GlaxoSmithKline (919) 483-2100
PO Box 13398 (919) 483-2700 (24 hour contact)
5 Moore Drive
RTP, NC 27709 Effective Date: 9/07/99
MATERIAL SAFETY DATA SHEET
SECTION 1: CHEMICAL SUBSTANCE
Relenza® (zanamivir for inhalation)
COMMON NAME:
CHEMICAL NAME: 5-(acetylamino)-4-[(aminoiminomethyl)-amino]-2,6-anhydro-3,4,5-trideoxy-D-glycero-D-
galacto-non-2-enonic acid
Relenza for Inhalation; Relenza® Rotadisk® ; Relenza Rotadisk; zanamivir; GR121167X; GR
SYNONYMS:
121167X; GR121167; GG167
SUBSTANCE CLASS: Neuraminidase Inhibitor; Anti-influenza
SECTION 2: HAZARDOUS INGREDIENTS
NAME CAS/EINECS/ELINCS # % GW LIMITS OTHER LIMITS
(mcg/m3) (mcg/m3)
w/v or w/w
1000 mcg/m3
zanamivir 139110-80-8 100 Not established
(8 hr TWA) OEL
(pure substance)
SECTION 3: HAZARDS IDENTIFICATION
THE RISK OF HEALTH HAZARDS MAY BE REDUCED WHEN RELENZA® IS HANDLED IN UNIT DOSAGE FORM.
Zanamivir, the active ingredient in Relenza®, is not a significant health hazard.
(See SECTION 8: EXPOSURE CONTROLS / PERSONAL PROTECTION and SECTION 11: TOXICOLOGICAL INFORMATION.)
SECTION 4: FIRST AID MEASURES
If in Eyes: Flush immediately with large quantities of water for 15 minutes. Obtain medical attention.
If on Skin: Remove contaminated clothing. Flush exposed skin with water and wash thoroughly with soap and
water. Obtain medical attention.
If Inhaled: If not breathing, give artificial respiration or CPR. If breathing is difficult, give oxygen. Remove person
to fresh air. Obtain medical attention.
If Ingested: If conscious, rinse mouth with water. Never give anything by mouth if unconscious. Obtain medical
attention.
TO THE BEST OF OUR KNOWLEDGE THE INFORMATION CONTAINED HEREIN IS ACCURATE AS OF THE DATE HEREOF. ANY DETERMINATION AS TO THE
SUITABILITY OF THE PRODUCT FOR ANY PARTICULAR PURPOSE, ITS SAFE USE OR DISPOSAL SHALL BE THE RESPONSIBILITY OF THE USER. THE
INFORMATION CONTAINED HEREIN IS IN NO WAY INTENDED TO SUPPLEMENT, MODIFY OR SUPERSEDE THE INFORMATION PROVIDED IN THE PRODUCT
PACKAGE INSERT WITH RESPECT TO THE USE OF THE PRODUCT FOR MEDICAL PURPOSES. PLEASE REFER TO THE PRODUCT PACKAGE INSERT FOR
INFORMATION REGARDING THE USE OF THE PRODUCT FOR MEDICAL PURPOSES.
Relenza® Effective Date: 9/07/99
SECTION 5: FIRE/EXPLOSION HAZARDS & FIRE-FIGHTING MEASURES
FLASHPOINT/TEST METHOD: Not Applicable (powder).
LEL / UEL: Not Applicable (powder).
SPECIAL FIRE-FIGHTING PROCEDURES: As with any organic dust, there is potential for explosion when suspended
in air in high concentrations.
MIE (Minimum Ignition Energy): The minimum ignition energy of zanamivir, the active ingredient in
Relenza® , is >500mJ. This indicates the material is not prone to ignition
by static electricity.
EXTINGUISHING MEDIA: Water spray, Multi-purpose dry chemical.
FIRE-FIGHTING PROCEDURES: Wear full protective clothing and use self-contained breathing apparatus
(SCBA).
SECTION 6: SPILL AND LEAK PROCEDURES
SPILL RESPONSE PROCEDURES (Liquid, Solid, Gas/Vapor):
Protective equipment may be necessary for spills. (See Section 8, “Exposure Controls / Personal Protection� for
guidance).
For small quantities associated with normal therapeutic use, collect spillage and transfer to a closed waste container
for disposal. For large or bulk quantities, collect spillage by carefully wet wiping or HEPA vacuuming and place in a
labeled, sealed container for disposal. Wash spill area (floor and other contact surfaces) with suitable cleaning
solvent, such as soap and water.
SECTION 7: HANDLING AND STORAGE
HANDLING: Avoid contact with eyes, skin, and clothing. Minimize generation and accumulation of dusts and mists
containing this substance. Clean surfaces that may be contaminated with the substance, such as
hands, skin, and equipment surfaces, before leaving the work area. Use only in a well ventilated area;
aerosol-generating procedures should be conducted in a laboratory fume hood or with other suitable
local exhaust ventilation.
Store Relenza® at 25°C (77°F); excursions permitted to 15°to 30°C (59°to 86°F).
STORAGE:
SECTION 8: EXPOSURE CONTROLS/PERSONAL PROTECTION
ENGINEERING CONTROLS: No special ventilation requirements for therapeutic dosage and administration. For
aerosol-generating processes, use process containment, local exhaust ventilation, or
other engineering control devices to control airborne levels to below the occupational
exposure limit (OEL).
PERSONAL PROTECTION:
Respiratory: Not required under normal conditions of therapeutic use and storage. For aerosol-
generating procedures and in the absence of sufficient engineering controls, use
NIOSH-approved respiratory protection. See Section 5 � � / Explosion Hazards &
Fire
Fire-Fighting Measures� for respiratory protection in the event of a fire.
Eye: Workers should wear adequate eye protection to prevent eye contact.
Clothing: Adequate protective clothing should be worn to prevent occupational skin contact.
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Relenza® Effective Date: 9/07/99
SECTION 8: EXPOSURE CONTROLS/PERSONAL PROTECTION (cont'd)
Gloves: Impermeable gloves should be worn when routine handling or spill cleanup may result in skin
contact. Dispose of gloves according to federal, state, and local regulations.
WORK PRACTICES: Special care should be taken to ensure that contaminated clothing, equipment, and work
surfaces are properly cleaned or disposed of after use. Potentially contaminated clothing should
be packaged for laundering to prevent exposure of laundry personnel. Wash hands and other
areas of skin contact thoroughly after handling this material.
SECTION 9: PHYSICAL/CHEMICAL PROPERTIES
Zanamivir, the active ingredient in Relenza® , is a white to off-white powder.
APPEARANCE AND ODOR:
Relenza® is supplied in a circular double-foil pack (Relenza® Rotadisk® )
containing 4 blisters of zanamivir. Five Rotadisks are packaged in a white
polypropylene tube. The tube is packaged in a carton with 1 blue and gray
Diskhaler inhalation device.
PHYSICAL STATE (liquid/solid/gas): Solid.
MELTING POINT (deg. C): Zanamivir >240°C (decomposes).
Zanamivir, the active ingredient in Relenza® , is soluble in water (18 mg/mL at
SOLUBILITY/MISCIBILITY (% w/v):
20°C).
SECTION 10: STABILITY AND REACTIVITY
CHEMICAL STABILITY: Zanamivir is decomposed exothermically on heating (DSC, 10 deg.C/min,
onset: 230 deg.C, 40 J/g). Any risk from self-heating of Relenza® is
negligible.
Not determined for Relenza® .
CONDITIONS TO AVOID:
HAZARDOUS DECOMPOSITION PRODUCTS: Thermal decomposition products of zanamivir, the active ingredient in
Relenza® , may include toxic and/or corrosive oxides of nitrogen.
INCOMPATIBILITY WITH OTHER MATERIALS: No known incompatibilities have been identified for zanamivir.
SECTION 11: TOXICOLOGICAL INFORMATION
®
THE RISK OF HEALTH HAZARDS MAY BE REDUCED WHEN RELENZA IS HANDLED IN UNIT DOSAGE FORM.
Zanamivir, the active ingredient in Relenza® , is a potent and selective inhibitor
PHARMACOLOGICAL ACTIVITY:
of influenza virus neuraminidase, an enzyme which assists the spread of virus
particles in the body. Relenza® is indicated for treatment of uncomplicated
acute illness due to influenza virus in persons more than 12 years of age who
have been symptomatic for no more than 2 days.
OCCUPATIONAL EXPOSURE LEVEL: For zanamivir, the active ingredient in Relenza® , the Glaxo Wellcome estimated
safe working level is an eight hour time-weighted average (TWA) of 1000
mcg/m3.
ACUTE TOXICITY: No evidence of target organ toxicity or respiratory tract irritation was observed
in acute studies with zanamivir involving mice or rats. Maximum single non-
lethal doses of zanamivir were:
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Relenza® Effective Date: 9/07/99
SECTION 11: TOXICOLOGICAL INFORMATION (cont'd)
ACUTE TOXICITY (cont'd): Mouse (Oral) > 2000 mg/kg
Rat (Oral) > 1740 mg/kg
Rat (Inhalation) > 348 mcg/L (four hour exposure)
Little is known regarding the potential adverse health effects of occupational exposure
to zanamivir. From the data currently available, zanamivir would appear not to be a
significant acute health hazard. Acute exposures may cause symptoms similar to those
reported in medicinal use of this drug substance (see “Clinical Safety� below).
,
REPEAT DOSE TOXICITY: In standard tests , zanamivir has little toxic potential following repeated inhalation or
intravenous exposure. However, the potential adverse health effects of repeated
occupational exposure to this substance are unknown. Repeated occupational exposure
to zanamivir may produce effects similar to those observed in clinical trials of its
medicinal formulations (see � Clinical Safety� below).
,
IRRITATION: Experimental data indicate that this material is not irritating to the eyes. Standard
laboratory tests indicate that this material is not irritating to the skin after a single
application.
SENSITIZATION: There is no evidence that this substance has skin sensitizing potential when tested by the
Magnusson and Kligman procedure.
REPRODUCTIVE EFFECTS: Studies in laboratory animals have shown no effects on fetal development in the
following species: rat and rabbit. Zanamivir had no effect on the post-natal
development, fertility, reproductive performance, or parturition of the offspring of rats
treated with the drug. For recommended dosage and administration, Relenza® is
classified as “Pregnancy Category B� There are no adequate and well-controlled studies
.
of Relenza® in pregnant women. Relenza® should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus. Although studies indicate that
zanamivir is excreted in the milk of rats, it is not known whether zanamivir is excreted in
human milk. Because many drugs are excreted in human milk, caution should be
exercised when Relenza is administered to a nursing mother. Medical evaluation of
exposure and attention to compliance with standard operating procedures and/or other
workplace health and safety directives is advised.
GENOTOXICITY: No mutagenic (DNA-damaging) activity has been demonstrated in the following in vitro
systems: Ames bacterial test in the presence and absence of metabolic activation,
L5178Y mouse lymphoma cells. Zanamivir did not cause chromosomal damage in
mammalian cell cultures or when tested in the mouse micronucleus assay.
CARCINOGENICITY: Zanamivir has shown no evidence of carcinogenicity in the mouse or rat.
CLINICAL SAFETY: The recommended therapeutic inhalation dose of zanamivir, the active ingredient in
Relenza® , is 10 mg twice per day for 5 days. In clinical studies, the overall incidence of
adverse effects was similar for patients treated with Relenza and placebo. Adverse
effects noted in patients receiving either drug or placebo included: headache, diarrhea,
nausea, vomiting, nasal signs and symptoms, bronchitis, cough, sinusitis, ear, nose, and
throat infections, and dizziness.
There have been no reports of overdosage from administration of zanamivir. However,
doses up to 64 mg/day (administered by nebulizer) and 1200 mg/day (administered
intravenously) have produced adverse effects similar to those observed in clinical studies
at the recommended dose.
Page 4 of 6
Relenza® Effective Date: 9/07/99
SECTION 12: ECOLOGICAL INFORMATION
ENVIRONMENTAL EFFECTS: Environmental effects testing is currently underway. Until environmental effects have
been determined, dispose of unused compound or process wastes by incineration.
ENVIRONMENTAL FATE: Zanamivir will compartmentalize into the aquatic environment.. It is not readily
biodegradable in the water and soil compartments and is unlikely to bioaccumulate.
ENVIRONMENTAL TEST RESULTS:
STUDY NAME RESULTS COMMENTS
Water Solubility: 0.001mg/ml
Hydrolysis Rate: Not available
Vapor Pressure: Not available
Dissociation Constant: Not available
n-Octanol/Water Partition Coefficient: Mean Pow -2.5 pH 0.0033 Mean
log10 Pow 7
UV/Visible Spectrum: Not available
Aerobic Biodegradation (soil) <50% mineralization (64 days) Slow biodegradation occurred
between 6 - 36% in differing soil
types at 64 days.
Soil Absorption/Desorption: Clay loam, pH 6.0, Koc 8.3 Mobile in clay and sandy loam soils
Sandy loam, pH 6.2, Koc <15 with pH between 6 and 8.
Sandy loam, pH 8.2, Koc <6.6
Activated sludge respiration inhibition test >1000mg/L Low order of toxicity
Five day bacterial inhibition Not available
Acute toxicity to Daphnia >1000mg/L Low order of toxicity
Biodegradablity in water < 1% mineralizaton within 28 Zanamivir is non-readily
days. biodegradable.
SECTION 13: WASTE DISPOSAL
ROUTINE: Unused compound should be disposed of at an approved facility in accordance with federal,
state and local regulations.
ACCIDENTAL RELEASE: Clean up spills immediately, observing precautions in SECTION 8: PERSONAL PROTECTION.
Do not flush to sewer. Avoid runoff into storm sewers and ditches which lead to waterways.
SECTION 14: TRANSPORTATION INFORMATION
Formulation 1: 100% (pure active)
US Department of Transportation
Proper Shipping Name: Not Regulated in transportation
IATA/ICAO
Proper Shipping Name: Not Regulated in transportation
IMDG
Proper Shipping Name: Not Regulated in transportation
RQ: None Marine Pollutant: No
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Relenza® Effective Date: 9/07/99
SECTION 15: REGULATORY INFORMATION
EC PACKAGING AND LABELING FOR SUPPLY:
Classification under the UK Chemicals (Hazard Information and Packaging for Supply) (Amendment) Regulations
1996 is not applicable on the basis of currently available information, but the substance is known to be
pharmacologically active. It is recommended that packages are labeled 'Caution - Substance not yet fully tested'.
OTHER LEGISLATION: Not determined.
SECTION 16: OTHER INFORMATION
EFFECTIVE DATE: 9/07/99 SUPERSEDES: Not Applicable
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