetylglutamine, should he monitored periodically.
`ated immediatelytoimprove survival. Any episode of acute
`and has a strong salty taste. Sodium phenylbu! rate also is
`
`Carcinogenesis, Mutagenesis, impairment of Fertility:
`hyperammenemia should be treated as a Ife threatening
`freely soluble in methanol and practically insoluble in ace-
`emergency.
`
`Carcinogenicity, mutagenicity, and fertility studies of so-
`
`
`dium phenylbutyrate have not been conducted
`tone and diethyl ether, It is known chemically
`as 4-phenyl-
`BUPHENYT. must be combined with dietary protein restric-
`
`Pregnancy:
`butyric acid, sodiumsalt with a molecular
`tof 186 and
`tion and, in somecases, essential amino acid supplementa-
`the molecular formula CyyH,,0.Na.
`Pregnancy Category C. Animal reproduction studies have
`Chemieal Structure:
`tion. (See Nutritional Supplementation subsection of the
`not been conducted with BUPHENYL.It is also not known
`DOSAGE AND ADMINISTRATIONsection.)
`whether BUPHENYL can cause fete] harm when ad-
`Previously,
`neonatal-onset disease was almost universally
`
`fatal within the firsi year of lif, even when treated with
`ministered to a pregnant womanor can affect reproduction
`capacity.
`peritoneal
`ysis and essential amino acidsortheir nitro-
`
`gen-free analogs. However, with hemodialysis, use ofalter-
`BUPHENYL should be given te a pregnant woman. only if
`clearly needed.
`native waste nitrogen cxeretion pathways (sodium phenyl.
`
`Nursing Mothers:
`butyrate, sodium benzoate, and sodium phenylacetate),
`It is not known whether this drug is excreted in human
`dietary protein restriction, and, in some cases, essential
`milk. Because many drugsare excreted in human milk, cau-
`ainine acid supplementation, the survival rate in newborns
`tion should be exercised when BUPHENYL is administered
`diagnosed after birth but within the first month oflife is
`to a nursing woman.
`Pediatric Use:
`almost 80%. Most deaths have occurred during an episode of
`acute hyperammonemic encephalopathy. Patients with neo-
`_ The use of tablets for neonates, infanis and children under
`natal-onset disease have a high incidence of mental retar-
`dation. Those who had IQ tests administered had an inci-
`AND ADMINISTRATION).
`dence of mental
`retardation as
`follows: ornithine
`ADVERSE REACTIONS
`wanscarbamylase deficiency, 100% (14/14 patients tested);
`‘argininosuccinic acid synthetase deficiency, 88% (15/17 pa-
`The assessmentofclinical adverse evenis came from 206
`tients tested); and carbamyl phosphate
`systhetase defi
`patients treated with sodium phenylbutyrate. Adverse
`ciency, 57%(4/7 pationts tested). Retardation was severe in
`events (both clinical and laboratory) were not collected sys-
`the’majority of the retarded patients.
`tematically in these patients, but were obtained from pa-
`In patients diagnosed during gestation and treated prior to
`fient-visit reports by the 65 co-investigators. Causality of
`any episade of hyperammonemic encephalopathy, survival
`adverse effects is sometimes difficult, to determine in this
`
`is 100%, but even in these patients, most subsequently dem-
`patient population because they mayresult from either the
`onsLrale cognitive impairment or other neurologic deficits.
`underlying disease, the pationt’s restricted diet, intercur-
`In late-onset deficiency patients, including females hetero-
`rent Hlness, or BUPHENYL.Furthermore, the rates may be
`zygous for ornithine transcarbamylase deficiency, who re-
`| under-estimated because they were reported primarily by
`cover from hyperammonemic encephalopathy and are then
`parent or guardianandnotthe patient.
`Clinical Adverse Events
`treated chronically with sodium phenylbutyrate and dietary
`protein restriction, the survival rate is 98%: The two deaths
`Tn female patients. the most. common clinical adverse event
`in this group of patients occurred during episodes of hyper-
`reported was amenorrhea/menstrual dysfunction (irrogular
`ammonemic encephalupathy. However, compliance with the
`menstrual cycles), which occurred in 23% of the menstruat-
`therapeutic regimon has not been adequately documented
`ing patients.
`to allow evaluationof the potential for BUPHENYI and di-
`etary protein restriction to prevent mental diterioration
`Decreased appetite occurred in 4% of all patients. Bodyodor
`(probably caused by the metabolite, phenylacetate} and bad
`and recu:rence of hyperammonemie encephalopathyif care-
`taste or taste aversion were eachreported in 3%of patients.
`fully adhered to. The majority of these patients tested
`Other adverse events reported in 2%or fewer patients were:
`(30/46 or 65%) have IQ's in the average to low average/
`Gastrointestinal:
`abdominal pain, gastritis, nausea and
`borderline mentally retarded range. Reversal of pre-existing
`vomiting; constipation, rectal bleeding, peptic uleerdisease,
`neurologic impairmentis notlikely to occur with treatment
`and pancreatitis each occurred in one patient.
`and neurologic deterioration may continue in some patients.
`Hematologic,
`aplastic anemia and eechymoses cach
`Even on therapy, acute hyperammonemic encephalopathy
`occurred in one pationt.
`recurred in the majority of patients for whom the drug is
`indicated.
`Cardiovascular:
`arrhythmia and edema each occurred in
`one patient.
`
`BUPHENYL may be required life-long unless orthotopic
`Ren:
`renal tubular acidosis
`liver transplantation is elected.
`depression
`(See CLINICAL PHARMACOLOGY, Pharmacodynamics
` rash:
`subsection for the biochemical effects of BUPHENYL).
`
`CONTRAINDICATIONS
`Miscellaneous: headache, syncope, and weight gain
`Neurotoxicity was reported in cancer patients receiving in-
`BUPHENYL should not be used to manage acute hyperam-
`wavenous phenylacetaie, 240-300 mg/kg/day for 14 days,
`monemia, which is a medical emergency,
`WARNINGS
`repeated at 4-week intervals. Manifestations were predom-
`inately somnolence, fatigue, and lightheadedness; with less
`Each BUPHENYL Tablet contains 62 mg of sodium (9.2%
`frequent headache, dysgeusia, hypoacusis, disorientation,
`
`why) (corresponding to 124 mg of sodium per gram of so-
`
`impaired memory, and exacerbation of
`pre-existing neu-
`dium phenylbutyrate [12.4% wéw]) and BUPHENYL Pow-
`ropathy. These adverse events were
`mainly mild in severity.
`der contains 11.7 gramsof sodium per 100 gramsof powder,
`The acute onset and reversibility when the phenylacetate
`corresponding to 125 mg of sodium per gram of sodium phe-
`infusion was discontinued suggest a druig effect.
`nylbutyrate (12.4% wiv), BUPHENYL should be used with
`Laboratory Adverse Events
`great care, if at all, in patients with congestive heart failure
`
`In patients with urea cycle disorders, the frequency of Iab-
`or severe renal insufficiency, and in clinical states in which
`oratory adverse events by body system were:
`there is sodium retention with edema.
`Metaholic:
`acidosis (14%), alkalosis and hyperchloremia
`Because BUPHENYLis metabolized in theliver and kidney,
`(each 7%), hypophosphatemia (6%), hyperuricemia and hy-
`and phenylacetylghatemineis primarily excreted by the kid-
`perphosphatemia (each 2%), and hypernatremia and
`hypokaleraia (each 1%).
`ney, use caution when administering the drug to patients
`with hepatic or renal insufficiency or inborn errors of beta
`iti
`hypoalbuminemia (11%) and decreased total
`
`oxidation. Probenecid is known to inhibit the renal trans-
`port of many organic compounds, including hippuric acid,
`Hepatic;
`increased alkaline phosphatase (6%), incrcased
`and mayaffect renal excretion of the conjugated product of
`liver transaminases (4%), and hyperbilirubinemia (1%).
`BUPHENYL as well as its metabolite.
`
`Hematologic:
`anemia (9%), leukopenia and leukocytosi:
`Useofcorticosteroids may cause the breakdown of bodypro-
`
`feach 4%), thrombocytopenia (8%), and thrombocytosis(
`tein and increase plasma ammonialevels,
`PRECAUTIONS
`Theclinician is advised to routinely perfurm urinalysis,
`General:
`blood chemisiry profiles, and hematologic tests,
`OVERDOSAGE
`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 be-
`ing induced by haloperidol and valproate.
`Neurotoxicity of phenylacetate in animats:
`When given subcutaneouslyto rat pups, 190-474 mg/kg
`phenylacetate caused decreased proliferation and increased
`loss of neurons, and it reduced CNS myelin. Cerebral syn-
`
`|
`
`|
`
`_
`
`|
`
` the weight of 20 kg is not reeemmended. (See DOSAGE
`
`No adverse experiences have been reported involving over-
`doses of sodium phenylbuiyrate in patients with urea cycle
`disorders.
`Tn the event of an overdose, discontinue the drug and insti-
`tute supportive measures.
`Hemodialysis or peritoneal dialysis may be beneficial.
`Continued on next page
`Consult 2006 PDR® supplements and future editions for revisions
`
`Page 2 of 3
`
`LUPIN EX. 1018
`
`
`
`Page 2 of 3
`
`LUPIN EX. 1018
`
`

`

` PHYSICIANS’ DESK
`
`Contents
`_ CardioEssentials features a
`proprigt;
`thine, L-taurine, and Hawthorn, vist
`
`Coenzyme Q10.
`
`For
`detailed
`dietary
`inforniation
`
`www.makelifebetter.com
`SAFETY AND WARNINGS
`
`
`CardioEssentials is well accepted. Same g
`discomfort may be experienced agi
`supplement.
`: HOW SUPPLIED
`Available in bottles of 180 tablets,
`
`Manufactured for: Ucyelyd Pharma, Inc., Seotisdale, AZ
`85258
`By: Pharmaceutics International, Ine. Hunt Valley, MD
`21031
`NDC 62592-496-03 bottie of 500 mg tablets.
`NDC 62592-188-64 bottle containing 260g of sodium phe-
`nylbutyrate powder.
`Prescribing Information as of August 2003
`
`49608-084
`
`
`
`Unicity International
`THE MAKE LIFE BETTER COMPANY
`1201 NORTH 800.EAST
`OREM, UT 84097
`
`3328/UCYCLYD
`
`Buphenyl-——Cont.
`DOSAGE AND ADMINISTRATION
`For oral use only.
`The use of BUPHENYLTablets is indicated for children
`weighing more that 20 kg and for adults. The usual total
`daily dose of BUPHENYL Tablets and Powder for patients
`with urea cycle disorders is 450 ~ G00 mg/kg/day in patients
`weighing less than 20 kg, or 9.9 - 13.0 g/m®/day in larger
`patients. The tablets and powder are to be taken in equally
`divided amounts with each’ mealor feeding (ie., three to six
`times per day).
`BUPHENYL Powder is indicated for oral use (via mouth,
`gastrostomy, or nasogastric tube) only. The powderis to be
`mixed with food (solid or liquid). Sodium phenylbutyrate
`is very soluble in’ water (5 grams per 10 mL). When
`BUPHENYLPowder is added to-a quid, only sodium phe-
`nylbutyrate will dissolve, the excipients will not. The effect
`of food on sodium phenylbutyrate has not been determined.
`Each level teaspoon (enclosed) dispenses 3.2 grams of pow:
`der and 3.0 grams of sodium’phenylbutyrate. Each level ta-
`blespoon (enclosed) dispenses 9.1 grams of powder and
`8.6 gramsof sodium phenylbutyrate.
`Shake lightly before use.
`‘Thesafety or efficacy ofdoses in excess of 20 prams (46 Tab-
`lets) per day has not been established.
`NUTRITIONAL MANAGEMENT
`To promote growth and:development, plasma levels of am-
`monia, arginine, branched-chain amino acids, and:serum
`protein should be maintained within normal limits while
`plasma glutamine is maintained at
`levels ‘less
`‘that
`1,000 pmol/L. Minimum daily protein intake for a patient:of
`a partictilar.age shouldbe taken from,fer example, “Recom-
`mended‘ Dietary Allowances”, 10th ed., Food and Nutrition
`Board, National Academy of Sciences, 1989. Theallocation
`of dietary nitregen into natural protein-and. essential amino
`acids is a function of age, residual urea-cycle enzyme activ-
`ity, and the dose of sodium phenylbutyrate.
`At the recammended dose of sodium phenylbutyrate, it is
`suggested that infants with neonatal- onset CPS and OTC
`deficiencies initially receive a daily dietary protein intake
`limited te approximately 1.6 g/kg/day for thefirst 4 months
`oflife. If tolerated, the daily protein intake may be in-
`creased to 1.9 g/kg/day during this period. Protein tolerance
`will decrease as the growth rate decreases, requiring a re-
`duction in dietary nitrogen intake. From 4 monthsto 1 year
`of age, it is recommended that the infant receive at least
`lAg/kg/day, but 1.7g/kg/day is advisable, From 1 to 3 years
`of age, the protein intake should not be less than 1.2 g/ke/
`day; 1.4 g/kg/day is advisable during this period’ For neona-
`tal-onset patients with earbariylphosphate synthetase defi-
`ciency or ornithine transcarbamylase deficiency who are at
`least 6 months ofage,it is recommended that the daily pro-
`tein intake be equally divided between natural protein and
`supplemental dssential amino’ acids,
`Patients with argininosaccinic acid synthetase: deficiericy
`and those with late-onset disease (partial deficiéncies,
`in-
`cluding females heterozygous fer ornithine transcarbamy-
`lase)}, initially may receive a diet contaming the age-deter!
`mined taiuimaldaily natura! protein allawance. The protein
`intake uiay be increased as tolerated and determined by
`plasma ghitamine and other amino acid-levels. However,
`many patients with partial deficiencies avoid: dietary
`protem,
`Citrulline supplementation is required and recommended
`for patients diagnosed with neonatai-onset deficiency of car-
`
`bamylphosphate synthetase or ornithine transcarbamylase;
`citrulline daily intake is recommended at 0.17 g/kg/dayor
`3.8 g/m*/day.
`The free-base form.of arginine may. be used insteadof cit-
`rulline in patients with milder forms of carbamylphosphate
`synthetase and orinthine transcarbamylase deficiency
`(daily intake is recommended at 0.17 g/ig/day or 3.8 p/m*/
`day).
`Arginine supplementation is needed for patients diagnosed
`withdeficiency of argininosuccinic acid synthetase; arginine
`(free base) daily intake is recommended at 0.4 ~ 0.7 p/kg/day
`or 8.8 ~ 15.4 g/mday.
`Ifcaloric supplementation is indicated, a protein-free prod-
`uct is recommended. Calorie intake should he hased upon
`the “Recommended Dietary Allewances’, 10th ed., Food and
`Nutrition Board, National Research Council, National
`Acaderyof Sciences, 1989.
`HOW SUPPLIED
`BUPHENYL Tablets are available in 250 ce bottles, which
`contain 250 sodium phenylbutyrate Lablets (NDC 62492-
`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 phenylbu-
`tyrate.. STORE AT ROOM TEMPERATURE 15°C-30°C (53°F~
`86°F). AFTER OPENING, KEEP BOTTLE TIGHTLY CLOSED.
`BUPHENYLPowder. is available. in 500 cc bottles, which
`hold 266 grams of powder, containing 250 grams of sodium
`phenylbutyrate (NDC 62592-188-64). The bottles dre
`equipped with child-resistant caps. Measuters are provided.
`Bachlevel teaspoon. (enclosed) dispenses 3.2 grams of pow-
`der and 3.0 grams of sodium phenylbutvrate. Each level ta-
`dlespoon (enclosed) dispenses 9.1 grams of powder and
`8.6 grams of sadium phenylbutyrate. STORE AT 15°C~30°C
`{53°F-86°F). AFTER OPENING, KEEP BOTTLE TIGHTLY
`CLOSED.
`US Patent number 4.457.942.
`
`
`
`
`
`
`
`*THESE STATEMENTS HAVE NOT. BEEN
`BY THE FOOD AND DRUG ADMINISTER
`
`PRODUCT IS NOT INTENDED TO.DIAG.
`_ CURE, OR PREVENT ANY DISEASE:
`| REFERENCES
`
`1092-1100.
`sejeebhay, F et af (2902), Ameritan He
`
`
`Direct Inquiries to:
`(861) 226° 2660
`www.makelifebetter.com
`science@unicity net
`Products of Unicity International, The Make Life Better
`Company are distributed through independent distributors.
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`CM PLEX” AND CM PLEX™ CREAM
`ICM piéks]
`of osteo arthritis*
`Proprietary fatty acid bland to help alleviate
`BIOSLIFE 2@
`[bi-6s tif 2]
`DESCRIPTION
`Advanced Fiber and Nutrient Drink
`&
`CM Plex and CM Plex Cream area softgel
`DESCRIPTION
`eream product respectively, combining fattyacids;
`BiosLifé 2 is a-nutrient-rich fiber drink mix that contains
`
`prietary blend of cety] myristate, cetyl’:muyris é
`. other catyl esters.
`patented complex of soluble and msoluble fibers, vitamins,
`Benefits and research
`
`and minerals.
`| Cetyl myristoleate and related fatty acids hai
`BENEFITS AND RESEARCH
`
`to improve jomt health, throughtheir antien
`BiosLife 2 —a good source of dietary fiber-— when included
`foets. A clinical study indicated that subjects
`|
`as part of a healthy diet, may help lower your blood choles-
`
`
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`pravements in knee flexion compared to placeby
`terel levels arid reduce your risk of heart disease, Eight
`) study indicated the cream is éffective fort
`weeks of BiosLife 2 showed a significant reduction in LDL-c
`range of motion, improving ability to climb st
`compared to placebo. The mechanismof BiosLife 2 in cho-
`
`
`a chair, and walk, and improving balance,strengt!
`lesterol reduction is though bile-acid sequestration.
`durance.*
`
`SUGGESTED USE
`| SUGGESTED USE
`
`First users: dissolve-the contents.of one packet into 8 to 10
`Softgels: Take one or twosoftgeis-three tim
`fl. oz. of liquid (wateror juice), stir vigorously.and drink im-
`| meals: Cream: Apply generously onto clean'skin
`mediately 5 to 10 minutes before the. main.meals. After fiber
`massage until the cream disappears. Repeat:3
`adjustment use as: directed above up to three times daily |
`
`daily as necessary. For maximum results co:
`before every meal,
`.
`
`CONTENTS.
`products.
`:
`Contents
`
`One. packet of BiosLife 2 contains 4.5 gramfiber, comprising
`
`CMPlex contaime a proprietary blend of cetyl im!
`of 4-grams of soluble fiber. Added to this fiber mix are. o
`
`tyl myristoleave, and other cetyl esters. For detai
`maldaily levels-and bic-available forms of several vitamins,
`information, please see. www.unicity net.
`
`and chromium (as ChromeMate™), BiosLife 2 is available
`| Safety and Warnings
`in Natural, Original, and Tropical Fruit flavors. For detailed
`| OMPlex Soltgels and: Cream are well accepted.
`
`dietary information, please see www.unicity.net
`
`trointestinal discornfort may be experienced with:
`SAFETY AND WARNINGS
`Softgels as with any dietary supplement.
`HOW SUPPLIED
`BiosLife 2 is well accepted. Some users report mild gastro:
`intestinal discomfort after first use. This is a nornial effect
`CM. Plex is available in both cream and soft gel
`of increased fiber intake and normally disappears within 30
`REFERENCES
`Pa
`days. Taking this product without adequate liqnid can re-
`sult in complications. If you are a diabetic, consult a physi-
`Hesslink, R et a) (2002), Journal ofRheumatology.
`1712.
`cian for proper use of this product, as the chromium may
`reduce the need for medication.
`Kraemer, Wd ef al (2004). Journal of Rheumal
`167-774,
`HOW SUPPLIED
`Conveniently packaged in single-serving packets or bulk
`canisters.
`REFERENCES
`Sprecher, DL and Pearee CL (2002), Metabolism 51: 1166~
`7.
`Verdegem, PJE; Freed, S and Joffe B (2005), American Di-
`abetes Assocation 65"Scientific Sessions, San Diego.
`US Patent 4,883,788 and US Patent 4,824,672.
`*THESE STATEMENTS HAVE NOT BREN. RVALUATED
`BY THE FOOD AND DRUG ADMINISTRATION. THIS
`PRODUCT 1S_NOT INTENDED TO DIAGNOSE, TREAT
`CURE, OR PREVENT ANY DISEASE.
`
`
`
`*THESE STATEMENTS HAVE NOT BEEN EVAL
`BY THE FOOD AND DRUG ADMINISTRATIO:
`PRODUCT IS NOT INTENDED TO THAGNOSE, T
`CURE, OR PREVENT ANY DISEASE.
`
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`VISUTEIN®
`{vts-u-tén]}
`
`
`Clinically prover: to support healthy eyes and vision
`DESCRIPTION
`
`ViSUtein is Unicity’s product providing key nutrient
`the eye.
`Benefits and research
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`The carotenoids lutein and zeaxanthin play an japo
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`role. in eye health. Low concentrations of these phyten
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`ents in the retina have been associated with age-te
`5!
`macula degeneration (AMD). Studies have shown, that
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`plementation with high levels of lutein, as. pres
`VISUtein, can restore the lutein concentraetion vh the re
`
`enoids that are importantin pres
`2
`
`is add
`and_Suppering clearvision. Ne
`ysteing.
`Low glutath
`
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`els have"Bean
`OWRD, to reduce protection of the eye
`oxidative stress, A recentclinical study with ViSUtel
`
`
`own that AMD patients expericnce clear improvements
`ensitivily, and recovery fro)
`
`ore
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`CARDIOCESSENTIALS®
`Caring fer your heart
`DESCRIPTION
`CardioEssentials is Unicity’s superior heart product.
`Benefits and research
`| CardioEssentials provides nutrients for the heart muscle,
`:) and supports healthy heart function. The combination of
`Learnithine, L-taurine, and Coenzyme Q10 has been shown
`to benefit congestive heart failare patients in a clinical
`study. In this study,
`jefl ventricular size was reduced in
`| CHFpatients, giving them d better prognosis. These ingre-
`dients are knownto be important. in providing adequate en-
`ergy for the heart muscle. CardioRssentials provides ade-
`quale amounts of these ingredients, ie. 100 mg of CoQio.
`Hawthorn extract is traditionally used in supyorting the
`heart function,
`SUGCESTED USE
`Take six capsules daily with feud.
`
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`LUPIN EX. 1018
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