Material Safety Data Sheet
1. PRODUCT IDENTIFICATION
Product Name Flumazenil Injection
Product Use Medical Treatment; Antagonizes the action of benzodiazepines on the central
nervous system.
Manufacturer Teva Parenteral Medicines, Inc.
Address 11 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
Flumazenil Injection
Common Names Romazicon?br>
Chemical Name Ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo-
[1,5-a][1,4]benzodiazepine-3-carbonxylate
Chemical Formula C15H14FN3O3
Chemical Family Benzodiazepine antagonist
How Supplied 0.1 mg/mL concentration in 5 mL and 10 mL vials
Date of Preparation: July 23, 2002
2. COMPOSITION AND INGREDIENTS
EXPOSURE LIMITS IN AIR
CHEMICAL NAME CAS# % by wt ACGIH OSHA IDLH OTHER
TLV STEL PEL STEL
Flumazenil 78755-81-4 0.01 NE NE NE NE NE NE
Methylparaben 99-76-3 0.18 NE NE NE NE NE NE
Propylparaben 94-13-3 0.02 NE NE NE NE NE NE
Edetate Disodium 139-33-3 0.01 NE NE NE NE NE NE
Sodium Chloride 7647-14-5 0.9 NE NE NE NE NE NE
Glacial Acetic Acid 64-19-7 0.01 10ppm 15ppm 10ppm 25ppm 50ppm NE
0.05 N HCl 7647-01-0 0.5 NE 5ppm (C) NE 5ppm (C) 50ppm NE
or or
2mg/m3 (C) 2mg/m3 10mg/m3
0.05 N NaOH (to adj. pH) 1310-73-2 NE
Water (for injection) 7732-18-5 Balance NE NE NE NE NE NE
C = CEILING
NE - Not Established C - Ceiling Limit
NOTE: All WHMIS required information is included. It is located in appropriate sections based on the ANSI Z400.1 ?1998 format
CHEMTREC NUMBER: Use only in the event of a chemical emergency involving a spill, leak, fire, exposure or accident involving this
drug.
3. HAZARD IDENTIFICATION
EMERGENCY OVERVIEW: Material is a clear, colorless solution. May be harmful if swallowed.
Avoid contact with eyes, skin and clothing. Do not taste or swallow. Wash thoroughly after handling.
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Material Safety Data Sheet
3. HAZARD IDENTIFICATION cont.
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.
Contact with Skin or Eyes: Flumazenil may be mildly irritating to eyes and skin. Eye contact may cause
stinging, watering, and redness. Skin contact may cause redness, itching, and burning.
Ingestion: Although ingestion is not an anticipated route of occupational exposure, this material is
Flumazenil Injection
moderately toxic and may be harmful if swallowed. Symptoms similar to those identified under acute
injection may occur, including impaired vision, headaches, drowsiness, lack of muscular coordination,
increase or decrease in blood pressure, chest pains and cardiac arrest.
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 mild irritation of eyes
and skin as well as redness and local swelling after accidental injection. In case of over-exposure by
injection, impaired vision, headaches, dizziness, drowsiness, fatigue, nausea, vomiting, lack of muscular
coordination, increase or decrease in blood pressure, irregular heartbeat, chest pains and cardiac arrest
may occur.
Chronic: No chronic adverse effects known.
Target Organs: This product may produce adverse effects on the cardiovascular system (see Section
11).
Other Comments: Use has been associated with the occurrence of seizures (see package insert).
Pre-Existing Medical Conditions: Conditions aggravated by exposure may include respiratory disorders.
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.
Eye Exposure: Move victim away from exposure and into fresh air. If irritation or redness develops, flush
eyes with clean water and seek immediate 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: If respiratory symptoms develop, move victim away from source of exposure and into fresh
air. If symptoms persist, seek 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.
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Material Safety Data Sheet
4. FIRST-AID MEASURES cont.
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.
5. FIRE-FIGHTING MEASURES
Flumazenil Injection
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). 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.
NFPA HAZARD CLASS: Health: 2 (Moderate)
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. Dike far ahead of spill for later recovery or disposal. Spilled material may be
absorbed into an appropriate absorbent material. Notify appropriate federal, state, and local agencies.
Immediate cleanup of any spill is recommended.
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Material Safety Data Sheet
7. HANDLING and STORAGE
Work and Hygiene Practices: 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.
Flumazenil Injection
Expulsion of air from drug-filled syringes.
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 in dry place at room temperature. Product must not be used if it is
discolored or contains a precipitate.
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.
8. EXPOSURE CONTROLS - PERSONAL PROTECTION
Ventilation and Engineering Controls: Use with adequate ventilation. Follow standard medical product
handling procedures.
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's 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: The use of a face shield and/or chemical goggles to safeguard against potential eye
contact, irritation, or injury is recommended.
Hand Protection: Use latex, nitrile, or rubber gloves. Check gloves for leaks. Wash hands before and
after using gloves.
Body Protection: No special body protection required for routine, medical administration of this product.
Wear lab coat, gown, or smock, as appropriate for procedure.
Product Preparation Instructions for Medical Personnel: Follow standard procedure for handling
pharmaceutical materials and recommendations presented on the Package Insert.
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Material Safety Data Sheet
9. PHYSICAL and CHEMICAL PROPERTIES
Relative Vapor Density (air = 1): ND Evaporation Rate (n-BuAc=1): <1
Specific Gravity (water = 1): ND Melting/Freezing Point: ND
Solubility in Water: Insoluble Boiling Point: 100癈 (212癋)
ND pH: ND
Vapor Pressure, mm Hg @ 25癈.
. Odor Threshold: Odorless
Appearance and Color: Clear, Colorless Solution
ND = No Data
10. STABILITY and REACTIVITY
Flumazenil Injection
Stability: Stable under normal conditions of storage and handling.
Materials With Which Substance is Incompatible: This product is generally compatible with other
common materials in a medical facility. Avoid contact with acids and bases (hydrolysis).
Hazardous Polymerization: Will not occur.
Conditions To Avoid: Protect from refrigeration and freezing.
11. TOXICOLOGICAL INFORMATION
Toxicity Data: The following information is for Flumazenil
IV LD50(rat) = 85 mg/kg Oral LD50(mouse) = 1300 mg/kg IP LD50(rat) = 1360 mg/kg
IV LD50(mouse) = 143 mg/kg Oral LD50 (rat) = 4200 mg/kg IP LD50(mouse) = 4 g/kg
Oral LD50 (rabbit) = 2 g/kg
Suspected Cancer Agent: This product has NOT been identified as a carcinogen by NTP, IARC or OSHA.
No studies in animas have been performed to evaluate the carcinogenic potential of Flumazenil.
Irritancy of Product: This product may be mildly irritating to eyes and other tissues.
Sensitization to the Product: This product may cause sensitization when administered intradermally.
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Material Safety Data Sheet
11. TOXICOLOGICAL INFORMATION cont.
Reproductive Toxicity Information: Listed below is information concerning the effects of Flumazenil
Injection on human and animal reproductive systems. This material is classified as a Pregnancy Category
C (Risk to Fetus Cannot be Ruled-Out).
Mutagenicity: Negative in the Ames Salmonella test system, S. cerevisiae D7, Chinese hamster cells,
peripheral human lymphocytes and in in-vivo mouse micronucleaus assays. Flumazenil caused a
slight increase in unscheduled DNA synthesis in rat hepatocyte culture at concentrations, which were
also cytotoxic. No increase in DNA repair was observed in male mouse germ cells in an in-vivo DNA
repair assay.
Flumazenil Injection
Embryotoxicity/Teratogenicity/Reproductive Toxicity: Flumazenil did not demonstrate teratogenic effects
in rats and rabbits following oral treatments during organogenisis of up to 150 mg/kg/day. In rabbits,
embryocidal effects were seen at 50 mg/kg (as evidenced by increased pre- and post-implantation
losses). When pregnant rats were given oral doses of 125 mg/kg/day, pup survival was decreased
during the lactation period, pup liver weight was increased at weaning and incisor eruption and ear
opening in the offspring was delayed. A reproduction study in male and female rats did not show any
impairment of fertility at oral dosages of 125 mg/kg/day.
ACGIH Biological Exposure Indices: Currently there are no Biological Exposure Indices (BEIs) associated
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 Flumazenil
on plants or animals in the environment.
Effect of Chemicals on Aquatic Life: Barely toxic for planktonic crustaceans (Daphnia magna)
EC50 (48 h) >518 mg/l
NOEC (48 h) 65.6 mg/l
(FDA Technical Assistance Document No. 4.08)
13. DISPOSAL CONSIDERATIONS
Preparing Wastes for Disposal: This material, if discarded as produced, is not a RCRA "listed" or
"characteristic" 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
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Material Safety Data Sheet
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.
Flumazenil Injection
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
15. REGULATORY INFORMATION
U.S. REGULATIONS:
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: Flumazenil is a "drug" 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's 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):
CAUTION! MAY BE HARMFUL IF SWALLOWED. Flumazenil should be administered under the
supervision of a qualified physician. Avoid over-exposure. Avoid contact with eyes, skin and clothing.
Do not eat, drink or smoke when handling Flumazenil Injection. Do not taste or swallow. Wash
thoroughly after handling. Clean up spills promptly.
CANADIAN REGULATIONS:
Canadian DSL/NDSL Status: Flumazenil is regulated by the Food and Drug Administration of Health
Canada and is therefore exempt from the requirements of CEPA.
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Material Safety Data Sheet
16. OTHER INFORMATION
Issue Date: 07/23/02
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
Flumazenil Injection
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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