Material Safety Data Sheet
1. PRODUCT IDENTIFICATION
Fludarabine Phosphate for Injection
Product Name Fludarabine Phosphate for Injection
Product Use Medical Treatment for B-cell Chronic Lymphocytic Leukemia (CLL)
Manufacturer Sicor Pharmaceuticals, Inc.
Address 19 Hughes
Irvine, CA 92618-1902
Chemtrec Emergency No. 1-800-424-9300 (United States)
1-202-483-7617 (International Collect)
Business Phone 1-800-729-9991
Website Address http://www.sicorinc.com
Common Names 2-Fluoio-ara-AMP, Fludara
Chemical Name 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-尾-D-arabinofuranosyl)
Chemical Formula C10H13FN5O7 P
Chemical Family Purine Nucleoside
How Supplied 50mg/ vial
Date of Preparation: September 14, 2000
2. COMPOSITION AND INGREDIENTS
EXPOSURE LIMITS IN AIR
CHEMICAL NAME CAS# % by ACGIH OSHA IDLH OTHER
wt/vial
TLV CEIL PEL STEL
Fludarabine Phosphate 75607-67-9 5 NE NE NE NE NE NE
Mannitol 69-65-8 5 NE NE NE NE NE NE
2mg/m3 2mg/m3
Sodium Hydroxide (for pH adj.) 1310-73-2 trace NE NE NE NE
NE - Not Established CEIL - Ceiling Limit
NOTE: All WHMIS required information is included. It is located in appropriate sections based on the ANSI Z400.1 鈥? 1998
format
CHEMTREC NUMBER: Use only in the event of a chemical emergency involving a spill, leak, fire, exposure or accident
involving this drug.
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Material Safety Data Sheet
3. HAZARD IDENTIFICATION
EMERGENCY OVERVIEW: Material is a white, lyophilized cake. Harmful or fatal if swallowed,
Fludarabine Phosphate for Injection
inhaled or absorbed through skin. Overexposure may cause damage to the bone marrow, nervous and
the male reproductive systems. May cause birth defects. Avoid breathing dust. Avoid contact with
eyes, skin and clothing. Avoid exposure during pregnancy. Do not taste or swallow. Wash thoroughly
after handling.
Symptoms of Overexposure by Route of Exposure: This material is intended for intravenous injection
under the supervision of physicians.
Inhalation: Inhalation of significant amounts of the product is not anticipated to occur because of the
small size of individual containers. However, Fludarabine Phosphate is toxic if inhaled.
Contact with Skin or Eyes: High concentrations of Fludarabine Phosphate are toxic by skin absorption.
Skin rashes have also been reported.
Ingestion: Although ingestion is not an anticipated route of occupational exposure, this material is toxic
and may be harmful or fatal if swallowed. Symptoms similar to those identified under injection may
occur, including severe myelosuppression (neutropenia-decrease neutrophilic white blood cells,
thrombocytopenia-decrease platelets and anemia-decrease red blood cells).
Injection: Local redness and pain are the primary symptoms of accidental injection in an occupational
setting. Medical personnel are not anticipated to experience over-exposures to the therapeutic doses of
this product. See package insert for adverse reactions associated with therapeutic doses of this
product.
Health Effects or Risks From Exposure (An explanation in lay terms):
Acute: The primary health effects anticipated in an occupational setting include irritation of eyes and skin
as well as redness and local swelling after accidental injection. In case of over-exposure by injection,
burning sensation, myelosuppression (neutropenia, thombocytopenia and anemia), fever, chills,
infection, nausea, vomiting, malaise, fatigue, anorexia and weakness may occur. Death can occur in
the event of accidental overdose.
Chronic: This product may cause male reproductive disorders. Exposure during pregnancy may cause
birth defects.
Target Organs: This product may produce adverse effects on the bone marrow and nervous system.
Pre-Existing Medical Conditions: Conditions aggravated by exposure may include skin, respiratory,
blood, male reproductive and nervous system disorders.
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Material Safety Data Sheet
4. FIRST-AID MEASURES
Skin Exposure: Remove contaminated shoes and clothing and cleanse affected area(s) thoroughly by
washing with mild soap and water. If irritation or redness develops and persists, seek medical attention.
Fludarabine Phosphate for Injection
Eye Exposure: If irritation or redness develops, move victim away from exposure and into fresh air.
Flush eyes with clean water and seek medical attention. For direct contact, hold eyelids apart and flush
the affected eye(s) with clean water for at least 15 minutes. Seek medical attention.
Inhalation: Immediately move victim away from exposure and into fresh air. If respiratory symptoms or
other symptoms of exposure develop, seek immediate medical attention. If victim is not breathing, clear
airway and immediately begin artificial respiration. If breathing difficulties develop, oxygen should be
administered by qualified personnel. Seek immediate medical attention.
Ingestion: If swallowed, seek emergency medical attention. If victim is drowsy or unconscious and
vomiting, place on the left side with the head down and DO NOT give anything by mouth. If not vomiting
and professional advice is not available, DO NOT induce vomiting. If possible, do not leave victim
unattended and observe closely for adequacy of breathing.
Victims of chemical exposure must be taken for medical attention. Take a copy of the MSDS to the
physician or health professional with victim. Physicians should refer to Section 11 (Toxicological
Information) as well as the Physicians Desk Reference for additional treatment information.
Recommendations to Physicians: Fatal pulmonary toxicity has been reported following the injection of
Fludarabine Phosphate in combination with pentostatin (deoxycoformycin).
5. FIRE-FIGHTING MEASURES
Flash Point: No data Autoignition Temperature: No data
Flammable Limits (in air by volume, %): Lower: No data Upper: No data
Fire Extinguishing Equipment: Use extinguishing agent suitable for type of surrounding fire.
Water Spray: OK Carbon Dioxide: OK Halon: OK
Foam: OK Dry Chemical: OK Other: Any "ABC" Class
Unusual Fire and Explosion Hazards: No unusual fire or explosion hazards are expected.
Explosion Sensitivity to Mechanical Impact: Not sensitive.
Explosion Sensitivity to Static Discharge: Not sensitive.
Special Fire Fighting Procedures: For fires beyond the incipient stage, emergency responders in the
immediate hazard area should wear bunker gear. When the potential chemical hazard is unknown, in
enclosed or confined spaces, or when explicitly required by DOT, a self-contained breathing apparatus
should be worn. In addition, wear other appropriate protective equipment as conditions warrant (see
Section 8).
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Material Safety Data Sheet
Special Fire Fighting Procedures cont.: Isolate immediate hazard area and keep unauthorized
personnel out. Contain spill if it can be done with minimal risk. Move undamaged containers from
immediate hazard area if it can be done with minimal risk. Cool equipment exposed to fire with water, if
it can be done with minimal risk.
Fludarabine Phosphate for Injection
NFPA HAZARD CLASS: Health: 3 (High)
Flammability: 0 (Least)
Reactivity: 0 (Least)
6. ACCIDENTAL RELEASE MEASURES
Spill and Leak Response:
For small releases of this product, wear latex or nitrile gloves and safety glasses. Absorb spilled liquid
and rinse area thoroughly with soap and water.
For large or uncontrolled releases, stay upwind and away from spill. Isolate immediate hazard area and
keep unauthorized personnel out. Contain spill if it can be done with minimal risk. Wear appropriate
protective equipment including respiratory protection as conditions warrant (see Section 8). Prevent
spilled material from entering sewers, storm drains, other unauthorized treatment drainage systems, and
natural waterways. Notify appropriate federal, state, and local agencies. Minimize dust generation.
Immediate cleanup of any spill is recommended.
7. HANDLING and STORAGE
Work and Hygiene Practices: FLUDARABINE PHOSPHATE FOR INJECTION IS A CYTOTOXIC
AGENT. ALL WORK PRACTICES MUST BE DESIGNED TO REDUCE HUMAN EXPOSURE TO THE
LOWEST LEVEL. As with all chemicals, avoid getting this product ON YOU or IN YOU. Do not eat,
drink, smoke or apply cosmetics while handling the product. Wash hands thoroughly after handling.
Particular care in working with this product must be practiced in pharmacies and other preparation
areas, during manufacture of this product, and during patient administration. Precautions should be
taken during the following activities:
Withdrawal of needles from drug vials.
Drug transfers using syringes and needles or filter straws.
Expulsion of air from drug-filled syringes.
DO NOT CLIP OR CRUSH NEEDLE WITH WHICH THIS COMPOUND HAS COME IN CONTACT. Use of
this compound should meet the following provisions:
Work should be performed in a designated area for working with hazardous drugs.
Containment devices, such as a biological safety cabinet, should be used.
Contaminated waste must be properly handled.
Work areas must be regularly decontaminated.
Storage and Handling Practices: Employees must be trained to properly use the product. Ensure vials
are properly labeled. Store only in approved containers. Keep away from any incompatible materials or
conditions (see Section 10). Store under refrigeration, between 2掳C - 8掳C (36掳F -46掳F).
Protective Practices During Maintenance of Contaminated Equipment: When cleaning non-disposable
equipment, wear latex or nitrile gloves (double gloving is recommended), goggles, and lab coat. Wash
equipment with soap and water. All needles, syringes, vials and other disposable items contaminated
with this product should be disposed of properly.
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Material Safety Data Sheet
8. EXPOSURE CONTROLS - PERSONAL PROTECTION
Ventilation and Engineering Controls: Use in containment device, such as biological safety cabinet.
Follow standard medical product handling procedures.
Fludarabine Phosphate for Injection
Respiratory Protection: Not normally required for routine, medical administration of this product. A
NIOSH certified air-purifying respirator with a type 95 filter may be used under conditions where airborne
concentrations are expected to be excessive. Protection provided by air purifying respirators is limited
(see manufacturer鈥檚 respirator selection guide). Use a positive pressure air supplied respirator if there is
potential for uncontrolled release, exposure levels are not known, or any other circumstances where air-
purifying respirators may not provide adequate protection. A respiratory protection program that meets
OSHA's 29 CFR 1910.134 and ANSI Z88.2 requirements must be followed whenever workplace
conditions warrant a respirator's use.
Eye Protection: Use of approved eye protection (i.e., safety glasses with side shields) to safeguard
against potential eye contact, irritation, or injury is required. Depending on conditions of use, a face
shield may be necessary.
Hand Protection: Use latex, nitrile, or rubber gloves. Check gloves for leaks. Wash hands before and
after using gloves.
Body Protection: Wear lab coat, gown, or smock, as appropriate for procedure. No special body
protection required for routine, medical administration of this product.
Product Preparation Instructions for Medical Personnel: Follow standard procedure for handling
pharmaceutical materials and recommendations presented on the Package Insert.
9. PHYSICAL and CHEMICAL PROPERTIES
Relative Vapor Density (air = 1): ND Evaporation Rate (n-BuAc=1): ND
Specific Gravity (water = 1): ND Melting/Freezing Point: ND
Solubility in Water: Soluble Boiling Point: ND
ND pH: 7.2-8.2
Vapor Pressure, mm Hg @ 25掳C.
Odor Threshold: Odorless
.
Appearance and Color: White, lyophilized cake
ND = No Data
10. STABILITY and REACTIVITY
Stability: Stable under refrigeration, between 2掳C - 8掳C (36掳F -46掳F).
Materials With Which Substance is Incompatible: This product is generally compatible with other
common materials in a medical facility.
Hazardous Polymerization: Will not occur.
Conditions To Avoid: Excessive heat.
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Materials Safety Data Sheet
11. TOXICOLOGICAL INFORMATION
Toxicity Data: The following information is for Fludarabine Phosphate
IV LD50(rat-male) = 910 mg/kg IV LD50(rat-female) = 1050 mg/kg
Fludarabine Phosphate for Injection
IV LD50(mouse-male) =1404 mg/kg IV LD50(mouse-female) = 1235 mg/kg
IV LD50(mouse-combined) = 1321 mg/kg
IV LD50-five daily doses(mouse-male) = 593 mg/kg
IV LD50-five daily doses(mouse-female) = 496 mg/kg
IV LD50-five daily doses(mouse-combined) = 542 mg/kg
Suspected Cancer Agent: This product as well as all components of this product have NOT been identified
as carcinogens by NTP, IARC or OSHA.
Irritancy of Product: This product may be irritating to contaminated skin, eyes and other tissues.
Sensitization to the Product: This product is not expected to cause sensitization although individual
sensitivities may vary.
Reproductive Toxicity Information: Listed below is information concerning the effects of Fludarabine
Phosphate on human and animal reproductive systems. This material is classified as a Pregnancy
Category D (Risk to Fetus).
Mutagenicity: Fludarabine phosphate was not mutagenic to several strains of Salmonella typhimurium,
including TA-98, TA-100, TA-1535 and TA-1537. Also, it was not mutagenc to Chinese Hamster
Ovarian (CHO) cells at the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) locus under
both activated and non-activated metabolic conditions. Chromosomal aberrations were observed in an
in-vitro assay using CHO cells under metabolically activated conditions. Fludarabine phosphate was
determined to cause increased sister chromatid exchanges (SCE) using an in-vitro SCE assay under
both metabolically activated and non-activated conditions. In addition, fludarabine phosphate has also
been shown to be mutagenic as indicated by an increase in the number of micronucleated erthrocytes
(red blood cells) in the in-vivo mouse micronucleus test at doses up to 1000 mg/kg.
Embryotoxicity/Teratogenicity/Reproductive Toxicity: Studies in mice, rats and dogs have demonstrated
dose-related adverse effects on the male reproductive system. Observations consisted of a decrease
in mean testicular weights in mice and rats with a trend toward decreased testicular weights in dogs
and degeneration and necrosis of spermatogenic epithelium of the testes in mice, rats and dogs. The
possible adverse effects on fertility in humans have not been adequately evaluated.
Fludarabine Phosphate was teratogenic in rats and rabbits when administered intravenously.
Intravenous doses of 0, 1, 10 or 30 mg/kg/day were given to pregnant rats on days 6 to 15 of gestation.
At 10 and 30 mg/kg/day, there was an increased incidence of various skeletal malformations. Doses of
0, 1, 5 or 8 mg/kg/day were given to pregnant rabbits on days 6 to 15 of gestation. Dose-related
teratogenic effects manifested by external deformities and skeletal malformations were observed in
rabbits at the 5 and 8 mg/kg/day dosage levels. Drug-related deaths or toxic effects on maternal and
fetal weights were not observed. There are no adequate and well-controlled studies in pregnant
women, however, a single case report of congenital malformations associated with first trimester, in
utero, fetal exsposre has been published.
Target Organ Toxicity Information: Fludarabine Phosphate can severely suppress bone marrow function
resulting in anemia, thromocytopenia, and neutropenia. Life-threatening and sometimes fatal autoimmune
hyemolytic anemia has been reported to occur in patients receiving injections of Fludarabine Phosphate. It
has also been associated with severe neurologic and central nervous system effects including blindness,
coma and death.
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Materials Safety Data Sheet
11. TOXICOLOGICAL INFORMATION cont.
ACGIH Biological Exposure Indices: Currently there are no Biological Exposure Indices (BEIs) associated
Fludarabine Phosphate for Injection
with the components of this product.
12. ECOLOGICAL INFORMATION
All work practices must be aimed at eliminating environmental contamination.
Environmental Stability: This product will be relatively stable under ambient environmental conditions.
Effect of Materials on Plants or Animals: No specific information is available on the effect of Fludarabine
Phosphate on plants or animals in the environment.
Effect of Chemicals on Aquatic Life: No specific information is available on the effect of Fludarabine
Phosphate on plants or animals in the aquatic environment.
13. DISPOSAL CONSIDERATIONS
Preparing Wastes for Disposal: This material, if discarded as produced, is not a RCRA 鈥渓isted鈥? or
鈥渃haracteristic鈥? hazardous waste. Use resulting in chemical or physical change or contamination may
subject it to regulation as a hazardous waste. Along with properly characterizing all waste materials
consult state and local regulations regarding the proper disposal of this material.
U.S. EPA Waste Number: None
14. TRANSPORTATION INFORMATION
This Materials is not Hazardous as Defined by 49 CFR 172.101 by the U. S. Department of
Transportation
Proper Shipping Name: Not applicable
Hazard Class Number and Description: Not applicable
UN Identification Number: Not applicable
Packing Group: Not applicable
DOT Label(s) Required: Not applicable
North American Emergency Response Guidebook Number (1996): Not applicable.
MARINE POLLUTANT: No component of this product is listed as a Marine Pollutant (49 CFR 172.101,
Appendix B)
Transport Canada Transportation of Dangerous Goods Regulations: Not applicable.
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Materials Safety Data Sheet
15. REGULATORY INFORMATION
U.S. REGULATIONS:
Fludarabine Phosphate for Injection
U.S. SARA Reporting Requirements: The components of this product are not subject to the reporting
requirements of Sections 302, 304 and 313 of Title II of the Superfund Amendments and
Reauthorization Act.
U.S. SARA Threshold Planning Quantity: Not applicable
U.S. CERCLA Reportable Quantities (RQ): Not applicable
U.S. TSCA Inventory Status: Fludarabine Phosphate is a 鈥渄rug鈥? as defined by the Federal Food, Drug
and Cosmetic Act and is therefore not a chemical substance under TSCA.
California Safe Drinking Water and Toxic Enforcement Act (Proposition 65): This product does NOT
contain a chemical known to the State of California to cause developmental and reproductive effects.
Other U.S. Federal Regulations: Based on this product鈥檚 use, the requirements of the OSHA
Bloodborne pathogen Standard (29 CFR 1910.1030) are applicable.
ANSI Labeling (Based on 129.1, Provided to Summarize Occupational Exposure Hazards):
WARNING! HARMFUL OR FATAL IF SWALLOWED, INHALED OR ABSORBED THROUGH SKIN.
OVEREXPOSURE MAY CAUSE DAMAGE TO THE BONE MARROW, NERVOUS AND MALE
REPRODUCTIVE SYSTEMS. MAY CAUSE BIRTH DEFECTS. Fludarabine Phosphate should be
administered under the supervision of a qualified physician. Avoid over-exposure. Avoid breathing
dust. Avoid exposure during pregnancy. Avoid contact with eyes, skin and clothing. Do not eat, drink
or smoke when handling Fludarabine Phosphate. Do not taste or swallow. Wash thoroughly after
handling. Clean up spills promptly.
CANADIAN REGULATIONS:
Canadian DSL/NDSL Status: Fludarabine Phosphateis regulated by the Food and Drug Administration of
Health Canada and is therefore exempt from the requirements of CEPA.
16. OTHER INFORMATION
Issue Date: 09/14/00
Previous Issue Date: None
The information in this document is believed to be correct as of the date issued. HOWEVER, NO
WARRANTY OF MERCHANTABILITY, FITNESS FOR ANY PARTICULAR PURPOSE, OR ANY
OTHER WARRANTY IS EXPRESSED OR IS TO BE IMPLIED REGARDING THE ACCURACY OR
COMPLETENESS OF THIS INFORMATION, THE RESULTS TO BE OBTAINED FROM THE USE OF
THIS INFORMATION OR THE PRODUCT, THE SAFETY OF THIS PRODUCT, OR THE HAZARDS
RELATED TO ITS USE. This information and product are furnished on the condition that the person
receiving them shall make his own determination as to the suitability of the product for his particular
purpose and on the condition that he assume the risk of his use thereof.
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