DECEMBER 15 1994
`
`AMERICA T f0fTRNAL OF HOSPITAL PHARMACY
`
`now oombined with CLINICAL PHARMACY
`
`Venladindtion A betwearelle windows
`
`Cleaapine therapy for Parkinsons disease
`and other movument disordora
`
`Opportunities for alliances
`between industry and pharniacy
`
`Subtleties of managing
`acetaminophen
`poisoning
`
`Annual
`
`Index
`
`Volume 51 Altnnber 24
`
`lharmacists h hg aid Memo he1ping people Inks 072 best used medications
`
`Ofrdrrf fonmal of the
`Americr Sot lay of llosp au iluiiiiiarists
`
`Abraxis EX2039
`Actavis LLC v Abraxis Bioscience LLC
`1PR201701101 1PR201701103 1PR201701104
`
`

`

`journal of the American Society of Hospital Pharmacists
`Official
`Joseph A Oddis
`Executive Vice President
`
`Copyright C 1994
`American Society of Hospital Pharmacists Inc
`All rights reserved
`
`AJHP is a federally registered
`
`trademark
`
`Printed on acid free paper effective with Volume 49 January 1992
`
`Commentaries
`
`3061 Opportunities for alliances between industry
`and pharmacy
`Gerald B Rosenberg
`
`3065 Subtleties of managing acetaminophen
`poisoning
`S Rutherfoord Rose
`
`Reflections
`
`3069 Birthday letter to a brother
`C Richard Talley
`
`ASHP Report
`
`EllEtrtiaralk22±cMrkLN
`3070 Acknowledgment
`to
`reviewersNovember
`1 1993 to October 31 1994
`
`At Large
`
`3096 National health care reform part 2
`Response to pharmacists
`
`3072 AJHP Continuing Education
`AJHP continuing education
`instructions and enrollment
`
`form
`
`3076
`
`Letters
`Infection rates in adult and pediatric
`inpatients when iv sets are
`changed every 72 hours
`Sheri L Baker Robert J Kuhn
`Sharon Berry
`Paclitaxel diluent and the case of the
`
`slippery spike Michael Martin
`Robert Bepko
`Improved extemporaneous
`formulation of cyclosporine
`ophthalmic drops
`
`David W Mueller
`
`Unit dose dispensing of chromic
`phosphate P 32 suspension
`Joseph C Hung
`Hydralazine injection still available
`Holly Bowlby
`Validity of originality assessment
`Mark H Gross Robert E Pearson
`Elizabeth L Allan
`
`3083 Career Opportunities
`
`3088 Current Literature
`Journal References
`Self study Materials Clinical Skills
`Program Patient Specific
`Pharrnacotherapy Series Module 4
`Designing and Recommending a
`Pharmacists Care Plan Jones
`Campbell Patricia A Chase
`
`3095
`
`Advertising Index
`
`3097
`
`Annual
`
`Index
`
`Vol 51 Dec 15 1994 Am J Hosp Pharm 3011
`
`

`

`This material may be protected by Copyright law Title 17 US Code
`
`Notes Injectable antimicrobials
`
`tiveness Drug safety is not a specific component of
`the scores although safety is indirectly accounted
`for
`In the formulary restriction and pharmacokinetic
`monitoring components It
`is possible for unsuitable
`drugs to have higher point
`totals than appropriate
`agents For example penicillin G injection might have
`no activity against methicillinresistant Staphylococcus
`auteus cultured from blood but might be assigned five
`has no formu
`points because it has an oral equivalent
`lary restrictions needs no pharmacokinetic monitor
`ing and is inexpensive On the other hand vancomy
`the
`it were active against
`cin injection even
`organism could be assigned a maximum of only four
`points because it has no bioavallable oral equivalent
`The possibility of such inappropriate rankings empha
`sizes the need for careful review before the system is
`in place at an institution Clearly drugs without
`put
`an organism have no place in the
`activity
`against
`rankings for that organism
`Conclusion A weighted point system can be used
`to rank injectable antimicrobials in the order of their
`for successful and economical use in empiri
`potential
`cal therapy
`
`if
`
`References
`1 Stratton CW Ratner H Johnston PE et al Focused microbio
`logical surveillance by specific hospital unit practical applica
`tion and clinical utility Clin Ther 1993 15Suppl A1220
`2 Bartlett RC Cost containment in microbiology Gun Lab Med
`1985 576191
`3 Bartlett RC Quintiliani RD Nightingale CH et al Effect of
`therapy in mi
`Including recommendations
`for antimicrobial
`Infect Dis 1991
`crobiology laboratory reports Diagn Microbial
`1415766
`4 Washington JA IL The clinical microbiology laboratory utiliza
`tion and cost effectiveness Am IMed 1985 78Suppi 68816
`5 Evans RS Classen DC Pestotnick SL et al Improving empiric
`antibiotic selection using computer decision support Arch In
`tern Med 1994 15487884
`6 Marr JJ Moffet HE Kunin CM Guidelines
`for improving the
`use of antimicrobial agents in hospitals a statement by the
`Infect Dir 1988
`Diseases Society of America I
`Infectious
`15786976
`
`Stability of paclitaxel
`dextrose injection or 09 sodium
`chloride injection at 4 22 or 32 °C
`
`in 500
`
`QUANYUN XU LAWRENCE A TRISSEL AND
`JUAN F MARTINEZ
`
`AmJ Hosp Pharm 1994 51305860
`
`to the package
`
`insert paclitaxel
`
`mixed in 5 Dextrose Injection USP or 09
`According
`Sodium Chloride Injection USP to a concentra
`tion of 0312 mgmL is stable for 27 hours at 25 °C1
`This is a brief period but it
`is adequate for a singleday
`for continuous
`Infusion For clinical
`that call
`trials
`Infusions over several days however a 27 hour stabili
`ty limit is problematic A new container must be made
`up each day and the patient must return to the insti
`tution each day to have the bag changed This is in
`to patients and staff and increases the cost
`convenient
`therapy Furthermore the multiple breaks in the
`of
`infusion system that are necessary to change bags each
`day may increase the risk of colonization of the cathe
`ter by pathogenic microbes Clearly it would be ad
`is stable in iv
`to establish that paclitaxel
`vantageous
`admixtures for at least several days
`this study was to determine the
`The purpose of
`chemical stability and physical compatibility of pacli
`taxel 01 and 1 mgml in 5 dextrose injection and in
`09 sodium chloride injection when stored at 4 22
`or 32 °C for periods up to 31 days
`Methods Preparation of admixtures Triplicate test
`solutions of paclitaxela 01 and 1 mgmL were prepared
`In 5 dextrose injectionb and in 09 sodium chloride
`injection in 150mL polyolefin minibags and stored
`statically at 4 22 or 32 °C One 2mL sample was
`removed from each bag immediately and after one
`three five and seven days and stored in 2mL sterile
`vialsd at 70 °C until assayed Preliminary studies
`showed that storage at 70°C does not adversely affect
`
`QUANYUN XU PHD Is Pharmaceutical Chemist Pharmaceutical
`LAWRF2sICE A TRISSEL
`FASHP is Director
`Analysis Laboratory
`Drug Delivery and Stability Research and JUAN F MAIMNEZ
`II Pharmaceutical Analysis Laboratory Di
`Laboratory Technician
`vision of Pharmacy The University of Texas M D Anderson
`
`is
`
`Cancer Center Houston
`Address reprint requests to Mr Trissel at the Division of Phar
`macy Box 90 The University of Texas M D Anderson Cancer
`Center 1515 Holcombe Boulevard Houston TX 77030
`Supported by grant LS9327 from BristolMyers Squibb Prince
`ton NJ
`Presented at 51st ASHP Annual Meeting Reno NV June 8
`1994
`
`Copyright 0 1994 American Society of Hospital Pharmacists
`Inc All rights reserved 000292899412023058$0075
`
`3058 Am J Hosp Pharm Vol 51 Dec 15 1994
`
`

`

`the samples Solutions showing gross precipitation
`were assayed after 31 days of storage
`
`liquid chromatography
`Analysis by highperformance
`Paclitaxel concentrations were determined by using
`liquid chro
`the stability indicating highperformance
`matographic HPLC assay described by Waugh et al2
`modified to achieve satisfactory chromatography in
`our laboratory The liquid chromatograph consisted of
`a multisolventdelivery pumpe a programmable multi
`a WISP
`light detector
`ple wavelength ultraviolet
`autosamplerg and a C analytical column The sys
`tem was controlled
`and integrated by a personal
`computer The mobile phase consisted of 53 aceto
`nitrile HPLC grade in water The flow rate was 15
`mLmin and detection was performed at 254 nm and
`05 absorbance unit fullscale The retention time for
`paclitaxel was 609 minutes Samples were passed
`through 5µm filter needles Samples of paclitaxel 1
`mgmL solution were diluted 10 fold with the respec
`tive infusion solution before analysis Duplicate HPLC
`determinations were performed on each sample of
`each test solution
`The HPLC method was validated as stability indi
`cating by accelerating the decomposition of paclitaxel
`The pH of freshly prepared paclitaxel 01mgmL solu
`tion was adjusted to 111 with 01 N sodium hydroxide
`solution After one hour at room temperature 78 of
`the original paclitaxel concentration remained A ma
`jor decomposition peak appeared at 902 minutes and
`several small peaks were observed between 200 and
`418 minutes The decomposition peaks did not
`inter
`fere with the parent peak For a nominal 01mgmL
`the mean ± SD precision of the
`solution of paclitaxel
`assay determined from 10 replicate injections was
`
`Paclitaxel Notes
`
`00993 ± 00008 mgmL Precision expressed as percent
`relative standard deviation was 076 Calibration
`curves were constructed from a linear plot of peak area
`reference standard
`versus concentration of paclitaxel
`0025015 mgmL The correlation coefficient of the
`than 09999 The within
`standard curve was greater
`day and between day coefficients of variation were
`
`14 and 20 respectively
`Stability was defined as at least 90 of the initial
`paclitaxel concentration remaining
`Analysis by visual examination and turbidimetry Phys
`ical compatibility was evaluated by using previously
`described techniques of visual examination and turbi
`dimetry34 Visual examination of the samples was per
`formed with the unaided eye in normal
`laboratory
`fluorescent light and by using a high intensity mono
`light source Tyndall beam m Turbidimet
`directional
`ric assessments of
`the normally hazy paclitaxel
`solutions were made with a color correcting
`inspections and turbidimetric as
`turbidimeter Visual
`sessments were performed immediately after the solu
`tions were prepared and after 1 3 5 7 14 and 31 days
`of storage at each temperature protected from light
`Compatibility was defined as the absence of partic
`ulates under visual examination and no change in
`turbitidy exceeding 05 nephelometric turbidity unit
`under turbidimetric examination
`Results and discussion Paclitaxel 01 and 1 mg
`mL was stable throughout
`the study as long as the drug
`remained dispersed in the infusion solutions Tables 1
`and 2 All concentrations
`remained above 90 of the
`initial value and most were near 100 No evidence of
`in the chromato
`decomposition products appeared
`grams These findings are consistent with those of Chin
`
`Table 1
`
`Stability of Paclitaxel 01 and 1 mgmL in 5 Dextrose Injection
`
`Temperature
`°C
`
`Sample
`
`Actual
`Concentration mgn1Pa
`
`Initial
`
`1 Day
`
`3 Days
`
`5 Days
`
`7 Days
`
`c0 Initial Concentration Remaininga
`
`0102 0101
`0101 0102
`0101 0101
`0100 0101
`0100 0099
`0100 0102
`0107 0107
`0104 0106
`0106 0105
`
`0955 0960
`0942 0944
`0959 0959
`0960 0962
`0983 0986
`1009 1009
`10131010
`0997 0994
`0985 0993
`
`996 1006
`996 1008
`1003 1014
`998 1004
`1006 1005
`991 991
`989 1009
`1006 1007
`984 995
`
`986 997
`1014 1004
`1006 1012
`992 993
`978 984
`983 993
`989 996
`1004 1002
`1006 1003
`
`1001 1006
`1002 1004
`1000 1011
`993 991
`1008 1017
`991 1004
`989 993
`1002 1005
`991 1004
`
`989 991
`999 999
`1003 1010
`1003 1003
`1001 994
`991 1000
`997 988
`1000 1004
`994 1001
`
`10001017
`998 1003
`996 1014
`991998
`1011 1009
`994 992
`987 992
`1003 1001
`998 997
`
`991 992
`990 990
`1001 1002
`998 998
`981 982
`992 998
`1000 995
`1001 1012
`1003 1005
`
`10001003
`999 1000
`1005 1014
`1001 1011
`996 1006
`993 999
`1004 997
`994 1012
`995 1000
`
`993 990
`999 1000
`997 997
`992 984
`1001 1003
`997 991
`1008 1007
`994 986
`1000 1006
`
`Vol 51 Dec 15 1994 Am J Hosp Pharm 3059
`
`1 2 3 4 5 6 7 8 9
`
`1 2 3 4 5 6 7 8 9
`
`Paclitaxel 01 mgmL
`4
`
`22
`
`32
`
`Paclitaxel
`4
`
`1 mgmL
`
`22
`
`32
`
`a Duplicate determinations
`
`

`

`Notes Paclitaxel
`
`Table 2
`Stability of Paclitaxel 01 and 1 mgmL in 09 Sodium Chloride Injection
`
`Temperature
`°C
`
`Sample
`
`Actual
`
`Initial
`
`Concentration mgmLa
`
`1 Day
`
`3 Days
`
`5 Days
`
`7 Days
`
`Initial Concentration Remaininga
`
`0101 0101
`0100 0100
`0100 0100
`0101 0100
`0102 0103
`0103 0103
`0102 0102
`0104 0105
`0102 0102
`
`0997 1002
`0995 0995
`0985 0982
`0955 0948
`0971 0970
`0961 0963
`0973 0970
`0982 0975
`0980 0977
`
`995 995
`992 1007
`996 994
`1002 998
`996 1006
`1001 1000
`1010 1004
`1001 1007
`995 1008
`
`1013 1013
`975 967
`978 979
`979 1000
`975 978
`995 981
`999 1003
`997 993
`1003 997
`
`1000 995
`1006 1018
`1002 989
`1003 1007
`993 998
`1000 1006
`1009 1013
`1007 1001
`998 982
`
`998 996
`988 987
`990 986
`992 988
`971 990
`990 986
`1004 1010
`998 994
`1002 1004
`
`998 998
`1000 1003
`997 985
`1006 1006
`991 995
`989 996
`1001 1017
`994 1001
`995 982
`
`991 979
`984 964
`960 958
`1013 982
`987 974
`994 984
`992 992
`1001 1002
`1006 1011
`
`987 996
`999 1011
`1001 1001
`999 1006
`996 1001
`994 998
`1015 995
`1002 1000
`980 990
`
`987 982
`971 947
`973 962
`1006 980
`987 988
`988 984
`999 1003
`1001 1004
`1009 1005
`
`1 2 3 4 5 6 7 8 9
`
`1 2 3 4 5 6 7 8 9
`
`Paclitaxel 01 mgmL
`4
`
`22
`
`32
`
`Paclitaxel
`4
`
`1 mgmL
`
`22
`
`32
`
`a Duplicate determinations
`
`et al who found that paclitaxel admixtures were stable
`for 48 hours However
`there were paclitaxel
`losses of
`3050 in our solutions that had gross precipitation
`When viewed with the Tyndall beam all samples
`free of particulate matter but had the
`were initially
`normal haze of paclitaxel solutions Turbidity did not
`for solutions with
`change during the study except
`noticeable precipitation Large amounts of white floc
`culent precipitate appeared in many of the solutions
`after 31 days of storage and in a few solutions after 14
`days Crystalline and needle like precipitation visible
`only with the Tyndall beam began much earlier Two
`solutions one with 5 dextrose injection and one
`with 09 sodium chloride injection had small
`amounts of crystalline precipitate within five days of
`storage Most solutions had crystalline precipitate
`within a week Compatibility was maintained for at
`least three days at all three temperatures in these static
`solutions It
`is possible that agitation or other factors
`could reduce the time to precipitation
`Conclusion Paclitaxel 01 and 1 mgmL in 5
`dextrose injection or 09 sodium chloride injection
`three days at 4
`was stable and compatible for at least
`22 or 32 °C Precipitation may occur after three days
`and is the primary factor limiting storage time
`
`aBristolMyers Squibb Princeton NJ 08543 lot E3F32A
`
`bMcGaw Irvine CA 927145895 lot J30960
`cMcGaw lot J3E907
`Laboratories Franklin Park IL 60131 lot 930257
`dSolopak
`eModel 600E Waters Chromatography Milford MA 01757
`fModel 490E Waters
`gModel 712 Waters
`bVydac 5 um particle size 250 x 46 mm Separations Group
`Hesperia CA 92345 lot 9004239RE
`Boxborough MA
`NEC Powermate SX16 NEC Technologies
`01719
`Milli Q Plus Millipore Corporation Bedford MA 01730
`kl3urron Medical Inc Bethlehem PA 18018 lot 585400
`IBristolMyers Squibb batch 80617492D
`Industries Woburn MA 01801
`mDolanJenner
`Hach Company Loveland CO 80539
`
`References
`
`insert Princeton NJ
`
`1 Mead Johnson Oncology Taxol package
`1992 Dec
`2 Waugh WN Trissel LA Stella VJ Stability compatibility and
`plasticizer extraction of taxol NSC125973 injection diluted in
`infusion solutions and stored in various containers Am I Hosp
`Pharm 1991 4815204
`3 Trissel LA Bready BB Turbidimetric assessment of the compati
`bility of taxol with selected other drugs during simulated Ysite
`injection Am f Hosp Pharm 1992 4917169
`4 Trissel LA Martinez JF Turbidimetric assessment of the compat
`Y site
`ibility of taxol with 42 other drugs during simulated
`injection Am J Hosp Pharm 1993 503004
`5 Chin A Ramakrishnan RR Yoshimura NN et al Paclitaxel stabil
`ity and compatibility in polyolefin containers Ann Pharmacorh
`er 1994 28356
`
`3060 Am J Hosp Pharm Vol 51 Dec 15 1994
`
`