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Levobunolol hydrochloride

MATERIAL SAFETY DATA SHEET

Issued: 09/07/94 Prepared by: Gary Wong
Revised: 01/29/02 Manager EHS
Revision: 01 Core No. 284

1. PRODUCT AND COMPANY IDENTIFICATION

Levobunolol Hydrochloride Ophthalmic Solution USP, 0.25%
Product Name:
Same
Generic Name:
24208-545-05 ( 5 ml)
NDC No.
24208-545-10 (10 ml)

Prescription only medicine, filled inside plastic bottle suitable
Legal Category:
for dispensing, and overpacked inside a cardboard carton.

Drug Composition: Beta-adrenoceptor blocker (Reduces intraocular pressure in
the eye)

BAUSCH & LOMB PHARMACEUTICALS, INC.
8500 Hidden River Parkway
Tampa, FL 33637
Information: (800) 323-0000 (M-F) 8am-5pm EST
Emergency: (800) 227-1427 24 hrs

2. COMPOSITION/INFORMATION ON INGREDIENTS
3 3
Description CAS # TLV (mg/m ) PEL(mg/m ) % Content

Levobunolol HCL 27912-14-7 NE NE 0.25
Polyvinyl Alcohol 9002-89-5 NE NE >1

Ingredients <1% - Sodium Chloride, Sodium Phosphate, Edetate Disodium, Sodium
Metabisulfite, Potassium Phosphate, Benzalkonium Chloride

BAUSCH & LOMB Pharmaceuticals Division
MSDS: Levobunolol Hydrochloride Ophthalmic Solution USP, 0.25%

3. HAZARDS IDENTIFICATION

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EMERGENCY OVERVIEW

Plastic bottle in a cardboard box. Clear, colorless to light yellowish solution. Potent
medication. Individuals with asthma, cardiac disease and diabetes may be more
susceptible to systemic effects. Patients taking phenothiazine and beta-adrenergic
compounds can experience additive low blood pressure effects. Persons with
various strong allergies can have an anaphylactic reaction to this preparation.
Toxic by ingestion.

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POTENTIAL HEALTH HAZARDS

(NTP) No No No
Carcinogenicity: (IARC) (OSHA)

Eye: May cause irritation, slight burning sensation on application and
hypersensitivity (anaphylactic), especially in individuals subject to allergies. Topically
administered beta-adrenergic compounds can be absorbed systemically (whole
body) and effects may include acute toxicity. Acute toxicity effects include severe
respiratory distress (especially asthma sufferers), cardiac effects and heart failure.
Symptoms of thyroid over activity (thyrotoxicosis) and low blood sugar
(hypoglycemia) may be masked by the effects of levobunolol. It is not known
whether levobunolol is excreted in the milk of nursing mothers. Systemic beta-
blockers are known to be excreted in breast milk.

Skin: May cause irritation. Can cause hypersensitivity, including localized and
generalized rash. Systemic absorption is possible with repeated or prolonged
contact.(See Eye).

Ingestion: May cause irritation and hypersensitivity, especially in individuals with
other allergies. Toxic by ingestion due to systemic absorption. Can also cause
nausea and diarrhea.(See Eye).

Inhalation: May cause irritation and hypersensitivity. May cause systemic
effects.(See Eye).

Chronic Effects: As with other topically administered ophthalmic drugs, levobunolol
may be absorbed systemically. The same adverse reactions found with systemic
administration of beta-adrenergic blocking agents may occur with topical
administration. Severe respiratory and cardiac reactions, including death due to
bronchospasm in patients with asthma, and death in association with cardiac failure
have been reported with topical application of beta-adrenergic blocking agents.
Levobunolol may mask signs (e.g. rapid heart beat) of thyrotoxicosis. This product
BAUSCH & LOMB Pharmaceuticals Division
MSDS: Levobunolol Hydrochloride Ophthalmic Solution USP, 0.25%

contains sodium metabisulfite which can cause allergic-type reactions in some
individuals.

Target Organs: Eye, heart, skin, digestive and respiratory tract, brain and thyroid.

Medical Conditions Aggravated by Long Term Exposure: Patients with
hypersensitivity to other beta-adrenergic agents may have reactions to levobunolol.
Individuals with a hypersensitivity to any component of this product. Patients
conditions which may be affected include bronchial asthma, severe chronic
pulmonary disease and cardiac disease. Beta adrenergic agents can mask the
symptoms of hypoglycemia in diabetic patients. Levobunolol can mask signs (e.g.
tachycardia) of thyrotoxicosis.

4. FIRST AID MEASURES

Eyes: If not prescribed this medication, rinse immediately with copious amounts of
water for at least 20 minutes. Contact a physician.

Skin: Remove all contaminated clothing and wash skin with copious amounts of
water for at least 20 minutes. Contact physician if skin becomes irritated.
Ingestion: Wash out mouth and give plenty of water and bland fluids. Seek
professional assistance.

Inhalation: Remove person to fresh air, and if breathing stops, use artificial
respiration. Contact physician immediately.

Note to Physicians:
?? Non-cardioselective beta-adrenoceptor blockers reduce cardiac output.
?? Patients conditions which may be affected include bronchial asthma, severe
chronic pulmonary disease, sinus bradycardia, second and third degree
atrioventricular block, overt cardiac failure, cardiogenic shock or hypersensitivity to
any component of this product.
?? Beta adrenergic agents may mask the symptoms of hypoglycemia in diabetic
patients.
?? Levobunolol can mask signs (e.g. tachycardia) of thyrotoxicosis.
?? Persons with a history of serious anaphylactic reactions may be more reactive to
repeated contact to levobunolol, either accidental, diagnostic, or therapeutic.
Patients with hypersensitivity reactions may be unresponsive to the usual doses of
epinephrine used to treat allergic reactions.

5. FIRE FIGHTING MEASURES

Flammable Properties: Flash point: NE Method: NE

Hazardous Products: Acetaldehyde, crotonaldehyde, acetone, sulfur dioxide (SO2)
and toxic fumes.
BAUSCH & LOMB Pharmaceuticals Division
MSDS: Levobunolol Hydrochloride Ophthalmic Solution USP, 0.25%

Extinguishing Media: Dry chemical, carbon dioxide, halon, water spray or fog, and
foam on surrounding materials.

Fire Fighting Instructions: Wear self-contained breathing apparatus and protective
clothing. Use water spray to keep fire-exposed containers cool. Do not spray water
into the burning material.

6. ACCIDENTAL RELEASE MEASURES

Large/Small Spills: Use personal protective equipment. Contain the spill to
prevent drainage into sewers, drains or streams. Use absorbent material to solidify
the spill. Shovel or scoop up solidified waste. Dispose of material according to
Federal, State and Local regulations.

7. HANDLING AND STORAGE

Handling: Avoid contact with product and use caution to prevent puncturing
containers. No special protective equipment or procedures are required in the
clinical or home environment.

Storage: Store product upright in original containers with the cap tightly closed at a
0 0 0 0
controlled room temperature 15 -30 C (59 - 86 F). KEEP THIS AND ALL DRUGS
OUT OF THE REACH OF CHILDREN.

8. EXPOSURE CONTROL/PERSONAL PROTECTION

Engineering Controls: In the manufacturing plant, provide adequate ventilation for
the raw material handling and compounding process which will maintain the dust
and vapor levels below the TLV, STEL, and PEL values for the ingredients.
Ventilation fans should be explosion proof. Use adequate personal protective
equipment e.g. NIOSH-approved respirators, goggles or safety glasses, gloves and
protective clothing. Ensure training in the handling of chemical material and use
current Material Safety Data Sheets.

Eye Protection: (29 CFR 1910.133) Recommend goggles or chemical safety
glasses.

Skin Protection: Thick impermeable gloves and protective clothing.

Respiratory Protection: (29 CFR 1910.134) NIOSH approved respirator, with
organic vapor, acid gas and HEPA filter recommended for handling raw materials.
Warning: Do not use air purifying respirators in oxygen depleted
environments. No respiratory protection is required in the clinical or home
environment.

Other: None
BAUSCH & LOMB Pharmaceuticals Division
MSDS: Levobunolol Hydrochloride Ophthalmic Solution USP, 0.25%

Ventilation: Recommended

Contaminated Equipment: Wash contaminated clothing separately. Wash
equipment with soap and water. Release rinse water into an approved wastewater
system or according to Federal, State and Local regulations.

9. CHEMICAL & PHYSICAL PROPERTIES

Appearance & Odor: Clear, colorless to light yellowish solution.
Boiling Point: NE Evaporation Rate: NE
Specific Gravity: 1.0 Vapor Density: NE
Vapor Pressure: NE Viscosity: NE
Water Solubility: Miscible Percent Volatile by Volume: <1

10. STABILITY AND REACTIVITY

Chemical Stability: Stable

Conditions to avoid: Extreme heat or cold.

Incompatibility: This product has the incompatibilities of water e.g. strong acids,
bases, alkali metals, alkali hydrides and silver preparations.

Hazardous Decomposition Products: Acetaldehyde, crotonaldehyde, acetone,
sulfur dioxide (SO2) and toxic fumes.

Hazardous Polymerization: Should not occur.

11. TOXICOLOGY INFORMATION

Summary of Risks: Toxicological information refers to raw materials product.
Concentrations and toxicological effects are substantially reduced in the product.
For more detailed information see MSDS on chemical material.

CAS #

27912-14-7 Levobunolol Hydrochloride
May cause irritation to the eye, skin, respiratory and digestive tract. Can cause
hypersensitivity (anaphylactic) especially in individuals with a history of various
strong allergic reactions. Systemic toxicity effects include inflammation and irritation
of the eye, skin rash, itching or hives, headaches, vomiting, diarrhea, lethargy, lack
of coordination and chest pain. Severe respiratory and cardiac reactions including
death due to bronchospasm in patients with asthma; and death in association with
cardiac failure, have been reported with topical application of beta-adrenergic
blocking agents. Symptoms of thyroid over activity (thyrotoxicosis) and low blood
sugar (hypoglycemia) may be masked by the effects of levobunolol. Fetotoxicity has
BAUSCH & LOMB Pharmaceuticals Division
MSDS: Levobunolol Hydrochloride Ophthalmic Solution USP, 0.25%

been demonstrated in rabbits when 200 and 700 times the recommended human
dose was administered, but fetotoxicity has not occurred in rats when 1800 times the
human recommended dose was administered. Oral-rat LD50 700 mg/kg.
Intravenous-rat LD50 25 mg/kg. Oral-dog LD50 100 mg/kg.

9002-89-5 Polyvinyl Alcohol
Dust may cause irritation to eyes and respiratory tract. No known effects by skin
contact or ingestion. Inhalation of dust can induce bronchitis or asthma attacks in
some individuals. No known dermal effects due to acute exposure.Degradation
3
products of stored material are methanol (PEL=260 mg/M ) and methyl acetate
(TLV=200 ppm). Decomposition products are acetaldehyde, crotonaldehyde and
acetone. Oral-rat LD50 >10 mg/kg. Acetaldehyde: CAS# 75-07-0; TLV=100 ppm;
Suspected Carcinogen. Crotonaldyhyde: CAS# 4170-30-3; PEL=2 ppm; Suspected
Carcinogen. Acetone: CAS# 67-64-1; TLV= 750 ppm.

12. ECOLOGICAL INFORMATION

Chemical Fate Information: Product administered to patients presents a negligible
impact on the environment.

13. DISPOSAL INFORMATION

Dispose of material according to Federal, State, and Local regulations. The
method typically used is incineration.

RCRA Hazardous Waste: Not Listed
EPA Designations:

Not Listed
SARA Title III:

14. TRANSPORTATION INFORMATION

Not classified as hazardous by DOT regulations.
Transportation Data:

15. REGULATORY INFORMATION

Not classified as hazardous by DOT regulations.
DOT Designations:

RCRA Hazardous Waste
EPA Designations:
(40 CFR 261.33) Not Listed

Prescription only medication.
FDA Designations:
NDC No. 24208-545-05 ( 5 ml)
NDC No. 24208-545-10 (10 ml)

(29 CFR 1910.1000, Table Z)
OSHA Designations:
Not Listed
BAUSCH & LOMB Pharmaceuticals Division
MSDS: Levobunolol Hydrochloride Ophthalmic Solution USP, 0.25%

Not listed under Section 313 of Toxic Release Reporting.
SARA Title III:

CALIFORNIA PROPOSITION 65: Not Listed

16. OTHER INFORMATION

None

The information contained herein is furnished without warranty of any kind. The
above information is believed to be correct but does not purport to be all-inclusive
and should be used only as a guide. Users should make independent
determinations of the suitability and completeness of information from all sources to
assure proper use and disposal of these materials and the safety and health of
employees and customers.

NA ?? Not Applicable
NE - Not Established
< - Less Than
> - Greater Than

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