Material Safety Data Sheet
1. PRODUCT IDENTIFICATION
TRIMETHOPRIM (SMX-TMP) Injection, USP
Product Name SULFAMETHOXAZOLE and TRIMETHOPRIM (SMX-TMP) Injection,
USP
Product Use Medical Treatment; Antimicrobial
Manufacturer Teva Sicor Pharmaceuticals, Inc.
Address 11 Hughes
Irvine, CA 92618-1902
SULFAMETHOXAZOLE and
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
Common Names SMX-TMP
Chemical Name 4-Amino-N-(5-methyl-3-isoxazolyl) benzenesulfonamide) &
5-[(3,4,5-trimethoxyphenyl)methyl]-2,4-pyrimidinediamine
Chemical Formula C10H11N3O3S and C14H18N4O3
Chemical Family Antibacterial
How Supplied 80 mg SMX/16 mg TMP per mL in 5 mL, 10 mL, and 30 mL vials
Date of Preparation: January 27, 2006
2. COMPOSITION AND INGREDIENTS
EXPOSURE LIMITS IN AIR
CHEMICAL NAME CAS#
% ACGIH OSHA Other
TLV CEIL PEL CEIL
NE NE NE NE NE
Sulfamethoxazole 723-46-6 8
NE NE NE NE NE
Trimethoprim 738-70-5 2
NE NE NE NE NE
Propylene Glycol 57-55-6 40
1000 ppm NE 1000 ppm NE NE
Ethyl Alcohol 64-17-5 10
NE NE NE NE NE
Benzyl Alcohol 100-51-6 1
2 mg/m3- NE NE NE NE
Diethanolamine 111-42-2 <1
Skin
5 mg/m3 NE NE NE NE
Sodium Metabisulfite 7681-57-4 <1
NE NE NE NE NE
Water for Injection 7732-18-5 >37
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 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
TRIMETHOPRIM (SMX-TMP) Injection, USP
3. HAZARD IDENTIFICATION
EMERGENCY OVERVIEW: Material is a clear, pale yellow viscous solution. Eye and skin
Irritant. Injection or ingestion in large quantities may be harmful. May cause allergic skin and/or
respiratory reactions. May cause liver, blood or metabolic disturbances. Avoid contact with
eyes, skin and clothing. Do not taste or swallow. Wash thoroughly after handling.
Symptoms of Overexposure by Route of Exposure: This material is intended for intravenous infusion
SULFAMETHOXAZOLE and
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,
redness and damage of the eyes and redness, itching, burning and skin damage. May cause
allergic skin reactions.
Ingestion: Although ingestion is not an anticipated route of occupational exposure, this material has
a moderate degree of toxicity 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. However, effects including decreased urine volume, complete
cessation of urine production, dermatitis, rash and systemic metabolic changes may occur. See
package insert for other adverse reactions associated with therapeutic doses of this product.
Other: This product contains sodium metabisulfite and the symptoms of hypersensitivity or sulfite
allergy may include rash, fever, respiratory difficulty or asthma-like symptoms.
Contains benzyl alcohol which is potentially toxic when administered locally to neural tissues.
Benzyl alcohol has been reported to be associated with fatal 鈥済asping syndrome鈥? in premature
infants.
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. Over-exposure may affect the
kidney and the body鈥檚 ability to produce urine. Rash or other metabolic symptoms may occur.
Allergy-like reactions may develop.
Cancer: Limited animal studies suggest this product may be carcinogenic, but no human data are
available (see Section 11).
Chronic: Based on animal data, this material is not considered a reproductive toxicant (see Section
11).
Target Organs: Potential hazard to the liver and blood (see Section 11).
Pre-Existing Medical Conditions: Conditions aggravated by exposure may include skin, blood and
liver disorders.
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Material Safety Data Sheet
TRIMETHOPRIM (SMX-TMP) Injection, USP
4. FIRST-AID MEASURES
Skin Exposure: Remove contaminated shoes and clothing and flush affected area(s) with large
amounts of water. If skin surface is damaged, apply a clean dressing and seek medical attention. If
skin surface is not damaged, 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 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.
SULFAMETHOXAZOLE and
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 Physicians Desk Reference for additional treatment information.
5. FIRE-FIGHTING MEASURES
Flash Point: >200藲F Autoignition Temperature: Not applicable
Flammable Limits (in air by volume, %): Lower: Not applicable Upper: Not applicable
Fire Extinguishing Equipment: The size and nature of this product is such that it will not contribute to
the intensity of a fire. 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: When heated to decomposition, this product may emit toxic
fumes containing oxides of nitrogen.
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.
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Material Safety Data Sheet
5. FIRE-FIGHTING MEASURES cont鈥?
TRIMETHOPRIM (SMX-TMP) Injection, USP
NFPA HAZARD CLASS: Health: 1 (Slight)
Flammability: 1 (Slight)
Reactivity: 0 (Least)
6. ACCIDENTAL RELEASE MEASURES
Spill and Leak Response:
SULFAMETHOXAZOLE and
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. 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. Keep away from any incompatible materials
or conditions (see Section 10). Store at temperatures between 15掳C and 30掳C. Do not refrigerate.
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
TRIMETHOPRIM (SMX-TMP) Injection, USP
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
SULFAMETHOXAZOLE and
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, 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.
9. PHYSICAL and CHEMICAL PROPERTIES
Relative Vapor Density (air = 1): Negligible Evaporation Rate (n-BuAc=1): NA
Specific Gravity (water = 1): ND Melting/Freezing Point: NA
Solubility in Water: Soluble Boiling Point: NA
ND pH: 3-5 in solution
Vapor Pressure, mm Hg @ 25掳C.
Odor Threshold: ND
Appearance and Color: Clear to yellow liquid
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. Keep away from acids, caustics and avoid extreme pH
conditions.
Hazardous Polymerization: Will not occur.
Conditions To Avoid: Heat and contact with incompatible materials.
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Material Safety Data Sheet
TRIMETHOPRIM (SMX-TMP) Injection, USP
11. TOXICOLOGICAL INFORMATION
Toxicity Data - Sulfamethoxazole:
Oral LD50(rat) =6200 mg/kg IP LD50(rat) = 2690 mg/kg SubQ LD50(rat) >5 g/kg
Oral LD50(mouse) = 2300 mg/kg IV LD50(mouse) = 1460 mg/kg SubQ LD50(mouse) > 5g/kg
Toxicity Data 鈥? Trimethoprim:
Oral LD50(rat) = 500 mg/kg IP LD50 (rat) = 500 mg/kg SubQ LD50 (rat) >5 g/kg
SULFAMETHOXAZOLE and
Oral LD50(mouse) = 2764 mg/kg IP LD50 (mouse) = 400 mg/kg SubQ LD50 (mouse) >5 g/kg
IV LD50 (mouse) = 132 mg/kg
Suspected Cancer Agent: Long-term studies in animals to evaluate carcinogenic potential have not
been conducted. However, sulfamethoxazole was tested by oral administration in one study in rats. It
produced follicular-cell adenomas and carcinomas of the thyroid. It has not been listed as
carcinogenic by NTP, IARC or OSHA.
Irritancy of Product: This product is expected to be irritating to contaminated skin, eyes and other
tissues.
Sensitization to the Product: Sulfamethoxazole belongs to a class of drugs (sulfonamides) that are
considered sensitizers. The combination product has been reported to cause allergic responses when
given systemically.
Target Organ(s): Fatalities associate with administration of sulfonamides, although rare, have occurred
due to severe reactions, including Steven-Johnson Syndrome, toxic epidermal necrolysis, fulminant
heptatic necrosis, acranulocytosis, aplastic anemia and other blood dyscrasias.
Reproductive Toxicity Information: Listed below is information concerning the effects of Trimethoprim
and Sulfamethoxazole on human and animal reproductive systems. This material is classified as a
Pregnancy Category C: (Risk to Fetus Cannot be Ruled-Out)
Mutagenicity: Bacterial mutagenic studies have not been performed with sulfamethoxazole /
trimethoprim in combination. Trimethoprim was demonstrated to be non-mutagenic in the Ames
assay. In studies at two laboratories, no chromosomal damage was detected in cultured Chinese
hamster ovary cells at concentrations approximately 500 times human plasma levels; at
concentrations approximately 1000 times human plasma levels in these same cells, a low level of
chromosomal damage was induced at one of the laboratories. No chromosomal abnormalities
were observed in cultured human leukocytes at concentrations of trimethoprim up to 20 times
human steady-state plasma levels.
No chromosomal effects were detected in peripheral lymphocytes of human subjects receiving
320 mg of trimethoprim in combination with up to 1600 mg of sulfamethoxazole per day for as
long as 112 weeks.
Embryotoxicity/Teratogenicity/ReproductiveToxicity: Negative for fertility impairment in rats
treated with the combination of 350 mg/kg of sulfamethoxazole and 70 mg/kg of trimethoprim.
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Material Safety Data Sheet
TRIMETHOPRIM (SMX-TMP) Injection, USP
11. TOXICOLOGICAL INFORMATION cont鈥?
In rats, very high oral doses of 533 mg/kg sulfamethoxazole or 200 mg/kg trimethoprim produced
teratologic effects manifested mainly as cleft palates. The highest dose which did not cause cleft
palates in rats was 512 mg/kg sulfamethoxazole or 192 mg/kg trimethoprim when administered
separately. In two studies in rats, no teratogenicity was observed when 512 mg/kg of
sulfamethoxazole was used in combination with 128 mg/kg of trimethoprim. In one study, however,
cleft palates were observed in one litter out of 9 when 355 mg/kg of sulfamethoxazole was used in
combination with 88 mg/kg of trimethoprim. In some rabbit studies, an overall increase in fetal loss
SULFAMETHOXAZOLE and
(dead and resorbed and malformed conceptuses) was associated with doses of trimethoprim 6
times the human therapeutic dose.
While there are no large, well-controlled studies on the use of sulfamethoxazole; trimethoprim in
pregnant women, Brumfitt and Pursell as reported in the package labeling, in a retrospective study,
studied the outcome of 186 pregnancies during which the mother received either placebo or oral
sulfamethoxazole; trimethoprim. The incidence of congenital abnormalities was 4.5% (3 of 66) in
those who received placebo and 3.3% (4 of 120) in those receiving sulfamethoxazole /trimethoprim.
There were no abnormalities in the 10 pediatric patients whose mothers received the drug during
the first trimester. In a separate survey, Brumfitt and Pursell also found no congenital abnormalities
in 35 pediatric patients whose mothers had received oral sulfamethoxazole/trimethoprim at the time
of conception or shortly thereafter.
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: Studies indicate that this product should not cause significant
impact on plants or animals.
Effect of Chemicals on Aquatic Life: No specific information is available on the effect 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
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Material Safety Data Sheet
14. TRANSPORTATION INFORMATION
TRIMETHOPRIM (SMX-TMP) Injection, USP
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)
SULFAMETHOXAZOLE and
Transport Canada Transportation of Dangerous Goods Regulations: Not applicable
15. REGULATORY INFORMATION
U.S. REGULATIONS
U.S. SARA Reporting Requirements: The component diethanolamine is 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: Ciprofloxacin 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 cancer or 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.
CANADIAN REGULATIONS
Canadian DSL/NDSL Status: SULFAMETHOXAZOLE and TRIMETHOPRIM (SMX-TMP) is regulated
by the Food and Drug Administration of Health Canada and is therefore exempt from the requirements of
CEPA.
ANSI Labeling (Based on 129.1, Provided to Summarize Occupational Exposure Hazards): Eye and
Skin Irritant. Injection or ingestion in large quantities may be harmful. May cause allergic skin and/or
respiratory reactions. May cause liver, blood or metabolic disturbances. Avoid contact with eyes, skin
and clothing. Do not taste or swallow. Wash thoroughly after handling. This material should be
administered under the supervision of a qualified physician. Do not eat, drink or smoke when
handling this material. Clean up spills promptly.
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Material Safety Data Sheet
16. OTHER INFORMATION
TRIMETHOPRIM (SMX-TMP) Injection, USP
Issue Date: 1/27/06
Previous Issue Date: 8/04/94
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
SULFAMETHOXAZOLE and
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 assumes the risk of his use thereof.
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