PDR®
`
`60
`
`EDlTiON
`
`2ooo
`
`PHYSICIANS’
`DESK
`l?EFEl?El\lCE®
`
`Senior Vice President, PDR Sales and Marketing: Dikran N, Barsamian
`Vice President, Product Management: William T. Hicks
`Vice President, Regulatory Affairs: Mukesh Mehta, RPh
`Vice President PDR Services: Brian Holland
`Senior Directors, Pharmaceutical Solutions Sales: Chantal Coroos,
`Anthony Sorce
`National Solutions Managers: Frank Karkowsky, Marion Reid, RPh
`Senior Solutions Managers: Debra Goldman, Elaine Musco.
`Warner Stuart. Suzanne E. Yarrow, RN
`'
`Solutions Managers: Eileen Bruno, Cory Coleman, Marjorie A. Jaxel,
`Kevin McGlynn, Lois Smith, Richard Zwickel
`Sales Coordinators: Arlene Phayre, Janet Wallendal
`_
`59“'°' Di"9°t°'v 3'3"“ 3"“ P'°d”°t Managemem‘ Va"3"'e Er Berger
`Associate Product Managers: Michael Casale, Andrea Colaveochio
`Senior Director, Publishing Sales and Marketing: ivlichael Bennett
`Director, Trade Sales: Bill Gaff-ney
`Associate Director, Marketing: Jennifer M. Fronzaglia
`Senior Marketing Manager: Kim Marich
`Direct Mail Manager: Lorraine M. Loening
`Manager, Marketing Analysis: Dina A. Maeder
`Promotion Manager: Linda Levine
`Director of Operations: Robert Klein
`Director, PDR Operations: Jeffrey D. Schaefer
`Director of Finance: Mark S. Ritchin
`
`Director, Client Services: Stephanie Struble
`Director, Clinical Content: Thomas Fleming, PharmD
`Director, Editorial Services: Bette LaGow
`.
`.
`.
`’
`,
`h
`,
`:
`'
`2;‘: ISn§);’Tk?t'§;:a:|:::'?£:;sTam;:h‘;E;hDeLuCa P armo MBA’
`P
`t Ed-t
`, N -I Ch >‘/‘
`H
`- H
`»
`5:55;: Edi;o(::sL'Orie,:AUrr:)?dnOw'
`ams
`emmg
`senior Pmducflm Editor: Gwymed L Kefiy
`_
`_
`Manage” P"?d"°t'°" P“"°"'35'“55 Thomas Westbmgh
`PDR P"°d'-'°“°“ Ma"ag°"‘ Stew“ Mam’
`P"°d"°t§°" Ma"a_§°'= Gay‘? C_;"aiZZa,"°
`Production Specialist: Christina Klmger
`Senior Production coordinators: Gianna Caraolonna, Yasmin Hernandez
`pmducfion coordgnamn Nick W_ Cram
`senior Index Editms; Noe; Deioughery’ Shannon Remy
`Format Editor: Michelle G. Aurrant
`Traffic Assistant; Kim cgndon
`Production Design Supervisor: Adeline Rich
`Senior Electronic Publishing Designer: Livio Udina
`Electronic Publishing Designers: Bryan C. Dix, Carrie Faeth,
`Monika Popowitz
`Production Associate: Joan K. Akeriind
`Digital imaging Manager: Christopher l-lusted
`Digital imaging Coordinator: Michael Labruyere
`
`Copyrighl © 2006 and published by Thomson PDR at Monh/ale, NJ 07645-1742. All rights reserved. None of the content of this publication
`T}-|©|\(|5c)|\]
`W may be reproduced, stored in a retrieval system, resold. redistributed, or transmitted in any form or by any means (electronic. mechanical,
`E“
`photocopying, recording, or otherwise) without the prior written permission of the publisher. Physicians‘ Desk Fieferencea, PDR5, Pocket
`PDR”. PDR Family Gusde lo Prescription Drugs? PDR Family Guide lo Women's Health and Prescription Drugs? and PDR Family Guide to
`PDR
`Nutrition and Health“; are regislered lrademarks used herein under license. PDR“ for Ophthalmic l"/ledlclnes, PDR?‘ for Nonprescription Drugs and Dietary Supplemenls. PDR“
`Companion Guide. PDRP Pharmacopoeia. PDR“lor Herbal Medicines, PDFP for Nutritional Supplements, PDFP Medical Dictionary, PDFP Nurse‘-5 Drug Handbook. PDR“
`Nurses Dictionary, PDRP Family Guide Encyclopedia of Medical Care. PDW Family Guide to Natural Medicines and Healing Therapies. PDR“ Family Guide to Common
`
`Ailments, PDR‘ Family Guide to 0ver—the-Counter Drugs, PDi—'i’:“‘ Family Guide to Nutritional Supplements, and PDRP Electronic Library are lradernarks used herein underlicense.
`
`officers of Thomson Healthcare, lnc.: President and Chief Executive Officer: Kevin King; Chief Financial Officer: Paui Hilger; Chief Medical Offiner: Rich Klasco, MD, FACEP;
`Execuiive Vice President, Medsrat: Carol Diephuis: Executive Vice President, M/‘cromedex: Jeff Reihl: Senior Vice President. Markefing: Timothy Murray; Senior Vice President,
`Technology: Michael Karainanz Vice President. Finance: Joseph Scarione: Vice President, Human Resources: Pamela M. Bilash
`
`EZX 1020
`
`1 of 3
`
`

`

`,
`-
`
`PRODUCT ENFORMATION
`
`BUP!-!ENYL®
`lbzz 7221: oil
`{sodium phenyibutyratel
`Tablets
`BUPHEN‘fL®
`(Sodium phenylhufyrate}
`Powder
`Rx only
`DESCRIPTEON
`Bupiien;-‘l® {sodium phc
`istratior. and Buplicnylv‘
`
`contain sodium phcnylbuzyrate. Sodium phenyl utyz'ate is
`an ofi"-it he crystalline substance winch is soluble in Walter
`and has a strong salty taste. Sodium pbenylhu ,,rate also is
`freely soluble in methanol and practicali
`insoluble in ace-
`ton* and dietlzyl ether. It is known che ical
`as 4-phenyl
`butyric acid, sodium salt with 9. molecular
`of 186 and
`the molecular formula C1-Uii“O.3i\'a.
`Chemical Structure:
`
` cH,oH,cH3cooria
`Each tablet of BUPHENYL contains .300 mg of sodium phe-
`iiyllmryrate and the inactive ingredients microcrystalline
`cellulose, magnesium stearate, and colloidal s’ icon dioxide.
`Each gram of BUPHENYL Powder contains 0.94 grams of
`sodium phenylbutyrate and the inactive ingredients cal-
`ciuni stearate, and colloidal silicon dioxide.
`CLINICAL PHARMACOLOGY
`Sodium phenylhutyrate is 3 pro-drug and is rapidly metab-
`olized to phenylacetate. Phenylaoetate is a metabolically-
`ac 've compound that conjugates with glutamine via
`acctylation to form phenylacetylglul:-amine. Pl1enylaoetyl-
`glutamine then is excreted by the kidneys. On a molai
`sis, it is comparable :0 urea (each containing two moles
`;
`nitrogen). Therefore, phenylacct-ylglutamine provides an al-
`ternate vehicle for waste nitrogen excretion.
`PHARMACOKINETICS
`General:
`Pharmacokinetic studies have not been CDll(li.lL‘l.BCl in the
`primary patient population ineonates, infants, and chil-
`dren}, but pharmocokinetic data were obtained from normal
`adult suhj
`Absorptio
`Peak plasma levels of phenylbutyrate occur within 1 hour
`after a single dose of5 grams of soilium phenylbutyr-ate tab-
`let with a C,,,,,,. of 218 pg/mL under fasting conditions; peak
`plasma levels of phcnylhutyrate occur within 1 hour after a
`single dose of 5 grams of sodium phenylbutyrato powder
`with a Cm“ of 195 pg/ml. under Fasting conditions. The ef-
`fect of food on phcn_\'lbutyrato‘s absorption is unknown.
`Disposition:
`The overall dzsposition of sodium phenylliulyrate and its
`metabolites has not been characterized fully. However, the
`drug is known to bc metabolized to plienyl zetate and sub-
`sequently to plat-.11ylacetylglutamine. Following oml admin-
`istration of 5 grams (tablets), measurable plasma levels of
`plie y‘-luityraie and phenylacetate were detected 15 and 30
`minutes after dosing.
`respe
`ely, and pl:enylacetyl-
`glutamine was detected shortly Lhcrcolter. The pharmaco-
`kinetic parameters for plienylbutyrate for Cm, {pg/:nL).
`’l‘,,m (hours)-, and elimination half-life (hours) were 218,
`1.35. and 0.77, respectnely, and for phenylacetate were
`48.5, -3.74, and 1.15, rcepoctively.
`Following oral adiiiiriisiraiion of 5 grams of the powder,
`measurable plasma levels of phenylbutyi-ate and phenylao
`state were (letcrted 15 and 30 minutes after dosing, respec-
`tively, and phcnylacetyglutamine was Llelerted shortly
`tliei-caller The pharmacokinetic parameter. for phenylbu-
`tyrato for Cm, lug/mL\,r, Tm” lhours). and elimination half-
`life (hours) were 1.95, 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 phenylbutyrale
`are the liver and kidney,
`Excretion:
`A majority of‘the administered compound (approximately 80
`— 1.00%) was excreted by the kidneys within 24 hour‘: as the
`conjugation pmduct, phenylacetylglutamine. For each gram
`of sodium phonylbutyrate administered. it is estimated that
`between 0.12 — 0.15 grams of phenylacetylglutaminc nitrrr
`gen are produced.
`Pharmacodynamics:
`In patients with urea cycle disoirlers, BUPHENYL de-
`creases 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 ’
`kinetics of phcnylbutyrate and phenylac are but not for
`plienylacetylglutamine. The pharmacokinctic parameters.
`{AUC and E‘.,,,,,,,}. for both plasma plienylloutyraze and phe-
`nylaceiate were about 30 to 50 percent greater in feiiiales
`than in males.
`Hepatic insufficiency:
`ln patients who did not have urea cycle disorders but had
`impaired hepatic function, the metabolism and excretion of
`
`‘
`
`sodium phenylbutyrate wt-*r(>. not afiecied, However. this in-
`formation was obtained from unvalidatcd. uncontrolled Case
`studies.
`INDICATIONS AND USAGE
`BUPHENY1 is indicated as adjumrtive llierupy in the
`clironlc management of patie
`s with urea c cle disorders
`involving deficiencies of CEil‘lJaI\1_Ylpl1US[.}llPl.. syntlietase
`(CPS). ornifhine transcarbamylase (O’:‘(J). or arginincsuo
`cmic acid eynthetase {AS}. It is imlirnred in all patients with
`ueon.ar.al-onset deficiency tcoinplotc cnzymatic deficiency,
`presenting VV him the 51st 28 ,i;iys of life). It is also indi-
`cated in patients with late-onset disease (partial enzyinzztic
`deficiency, presenting after the first month of life) who have
`3 l1iSt():”_V of hype-rammoncmic encephalopathy, lt is impor-
`tant that the diagr
`he made early and treatment initi-
`ated immediatelv
`improve survival. Any epis lie of acute
`l1}"}’)G1‘al1il1l0II!-31l‘I1H should be treated as 9. life threatening
`emergency.
`l3UPHE?\'Yl. must. be combined with diets ' protein restric-
`tion and, in some cases, essential amino acid supplementa-
`tion. (See Nutritional Supplcnicntation subsection of the
`DOSAGE AND ADMINISTRATION section.)
`Previou
`neonatal-onset disease was almost universally
`. the firs]. year of‘ life. even when treated with
`sis and essential amino acids or their nitro-
`.
`gen-free analogs. However, with hemodialysis, use of alter-
`native waste nitrogen excretion patltways (sodium plmny -
`, butyrate, sodium beuzoate, and sodium phenylacetate).
`dietary protein restriction, and, in some (
`., essential
`amino acid supplementatioii, the survival rate in newborns
`diagnosed after birth but within the first month of life is
`almost 80%. Most deaths have occurred tlurixfg an episode of
`acutc bypcrammoriemic encephalopathy. Patients with neo-
`natal-nnset disease have a high inczdonce of mental retar-
`dation. Those who had IQ Le:<l..~: mlministered had an inci-
`dence
`of‘ mental
`retardation as
`follows: ornithiue
`transcarbamylase cleiicieucy, 700% (14/14 pat nts tested >;
`‘argininnsuccinic acid synthetase deficiency, 88% .15/17 _z)2~i«
`tients tested); and car-lmmyl phosphate vsthetase defi
`' ciency, 57% (4/7 patients tested). Retardation was severe in
`the majorily urthe retarded patients.
`In patients diagnosed during gestation and tre:—il.<-.:l prior to
`any episode of hyperammonemic encephalopathy, survival
`is 100%, but even in these patients, uiost subsequently dem-
`onstrate cognitive impairment or other neurologic deficits.
`In late-onset deficiency patieiits, inuliiding females hetero-
`zygous for ornithino transcarbamylase deficiency. who re-
`cover from hyperainmonemic encephalopathy and are then
`treated chronically with sodium phenylbutyrate and rlielary
`protein restriction, the survival rate is 98%. The two tleaths
`in this group of patients occurred during episodes of hyper-
`ammcnemic enccplialopathy. However, compliance w:th the
`therapeutic regimen has not been adequately docuinentetl
`to allow evaluation of the potential for BUPHENYL and di-
`etary prote:n restriction to prevent mental (ll-¢l.£’.l‘lU1"3tlDn
`and 1'ecu."1‘ence of hyperammonernic encephalopathy if care-
`fixlly 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 preexisting
`neurolngic impairment is not likely to occur with treatment
`and nourologic deterioration may continue in some patients.
`liver) on therapy, acute hyperammonemic encephalopathy
`recurred in the majority of patients for vchom the drug is
`indicated.
`BUPHENYL may be required life-long unless orthotopic
`liver transplantation is clected.
`(See CLINICAL PHARMACOLOGY, Pharmacodynnmics
`subsection for the biochemical efiects of BUPHENYL).
`CONTRAINDICATIONS
`BUPHENYL should not be used to manage acute hyperam-
`monomia, which is a medical emergency.
`WARNINGS
`Each BUPHl<‘.1\.'YL Tablet contains 62 mg of sodium (9.2%
`W/w) ‘.COITCSD0l.'ld'll'lg to 124 mg ol‘ sodium per gram of so-
`dium phenylbutyrate [l2.4% v.‘/wl) and BUPHENYL Pow-
`der contains 11.7 grams of sodium per 100 grams of powder,
`mrresponding to 125 mg of sodium per gram of sodium plie-
`nylbutyrate (12.4% W/w). BUPHENYL should be used with
`great care, if at all. in patients with congestive heart failure
`or severe renal ll]Sl1fi_lClH!
`and in clinical states in which
`there is sodium retention with edema
`Because BUPHENYL is metabolized in the liver and kidney,
`and phenylacetylglutumine is primarily excreted by the kid-
`ney. use caution when administering the drug to patients
`with hepatic or renal insufliciency or lnliurn errors of beta
`oxidation. Probenecid is known to inhibit the renal trans-
`port of many organic compounds, including hippuric acid,
`and may affect renal excretion of the conjugated product of
`BUPHENYL as well as its rnetabolite.
`Use ofcorticosteroids may cause the breakdown of body pro-
`tein and increase plasma zrnmonia 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 hyperammoncmia be-
`ing induced by hnioperidol and valproate.
`Neurotoxicity of phenylacetate in animals:
`When given subcutaneously to rat pups, 190-474 mg/kg
`plieriylacerate caused decreased proliferation and increased
`loss of neurons, and it reduced CNS myelin. Cerebral syn-
`
`UCYC LYD/3327
`
`apse maturation was re..arde-rl, and the number of function-
`ing nerve terminals in the ccrebrum was recluced, which re-
`sultrai in impaired l>IԤIl'1 growth. P: natal exposure of rat
`pups to phenylac ate produced lesions in layer 5 in” the cor.
`tical pyramidal cells; rlcritirit
`spines were longer and thin-
`ner than normal and reduceo in number.
`lnformzztion for the Patients:
`The full text of the separate insert of information for pe-
`tlents is rcprintecl at the end of the labeling.
`Laboratory Tests:
`V Plasviia levels of ammonia, e.i'g’ir.inc, ‘omnched~chain amine;
`acids, and serum proteins should be maintained Within nor-
`mal limits, and plasma gluearninc should be maintainer} of
`levels less than 1,000 iiiucil/L Serum drug levels of phony -
`butyrate and its xrietaholiteo, phenylacctate a i
`,
`ylacetylglutaniine, Sllflulll be monitored periodically:
`Carcinogenesis, Mutagenesis, impairment of Fertility:
`Carcinogeui
`’ly, vmitagenicity. and fertility studies of so-
`dium phenylbutyrotc have not been comlui-ted
`Pregnancy:
`Pregnancy Category C. Animal r.-eproduccion studies have
`not lienn conducted with BUPHENYL. lt is also not knmm
`' whczher BUPHENYL can cu se fetal harm when ad-
`rrinisterecl to a pregnant woznan or can alfect reproduction
`capacity.
`BUPHENYL should be given to a pregnant Woman only if
`' clearly needed.
`Nursing Mothers:
`It is not known wlieiber this drug is excreted in human
`milk, Because many drugs are excreted in human milk. cau-
`tion should be exercised when BUPHENYL is administered
`to a nursing woman.
`Pediatric Use:
`, The use of tablets for neonates, infants and children under
`the weight of 20 kg is not recommended. (See DOSAGE
`‘
`imp ADMI.\'lS'I'RATIONt
`ADVERSE REACTIONS
`The assessment of clinical adverse events came from 208
`patients t.real.~=¢l with sodium phenylbutyrate. Adverse
`events (both clinical and laboratory) werr- not collected sys-
`leinutically in these patients, but were obtained from pa-
`tient visit reports by the G5 co-investigators. Causality of
`adverse elfects is sometimes difficult to determine in this
`patient population because they may result from either the
`underlying disease. the patients restricted diet, 1 mur-
`rent. illness. or BUFHENYL Furthermore, the rates may be
`K under-estimated because they were reported prliuarily by
`parent or g-uardiau and not the patient.
`Clinical Adverse Events
`In female patients. the most common clinical adverse event
`reported was amenorrln-ea/menstrual dysfunction Ifirrcgnlar
`menstrual cycles). which occurred in 23% oi" the menstrual-
`ing 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 11-=p(n1'ECl in 3% of patients.
`Other adverse events reported in 2% or fewer patients were:
`GaSl.!‘Dl.'Jl.BStlna]‘
`abdominal pain, gastritis, nausea and
`vomiting: constipation, rectal bleeding, peptic ulcer disease,
`and pancreatitis each occurred in one patient.
`Hematologic.
`aplaslic snernia and ecehymoses cach
`occurred in one patient.
`Cardiovascular".
`arrhythmia and edema each occurred in
`one patient.
`renal tubular acidosis
`'
`depression
`
`Lfiscellaneous: headache. syncope, and weight gain
`Neurotoxicity was reported 1!) cancer patients receiving in-
`ti-avenous phenylacetate, 250-300 mg/kg/day for 14 days,
`repeated at 4-Week intervals. Manifestatioiis were predom-
`inately somnolence, fatigue, and lightheadedness; with less
`frequent headache, dysgeusia, hypoacusis, i_l.lb'OI'lPl'1l'.Rl1l0D,
`impaired uieinory, and exacerbation "
`pro-existing neu-
`ropathy. These adverse events were
`inly mild in severity.
`The acute oiisc-J. and reversibility when the phenylacetate
`infusion was discontinued suggest a drug eflect.
`Laboratory Adverse Events
`In patients with urea cycle disorders, the frequency of lab-
`oratory adverse events by body Sysl/8111 were:
`Metabolic:
`acidosis (14%), alkalosis and hyperchloreinia
`(each I ,c), hypophospliaiemia (6%), hyperuricomia and hy-
`perpbosphatemia (each 2%), and hypernatreinia and
`hypokalcmia (each 1%}.
`_N tritiona
`hypoalbuminemia (11%) and decreased total
`
`increased alkaline phosphatase (6%), increased
`.
`liver transaminascs (492), and hyperbilirubiuemia (1%).
`Heinatologcr
`anemia ’ %), leukopenia and leukocytosi
`(each 4%,), thronibocytopenia (3%), and thrombocytosis 4
`The clinician is advised to routinely perfurin urinalysis,
`blood clieiiiiszry profiles, and hematologic tcsts.
`OVERDOSAGE
`
`No adverse experiences have been reported involving over-
`doses of sodium phenyllmiyraie in patients with urea cycle
`disorders.
`in 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 2 00 6 PDR5' supplements and future editions for revisions
`
`'
`
`1
`
`2 of 3
`
`

`

`3328/UCVCLYD
`
`~'t96{)3~08e\
`
`Unicity International
`THE MAKE LIFE BETTER COMPANY
`1201 NORTH 800 EAST
`OREM. UT 84097
`
`Direct Inquiries to:
`WOW) 226 2600
`www.makelifehetter.com
`scisnce@unicity net
`Products of Unicity International. The Make Life Better
`Company are distributed through independent distributors.
`
`PHYSICIANS‘ DESK
`.
`Contenrs
`_ Cardiolissentials features 1‘;
`vr0P1"‘eit
`thine, L-taurine, and Hawthorn fiiltflats
`1
`Coenzyme Q10.
`For
`detailed
`dietary
`information
`wwvw.mal:elil‘cbetl:er com
`SAFlL'l‘Y AND WARNINGS
`
`Cnrdiolissentials is well accepted. some g
`discomfort may he experienced as W-
`suppiemcm.
`i HOW SUPPLIED
`Available in bottles 01180 tablets.‘
`
`“’l'liEa‘E S'l‘A'l'EMElN'l‘S llAVE NOT
`BY THE FOOD AND DRUG ADMJNLST '
`PRODUCT IS NOT INTENDED TO DIAC.
`‘ CURE, OR PREVENT ANY DISEASE.
`—‘ REFERENCES
`,r>jeelilmy_ F pt
`1092,1100.
`
`(11 mo-2;, American He
`~
`
`I Manufactured for: UL-yclycl Pharma, Inzn, Scottsdale AZ.
`35258
`BuphenyI——Cont.
`By‘ Pllil."!’l)8(’.Pllll!‘.~‘» lnmrnational. Inc Hunt Valley, MD
`21031
`DOSAGE AND ADMINISTRATION
`NDC 62592»496v03 bottle of 500 mg tablets.
`For oral use only.
`NDC 62592-l88~64 bottle containing 250g of sodium phev
`The use of BUPI-IEVYL Tablets is indicated for children ,
`' nylbutyrate powder.
`iveighiéig more that 20 kg and for adults. The usual total
`Prescribing lriformation as ofAo,—;uet 2003
`daily dose of BTJYHENYL Tablots and Powder for patients
`with urea cycle disordels is 450 »- G00 mg/Kg/da in patients
`weighing less than 20 Kg, or 9.9 — 13.0 g/mg/dny m larger
`patients. The tablets and powder are to be taken in equally
`divided amounts with each meal or feeding il.e., three to six .
`l.lI})f’.S per day}.
`BUPHENYL Powder is indicated for oral use (‘no mouth.
`gasrrnstnmy, or namggastric tube) only The powder is to be
`rmxed 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 pheuylbntyrate has not been deterrninerl.
`Each level teaspoon (enclosed) dispenses 3.2 grams of pow-
`der and (LO grams of sodiumphenylbutyrate. Each level to»
`blespoon (enclosed) dispenses 9.l grams of powder and
`8.6 grams of sodium phenylbotymte.
`Shake lightly before use.
`The safety or efliracy ofdoscs in excess of 20 grains (40 Tali-
`lcts) per clay has not been established.
`NUTRITIONAL MANAGEMENT
`To promote growth and development, plasma levels of am-
`monia, orginine, l3mnche(l»chain amino acids, and serum.
`protein should be maintained within normal limits while
`plasma glutamlne 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 Diemy Allowances". 10th ed., Food and Nutrition
`Board, Nut1onalAoade.my ofSc1ence:s,
`i989. The allocation
`of dietary nitrogen into natural protein and esseritial amino
`aczds IS a function of age, residual urca~cycl0 enzyme octiv»
`sly, Ami the «intro nfsndinm plienylhutyraha.
`At the rsoommended dose of sodium phenylbutyrate, it is
`suggested that infants with rieonatal~ 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 in~
`creased to 1.9 g/kg/day during this period. Protein tolerance
`will decnease as the growth rate decreases, requiring :1 rev
`_
`,
`,
`,
`,
`,
`duction in dietary nitrogen intake. From 4 months to 1 your
`of age, it is recommended that the mom r+>.(wiw= or. least
`l.<lg/kg/day, but l.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; L4 g/kg/day is advisable during this period. For ‘neona-
`tnl-onslot patients with 03 rlaamylphosplinte synthetzise defi-
`ciency or nrnithine transcarbamylase 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 syntlietase deficiency
`and those with latevunset disease (partial deficiencies, in
`cluding fentales hetemqygous for ornitlilma trausr:arl»amy~
`lose), initially may receive a diet containing the agc-dc:cr-
`mined iniuiznnl daily mituml prnu-:in allnwonrc 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
`prowin.
`Citrullinc supplementation is required and recommended
`for patients diagnosed with neonntahonsct deficiency of car~
`ham ylphosplmte synthetasc or ornithine transc
`amylase;
`citrulline daily intake is recommended at 0.17 g/kg/day or
`3.8 g/m2/day,
`,
`The frewbaso form of arginine may be used instead of cit-
`rulllne in patients with milder forms of carbarnylphosphats
`synthetase and orinthine Lronscorbomylase deficiency
`(daily inlzike is rccommcridcd at 0.17 glkglklay or 3.8 g/mg]
`day).
`Arglnine supplementation is needed for patients diagnosed
`with deficiency’ of argil1inosuct;inic acid synthuuisu, nrgininc
`(free base) daily intake is recommended at 0.4 - 0.7 g/Q/(lay
`or 3.2 _ 15,4 g/m2/day
`lfcaloric supplementation is indicated, a prctcinlrce prod»
`ucl is roc\)ir1;iieizde(i. Caloric ll1EZil(E slioiulri he hosed upon
`the Recommended Dietary Allowances“, lOth ed., Food and
`Nulritiun Board, Nmional Resparcli Council, Nutiomél
`Academy ofscicencc... 1989.
`HOW SUPPLIED
`BUPHENYL Tablets are available in 250 cc hottlos, which
`contain 250 sodium })llEl}_)'llluliyl'al.P l.alilel..~z (NDC 62592-
`49603). The bottles are equipped with childrcsismnt caps.
`Each tablbi is utl'-white. oval, and F1’1)l‘.4')SSP.(l with “UCY
`500”. Each tablet CO1'l5l1ll):"» 500 mg of sodium phenylbw
`tymla. STORE AT ROOM TEMPERATURE ‘l5‘(‘r30°C l‘.i8°F~
`86°F}. AFTER OPENING, KEEP BOTTLE TlGHTLV CLOSED.
`BllP‘.FllCN‘r'l. Powder is availalile in 500 cc bottles, which
`hold 266 grams of powder. containing 250 grams of sodium
`phenylhutyratca (NDC 62592-188645. The bottles are
`equipped with ch1'ld«resist:snt caps. Measurers are provided,
`Each level teaspoon (enclosed; dispenses 3.2 grams ofpow»
`dcr and (3.0 yams ofsodiurn phe-nylliutyrate. Each level to-
`oleapoon (enclosed) dispenses 9.1 grams of powder and
`8.6 grams of sodium plicnylbutyratc. STORE AT 15"C—30"C
`l59“F—86‘F}.
`IXFTER OPENING. KEEP BOTTLE TIGHTLV
`CLOSED.
`US Pazent rmrnbcr 4,4:37.$M‘Z.
`
`can FLEX” AND cm PLEXWVCREAM
`[CM piéksl
`, Proprietary fatty acid blend to help alley/late‘
`BIDSLIFE 2®
`of osteo arthritis‘
`V
`:
`[bi-6.5‘ lif 2']
`Advanced Fiber and Nutrient Drink
`.,
`DESCRIPTION
`,
`2.
`CM Plex and CM Plex Cream are a softge.
`DESCRIPTION
`cream product respectively, combining fatty
`BiosLiie 2 is :1 nutrient-rich fiber drink mix that contains
`prictary blend oi’ cetyl myristate, Cet_yl.mytis ‘
`I other cetyl esters.
`,
`patented complex of soluble and insoluble fibers, vitamins,
`Benefits and research
`'
`and minerals.
`: Cetyl myristolentc and related fatty acids ha
`BENEFITS AND RESEARCH
`to improve joint lroaltli, through Llmir zmti~i
`BiosLifs 2 ——a good source ofdietnry fiberm when included
`‘
`fccts. A clinical study indicated that subjects
`as part ofa healthy diet, may help lower your blood choles»
`pmvements in knee ficxinn compared to pluoeb
`terol levels and reduce your risk of heart -disease. Eight
`, study indicated the crc.-urn is effective for”
`weeks of BiosLife 2 showed a significant reduction in LDL~c
`range of motion, improving ability to climb is
`compared to placebo. The mechanism of Bmshlfe 2 in cho~
`a chair. and walk, and improving balance, rsfcrs-ngt
`lesteml reduction is though bile-acid sequestration.
`durnnce.‘
`. SUGGESTED USE
`‘ SIJGGESTED USE
`, First users: dissolve the contents of one packet into 8 to H}
`Sofigels Take one or two softgeis three tim
`'
`fl. oz. ofliquid (water or juice), stir vigorously and drink 1m‘
`‘ meals Cream: Apply generously onto clean skin
`: mediately 5 to 10 minutes before the main nieals. After fiber
`massage until the cream disappears. Repeat 3
`adjustment use as directed above up to three times daily i
`daily as necessary. For maximum results co
`before every meal.
`\
`CONTENTS
`‘ products.
`‘ Contents
`One packet oflliosliafe 2 cunLain5 4.5 grain fiber, mmprlsing
`CM‘ Plex contains a proprietary blend of cetyl in
`of 4 grams of soluble fibor. Added to this fiber mix are o
`‘
`~a. For dsta
`tyl riiyrlsuilezlte, and other rrmyl cstn
`3
`mal daily levels and bxoavailable forms of several vitamins,
`information, please see www.unicity.not;
`i
`and chromium (as Chromelvloter’-“). BiosLife 2 is available
`3 Safety and Warnings
`in Natural, Original, and Tropical Fruit flavors. For detailed
`, GM Plex Sollgels and Cream are well accepted
`dietary infunnation, please see www.unicity.net
`—
`trointcstinal L
`rnfort may be experienced with
`SAFETY AND WARNIN GS
`Soltgels as with any dietary supplement.
`HOW SUPPLIED
`Bioshife 2 is well accepted. Some users report mild gastro-
`intestinal disconifort after first use. This is a normal effect
`Ulvl Flex 18 available in both creaxn mid soft gel
`of increased fiber intake and normally disappears within 30
`days Taking this product without adequate liquid can re-
`‘ REFERENCES
`sult in complications. It" you are a diabetic, consult a physi-
`Hesslink, R at al 42002}, Journal ofR/wumaiology
`1712.
`cian for proper use of this product, as the cnromiuin may
`reduce the need for incclicatron.
`llrnnmor. ‘NJ at al (12004). Journal of Rh\?LlmQ
`7679774.‘
`HOW SUPPLIED
`Conveniently packaged in singlc—serving packets or bulk
`canisters.
`REFERENCES
`l16S—
`Syirochor DI. and Pearce GL (2002). Metabolism 51:
`70.
`,
`Vcrdegem, PJE; Freed, S and Jolie D (2005), American Di-
`abetes Assocation 65'“ Scientific Sessions, San Diego.
`US Patent 4,883,788 and US Patent 4,824,672.
`“l‘llESB STATEMENTS HAVE NOT BEEN EVAl.l7A’!‘ED
`BY THE FOOD AND l)ll.LG Al)MlNlS’i‘RA'I‘lON. Tl-HS
`l’R()DUC'l‘ IS NOT lN’l‘l*}NDFl) 'l‘() IHAGNOSE, ’l‘P.EA'1‘
`CURE, OR l’liE\'EN'I' ANY DISEASE.
`
`*’l‘Hl7.‘.RE STA'l‘EMEN'l‘S HAVE NOT BEEN EVAL
`BY THE FOOD AND DRUG ADMlNlS'l"RATlQ
`PRODUC1‘ IS NOT INTENDED TO DIAGNOSEV ,
`CURE, OR PREVFINT ANY l)l.‘iE!\Sl?.
`'
`
`VlSUTElN®
`.
`[nr?i:—11<rEnl
`Clinically proven to support healthy eyes and Vision
`DESCRIPTION
`VlSl.'Lein is Unicit}/s pmduc: providing key’ riutrien.
`the cyu.
`,
`Benefits and research
`\
`The carotenoids luleui and I/E!'rL‘(i-lIlLl]ll) play an impo
`role in eye lac" h. Low c()IxCL'n‘ll‘.'JtI0ns olilicsc phytoll
`mils in the retina. have lwen associated with age-I .
`mncula dcgc11eratiCn(AlVll)). Studios have shown, th S
`plmnammiixiri witli high lei 015 of lutcin, as pres
`VlSUtc»in, can restore the lut-oin ooriccntxotion in the 1'3
`The product further features impo uni vi:
`'
`enoids that are important :11 pros
`in: 0 I
`'
`.
`and su;)pcrting clear vi on,
`.mine is odd
`boost the g utathicn l?\'(>l.~ in the ietum. Low glutath
`sis have been
`own to reduce protection of the eye
`l)Xli'lf1llY\“. st: so. A iizwiil, Cllllllliil atully with VIISLY
`own thutAMD patiorts experience clear improveméfl ,
`visu
`cuity. C(Il;‘l.l‘
`P:I.si’uvily. and recovery Eff)
`llash.*
`SU(}(lES'I‘iéID U ‘
`‘
`' zakc: two L
`‘
`Contents
`Jilr‘;
`VlSUtein pl‘UV’lLle.*: 28 mg iii" liitpin.
`Macctyl cvstcin, zmrl 60 mg umhocvzmi
`
`7 with 200 mg 4‘
`, from liilbefwv
`
`; CARDIOES$ENT|ALS®
`‘ Caring for your heart
`
`i2
`
`l l1 l 1
`
`1 DESCRlP'I‘ION
`Carrliollssentials is Unicity’s superior heart product.
`Benefits and research
`\ Czlrwiiolisscntials pmvitlsas nutrients for the limit muscle,
`‘ and supports. healthy heart function. The combination of
`licarnzthine, Utaurine, and Coenzyme Q10 has lieu) sliovui
`to lisnefit congestive heart failure patients in a clinical
`study. In this study, Eel"! venl.ri<:ular .~<i/.9 woo reduced in
`‘ Cl-lF patients, giving them 3 better prognosis. “fincsc in[.«:rs~
`‘ dionls im: lmnwn tn lw importmit in prnvirling R(l(’ql.lS\l.P en’
`ergy for this heart muscle. CarcioFl5sential.. provides adv
`quote mnoniits of l.l‘lf-‘M!
`l\'1gl"(‘f'll€'i‘.l§.
`is. 100 mg of CoQlD.
`tluwthom extract is traditionally used zn supporting the
`ll(‘ill‘l. fiiri('!\nn.
`SUGGESTED USE
`3 Take six capsules daily with food.
`
`3 of 3
`
`