`
`EDiTiON
`
` PDR®
`
`60
`
`
`
`2006'
`
`
`
`699955113333 _ ~ ,
`deanw
`
`DEC 912065
`
`RECESVED
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`
`
`PHYSICIANS
`DESK
`REEEPENCE
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`Page 1 of 3
`
`LUPIN EX. 1018
`
`Page 1 of 3
`
`LUPIN EX. 1018
`
`

`

`PRODUCT ENFORMATION
`
`.
`
`©‘cwouacngcooria
`Each tablet of BUPHEN'YL contains 500 mg of sodium phe-
`nyllmryrate and the inactive ingredients microcrystalline
`
`,
`cellulose, magnesium stearate, and colloidal s’ icon dioxide.
`Each gram of BUPHENYL Powder contains 0,94 grams of
`sodium phenylbutvrate and the inactive ingredients calA l
`m‘um stearate, and colloidal silicon dioxide.
`CLINICAL PHARMACOLOGY
`Sodium phenylhutyrate is a pro-drug and is rapidly metab-
`olized to phenylacetate. Phenylacetate is a metabolically;
`ac 've compound that conjugates with glutamine via
`acetvlation to form phenylacetylglulamine. Phenylaoetyh ,
`
`glutamine then is excreted by the kidneys On a mola1
`
`sis, it is comparable :o urea (each containing two moles
`nitrogen). Therefore, phenylacet-ylglutamine provides an ul~
`tomato vehicle for waste nitrogen excretion,
`PHARMACOKINETICS
`General:
`Pharmacokinetic studies have not been conducted in the 1
`primary patient population ineonates, infants, and chil-
`dren}, but pharmacokinetic data were obtained From normal
`adult subj
`Absorptio
`
`Peak plasma levels of phenylbutyrate occur within 1 hour
`after a single dose of5 grams of sodium phenylbutyrate tab-
`let with a C,“Bx of 218 pg/mL under fasting conditions; peak
`plasma levels of phcnylbutyrale occur within 1 hour after a
`single dose of 5 grams of sodium phenylbutyrate powder
`with a Cmm of 195 rig/nil. under Fasting conditions. The eil
`feet of food on phenylbutyrato‘s absorption is unknown.
`Disposition:
`The overall dispoSItion of sodium phenylbutyrate and its
`metabolites has not been characterized fullv. However, the
`
`drug is known to be metabolized to phenyl ethic and sub-
`sequently to plumylacetylglutamine. Following orol admin—
`
`istration of 5 grams (tablets), measurable plasma levels of
`pllb‘ ylhntyrate and phenylacetate were detected 15 and 30
`
`minutes after dosing.
`respe
`ely, and phenylacetyh
`glutamine was detected shortly therealter. The pharmaco-
`kinetic parameters for plienylhutyrate for Cmax (pg/mL).
`’l‘3m (hoursl, and elimination halfelife (hours) were 218.
`1.35. 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 plasma levels of phenylbutyrate and phenylac‘
`state were detected 15 and 30 minutes after dosing, respec-
`
`tiirely, and phenylacetyglutamine was detected shortly
`thereafter The pharmacokinetic parameter. for phenylbu-
`tyrato for Cm, lug/mill, Tm”, lhoursl, and elimination half:
`life (hours) were 195, 1.00, and 0.76, respectively, and for
`phenylacetate were 45.3, 3.55, and l 29, respectively.
`The major sites for metabolism of sodium phenylbutyrate
`are the liver and kidney.
`Excretion:
`A majority 05‘the administered compound (approximately 80
`_ 100%) was excreted by the kidneys within 24 hours as the ;
`conjugation pmduct, phenylacetylglutamine. For each gram
`of sodium phenylhutyrate administered, it is estimated that
`between 0.12 — 0.15 grams of phenylacetyiglutaminc nitro
`gen are produced.
`Pharmacodynamics:
`In patients with urea cycle disorders, BUPHENYL de-
`creases elevated plasma ammonia glutamine levels. It iir
`creases waste nitrogen excretion in the form of phenyl
`acetylglutamine,
`Special Populations:
`Gander:
`
`the pharmaco»
`Significant gender differences were found '
`
`kinetics of phonylbutyrate and phenylac are but not for
`plienylacetylglutamine. The pharmacokinctic parameters.
`{AUC and Chm}, for both plasma plienylbutyrate and phe-
`nylacelate were about 30 to 50 percent greater in females
`than in males.
`Hepatic insufficiency:
`in patients who dill not have urea cycle disorders but had
`impaired hepatic function, the metabolism and excretion of
`
`
`
`‘
`
`l
`
`UCYC LYD/3327
`
`BUPHENYL®
`
`’93
`sodium phenylbutyrate were no: afieczed. However, this in-
`lbzz 7221: all
`apse maturation was regarded, and the number of function-
`formation was obtained from unve
`lidatcd. uncontrolled case
`studies.
`{sodium phenylbutyratel
`ing nerve terminals in the ccrebrum was reduced, Which re-
`
`Tablets
`sultai in impaired lrrniu growth. P: natal exposure of rat
`. MICATIONS AND USAGE
`
`pups to phenylac ate produced lesions in layer 5 m” the cor.
`BLIPI-IEN‘FLGEl
`lical pyramidal cells; rlondrit
`spines were longer and thinv
`BUFHENYI is indicated as adjunctit'e llierapy in the
`
`ner than normal and reduced in number,
`(Sodium phenylbuiyrate}
`chronic management of patie
`s with urea c cle disorders
`informstion for the Patients:
`
`Powder
`involving deficiencies of carbamylpliosplia ,. syntltetase
`Rx Only
`The full text of the separate insert of infhrmation for pa-
`(CPS). ornithine transcarbamylase (OTC). or arginincsuc-
`tients is reprinted at the end of the labeling.
`cmic acid svntbetase {AS}. It is indicated in all patients with
`Laboratory Tests:
`DESCRIPTEON
`
`
`neonatal-onset deficiency tcomplctc cnzvmatic deficiency,
`Plasma levels of ammonia, arg’ininc, branched-chain amino
`presenting it him the first 28 .inys of life). it is also indi-
`
`,tyratel Tab tC for oral admin-
`Bupiieuyl® lsodium phc
`acids, and serum proteins should he maintained Within more
`
`
`cated in patients with lateonset disease (partial enzymzziic
`istration and Buphcnylvi (sodium pheny m‘
`tel Powder
`mal limits, and plasma glueamine should be maintained at
`deficiency, presenting alter the first month of life) who have
`for oral, nasngssm'c, or gastrostomy tube adrm ’
`levels less than 1,000 umol/L Serum drug levels of phony ~
`
`a history of hyperammoncmic encephalopathy, it is impor»
`
`contain sodium phenylbuxyratc. Sodium phenyl utyrate is
`tant that the diagr
`he made early and treatment initir
`butyrate and its metabolites, phenylacetate a l
`,
`*
`
`an ofiiw he crystalline substance which is soluble in water
`
`ylacetylglutamine, should he monitored pericdicallv
`ated immediately
`improve survival. Any epis do of acute
`and has a strong salty taste. Sodium phonylhu ,rate also is
`
`Carcinogenesis, Mutagenesis, impairment of Fertility:
`hyperammonemia should be treated as a life tzn~oatening
`freely soluble in methanol and practicall
`insoluble in ace-
`emergency.
`
`Carcinogeui
`'ly, nuitagenicity. and fertility studies of so—
`
`
`dium phenylbutyrotc have not been conducted
`tonr and dietltyl other. It is known (the
`1cal
`as 4-phenylr
`EUPHENYL must. be combined With diets ' protein restric—
`
`Pregnancy:
`hutyric acid, sodium salt with a molecular
`of 186 and
`tion and, in some cases, essential amino acid supplements
`the molecular formula ClUHIZOENa.
`Pregnancy Category C. Animal reproduction Studies have
`Chemical Structure:
`tion. (See Nutritional Supplementation subsection of the
`not been conducted with BUFHENYL. it is also not known
`DOSAGE AND ADMINISTRATION section.)
`whether BUPHENYL can ca se fetal harm when ad
`Premou
`neonatal-onset disease was almost universally
`
`fatal W1
`. the first year of life, even when treated With
`ministered to a pregnant woman or can affect reproduction
`capacity.
`peritonea
`*sis and essential amino acids or their nitrir
`
`gen-free analogs. However, with hemodielysis, use of alter
`BUPHENYL should be given to a pregnant woman only if
`clearly needed.
`native waste nitrogen excretion pathways (sodium phony -
`
`Nursing Mothers:
`butyrate, sodium henzoats, and sodium phenylacetate),
`It is not known whether this drug is excreted in human
`dietary protein restriction, and, in some i
`,, essential
`milk. Because many drugs are excreted in human milk. can.
`amino acid supplementation, the survival rate in newborns
`tion should be exercised when BUPHENYL is administered
`diagnosed after birth but within the flrsl month of life is
`to a nursing woman.
`Pediatric Use:
`almost 80% Most deaths have occurred durixfg an episode of
`acute bypcrammoaemic encephalopathy Patients with neo-
`, The use of tablets for neonates, infants and Children under
`natal-onset disease have a high inczdence of mental retar-
`the weight of 20 kg is not recommended. (See DOSAGE
`dation. Those who had IQ tests administered had an inci»
`AND ADMINISTRATION l.
`dance of mental
`retardation as
`follows: ornithine
`ADVERSE REACTIONS
`transcarbamylase deficiency, 700% (14/14 pat nts tested l;
`‘argininosuccinic acid synthetase deficiency, 88% .15/17 pa‘
`The assessment of clinical adverse events came from 206
`tients tested); and carlmmyi phosphate vsthetase defi
`patients treated with sodium phenylbutyrate. Adverse
`ciency, 57% (4/7 patients tested). Retardation was severe in
`events [both clinical and laboratory) were not collected sys
`the majority ul‘the retarded patients.
`lematically in these patients, but were obtained from pa~
`In patients diagnosed during gestation and treated prior to
`tient visit reports by the G5 co-investigators. Causality of
`any episode of hyperammenemic encephalopathy, survival
`adverse elfects is sometimes difficult to determine in this
`
`is 100%, but even in these patients, most subsequently Clem»
`patient population because they may result from either the
`castrate cognitive impairment or other nourologic deficits.
`underlying disease. the patients restricted diet, 1 mur-
`In lute-onset deficiency patients, including females hetero-
`rent. illness. or BUFHENYL 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 guardian and not the patient.
`Clinical Adverse Events
`treated chronically with sodium phenylbutyrate and dielary
`protein restriction, the survival rate is 98%. The two deaths
`In female patients, the most common clinical advmse event
`in this group of patients occurred during episodes of hyper
`reported was amenorrhea/menstrual dysfunction (irregular
`ammcuemic encephalopathy However, compliance w3lh the
`menstrual cycles). which occurred in 23% of the menstrual»
`therapeutic regimen has not been adequately documented
`ing patients.
`to allow evaluation of the potential for BUPHENY'L and di-
`etary protem restriction to prevent mental deterioration
`Decreased appetite occurred in 4% of all patients. Body odor
`(probably caused by the metabolite, phenylacetate) and bad
`and recurrence 0:” hyperammonemic encephalopathy if care-
`taste or taste aversion were each reported in 3% of patients.
`fially 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 preexisting
`vomiting: constipation, rectal bleeding, peptic ulcer disease,
`neurologic impairment is not likely to occur with treatment
`and pancreatitis each occurred in one patient.
`and ncurologic deterioration may continue in some patients.
`Hematologic.
`aplaslic anemia and eeehymoses each
`Even on therapy, acute hyperammonemic encephalopathy
`occurred in one patient.
`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 lifelong unless orthotopic
`Ren
`renal tubular acidosis
`liver transplantation is elected.
`'
`depression
`(See CLINICAL PHARMACOLOGY, Pharmacodynnmics
`
` rash
`subsection for the biochemical efiects of BUPHENYIJ.
`CONTRAYNDICATIONS
`Miscellaneous: headache, syncope, and weight gain
`Neurotoxicity was reported in cancer patients receiving in
`BUPHENYL should not be used to manage acute hyper—am»
`travenous phenylacetate, 250-300 mg/kg/day for M days,
`monomia, 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,
`
`w/w) icorrcsponding to 124 mg ol‘ sodium per gram of so»
`
`preexisting neu-
`impaired memory, and exacerbation
`dium phenylbutyrate [12.4% w/wll and BUPHENYL Pow~
`ropathy. These adverse events were
`inly mild in severity.
`der contains 11.7 grams of sodium per 100 grams of powder,
`The acute onset and reversibility when the phenylacetate
`mm—isponding to 125 mg of sodium per gram of sodium phe-
`infusion was discontinued suggest a drug efl‘ect.
`nylbutyrate (12.4% w/wl. 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 lab-
`or severe renal insufliciei y and in clinical states in which
`oratory adverse events by body system were:
`there is sodium retention with edema
`Metabolic:
`acidosis (14%), alkalosis and hyperchloremia
`Because BUPHENYL is metabolized in the liver and kidney,
`(each I ,c), hypophosphalemia (6%), hyperuricomia and by
`and phenylacetylglutomine is primarily excreted by the kid-
`perphosphatemia (each 2%), and hypernatremia and
`hvpokalemia (each 1%}.
`ney, use caution when administering the drug to patients
`with hepatic or renal insufficiency or inborn errors of beta
`_N tritiona
`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%), increased
`and may affect renal excretion of the conjugated product of
`liver transaminascs (492), and hyperbilirubiuemia (1%).
`BUFHENYL as well as its metabolite.
`
`Hematologc:
`anemia l 90), leukopenis and leukocytesi
`Use ofcorticosteroids may cause the breakdown of body pro
`
`leach 4%], thrombocytopenia (3%), and thrombocytosis 4
`tein and increase plasma ammonia levels.
`PRECAUTIONS
`The clinician is advised to routinely perform urinalysrs,
`General:
`blood chemistry profiles, and hematologic tests.
`OVERDOSAGE
`BUPHENYL should not he administered to patients with
`known hypersensitivity to sodium phenylbutyrate or any
`component of this preparation.
`There have been published reports of hyperammoncmia be—
`ing induced by hnloperidol and valproate,
`Neurotoxicity of phenylacetate in animals:
`When given subcutaneously to rat pups, 190—474 mg/kg
`phenylacerale caused decreased proliferation and increased
`loss of neurons, and it reduced CNS myclin. Cerebral syn:
`
`-
`
`
`
`No adverse experiences have been reported involving over»
`doses of sodium phenylbulyrate in patients with urea cycle
`disorders.
`In the event of ar- overdose, discontinue the drug and insti»
`tute supportive measures.
`Hemodialysis or peritoneal dialysis may be beneficial.
`Continued an next page
`Consult Z 00 6 FUN supplements and future editions for revisions
`
`Page 2 of 3
`
`LUPIN EX. 1018
`
`Page 2 of 3
`
`LUPIN EX. 1018
`
`

`

` PHYSICIANS‘ DESK
`Contents
`
`_ CardioEsoentinls features1:
`propriet
`
`thine, Ltaurine and Hawthorn 30mg}
`Coenzymr Q10.
`For
`detailed
`dietary
`information
`wwvwmakclilhbettcr com
`
`SAFETY AND WARNINGS
`
`CnrdioEsscntials is well accepted, some g
`discomfort may be experienced as W'
`
`supplemcm.
`‘ HOW SUPPLIED
`Available in bottles 01'180 Lobletsd
`"11115313 Sfll‘A'lEME.NTS HAVE NOT BEEé}
`
`BY THE FOOD AND DRUG ADMJNXST '
`PRODUCT is NOT INTENDED TO DIAS.
`‘ CURE, OR PREVENT ANY DISEASE.
`-‘ REFERENCES
`
`
`1092 1100.
`,pjeclihny 1*1 p! a] 0007.}, America» He
`
`
`Manufactured for: Ucyclyd Pharma, 1111:, Scottsdale AZ.
`85258
`By" Pharmacomic: lniornational. lnc Hunt Valley, MD
`21031
`NDC 62592496413 bottle of 500 mg tablets.
`NDC 62592-188~64 bottle containing 250g of sodium pliev
`nylbutyrate powder.
`Prescribing Information as ofAuguet 2003
`
`49603~08A
`
`
`
`Unicity International
`THE MAKE LIFE BETTER COMPANY
`1201 NORTH 500 EAST
`OREM. UT 84097
`
`Direct Inquiries to:
`(801) 226 2600
`www.makelifehcttencom
`science®unicity not
`Products of Unicity International. The Make Life Better
`Company are distributed through independent distributors.
`
`:
`
`
`OTC
`
`BIOSLIFE 2®
`[bi-63 [:72]
`Advanced Fiber and Nutrient Drink
`a
`DESCRIPTION
`BiooLife 2 is a nutrient-rich fiber drink mix that contains
`patented complex of soluble and insoluble fibers, vitamins,
`and minnrnls.
`BENEFITS AND RESEARCH
`BiosLife 2 ~21 good source ofdietziry fiberw when included
`as part Ora healthy diet, may help lower your blood choles>
`tercl levels and reduce your risk of heart disease. Eight
`weeks of BiosLife 2 showed a significant red notion in LDIrc
`compared to placebo. Tho mechanism of Biosliife 2 in cho-
`lesteml reduction is though bile-acid sequestration.
`SUGGESTED USE
`First users: dissolve the contents of one packet into 8 to 10
`fl. oz. ofliquid (water or juice), stir vigorously and drink 1111A
`mediately 5 to 10 minutes before the main meals. Alter fiber
`adjustment use as directed above up to three times daily
`before every meal.
`\
`CONTENTS
`One packet ofBiosL.fee ‘2 winning 4.’a gram filwr,1riniprising
`
`11” grams of soluble fiber. Added to this fiber mix are 0
`mal daily levels and bio—available forms of several Vitamins,
`and chromium (as ChromeMoteP-‘ll. BiosLife 2 is available
`in Natural, Original, and Tropical Fruit flavors. For detailed
`dietary information, please see wwvv.unicity.net
`SAFETY AND WARNINGS
`Biosliife 2 is well accepted. some users report mild gastro-
`intestinal discomfort afler first use. This is a normal cfl'ect
`of increased fiber intake and normally disappears within 80
`days Taking this product without adequate liquid can ro-
`sult in complications. If you are a diabetic, consult a physi.
`clan for proper use of this product, as the chromium may
`reduce the need for medication,
`HOW SUPPLIED
`Conveniently packaged in single—Serving packets or bulk
`canisters.
`REFERENCES
`Sprechor DI. and Pearce GL (2002). Metabolism 51: 1166—
`70.
`V’crdegem, PIE; Freed S and Jolie D (2005), American Di—
`abetes Assocation 65'“ Scientific Sessions,“can Diego
`US Patent 4,883,788 and US Patent 4,824,672.
`“PURSE STATEMENTS HAVE NOT BEEN EVALUATED
`BY THE FOOD AND UltLG ADMlNlS’i‘RA’I’lON. THIS
`PRODUCT 18 NOT INTENDED TO lllAGNOSE, TREAT
`CURE, 0R PREVENT ANY DISEASE.
`
`
`
`
`CM ‘9ch and CM Plcx Cream are a softge.
`cream product respectively, combining fatty acids,
`
`prictary blend oi ceiyl myristate cetylmyrls ‘
`: other cotyl esters
`Benefits and research
`
`: Cetyl myristoleate and related fatty acids ha
`to improve joint licaltli,Lthrough their zintivi
`l'ccts. A clinical study indicated that subjects
`‘
`
`pmve‘ments in knee. ficxinn compared to placeb
`
`, study indicated the cream is effective for'
`range of motion improving ability to climb is
`
`a chair. and walk, and improving balance, strongt
`durnnco.‘
`
`‘ SUGGESTED USE
`Sofigels' Take one or two softgeis three tim
`. meals Cream: Apply generously onto clean 5km
`massage until the cream disappears. Repeat 3
`
`‘ daily as necessary. For maximum results co
`
`products.
`Contents
`
`
`(‘M Plex contains a proprietary blend of celyl m
`Lyl myriutuleute and mher ontyl ostp a, For (into
`information, please see wwwumcitynot;
`
`3 Safety and Warnings
`, CM Plcx Soltgel‘: and Cream are well accepted
`
`
`tromtcstinnl L
`mfort may be experienced with
`Soitgels as with any dietary supplement.
`HOW SUPPLIED
`UM Flex 19 available in both cream 11nd soft gel
`_
`REFERENCES
`-
`Hesslink, ll cl 0! @002), Journal ofR/u'umaiology
`1712.
`Kranmor. W] at al (2004). Jnurvzal of Rheum;
`767-7774.;
`
`3328/UCVCLYD
`
`BuphenyI—Cont.
`DOSAGE AND ADMINISTRATION
`For oral use only.
`The use of BUPHENYL Tablets is indicated for children
`weighing more that 20 kg and for adults. The usual total
`daily dose of BL'I’HENYL Tablots and Powder for patients
`with urea cycle disorders is 450 »- (500 mg/Kg/da in patients
`weighing loss than 2:) Kg, 11: 9.9 — 13.0 gong/tiny in larger
`patients. The tablets and powder are to be taken in equally
`dmded amounts with each meal or feeding (1.13., three to Six
`times per day}.
`BUPHENYL Powder is indicated for oral use lvru mouth.
`gourmetnmy, or nasagastric tube) only The powder is m be
`mzxed with food (solid or liquid). Sodium plicnylliutyrnlc
`is very soluble in water (5 grams per 10 mL) When
`BUPHENYL Powder is added to a liquid, only sodium phe‘
`nylbutyrate will dissolve, the excipients will not. The effect
`of food on sodium phenylhntyrote has not been detcrminerl.
`Each level teaspoon (enclosed) dispenses 3.2 grams of pow
`der and (1.0 grams of sodium 'phenylbutyratc. Each level to,
`blespoon (enclosed) dispenses 9.1 grams of powder and
`8.6 grams of sodium phenylbotymte,
`Shake lightly before use.
`The safety or eflimcy ofdoscs in excess of 20 grams (40 Till)-
`lots) per day has not been established.
`NUTRITIONAL MANAGEMENT
`To promote growth and development, plasma lcvcls of any
`mania, urginine, branchedchain amino acids, and serum
`protein should be maintained within normal limits while
`plasma glutam'me is maintained at
`levels loss that
`1,000 umol/L. Minimum daily protein intake for a patient of
`a particular age should be taken from, for example, 'Recom-
`mended Dietary Allowances". 10th ed, Food and Nutrition
`Board, National Academy of Sciences, 1989. The allocation
`of dietary nitrogen into natural protein and essential amino
`aczds IS a function of age residual urea cyclc enzyme octiv»
`sly, and thy. done 11.sodium phenylhutyranz.
`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 i1z~
`creased to 1.9 g/kg/day during this period. Protein tolerance
`will decwase as the growth rate decreases, requiring :1 rev
`duction in dietary nitrogen intake. From '4 months to 1 year
`of age, it is recommended that the mom mcoivp or. least
`14dequ but 1.7g’kg/doy is advisable. From 1 to 3 years
`of age, the pmtein intake should not be less than 1.2 g/kg/
`day; 1.4 g/kg/day is advisable during this period. For neona-
`tal-onset patients with carbnmylphospliote synthetase defi-
`ciency or nmithine tronscarbamylase deficiency who are at
`least 6 months of age, it is recommended that the daily pro-
`tein intake be equally divided between natural pmbein and
`supplemental essential amino acids.
`Patients with argininosuccinic acid syntlietnse deficiency
`and those with latounsot disease (partial deficiencies, in
`cluding females hetemzygous for nrnithinu trausnarliamy'
`lose), initially may receive a diet containing the ugc-dctcr-
`mined minimal daily natural pmlnin allnwnnr’r‘ Th0 protr‘in
`intake may be increased as tolerated and determined by
`plasma glutamine and other amino acid levels. However,
`many patients with partial dofldcncxcs avoid dietary
`prowin.
`Citrullinc supplementation is required and recommended
`for patients diugnoood with neonatal—onset deficiency of car—
`
`hamvlphospline synthetasc or omithine timm a;nylase;
`citrulline daily intake is recommended at O 1] g/kg/day or
`3.8 g/mz/day
`The freabase form of arginino may be used instead of cil—
`iulllne111 patients Willi mildcr forms ofcarbomylphosphote
`synthetase and on'nthine tronscarbamylase deficiency
`(daily inlakr‘, is recommended at 0.17 g/kg/day or 3.8 g/1112I
`day).
`Arginine supplementation is needed for patients diagnosed
`with deficiency ofaigininosuccinic acid syiithutusu, oiginino
`(free base) daily intakeis recommended at 04— 0.1‘ g/kO/day
`0r 3n — 154 g/mZ/day
`ll caloric supplementation is indicated, a proloinli’ce prod»
`11131 is rocmnumnduil. Caloric intake should he hosed upon
`the Recommended Dietary Allowances“, 10th ed, Food and
`Nulritiuu Board, National Refillal'Cl‘l Council, Notional
`Academy ol‘Scicncc... 1989.
`HOW SUPPLIED
`BUPHENYL Tablets are available in 250 cc bottlcs, which
`contain 250 sodium pliuiiylliuiyralr tablets (NDC 6259?.-
`4964131. The bottles are equipped with child~rcsismnt caps.
`Each tablet is oil-white. oval, and embossed with “UCY
`500”. Each tablet commas 500 mg of sodium phenylbu»
`tymlxe. STORE AT ROOM TEMPERATURE TWO-30°C (58°F—
`86“Fl. AFTER OPENING, KEEP BOTTLE TlGHTLV CLOSED.
`BllPlil‘lN‘fl. Powder is available in 500 cc bottles. which
`hold 266 grams of powder. containing 250 grams of sodium
`phenylhutyratc (NDC 62592-188645. The bottles are
`equipped with childresismnt caps, Measurers are provided.
`Each level teaspoon {enclosed} dispenses 3.2 grams, ol‘pow»
`dcr and (3.0 grams oi‘sodium phenylbutyratc. Each level to.
`oleapoon (enclosed) dispenses 9.1 grams of powder and
`8.6 gram»; of sodium phcnyllnityratc. STORE AT 15"C—30"C
`(59“F—86‘F}. AFTER OPENING, KEEP BOTTLE TiGHTLY
`CLOSED.
`US Patent number 4,457.94‘3.
`
`
`
`
`‘
`
`CM PLEX’“ AND cm PLEX'“ CREAM
`[CM piéksl
`Proprietary {any acid blond to help alleviate
`of osteo arthritis
`
`DESCRIPTION
`
`
`
`
`
`
`
`
`
`”WHERE STATEMENTS l’lAVE NOT BEEN EVAL
`BY THE FOOD AND DRUG ADMINISTRATIQ
`PRODUCT is NOT INTENDED TO DIAGNOSE, ,
`CURE, OR PREVENT ANY DlSlEASE.
`
`
`
`VISUTEIN®
`[1713.11 re‘nl
`Clinically proven to support healthy eyes and Vision
`
`DESCRIPTION
`
`VlSlltein is Unicity‘s product providing key outrion.
`the eye.
`Benefits and research
`
`The carotenoids 11119111 and IEaXrlllLllll) play on 1mm
`
`1'1 Low concentrations ol iliosc phyton
`rolein eye lac-v
`
`mils in tho rriinn have linen associated with ng'l'
`.
`mncula degeneration (AMD), Studios have shown, th $
`plemnnmiinn with high lowly. of lutLin,
`..s pres
`
`VlSUtrin can icstore the lutcin concentrl‘Lion in the re
`enoids that are important :11 pros
`and supporting clear vi on, N-
`els haw: been
`own to reduce protection of the eye
`oxidoiivr‘, 3m «5. A 11:17am, clinical otully with VlSlJt _
`
`own tliutAMD patiorts experience clear improvemen ,
`crisi’uvily.
`rind recovery Eff)
`
`
` ' :ikt‘, two L
`
`Contents
`
`OTC
`
`CARDIOESSENTIALS®
`Caring for your heart
`DESCRIP‘I‘ION
`Cardiolfissentials is Unicity’s superior heart product.
`Benefits and research
`‘ CardioEssontials provides nutrients for the Imam lllu‘oClH,
`‘ and supports healthy heart function. The combination of
`licornzthine, L~tourinc, and Cocnzyme Q10 14151191511 shown
`to benefit congestive heart failure patients in a clinical
`study, In this study,
`loll ventricular si/y woo reduced in
`(ll-1F patients, giving them a better prognosis, ’i‘nocc ingrEv
`dimll»on: known to ho important. in providing adequate en'
`ergy for tho hour! muscle‘. (arciol‘lfisentials proVides adv
`quote amounts of lhws- ingredients. 1'5.100 mg of CleD
`Hawthorn extract io traditionally used in supporting the
`limri, function.
`SUGGESTED USE
`Takv m capsules daily with food.
`
`Page 3 of 3
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`LUPIN EX. 1018
`
`Page 3 of 3
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`LUPIN EX. 1018
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`