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2,4-Imidazolidinedione,5,5-diphenyl-3-[(phosphonooxy)methyl]-, sodium salt (1:2)

Material Safety Data Sheet

1. PRODUCT IDENTIFICATION

Product Name Fosphenytoin Sodium Injection
Product Use Medical Treatment; Anticonvulsant
Manufacturer Teva Parenteral Medicines, Inc.
Address 11 Hughes
Fosphenytoin Sodium Injection

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.newsicor.com

Cerebyx?
Common Names

Chemical Name 5,5-diphenyl-3-{(phosphonooxy)methyl}-2,4-imidazolidnedione disodium salt
Chemical Formula C16H13N2Na2O6P
Chemical Family Hydantoin
How Supplied 75mg/mL in 2mL and 10mL vials

Date of Preparation: February 17, 2006

2. COMPOSITION AND INGREDIENTS
EXPOSURE LIMITS IN AI CHEMICAL NAME CAS#
Wt% ACGIH OSHA Other
TWA*
TLV CEIL PEL CEIL
0.6ug/m3
Fosphenytoin Sodium 92134-98-0 7.50 NE NE NE NE
Tromethamine, USP (Tris) 77-86-1 1.21 NE NE NE NE NE
Water (for injection) 7732-18-5 Balance NE NE NE NE NE
2mg/m3 2mg/m3
Trace NE NE NE
Sodium hydroxide (pH adjustment) 1310-73-2
7647-01-0 Trace NE 5ppm NE 5ppm NE
Hydrochloric acid (pH adjustment)

NE - Not Established C - Ceiling Limit * Warner Lambert Derived 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.
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Material Safety Data Sheet

3. HAZARD IDENTIFICATION

EMERGENCY OVERVIEW: Material is a clear, colorless to pale yellow solution.
Overexposure may cause damage to the liver and nervous systems. Avoid breathing vapor. Avoid
contact with eyes, skin and clothing. Do not taste or swallow. Wash thoroughly after handling.
Fosphenytoin Sodium Injection

Symptoms of Overexposure by Route of Exposure: This material is intended for intravenous or
intramuscular 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: Contact may cause irritation. Effects may include stinging, watering, and
redness of the eyes, and redness and a burning sensation on the skin. Skin rash may occur.
Ingestion: Although ingestion is not an anticipated route of occupational exposure, this material is toxic if
ingested. Symptoms similar to those identified under injection may occur.
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,
effects such as hypotension, nausea, vomiting, headache, central nervous system toxicity (clumsiness,
confusion, uncontrolled back-and-forth or rolling eye movements, slurred speech, stuttering, trembling of
hands, nervousness or irritability), as well as constipation, mild drowsiness, dizziness, sleep
disturbances, bleeding, tender or swollen gums, swelling of breasts in males and excessive hair growth
on body and face may occur. Although rare, serious reactions including fever, muscle pain, skin rash
and sore throat may indicate onset of lupus erythematosus, phenytoin hypersensitivity syndrome,
Stevens-Johnson syndrome, or toxic epidermal necrolysis and require immediate medical attention.
Possible allergic reaction to material if inhaled, ingested, or in contact with skin.
Cancer: Fosphenytoin is an injectable prodrug of Phenytoin. Phenytoin is classified by NTP and IARC
as possibly carcinogenic to humans. It is not listed as carcinogenic by OSHA.
Chronic: There is an unconfirmed association between the general use of antiepileptic drugs during
pregnancy and malformations and malignancies in human offspring (see Section 11).
Target Organs: Cases of acute liver toxicity, including liver failure, as well as unconfirmed reports of
lymph node abnormalities have been associated with phenytoin. (see Section 11).
Other: Due to an increased fraction of unbound phenytoin in patients with renal or hepatic disease, or in
those with hypoalbuminemia, the interpretation of total phenytoin plasma concentrations should be
made with caution

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Material Safety Data Sheet

3. HAZARD IDENTIFICATION cont.

Pre-Existing Medical Conditions: Conditions aggravated by exposure may include blood dyscrasias,
heart disease or function impairment, impaired liver or kidney function, and porphyria.
Fosphenytoin Sodium Injection

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: If irritation or redness develops, move victim away from exposure and into fresh air.
Flush eyes with clean water and 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.

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 Physician??s Desk Reference for additional treatment information. .

5. FIRE-FIGHTING MEASURES
Flash Point: Non-flammable Autoignition Temperature: Not applicable
Flammable Limits (in air by volume, %): Lower: Not applicable Upper: Not applicable

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.

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Material Safety Data Sheet

5. FIRE-FIGHTING MEASURES cont.

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
Fosphenytoin Sodium Injection

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 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. .

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.
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 under refrigeration at 20C to 80C (360F to 460F).
Keep away from sources of ignition and any incompatible materials or conditions (see Section 10).

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 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
Fosphenytoin Sodium Injection

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: Approved eye protection to safeguard against potential eye contact, irritation or injury is
recommended. Depending on conditions of use, a face shield may be necessary.
Hand Protection: Use latex or nitrile 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.

9. PHYSICAL and CHEMICAL PROPERTIES
Relative Vapor Density (air = 1): ND Evaporation Rate (n-BuAc=1): N Specific Gravity (water = 1): ~1 Melting/Freezing Point: 0??C (32??F)
Solubility in Water: Soluble Boiling Point: 100??C (212??F)
ND pH: 8.6 ?? 9.0
Vapor Pressure, mm Hg @ 25??C.
Odor Threshold: Odorless
.
Appearance and Color: Clear, colorless to pale yellow solution

ND = No Data

10. STABILITY and REACTIVITY

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.

Hazardous Polymerization: Will not occur.

Hazardous Combustion Products: Carbon monoxide and carbon dioxide.

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Materials Safety Data Sheet

11. TOXICOLOGICAL INFORMATION
Toxicity Data: The following information is for Phenytoin, the active metabolite of Fosphenytoin Sodium
Oral LD50(rat) =1.53 g/kg Oral LD50(mouse) = 165 mg/kg SubQ LD50 (g.pig) = 280 mg/kg
IP LD50(rat) =138 mg/kg IP LD50(mouse) = 103 mg/kg
SubQ LD50(rat) =230 mg/kg IV LD50(rat) = 90 mg/kg
Fosphenytoin Sodium Injection

SubQ LD50(mouse) =400 mg/kg IV LD50(mouse) = 98 mg/kg

The following information is for Fosphenytoin Sodium:

Suspected Cancer Agent: Fosphenytoin Sodium is an injectable prodrug of Phenytoin. Phenytoin is
classified by NTP and IARC as possibly carcinogenic to humans. It is not listed as carcinogenic by
OSHA.
Irritancy of Product: This product is not expected to be irritating to contaminated skin, eyes and other
tissues. The active ingredient is non-irritating to the eyes and the skin.
Sensitization to the Product: Persons sensitive to one hydantoin anticonvulsant may be sensitive to this
material also. Persons sensitive to barbiturates, succinimides, or oxazolidinediones may show cross-
sensitivity to this material.
Target Organ(s): Exposure to this material may cause liver (including liver failure) and nervous system
(numbness, tingling or pain in hands and feet) damage.

Reproductive Toxicity Information: Listed below is information concerning the effects of Fosphenytoin
Sodium on human and animal reproductive systems. This material is classified as a Pregnancy
Category D.

Mutagenicity: Fosphenytoin Sodium did not cause mutations in bacterial or mammalian cells, but
caused chromosome damage in one mammalian cell assay.

Embryotoxicity/Teratogenicity/Reproductive Toxicity: Some reports in clinical literature have indicated
that therapeutic use of certain hydantoin anticonvulsants during pregnancy may result in congenital
abnormalities in the offspring. However, a definite cause and effect relationship has not been
established, and most epileptic mothers have delivered normal babies. Exposure to hydantoins prior
to delivery may lead to serious bleeding problems in the mother and baby. Also, there have been
isolated reports of malignancies in children whose mothers received phenytoin during pregnancy.

In rats, Fosphenytoin sodium had adverse effects on fertility and, based on one study, caused some
birth defects.

ACGIH Biological Exposure Indices: Currently there are no Biological Exposure Indices (BEIs)
associated with the components of this product.

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Materials Safety Data Sheet

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
Fosphenytoin Sodium Injection

Fosphenytoin Sodium on plants or animals in the environment.
Effect of Chemicals on Aquatic Life: No specific information is available on the effect of Fosphenytoin
Sodium 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 ??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 .

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:
U.S. SARA Reporting Requirements: The components of this product are not subject to the reporting
Fosphenytoin Sodium Injection

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: Fosphenytoin Sodium 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):
OVEREXPOSURE MAY CAUSE DAMAGE TO THE LIVER and NERVOUS SYSTEMS. Fosphenytoin
Sodium should be administered under the supervision of a qualified physician. Avoid over-exposure.
Avoid breathing vapor. Avoid contact with eyes, skin and clothing. Do not eat, drink or smoke when
handling Fosphenytoin Sodium. Do not taste or swallow. Wash thoroughly after handling. Clean up
spills promptly.

CANADIAN REGULATIONS:
Canadian DSL/NDSL Status: Fosphenytoin Sodium is regulated by the Food and Drug Administration of
Health Canada and is therefore exempt from the requirements of CEPA. .

16. OTHER INFORMATION
Issue Date: 03/11/04
Previous Issue Date: 04/10/03

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 O 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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