Entereg庐 Capsules Effective Date: 17 July 2008
MSDS Number: 3
Version: 2
Adolor Corporation
877-857-7018 (24 h contact)
700 Pennsylvania Drive
Exton, PA 19341-1127
MATERIAL SAFETY DATA SHEET (MSDS)
Section 1. Product and Company Information
Entereg庐 Capsules 3, Version 2
Substance MSDS Number
Name
Alvimopan formulated product, alvimopan 12 mg capsules, ADL 8-2698, SB-
Synonyms
767905-KW, LY246736
[[2(S)-[[4(R)-(3-hydroxyphenyl)-3(R), 4-dimethyl-l-piperidinyl] methyl]-l-
Alvimopan
oxo-3-phenylpropyl] amino] acetic acid dihydrate
Chemical Name
Piperidine
Alvimopan
Chemical
Family
Capsule. Light blue opaque body with light blue opaque cap, hard gelatin
Appearance
capsule imprinted with ADL2698 in black ink on body and cap
Alvimopan is a peripherally acting mu-opioid receptor antagonist
Pharmaceutical
Category
Entereg庐 is indicated to accelerate the time to upper and lower
Medical
gastrointestinal recovery following partial large or small bowel resection
Indication
surgery with primary anastomosis.
Section 2. Composition and Information on Ingredients
Composition
Name CAS/EINECS/ELINCS#
(Wt %)
Alvimopan 170098-38-1 3.5 percent
Non-hazardous ingredients Not Assigned 96.5 percent
Section 3. Hazard Identification
Emergency Overview: Caution 鈥? pharmaceutical agent. Overexposure in the workplace may
lead to headache and gastrointestinal effects including nausea, vomiting, abdominal pain and soft
stools.
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Entereg庐 Capsules Effective Date: 17 July 2008
MSDS Number: 3
Version: 2
Eyes, Skin, Inhalation, and Ingestion
Relevant Routes of Exposure
Signs and Symptoms of Exposure
May produce slight irritation and stinging.
Eyes
May produce slight irritation. Stinging may occur if contact occurs with mucous
Skin
membranes or open wounds. Hypersensitivity reactions may occur.
Unknown, effects may be similar to those produced with ingestion (see below).
Inhalation
The effects of inhaling the capsule contents, or its vapors, have not been
determined. No specific studies have been conducted. Physical form suggests
that risk of inhalation is negligible.
Ingestion may cause headache, nausea, vomiting, abdominal pain, and soft stools.
Ingestion
Medical Conditions Aggravated By Exposure: Persons with current, prolonged use of opioids,
bowel disorders, or hypersensitivity to alvimopan may exhibit greater sensitivity to exposure.
Section 4. First Aid Measures - (by medical responders using 鈥淯niversal Precautions鈥?)
Exposed eyes should be irrigated with copious amounts of water for at least
Eyes
15 minutes. If irritation occurs and persists, seek medical attention.
Remove any contaminated clothing. Wash exposed area thoroughly with
Skin
soap and water. If irritation occurs or persists, seek medical attention.
Physical form suggests that risk of inhalation is negligible.
Inhalation
Do NOT induce vomiting unless directed to do so by medical personnel.
Ingestion
Never give anything by mouth to an unconscious person. If exposed subject
is conscious, give plenty of water to drink. If large quantities of this material
are swallowed, call a physician immediately.
There is no specific antidote. Symptomatic and supportive treatment of
Notes to Health
adverse effects is recommended. Persons with current, prolonged use of
Professionals
opioids, bowel disorders, or hypersensitivity to alvimopan may exhibit
greater sensitivity to exposure.
Refer to Section 11. Toxicological Information, for additional information on toxicity.
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Entereg庐 Capsules Effective Date: 17 July 2008
MSDS Number: 3
Version: 2
Section 5. Fire Fighting Measures
Not determined for Entereg庐 capsules. The flashpoint of
Flashpoint/Test method
alvimopan, the active pharmaceutical ingredient, is > 200 掳F
(closed cup).
Not expected for this product, although the packaging is
Fire and Explosion Hazards
combustible.
Not Determined
Lower Explosive Level/Upper
Explosive Level
Water spray, carbon dioxide or dry chemical.
Extinguishing Media
Fight fire from a safe distance. Wear full protective clothing.
Fire Fighting Instructions
Use water spray to keep exposed containers and equipment
cool. Toxic, corrosive or flammable thermal decomposition
products are expected when the product is exposed to fire.
Self-contained breathing apparatus and full protective
equipment is recommended for firefighters.
Section 6. Accidental Release Measures
Personal protective equipment should be worn when cleaning up a spill
Personal
(See Section 8. Exposure Controls and Personal Protection).
Precautions
Soak up contents of broken capsules with an absorbent material. Carefully
Clean-up
collect material and place in a properly labeled waste container for
Methods
disposal. Wash area of spill to remove from surfaces. Wash skin
thoroughly after handling. No specific decontamination or detoxification
procedures have been identified for this product. Take precautions to
prevent entry into waterways, sewers, or surface drainage systems.
Section 7. Handling and Storage
Avoid breaking or crushing capsules.
Handling
No storage requirements are necessary for occupational hazards. Follow
Storage
product information storage instructions to maintain efficacy.
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Entereg庐 Capsules Effective Date: 17 July 2008
MSDS Number: 3
Version: 2
Handling this product in final form presents minimal risk from occupational
Work/Hygiene
exposure. Normal room ventilation is expected to be adequate for routine
Practices
handling of this product. If capsules are crushed or broken, avoid contact
with skin, eyes, and clothing. If contact with skin or clothing occurs, wash
affected area thoroughly and change clothing. See also Section 4. First Aid
Measures.
Section 8. Exposure Controls and Personal Protection
If drug product handling produces broken capsules, a risk assessment of
Preventive
the procedure should be performed.
Measures
None required for normal handling. If capsules are crushed or broken,
Engineering
active drug substance may be released, and local exhaust ventilation may
Controls
be required.
Personal Protection:
Wear approved safety glasses with side shields or goggles where risk of
Eye and Face
eye exposure exists.
Protection
Avoid skin contact. Impervious gloves should be worn when handling
Skin Protection
capsules.
None normally required. Respiratory protection should be worn.
Respiratory
Respiratory protection must meet compliance with the OSHA 29 CFR
Protection
1910.134 and ANSI Z88.2 or equivalent, depending on local regulations.
Exposure Guidelines:
Ingredient ACGIH TLV OSHA PEL Adolor OEL
0.4 mg/m3
Alvimopan drug
Not established Not established
substance (8 hour TWA)
Section 9. Physical and Chemical Properties
Capsule. Light blue opaque body with light blue opaque cap, hard
Appearance/Physical
gelatin capsule imprinted with ADL2698 in black ink on body and cap.
State
Alvimopan is contained within a solid matrix.
Not applicable.
Melting Point
Not determined for Entereg庐 capsules. Alvimopan, the active
Solubility
pharmaceutical ingredient in alvimopan capsules, is insoluble in water
and soluble in ethanol and dimethyl sulfoxide (DMSO).
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Entereg庐 Capsules Effective Date: 17 July 2008
MSDS Number: 3
Version: 2
Section 10. Stability and Reactivity
This product is stable under normal handling and storage
Stability
conditions. Follow product information storage instructions to
maintain efficacy.
Oxidizers, excessive temperatures and an open flame.
Conditions to Avoid
Not determined for Entereg庐 capsules. Thermal decomposition
Hazardous Decomposition
products of alvimopan, the active pharmaceutical ingredient,
Products
include carbon oxides (CO, CO2), nitrogen oxides (NO, NO2),
sulfur oxides (SOx) and smoke.
Will not occur.
Hazardous Polymerization
Section 11. Toxicological Information
Pharmacological The active pharmaceutical ingredient in this product, alvimopan, is a
peripherally acting mu-opioid receptor antagonist.
Effects
Not expected to be toxic following ingestion.
Oral Toxicity
No studies have been conducted.
Inhalation
Toxicity
May produce slight irritation. Stinging may occur if contact occurs with
Skin Effects
mucous membranes or open wounds.
May produce slight irritation and stinging.
Eye Effects
Sensitization to alvimopan (allergic skin reaction) is not expected.
Sensitization
Sensitization to other components of the formulation may be possible.
Genetic Toxicity Not expected to be genotoxic under occupational exposure conditions.
Not expected to produce cancer in humans under occupational exposure
Carcinogenicity
conditions. No components are listed as carcinogens by Adolor, IARC, NTP
or US OSHA.
Not expected to produce adverse effects on fertility or development under
Reproductive
occupational exposure conditions.
Effects
Overexposure in the workplace might have the following effects: headache,
Other Adverse
nausea, vomiting, abdominal pain, and soft stools.
Effects
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Entereg庐 Capsules Effective Date: 17 July 2008
MSDS Number: 3
Version: 2
Section 12. Ecological Information
This material contains an active pharmaceutical ingredient. Local regulations
Summary
should be consulted prior to environmental release.
Specific information on alvimopan, the active pharmaceutical ingredient, is
provided below.
Ecotoxicity:
Aquatic
This material contains an active pharmaceutical ingredient that is not toxic
Activated Sludge
to activated sludge microorganisms.
Respiration
IC50: greater than 1000 mg/L, 3 hours, activated sludge
The 48-Hour EC50 for the test material to Daphnia magna, based on
Daphnid
nominal test concentrations, was 44 mg/L. The No Observed Effect
Concentration was 18 mg/L.
EC50: 44 mg/L, 48 hours, Daphnia magna
This material contains an active pharmaceutical ingredient that was not toxic
Algal
to algae at saturation in the test.
EC50: greater than 18 mg/L, 96 hours, Scenedesmus subspicatus, green
algae, non-static test
NOEL: 18 mg/L, 96 hours, Scenedesmus subspicatus, green algae, non-static
test
This material contains an active pharmaceutical ingredient that was not toxic
Fish
to fish at saturation in the test.
LC50: greater than 17 mg/L, 96 hours, semi-static test, rainbow trout
(Oncohyncus mykiss)
NOEL: 17 mg/L, 96 hours, semi-static test, rainbow trout (Oncohyncus
mykiss)
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Entereg庐 Capsules Effective Date: 17 July 2008
MSDS Number: 3
Version: 2
Mobility:
This material contains an active pharmaceutical ingredient that, for
Solubility
environmental fate predictions, has limited solubility in water.
This material contains an active pharmaceutical ingredient with octanol/water
Partitioning
partition coefficient data that suggests, for environmental fate predictions, the
active pharmaceutical ingredient will not have the potential to bioaccumulate
in the environment.
Persistence and Degradation:
No information available
Hydrolysis
No information available
Biodegradation
Section 13. Disposal Information
Collect for recycling or recovery if possible. The disposal
Waste Disposal
method for rejected products/returned goods must ensure that they
cannot be resold or re-used. The recommended method of
disposal is incineration.
Observe all local and national regulations when disposing of this
Regulatory Requirements
product.
Section 14. Transportation Information
This MSDS should accompany all shipments for reference in the event of spillage or accidental
release.
US Department of Transportation (DOT)
Proper Shipping Not regulated in transportation
Name
IATA/ICAO
Proper Shipping Not regulated in transportation
Name
IMDG
Proper Shipping Not regulated in transportation
Name
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Entereg庐 Capsules Effective Date: 17 July 2008
MSDS Number: 3
Version: 2
UN Classification and Labeling
Proper Shipping Transportation and shipping of this material is not restricted. It has no
Name known significant hazard requiring special packaging or labeling for air,
maritime, United States or European ground transport purposes
Section 15. Regulatory Information and Warning Labels
The following regulations apply to storage and/or handling. It is the responsibility of the end
user to determine the applicability of these regulations at their specific location.
This product is regulated under the Food, Drug, and Cosmetic Act.
This dosage form is exempt from the requirements of the OSHA
US OSHA 29CFR
Hazard Communication Standard
1910.1200
FDA-regulated material is exempt from TSCA
TSCA Status
Not listed
EPCRA Section 313
(SARA Title III)
Not listed
EPCRA Section 302
Not listed
CERCLA
Not a RCRA hazardous waste.
RCRA
Not applicable
DOT
Exempt from requirements of the EU Dangerous Preparations
EU
Directive. This product is regulated as a medicinal product, cosmetic
product or medical device.
Section 16. Other Key Information
None
Special Hazards
DISCLAIMER OF EXPRESSED AND IMPLIED WARRANTIES
Although reasonable care has been taken in the preparation of this document, Adolor
Corporation extends no warranties and makes no representations as to the accuracy or
completeness of the information contained therein, and assumes no responsibility regarding the
suitability of this information for the user's intended purposes or for the consequences of its use.
Each individual should make a determination as to the suitability of the information for his or her
particular purpose(s).
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