Pharmaceutical Data, Complete Document

U.S. DEPARTMENT OF HEALTHAND HUMAN SERVICESPublic Health ServiceNational Institutes otHealth

This document supports the Adobe PDF find function.

Find text in a PDF

The Find toolbar searches the currently open PDF.

1. Type the text you want to search for in the text box on the Find toolbar.

2. (Optional) Click the arrow next to the text box and choose one or more of the following:

Option Description

Whole words only

Finds only occurrences of the complete word

you type in the text box. For example, if you

search for the word stick, the words tick and

sticky arent found.

Case-Sensitive

Finds only occurrences of the words that

match the capitalization you type. For

example, if you search for the word Web, the

words web and WEB arent found.

Include BookmarksAlso searches the text in the Bookmarks

panel.

Include Comments Also searches the text of any comments.

4. Press Enter.

Acrobat jumps to the first instance of the search term, which appears highlighted.

5. Press Enter repeatedly to go to the next instances of the search term.

COVER

The inset on the cover is a representation of thetemozolomide molecule generated with the Hyperchemcomputer molecular modeling program which depictsbonding and arrangement of electrons. The backgroundfor the cover is a photograph of crystals of the samedrug. The graphics were generated respectively by Dr.E.M. Bellot of Pharm-Eco Laboratories and Mr. P.C.Reiman of the University of Iowa.

PREFACE

NCI Investigational Drugs - Pharmaceutical Data is a periodicalpublication prepared by the Pharmaceutical Resources Branch ofthe Developmental Therapeutics Program, Division of CancerTreatment, National Cancer Institute. Special thanks due are toJames W. Wilson ill, R.Ph., who assumed major responsibilityfor the preparation of the current volume prior to assuming aposition with the FDA. Thanks are also owed to Wayne E.Jackson for his exceptional efforts in facilitating the publication ofthis volume. Much of the data presented in the current volume hasbeen generated by National Cancer Institute's contractors whomanufacture the dosage forms described in the book, providerequired analytical services and perform shelf life surveillancestudies. Their cooperation and assistance is very muchappreciated.

Rao Vishnuvajjala, Ph.D.Esmail Tabibi, Ph.D.

1

DanielLednicer, Ph.D.Ravi Varma, Ph.D.

Copies of this publication may be requested by writing to thefollowing address:

Pharmaceutical Resources BranchNational Cancer InstituteExecutive Plaza North, Suite 818Bethesda, MD 20892

Phone: (301) 496-8780FAX: (301) 496-8333

Clinical drug supplies should be ordered via the appropriatemechanism from the Pharmaceutical Management Branch of theCancer Therapy Evaluation Program, National Cancer Institute.

Phone: (301) 496-5725

11

INTRODUCTION

NCI Investigational Drugs - Pharmaceutical Data is designed toprovide product information to health care practitioners who useinvestigational drug products under IND's sponsored by theDivision of Cancer Treatment, National Cancer Institute, forclinical trials. Monographs are presented on investigational agentscurrently being manufactured by the Division of Cancer Treatment(DCT). Products distributed by the NCI which are commerciallyavailable in the United States are not included because thenecessary pharmaceutical information is provided in theaccompanying package insert. Additionally, more comprehensiveinformation on the investigational drugs may be found in theclinical brochure available for each drug.

The Pharmaceutical Management Branch (PMB) of the CancerTherapy Evaluation Program (CTEP) has taken over control ofnon-commercial investigational drug "gift" supplies. Monographsfor these supplies are no longer included in this publication. Allinquiries for investigational drug supplies, expiration dating, andgeneral information are now screened through PMB (301-496-5725). The Pharmaceutical Resources Branch provides PMB withthe information on DCT manufactured drugs to allow thepractitioners the convenience of a central source for all druginformation questions within the National Cancer Institute.

III

GENERAL INFORMATION

Product information is presented in a uniform manner. Thestandardized format begins with the drug's labeled name as themonograph title. When a United States Adopted Name (USAN)is available, it is generally used. Otherwise, the name mostcommonly applied to the agent, or in some cases the chemicalname, may be used. Other identification data presented includethe structural formula, CAS registry number, chemical name, anycommon names other than those previously listed, the molecularformula and the molecular weight.

The composition and packaging of the investigational dosage formsare then described. Descriptive terminology for parenteral

d ( "S 'I "" fi I' , ") d fi ed i hpro ucts e.g. ten e , or njection as e In In t eofficial United States Pharmacopeia is utilized.

NSC Numbers:

Each investigational compound studied by the NCI is assigned aunique number. This universally recognized identification numberis called the "NSC" number, which refers to the former CancerChemotherapy National Service Center. The NCI maintains itsfiles and data for each compound based on its assigned NSCnumber. When information is requested on a particular NCIcompound, use of the NSC number will facilitate a response andassure that both the requestor and NCI are referring to the samecompound. NSC numbers for special diluents have been addedwhere appropriate.

Stability and Storage:

Recommended storage conditions for the intact dosage forms arepresented in each monograph. For new products, the

IV

recommendations are frequently based on accelerated shelf-lifestudies at elevated temperatures. Each new lot of investigationalproducts manufactured by a National Cancer Institute is placed ona shelf-life surveillance study. Generally, each lot is studied forfive years in the freezer (-10 C) and recommended storageconditions. Elevated temperatures are included as appropriate.The NCI receives updated stability data every three months for thefirst year, every six months for the second year and yearlythereafter.

Many of the product monographs in this book include stability datafor temperatures higher than the recommended storage condition.These data are provided to allow decisions on whether to useproducts which may have inadvertently been stored above thelabeled temperature for short periods of time (e.g. a product whichis labeled for refrigerated storage which is left at room temperaturefor a day or two).

Shipping:

Storage information is provided on the label. OccasionalIy,product labeling requires refrigeration, but the product is shippedwithout ice. These products are stable for short periods of time atroom temperature, but still must be stored under refrigeration uponreceipt.

Expiration Dating:

Older products carry an expiration date placed on the label, whichis based on real-time stability studies. The drug may be usedthrough the end of the month specified.

Newer drugs will carry only the manufacturing date; these drugsare undergoing stability evaluation but do not yet have an

v

established expiration date. The year that a drug was manufacturedby a National Cancer Institute contractor can also be determinedfrom the first two digits of the lot number (e.g. BV-87-301 andUI-90-202 were manufactured in 1987 and 1990, respectively).Any expired drug should be returned to the NCI Clinical DrugRepository along with a completed Return Drug Form.

Preparation Infonnation:

The recommended constitution and dilution directions are based onformulation and solution stability studies performed on each drug.0.9% Sodium Chloride Injection, USP, 5% Dextrose Injection,USP, or 5% Dextrose in 0.45% Sodium Chloride Injection, USP,the most common infusion vehicles, are usually selected forsolution compatibility studies. The omission of other vehicles doesnot imply incompatibility. The solution stability data which havebeen developed are presented.

Infrequently, the formulation of a product is changed or a new vialsize is made available in between editions of this book.Information in these monographs should not be used as a substitutefor the preparation instructions on the label of the product.

Compatibility:

Compatibility of the investigational agents with other drugs or withantibacterial preservatives is not usually evaluated. Investigationalagents manufactured by the NCI are designed as single-use dosageforms and admixture with other agents is, in general, notrecommended. Compatibility studies of selected investigationalagents in plastic are currently being conducted by NCI contractors.

VI

Proper Handling and Disposal of Anti-Cancer Drugs:

The potential risks to individuals working with antineoplastic drugshave been the subject of much interest and concern in the healthcare community. Procedures for proper handling and disposal ofanti-cancer drugs should be considered. Several guidelines on thissubject have been published to assist practitioners who prepare andadminister antineoplastic drugs in establishing a program ofprocedures designed to minimize inadvertent exposure to theseagents (1-3). In addition, a videotape entitled "Safe Handling ofCytotoxic and Hazardous Drugs", 1990 edition, is available fromthe American Society of Hospital Pharmacists and may be used intraining staff members. Although the nature and extent of anyrisks that might exist are uncertain, practitioners are encouragedto implement a program that will minimize their level of exposure.

Material Safety Data Sheets:

There have been several recent changes in the HazardCommunication Standard. The Hazard Communication Standardfinal rule was published August 24, 1987 and required thatchemical manufacturers, importers, and distributors ensure thatMaterial Safety Data Sheets (MSDS's) are provided with the nextshipment of hazardous chemicals to non-manufacturing employersor distributors after September 23, 1987 (Federal Register52:31852-31886, 1987). This revised standard exempted "drugswhen they are solid, and in final form for direct administration tothe patient (i.e., pills or tablets)".

Subsequently the final rule was amended December 4, 1987(Federal Register 52: 46075-46080) to exempt any drug regulatedby the FDA in the non-manufacturing sector from the requirementto supply MSDS's.

VB

The exemption attempts to avoid duplication of paperwork becausethe Food and Drug Administration requires the transmittal ofdetailed information from the manufacturer in the form of packageinserts and labels. Investigational drugs use clinical brochures asa substitute for the package insert.

Clinical brochures should be available on the clinical drugs at yourinstitution for personnel handling and administering these antitumoragents, please request them from:

Pharmaceutical Management BranchCancer Therapy Evaluation ProgramDivision of Cancer TreatmentNational Cancer InstituteRoom 804, Executive Plaza NorthBethesda, Maryland 20892

V111

TABLE OF CONTENTS

ACIVICIN 1

9-AMINOCAMPTOTHECIN 4

2-AMINO-1 ,3,4-THIADIAZOLE 7

AMONAFIDE 9

AMSACRlNE 12

AZACITIDINE 15

BROMODEOXYURIDINE 20

BRYOSTATIN 22

BSO 25

CAl 27

CARBOPLATIN 29

CHLOROZOTOCIN 32

CHLORSULFAQUINOXALlNE 34

CLOMESONE 36

CYCLOPENTENYLCYTOSINE 38

IX

DIAZIQUONE 40

DIBROMODULCITOL 45

DIDEMNINB 47

DIDEOXYINOSINE 49

DIHYDRO-5-AZACYTIDINE 53

ECHINOMYCIN 56

ETHIOFOS 59

FAZARABINE 61

FLUDARABINE PHOSPHATE 65

FOSTRIECIN SODIUM 68

GALLIUM NITRATE 71

HEPSULFAM WITH DILUENT 73

HEXAMETHYLMELAMINE 75

HMBA 77

HOMOHARRINGTONINE 80

HYDRAZINE SULFATE 82

IODODEOXYURIDINE 84

IPOMEANOL 86

x

LEUCOVORIN CALCIUM 90

MERBARONE 92

METHOTREXATE 95

6-METHYLMERCAPTOPURINE-RIBOSIDE 98

MISONIDAZOLE 101

MITOGUAZONE 104

PALA 106

PENCLOMEDINE 108

PENTOSTATIN 110

PIROXANTRONE 113

PORFIROMYCIN 116

PYRAZINE DIAZOHYDROXIDE 118

PYRAZOLOACRIDINE 120

RHIZOXIN 122

SEMUSTINE 125

SOLUBLE BAKER'S ANTIFOL 127

SURAMIN SODIUM 129

Xl

TAXOL 131

TEMOZOLOMIDE 134

TEREPHTHALAMIDINE 136

TEROXIRONE 138

TETRAPLATIN 141

THIOGUANINE 143

THYMIDINE 146

TIAZOFURIN 148

TMCA 150

TRICIRIBINE PHOSPHATE 152

TRIMETREXATE 154

URIDINE 157

xu

ACIVICIN

NSC - 163501

Acivicin is currently available from both the National CancerInstitute and from the Upjohn Company of Kalamazoo, Michiganfor clinical trials sponsored by the Division of Cancer Treatment,National Cancer Institute. Information relevant to both productsis provided below.

H

CI . IIII N H2

Chemical Name: a-Amino-3-chloro-4,5-dihydro-5-isoxazoleaceticacid, [S.-(R*,R*)]-

Other Names: AT-125, U-42126, Acivicin (USAN)

CAS Registry Number: 42228-92-2

M.W.: 178.6

1

Upjohn's Product:

How Supplied: For injection, 25 mg, vial: supplied as alyophilized powder with 39.45 mg of mannitol, USP, and 24 mgof citric acid in 10 mL flint vials.

Solution Preparation: 25 mg/vial: When constituted with 5 mLof Sterile Water for Injection, USP, each milliliter contains 5 mgof acivicin, 7.89 mg of mannitol, USP, 4.8 mg of citric acid andsodium hydroxide to adjust the pH to approximately 5.2.

Storage: Store the intact vials at room temperature.

NCI's Product:

How Supplied: For injection, 25 mg, vial: supplied as alyophilized powder with 25 mg of mannitol, USP in 10 mL flintvials.

Preparation: When constituted with 5 mL of BacteriostaticSodium Chloride Injection, USP, containing benzyl alcohol, theresulting solution contains 5 mg/mL of acivicin, and 5 mg/mL ofmannitol, USP, at pH 3.5-6.5.


2

Stability: Intact vials are stable for 5 years at room temperature(22-25 DC). Intact vials are stable for at least one year whenstored at elevated temperature (50C).

When constituted as directed, the solution exhibits nodecomposition in 48 hours at room temperature (22-25 DC) or in7 days under refrigeration (2-8 DC). Use within six hours isrecommended.

NOTE: Acivicin solutions exhibit very fine particlesand/or very light haze under high intensity light. Theparticulate burden is very low, and formulated lots havemet USP criteria for particulate matter. The lots areessentially free of visible particulate matter. Nevertheless,as a precaution, it is recommended that the constitutedsolution be filtered through a 0.22 J1 filter prior toinjection. Filtration does not reduce the drug content.

Further dilution to a concentration of 0.05 mg/mL in 5% Dextrosein 0.9% Sodium Chloride Injection, USP results in a solutionwhich exhibits no decomposition in 48 hours at room temperature.

A 10 mg/mL solution of acivicin in amino acid injection(Aminosyn", Abbott) showed no physical or chemical changesover a two-week observation period.

Route of Administration: Intravenous

3

9-AMINOCAMPTOTHECINWITH DILUENT

NSC - 603071

/ /N

Chemical Name: 9-Amino-20-(S)-camptothecin

Other Names: 9-AC


o

4

M.W.: 363.4

How Supplied: NSC - 603071 Injection, 5 mg, ampule: 5 mg/mLconcentrate, 1 mL, in dimethylacetamide,1 mL/amber ampule.

Special Diluent: NSC - 651935 Vial: Polyethylene Glycol 400,51 %, with 0.01 Molar Phosphoric AcidBuffer, 49%, 49 mLiamber vial.

Solution Preparation: Add one milliliter of the 9-amino-camptothecin /dimethylacetamide concentrate (use a glasssyringe) to the amber vial containing 49 milliliters of specialdiluent.

The resulting mixture contains 100 micrograms of 9-aminocamptothecin per milliliter in a 2% dimethylacetamide(v/v), 50% polyethylene glycol 400 (v/v), and 48% 0.01 Mphosphoric acid (v/v) solution, 50 mL per vial. Filter the finalsolution through a 5 micron filter. Use within 28 hours.

Note: Contact of the undiluted 9-aminocamptothecin/dimethylacetamide concentrate with plastic items, includingfilters and syringes, should be avoided.

Further dilution of the 100 mcg/mL solution with 0.9% SodiumChloride Injection must be targeted to a concentration of ::::;; onemicrogram/mL as precipitation will occur at higherconcentrations. Dilutions containing 0.1 to 1 mcg/mL of 9-aminocamptothecin in 0.9% Sodium Chloride Injection arestable for 28 hours. Those in 5 % Dextrose Injection are lessstable; this should not be used. These solutions may be preparedin PVC or polyolefin containers.

5

Caution: 9-aminocamptothecin is intended for appropriatesyringe pump administration only. The drug is not compatiblewith standard infusion fluids and therefore cannot be furtherdiluted (except as noted in the previous paragraph) nor can it bepiggybacked into an existing I. V. line port. Additional specialdiluent is available to facilitate larger doses and to flush centralvenous catheters to displace any aqueous solution present.

Storage: Store the intact ampules under refrigeration (2-8 C).

Stability: Shelf-life surveillance of the ampules and vials isongoing.

Constitution as recommended results in a solutionwhich is chemically and physically stable in the amberdiluent vial for at least 28 hours stored at refrigeratedtemperature (2-8C).


6

2-AMINO-l,3,4-TIDADIAZOLE

NSC - 4728

Chemical Name: 1,3,4-Thiadiazol-2-amine,2-Amino-1,3,4-Thiadiazole

Other Name: ATDA


M.W.: 101.1

How Supplied: Sterile, 200 mg, vial: supplied as a lyophilizedpowder in 30 mL flint vials.

7

Solution Preparation: 200 mg/vial: When constituted with19.9 mL of Sterile Water for Injection, USP, 0.9% SodiumChloride Injection, USP, or 5% Dextrose Injection, USP, eachmilliliter contains 10 mg of 2-amino-l,3,4-thiadiazole. The pHof the constituted solution is 5.5 to 7.0.


Stability: The intact vials are stable for 5 years at roomtemperature (22-25 C), and at least one year at elevatedtemperature (50 C).

Constitution as recommended results in a solution which ischemically stable for at least 72 hours at room temperature.Normal room light does not affect the stability of the constitutedsolution.

Further dilution of the constituted solution with 5% DextroseInjection, USP, 5% Dextrose in 0.9% Sodium ChlorideInjection, USP, or 0.9% Sodium Chloride Injection, USP, doesnot alter solution stability.

CAUTION: The single-use lyophilized dosageform contains no antibacterial preservatives.Therefore, it is advised that the constitutedproduct be discarded within 8 hours of initialentry.


8

AMONAFIDE

NSC - 308847

0,

How Supplied: Sterile, 500 mg (as the base), vial: supplied asa yellow to orange or red-orange lyophilized powder withsodium hydroxide to adjust pH in 30 mL flint vials.

Solution Preparation: 500 mg/vial: Constitution with 9.6 mLof Sterile Water for Injection, USP, or 0.9% Sodium ChlorideInjection, USP, results in a solution containing 50 mg/mL ofamonafide with sodium hydroxide to adjust to pH 5 to 7. Theconstituted solution may vary in color from yellow to red-orangeor red.

Storage: Store the intact vials under refrigeration (2-8 C).

Stability: Shelf-life surveillance of the intact vials is ongoing.Intact vials are stable for at least 3 years at room temperature(22-25 C) and under refrigeration (2-8 C). The intact vialsare stable for at least one year at elevated temperature (50C).

Amonafide is stable in aqueous phosphate-buffered solutionsover a pH range of 5.4 to 9.4 exhibiting little or nodecomposition over 8 hours at 90C. However, at lower pHvalues increased rates of decomposition occur.

When constituted as directed with Sterile Water for Injection,USP, or 0.9% Chloride Injection, USP, amonafide solutionsexhibit no decomposition over 14 days at room temperature orunder refrigeration,

10

Further dilution to a concentration of 0.25 mg/mL in 0.9%Sodium Chloride Injection, USP, in glass or PVC containersresults in a solution which exhibits no decomposition over 14days of storage at room temperature or under refrigeration.

Note: Amonafide is very unstable in dextrose-containingsolutions. Approximately 25 to 35% decompositionoccurs over 24 hours at room temperature in 5%Dextrose Injection, USP, 5% Dextrose in 0.9% SodiumChloride Injection, USP, and 5 % Dextrose in 0.45 %Sodium Chloride Injection, USP. The dextrose contentmay be catalyzing the degradation.



11

AMSACRINE

NSC - 249992

HN

-:N

Chemical Name: N-[4-(9-Acridinylamino)- 3-methoxyphenyl]-methanesulfonamide

Other Names: m-AMSA, acridinyl anisidide,methanesulfon-m-anisidide, 4' -(9-acridinylamino)-, Amsacrine(USAN)

CAS Registry Number; 51264-14-3

12

M.W.: 393.5

How supplied: Amsacrine is available in a duopack containingtwo sterile liquids that must be aseptically combined prior touse, forming what is termed the "combined solution".

Each duopack contains the following:

NSC - 249992: A 2 mL flint ampule containing 1.5 mL of a 50mg/mL solution of amsacrine (75 mg total) in anhydrousN,N-dimethylacetamide (DMA).

NSC - 367919: A 20 mL amber vial containing 13.5 mL of0.0353 M L-Iactic acid diluent.

Solution preparation:Aseptically add 1.5 mL of the contents of the ampule ofamsacrine, 50 mg/mL, to the vial containing 13.5 mL of 0.0353M L-Iactic acid. The resulting orange-red solution contains 5mg/mL of amsacrine in 10% v/v DMA and 0.0318 M L-Iacticacid.

NOTE: Contact of the undiluted amsacrine solution withplastic items, including filters and syringes, should beavoided because of the concentrated N,N-dimethylacet-amide solvent content. The use of glass syringes isrecommended.

CAUTION: Avoid direct contact of amsacrinesolutions with skin or mucous membranes due topossible skin sensitization.

Storage: Store the packages at room temperature (22-25 DC).

13

Stability: The intact drug and diluent bear a "do not use after"date.

The "combined solution" is physically and chemically stable forat least 48 hours at room temperature (22-25 C) under ambientlight.

The "combined solution" may be further diluted with 500 mL of5% Dextrose Injection, USP, and is physically and chemicallystable for at least 48 hours at room temperature (22-25 C)under ambient lighting.

Addition of the "combined solution" to 500 mL of 5% DextroseInjection, USP, containing 1 mEq of sodium bicarbonate resultsin an admixture which has been found to be chemically stablefor at least 96 hours at room temperature.

NOTE: The hydrochloride salt of amsacrine is poorlywater soluble. As a result, the "combined solution" isphysically incompatible with Sodium Chloride Injection,USP, and other chloride-containing solutions. Admixturewith these solutions may result in precipitation.

Evacuated flasks may contain a small amount of chloride-containing solution from the manufacturing process. Thisresidual chloride ion has been sufficient to cause precipitationwhen amsacrine solutions have been prepared in evacuatedflasks.

CAUTION: These single-use solutions do notcontain antibacterial preservatives. Therefore, itis advised that the vials be discarded within 8hours of initial entry.


14

AZACITIDlNE

NSC - 102816

HO

H0 0 H

Chemical Name: 4-Amino-l-{J-D-ribofuranosyl-l,3,5-triazin-2(lH)-one

Other Names: 5-Azacytidine, Ladakamycin, Mylosar",Azacitidine (USAN)


15

M.W.: 244.2

How Supplied: For injection, 100 mg, vial: supplied as a whitelyophilized powder with 100 mg of mannitol, USP, in 30 mLflint vials.

Solution Preparation: 100 mg/vial: When constituted with19.9 mL of Sterile Water for Injection, USP, each millilitercontains 5 mg of azacitidine and 5 mg of mannitol, USP. ThepH of the resulting solution is 6..0 to 7.5.

The constituted solution can be further diluted in LactatedRinger's Injection, USP. The pH of this solution, at aconcentration of 100 mg/500 mL, is approximately 6.4. LactatedRinger's Injection, USP, provides optimum pH for solutionstability.

Storage: Store the intact vials at refrigeration temperature(2-8 C).

Stability: The intact vials are stable for at least 4 years atrefrigeration temperature (2-8 C). Room temperature storage(22-25 C) has not altered the chemical potency of the productafter 3 years, but because of degradation at elevatedtemperatures, refrigeration storage is recommended whenpossible.

16

The constituted solutions hydrolyze at room temperature andshould be used within 30 minutes for delivery of maximumpotency.

The mode of decomposition in the neutral pH range involvesopening the triazine ring. Hydration of the 5,6-imine doublebond occurs, followed by bond cleavage to yield the formylderivative, N-(formylamidino)-N-{3-D-ribofuranosylurea.Evaluations of the kinetics and mechanism of degradation ofazacitidine have been reported in the literature (1,2,3,4). ThepH providing optimum stability has been shown to be 6.5 to 7(1,2,4).

Constitution as recommended with Sterile Water for Injection,USP, provides a solution with a pH value near the optimal pH.Nevertheless, the decomposition rate is rapid, and the time to10% decomposition is very brief. The constituted solutionshould be used immediately or further diluted in an appropriateinfusion solution and used within 30 minutes.

The stability of azacitidine 0.2 mg/mL and 2 mg/mL in severalintravenous infusion solutions has been studied (5). Using astability-indicating HPLC assay technique, azacitidine stabilitywas found to depend, to a degree, on drug concentration and thespecific infusion solution used. However, in all cases the timeto 10% decomposition at 25 0 C was found to be short. Theresults of the study are summarized in the following table:

17

Stability of Azacitidine inVarious Infusion Fluids at 25 0 C

Infusion Azacitidine Time to 10% ConcentrationSolution Concentration Decompn. after 6 hours

(mg/mL) (hr) (%)

NS

PVC 0.2 1.6 77

Glass 0.2 1.9 79

Glass 2 2.4 82

D5W

PVC

Glass

0.2

0.2

0.7

0.8

63

74

LR

PVC 0.2 2.0 80

Glass 0.2 1.9 79

Glass 2 2.9 82

NR

Glass

Glass

0.2

2

18

1.9

3.0

76

84

NS = 0.9% Sodium Chloride Injection, USPDSW = 5% Dextrose Injection, USPLR = Lactated Ringer's Injection, USPNR = Normosol - R (pH 7.4)PVC = Polyvinyl chloride bags

Route of Administration: Intravenous, subcutaneous

References:

1. Pithova P, Piskala J, Pitha J and Sorm F: Nucleic acidcomponents and their analogues. LXVI. Hydrolysis of5-azacytidine and its connection with biological activity,ColI Czech Chern Commun 30:2801-2811, 1965.

2. Notari RE and DeYoung JL: Kinetics and mechanismsof degradation of the anti-leukemic agent 5-azacytidinein aqueous solutions, J Pharm Sci 64:1148-1156, 1975.

3. Beisler JA: Isolation, characterization and properties ofa labile hydrolysis product of the antitumor nucleoside5-Azacytidine, J Med Chern 21:204-208, 1978.

4. Chan KK, et al.: 5-Azacytidine hydrolysis kineticsmeasured by high-pressure liquid chromatography and

13C - NMR spectroscopy, J Pharm Sci 68:807-812, 1979.

5. Cheung YW, Vishnuvajjala BR, Morris NL, Flora, KP,and Cradock, JC: Stability of Azacytidine in infusionfluids, Am J Hosp Pharm 41:1156-1159,1984.

19

BROMODEOXYURIDINE

NSC - 38297

oI I

HN~Br

O~N)

IOH

Chemical Name: 5-Bromo-2' -deoxyuridine

Other Names: BUdR, BrdUrd, Broxuridine (USAN)


20

M.W.: 307.1

How Supplied: Sterile, 500 mg, vial: supplied as a lyophilizedwhite crystalline material in 20 mL flint vials. Sufficient sodiumhydroxide is present for pH adjustment.

Solution Preparation: 500 mg/vial: When constituted with19.7 mL of Sterile Water for Injection, USP, or 0.9% SodiumChloride Injection, USP, each milliliter of solution contains25 mg of bromodeoxyuridine, pH 8.0 to 9.0.


Stability: The intact vials are stable for five years when storedat room temperature. Intact vials are stable for at least one yearwhen stored at elevated temperature (50 C).

Constitution as directed results in a solution which exhibits lessthan 1% decomposition during one week of storage underrefrigeration (4 C) or at room temperature (23 C).

BUdR solution in PVC bags at a concentration of 0.5 mg/mL in0.9% Sodium Chloride, USP is stable for seven days at roomtemperature.



21

BRYOSTATINWITH PET DILUENT

NSC - 339555

H 0 0 H

",H II "

Documents

Pharmaceutical Data, Complete Document