GLIADEL

SUMMARY OF PRODUCT CHARACTERISTICS

GLIADEL

WAFER

only

(polifeprosan 20 with carmustine implant)

DESCRIPTION

GLIADEL

Wafer (polifeprosan 20 with carmustine implant) is a sterile, off-white to

pale yellow wafer approximately 1.45 cm in diameter and 1 mm thick. Each wafer

contains 192.3 mg of polideprosan (a biodegradable polyanhydride copolymer and 7.7 mg

of carmustine [1,3-bis (2-chloroethyl)-1-nitrosourea, or BCNU]). Carmustine is a

nitrosourea oncolytic agent. The copolymer, polifeprosan 20, consists of poly[bis(p-

carboxyphenoxy) propane: sebacic acid] in a 20:80 molar ratio and is used to control the

local delivery of carmustine. Carmustine is homogeneously distributed in the copolymer

matrix.

The structural formula for polifeprosan 20 is:

The structural formula for carmustine is:

CLINICAL PHARMACOLOGY

GLIADEL

Wafer is designed to deliver carmustine directly into the surgical cavity

created when a brain tumor is resected. On exposure to the aqueous environment of the

resection cavity, the anhydride bonds in the copolymer are hydrolyzed, releasing

carmustine, carboxyphenoxypropane, and sebacic acid. The carmustine released from

GLIADEL

Wafer diffuses into the surrounding brain tissue and produces an

antineoplastic effect by alkylating DNA and RNA.

NCNHCH

Carmustine has been shown to degrade both spontaneously and metabolically. The

production of an alkylating moiety, hypothesized to be chloroethyl carbonium ion, leads

to the formation of DNA cross-links.

The tumoricidal activity of GLIADEL

Wafer is dependent on release of carmustine to

the tumor cavity in concentrations sufficient for effective cytotoxicity.

More than 70% of the copolymer degrades by three weeks. The metabolic disposition

and excretion of the monomers differ. Carboxyphenoxypropane is eliminated by the

kidney and sebacic acid, an endogenous fatty acid, is metabolized by the liver and expired

as CO

in animals.

The absorption, distribution, metabolism, and excretion of the copolymer in humans is

unknown. Carmustine concentrations delivered by GLIADEL

Wafer in human brain

tissue have not been determined. Plasma levels of carmustine after GLIADEL

Wafer

implant were not determined. In rabbits implanted with wafers containing 3.85%

carmustine, no detectible levels of carmustine were found in the plasma or cerebrospinal

fluid.

Following an intravenous infusion of carmustine at doses ranging from 30 to 170 mg/m

the average terminal half-life, clearance, and steady-state volume of distribution were 22

minutes, 56 mL/min/kg, and 3.25 L/kg, respectively. Approximately 60% of the

intravenous 200 mg/m

dose of

C-carmustine was excreted in the urine over 96 hours

and 6% was expired as CO

GLIADEL

Wafers are biodegradable in human brain when implanted into the cavity

after tumor resection. The rate of biodegradation is variable from patient to patient.

During the biodegradation process, a wafer remnant may be observed on brain imaging

scans or at re-operation even though extensive degradation of all components has

occurred. Data obtained from review of CT scans obtained 49 days after implantation of

GLIADEL

Wafer demonstrated that images consistent with wafers were visible to

varying degrees in the scans of 11 of 18 patients. Data obtained at re-operation and

autopsies have demonstrated wafer remnants up to 232 days after GLIADEL

Wafer

implantation.

Wafer remnants removed at re-operation from two patients with recurrent malignant

glioma, one at 64 days and the second at 92 days after implantation, were analyzed for

content. The following table presents the results of analyses completed on these

remnants.

COMPOSITION OF WAFER REMNANTS REMOVED FROM

TWO PATIENTS ON RE-OPERATION

Component

Patient A

Patient B

Days After GLIADEL

Wafer Implantation

Anhydride Bonds

None detected

None detected

Water Content (% of wafer remnant weight)

95-97%

74-86%

Carmustine Content (% of initial)

<0.0004%

0.034%

Carboxyphenoxypropane Content (% of initial)

Sebacic Acid Content (% of initial)

The wafer remnants consisted mostly of water and monomeric components with minimal

detectable carmustine present.

CLINICAL STUDIES

Primary Surgery

A randomized, double-blind, placebo-controlled clinical trial was conducted in adult

patients with newly-diagnosed high-grade malignant glioma undergoing initial

craniotomy for tumor resection. This trial determined the safety and efficacy of

GLIADEL

Wafer implants plus surgery and radiation therapy compared to placebo

implants plus surgery and radiation therapy. Two hundred and forty patients with newly-

diagnosed malignant glioma were enrolled. The most common tumor type was

Glioblastoma Multiforme (GBM) (n=207), followed by anaplastic oligoastrocytoma

(n=11), anaplastic oligodendroglioma (n=11), and anaplastic astrocytoma (n=2).

GLIADEL

Wafers were implanted at the time of the surgery in 120 patients and placebo

wafers were implanted in 120 patients. The majority of patients received 6-8 wafers.

Wafer

There were 17

patients (14.2%) in the

Wafer group and 12 patients (10.0%) in the placebo

group who received systemic chemotherapy during the study. All six patients with

anaplastic oligodendroglioma received chemotherapy within 30 days of

Wafer implantation. Patients were followed for at least three years or until death. Only

one patient was lost to follow-up. Median survival increased from 11.6 months with

placebo to 13.8 months with GLIADEL

Wafer (p-value <0.05, log-rank test). The

hazard ratio for GLIADEL

Wafer treatment was 0.73 (95% CI: 0.56-0.95).

Kaplan-Meier Overall Survival Curves for Patients Undergoing

I

I

n

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t

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H

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a

Months From Implant Surgery

Survival %

_______

GLIADEL

----------- Placebo

Log-

Rank

p<0.05

When only patients with Glioblastoma multiforme were included in the analysis, the

hazard ratio with GLIADEL

Wafer treatment was 0.78 (95% CI: 0.59-1.03, p=0.08,

log-rank test).

Surgery for Recurrent Disease

A randomized, double-blind, placebo-controlled clinical trial was conducted in adult

patients with recurrent malignant glioma. This trial determined the safety and efficacy of

Ninety-five percent of the patients treated with GLIADEL

Wafer had 7-8 wafers

implanted.

a who had failed initial surgery

and radiation therapy, the six-month survival rate after repeat surgery increased from 47%

(53/112) for patients receiving placebo to 60% (66/110) for patients treated with

GLIADEL

r. Median survival increased by 33%, from 24 weeks (5.5 months) with

placebo to 32 weeks (7.4 months) with GLIADEL

r treatment. In patients with

GBM, the six-month survival rate increased from 36% (26/73) with placebo to 56%

(40/72) with GLIADEL

treatment. Median survival of GBM patients increased

by 41% from 20 weeks (4.6 months) with placebo to 28 weeks (6.4 months) with

GLIADEL

r treatment. In patients with pathologic diagnoses other than GBM at

the time of surgery for tumor recurrence, GLIADEL

r produced no survival

prolongation.

INDICATIONS AND USAGE

For use as an adjunct to surgery to prolong survival in patients with recurrent glioblastoma

multiforme for whom surgical resection is indicated.

Gliadel implant is indicated in newly-diagnosed high-grade malignant glioma patients as an

adjunct to surgery and radiation.

Gliadel implant is indicated for use as an adjunct to surgery in patients with Recurrent

histogically proved glioblastoma multiforme for whom surgical resection is indicated.

CONTRAINDICATIONS

GLIADEL

Wafer contains carmustine. GLIADEL

Wafer should not be given to

individuals who have demonstrated a previous hypersensitivity to carmustine or any of the

components of GLIADEL

Wafer.

WARNINGS

Patients undergoing craniotomy for malignant glioma and implantation of GLIADEL

Wafer should be monitored closely for known complications of craniotomy, including

seizures, intracranial infections, abnormal wound healing, and brain edema. Cases of

intracerebral mass effect unresponsive to corticosteroids have been described in patients

treated with GLIADEL

Wafer, including one case leading to brain herniation.

Pregnancy: There are no studies assessing the reproductive toxicity of GLIADEL

Wafer.

Carmustine, the active component of GLIADEL

Wafer, can cause fetal harm when

administered to a pregnant woman. Carmustine has been shown to be embryotoxic and

teratogenic in rats at i.p. doses of 0.5, 1, 2, 4, or 8 mg/kg/day when given on gestation days

6 through 15. Carmustine caused fetal malformations (anophthalmia, micrognathia,

omphalocele) at 1.0 mg/kg/day (about 1/6 the recommended human dose (eight wafers of

7.7 mg carmustine/wafer) on a mg/m

basis). Carmustine was embryotoxic in rabbits at

i.v. doses of 4.0 mg/kg/day (about 1.2 times the recommended human dose on a mg/m

basis). Embryotoxicity was characterized by increased embryo-fetal deaths, reduced

numbers of litters, and reduced litter sizes.

There are no studies of GLIADEL

Wafer in pregnant women. If GLIADEL

Wafer is

used during pregnancy, or if the patient becomes pregnant after GLIADEL

Wafer

implantation, the patient must be warned of the potential hazard to the fetus.

PRECAUTIONS

General: Communication between the surgical resection cavity and the ventricular system

should be avoided to prevent the wafers from migrating into the ventricular system and

causing obstructive hydrocephalus. If a communication larger than the diameter of a wafer

exists, it should be closed prior to wafer implantation.

Computed tomography and magnetic resonance imaging of the head may demonstrate

enhancement in the brain tissue surrounding the resection cavity after implantation of

GLIADEL

Wafers. This enhancement may represent edema and inflammation caused by

GLIADEL

Wafer or tumor progression.

Therapeutic Interactions: Interactions of GLIADEL

Wafer with other drugs have not

been formally evaluated.

The short-term and long-term toxicity profiles of GLIADEL

r when given in

conjunction with chemotherapy have not been fully explored.

Carcinogenesis, Mutagenesis, Impairment of Fertility: No carcinogenicity,

mutagenicity or impairment of fertility studies have been conducted with GLIADEL

Wafer. Carcinogenicity, mutagenicity and impairment of fertility studies have been

conducted with carmustine, the active component of GLIADEL

Wafer. Carmustine was

given three times a week for six months, followed by 12 months observation, to Swiss

mice at i.p. doses of 2.5 and 5.0 mg/kg (about 1/5 and 1/3 the recommended human dose

(eight wafers of 7.7 mg carmustine/wafer) on a mg/m

basis) and to SD rats at i.p. dose of

1.5 mg/kg (about 1/4 the recommended human dose on a mg/m

basis). There were

increases in tumor incidence in all treated animals, predominantly subcutaneous and lung

neoplasms. Mutagenesis: Carmustine was mutagenic in vitro (Ames assay, human

lymphoblast HGPRT assay) and clastogenic both in vitro (V79 hamster cell micronucleus

assay) and in vivo (SCE assay in rodent brain tumors, mouse bone marrow micronucleus

assay). Impairment of Fertility: Carmustine caused testicular degeneration at i.p. doses of

8 mg/kg/week for eight weeks (about 1.3 times the recommended human dose on a mg/m

basis) in male rats.

Pregnancy: Pregnancy Category D: see WARNINGS.

Nursing Mothers: It is not known if either carmustine, carboxyphenoxypropane, or

sebacic acid is excreted in human milk. Because many drugs are excreted in human milk

and because of the potential for serious adverse reactions from carmustine in nursing

infants, it is recommended that patients receiving GLIADEL

Wafer discontinue nursing.

Pediatric Use: The safety and effectiveness of GLIADEL

Wafer in pediatric patients

have not been established.

ADVERSE REACTIONS

Adverse reactions for the trials are described in the tables below.

Primary Surgery

C

C

O

O

M

M

M

M

O

O

N

N

A

A

D

D

V

V

E

E

R

R

S

S

E

E

E

E

V

V

E

E

N

N

T

T

S

S

O

O

B

B

S

S

E

E

R

R

V

V

E

E

D

D

I

I

N

N

>

>

5

5

%

%

O

O

F

F

P

P

A

A

T

T

I

I

E

E

N

N

T

T

S

S

R

R

E

E

C

C

E

E

I

I

V

V

I

I

N

N

G

G

G

G

L

L

I

I

A

A

D

D

E

E

L

L

W

W

A

A

F

F

E

E

R

R

A

A

T

T

I

I

N

N

I

I

T

T

I

I

A

A

L

L

S

S

U

U

R

R

G

G

E

E

R

R

Y

Y

Body System

Adverse event

GLIADEL

®

Wafer N=120

n (%)

Placebo N=120

n (%)

Body as a whole

Aggravation reaction*

98 (82)

95 (79)

Headache

33 (28)

44 (37)

Asthenia

26 (22)

18 (15)

Infection

22 (18)

24 (20)

Fever

21 (18)

21 (18)

Pain

16 (13)

18 (15)

Abdominal pain

10 (8)

2 (2)

Back pain

8 (7)

4 (3)

Face edema

7 (6)

6 (5)

Abscess

6 (5)

3 (3)

Accidental injury

6 (5)

8 (7)

Chest pain

6 (5)

Allergic reaction

2 (2)

6 (5)

Cardiovascular system

Deep thrombophlebitis

12 (10)

11 (9)

Pulmonary embolus

10 (8)

10 (8)

Hemorrhage

8 (7)

7 (6)

Digestive system

Nausea

26 (22)

20 (17)

Vomiting

25 (21)

19 (16)

Constipation

23 (19)

14 (12)

Diarrhea

6 (5)

5 (4)

Liver function tests abnormal

1 (1)

6 (5)

Endocrine system

Diabetes mellitus

6 (5)

5 (4)

Cushings syndrome

4 (3)

6 (5)

Metabolic and nutritional disorders

Healing abnormal

19 (16)

14 (12)

Peripheral edema

11 (9)

11 (9)

Musculoskeletal system

Myasthenia

5 (4)

6 (5)

Nervous system

Hemiplegia

49 (41)

53 (44)

Convulsion

40 (33)

45 (38)

Confusion

28 (23)

25 (21)

Brain edema

27 (23)

23 (19)

Aphasia

21 (18)

22 (18)

Depression

19 (16)

12 (10)

Somnolence

13 (11)

18 (15)

Speech disorder

13 (11)

10 (8)

Amnesia

11 (9)

12 (10)

C

C

O

O

M

M

M

M

O

O

N

N

A

A

D

D

V

V

E

E

R

R

S

S

E

E

E

E

V

V

E

E

N

N

T

T

S

S

O

O

B

B

S

S

E

E

R

R

V

V

E

E

D

D

I

I

N

N

>

>

5

5

%

%

O

O

F

F

P

P

A

A

T

T

I

I

E

E

N

N

T

T

S

S

R

R

E

E

C

C

E

E

I

I

V

V

I

I

N

N

G

G

G

G

L

L

I

I

A

A

D

D

E

E

L

L

W

W

A

A

F

F

E

E

R

R

A

A

T

T

I

I

N

N

I

I

T

T

I

I

A

A

L

L

S

S

U

U

R

R

G

G

E

E

R

R

Y

Y

Body System

Adverse event

GLIADEL

®

Wafer N=120

n (%)

Placebo N=120

n (%)

*Adverse events coded to the COSTART term

aggravation reaction

were usually events

involving tumor/disease progression or general deterioration of condition (e.g.

condition/health/Karnofsky/neurological/physical deterioration).

Nervous system (continued)

Intracranial hypertension

11 (9)

2 (2)

Personality disorder

10 (8)

9 (8)

Anxiety

8 (7)

5 (4)

Facial paralysis

8 (7)

5 (4)

Neuropathy

8 (7)

12 (10)

Ataxia

7 (6)

5 (4)

Hypesthesia

7 (6)

6 (5)

Paresthesia

7 (6)

10 (8)

Thinking abnormal

7 (6)

10 (8)

Abnormal gait

6 (5)

6 (5)

Dizziness

6 (5)

11 (9)

Grand mal convulsion

6 (5)

5 (4)

Hallucinations

6 (5)

4 (3)

Insomnia

6 (5)

7 (6)

Tremor

6 (5)

8 (7)

Coma

5 (4)

6 (5)

Incoordination

3 (3)

8 (7)

Hypokinesia

2 (2)

8 (7)

Respiratory system

Pneumonia

10 (8)

9 (8)

Dyspnea

4 (3)

8 (7)

Skin and appendages

Rash

14 (12)

13 (11)

Alopecia

12 (10)

14 (12)

Special senses

Conjunctival edema

8 (7)

8 (7)

Abnormal vision

7 (6)

7 (6)

Visual field defect

6 (5)

8 (7)

Eye disorder

3 (3)

6 (5)

Diplopia

1 (1)

6 (5)

Urogenital system

Urinary tract infection

10 (8)

13 (11)

Urinary incontinence

9 (8)

9 (8)

Surgery for Recurrent Disease

The following post-operative adverse events were observed in 4% or more of the patients

receiving GLIADEL

Wafer

surgery. Except for nervous system effects,

where there is a possibility that the placebo wafers could have been responsible, only

events more common in the GLIADEL

Wafer group are listed. These adverse events

were either not present pre-operatively or worsened post-operatively during the follow-up

period. The follow-up period was up to 71 months.

COMMON ADVERSE EVENTS OBSERVED IN >4% OF PATIENTS

R

R

E

E

C

C

E

E

I

I

V

V

I

I

N

N

G

G

G

G

L

L

I

I

A

A

D

D

E

E

L

L

WAFER

A

A

T

T

S

S

U

U

R

R

G

G

E

E

R

R

Y

Y

F

F

O

O

R

R

R

R

E

E

C

C

U

U

R

R

R

R

E

E

N

N

T

T

D

D

I

I

S

S

E

E

A

A

S

S

E

E

Body System

Adverse Event

GLIADEL

Wafer

with Carmustine

[N=110]

n (%)

PLACEBO Wafer

without Carmustine

[N=112]

n (%)

Body as a Whole

Fever

Pain*

13 (12)

8 (7)

9 (8)

1 (1)

Digestive System

Nausea and Vomiting

9 (8)

7 (6)

Metabolic and Nutritional Disorders

Healing Abnormal*

15 (14)

6 (5)

Nervous System

Convulsion

21 (19)

21 (19)

Hemiplegia

21 (19)

22 (20)

Headache

16 (15)

14 (13)

Somnolence

15 (14)

12 (11)

Confusion

11 (10)

9 (8)

Aphasia

10 (9)

12 (11)

Stupor

7 (6)

7 (6)

Brain Edema

4 (4)

1 (1)

Intracranial Hypertension

4 (4)

7 (6)

Meningitis or Abscess

4 (4)

1 (1)

Skin and Appendages

Rash

6 (5)

4 (4)

Urogenital System

Urinary Tract Infection

23 (21)

19 (17)

*p < 0.05 for comparison of GLIADEL

Wafer versus placebo groups

Post-marketing experience includes spontaneous reports of cyst formation after

Gliadel

wafer implantation. These occurred at varying time intervals post-implantation.

Cyst formation has also been reported in patients following resection of malignant glioma

who have not had Gliadel

implanted.

The following four categories of adverse events are possibly related to treatment with

GLIADEL

Wafer. The frequency with which they occurred in the randomized trials along

with descriptive detail is provided below.

1. Seizures: In the initial surgery trial, the incidence of seizures was 33.3% in patients

receiving GLIADEL

Wafer and 37.5% in patients receiving placebo. Grand mal seizures

occurred in 5% of GLIADEL

Wafer-treated patients and 4.2% of placebo treated patients.

The incidence of seizures within the first 5 days after wafer implantation was 2.5% in the

GLIADEL

Wafer group and 4.2% in the placebo group. The time from surgery to the

onset of the first post-operative seizure did not differ between the GLIADEL

Wafer and

placebo treated patients.

In the surgery for recurrent disease trial, the incidence of post-operative seizures was 19%

in both patients receiving GLIADEL

Wafer and placebo. In this study, 12/22 (54%) of

patients treated with GLIADEL

Wafer and 2/22 (9%) of placebo patients experienced the

first new or worsened seizure within the first five post-operative days. The median time to

onset of the first new or worsened post-operative seizure was 3.5 days in patients treated

with GLIADEL

Wafer and 61 days in placebo patients.

2. Brain Edema: In the initial surgery trial, brain edema was noted in 22.5% of patients

treated with GLIADEL

Wafer and in 19.2% of patients treated with placebo.

Development of brain edema with mass effect (due to tumor recurrence, intracranial

infection, or necrosis) may necessitate re-operation and, in some cases, removal of

GLIADEL

Wafer or its remnants.

3. Healing Abnormalities: The following healing abnormalities have been reported in

clinical trials of GLIADEL

Wafer: wound dehiscence, delayed wound healing, subdural,

subgaleal or wound effusions, and cerebrospinal fluid leak. In the initial surgery trial,

healing abnormalities occurred in 15.8% of GLIADEL

Wafer treated patients and in

11.7% of placebo recipients. Cerebrospinal fluid leaks occurred in 5% of GLIADEL

Wafer recipients and 0.8% of those given placebo. During surgery, a water-tight dural

closure should be obtained to minimize the risk of cerebrospinal fluid leak.

In the surgery for recurrent disease trial, the incidence of healing abnormalities was 14% in

GLIADEL

Wafer treated patients and 5% in patients receiving placebo wafers.

4. Intracranial Infection: In the initial surgery trial, the incidence of brain abscess or

meningitis was 5% in patients treated with GLIADEL

Wafer and 6% in patients receiving

placebo. In the recurrent setting, the incidence of brain abscess or meningitis was 4% in

patients treated with GLIADEL

Wafer and 1% in patients receiving placebo.

The following adverse events, not listed in the table above, were reported in less than 4%

but at least 1% of patients treated with GLIADEL

Wafer in all studies. The events listed

were either not present pre-operatively or worsened post-operatively. Whether GLIADEL

Wafer caused these events cannot be determined.

Body as a Whole: peripheral edema (2%); neck pain (2%); accidental injury (1%); back

pain (1%); allergic reaction (1%); asthenia (1%); chest pain (1%); sepsis (1%)

Cardiovascular System: hypertension (3%); hypotension (1%)

Digestive System: diarrhea (2%); constipation (2%); dysphagia (1%); gastrointestinal

hemorrhage (1%); fecal incontinence (1%)

Hemic and Lymphatic System: thrombocytopenia (1%); leukocytosis (1%)

Metabolic and Nutritional Disorders: hyponatremia (3%); hyperglycemia (3%);

hypokalemia (1%)

Musculoskeletal System: infection (1%)

Nervous System: hydrocephalus (3%); depression (3%); abnormal thinking (2%); ataxia

(2%); dizziness (2%); insomnia (2%); monoplegia (2%); coma (1%); amnesia (1%);

diplopia (1%); paranoid reaction (1%). In addition, cerebral hemorrhage and cerebral

infarct were each reported in less than 1% of patients treated with GLIADEL

Wafer.

Respiratory System: infection (2%); aspiration pneumonia (1%)

Skin and Appendages: rash (2%)

Special Senses: visual field defect (2%); eye pain (1%)

Urogenital System: urinary incontinence (2%)

OVERDOSAGE

There is no clinical experience with use of more than eight GLIADEL

Wafers per surgical

procedure.

DOSAGE AND ADMINISTRATION

Each GLIADEL

Wafer contains 7.7 mg of carmustine, resulting in a dose of 61.6 mg

when eight wafers are implanted. It is recommended that eight wafers be placed in the

resection cavity if the size and shape of it allows. Should the size and shape not

accommodate eight wafers, the maximum number of wafers as allowed should be placed.

Since there is no clinical experience, no more than eight wafers should be used per surgical

procedure.

Handling and Disposal

1-7

: Wafers should only be handled by personnel wearing surgical

gloves because exposure to carmustine can cause severe burning and hyperpigmentation of

the skin. Use of double gloves is recommended and the outer gloves should be discarded

into a biohazard waste container after use. A surgical instrument dedicated to the handling

of the wafers should be used for wafer implantation. If repeat neurosurgical intervention is

indicated, any wafer or wafer remnant should be handled as a potentially cytotoxic agent.

GLIADEL

Wafer should be handled with care. The aluminum foil laminate pouches

containing GLIADEL

Wafer should be delivered to the operating room and remain

unopened until ready to implant the wafers. The outside surface of the outer foil pouch is

not sterile.

Instructions for Opening Pouch Containing GLIADEL

Wafer

Figure 1: To remove the sterile inner pouch from the

outer pouch, locate the folded corner and slowly pull in

an outward motion.

Figure 2: Do NOT pull in a downward motion rolling

knuckles over the pouch. This may exert pressure on the

wafer and cause it to break.

Figure 3: Remove the inner pouch by grabbing hold of the

crimped edge and pulling upward.

Figure 4: To open the inner pouch, gently hold the crimped

edge and cut in an arc-like fashion around the wafer.

Figure 5: To remove the GLIADEL

Wafer, gently grasp the

wafer with the aid of forceps and place it onto a designated

sterile field.

Once the tumor is resected, tumor pathology is confirmed, and hemostasis is obtained, up

to eight GLIADEL

Wafers (polifeprosan 20 with carmustine implant) may be placed to

cover as much of the resection cavity as possible. Slight overlapping of the wafers is

acceptable. Wafers broken in half may be used, but wafers broken in more than two pieces

should be discarded in a biohazard container. Oxidized regenerated cellulose (Surgicel

may be placed over the wafers to secure them against the cavity surface. After placement

of the wafers, the resection cavity should be irrigated and the dura closed in a water tight

fashion.

Unopened foil pouches may be kept at ambient room temperature for a maximum of six

hours at a time.

HOW SUPPLIED

GLIADEL

Wafer is available in a single dose treatment box containing eight individually

pouched wafers. Each wafer contains 7.7 mg of carmustine and is packaged in two

aluminum foil laminate pouches. The inner pouch is sterile and is designed to maintain

product sterility and protect the product from moisture. The outer pouch is a peelable

overwrap. The outside surface of the outer pouch is not sterile.

GLIADEL

Wafer must be stored at or below -20ºC (-4ºF).

REFERENCES

Recommendations for the Safe Handling of Parenteral Antineoplastic Drugs, NIH

Publication No. 83-2621. For sale by the Superintendent of Documents, U.S.

Government Printing Office, Washington, DC 20402.

AMA Council Report, Guidelines for Handling Parenteral Antineoplastics. JAMA,

1985; 253(11):1590-1592.

National Study Commission on Cytotoxic Exposure -- Recommendations for

Handling Cytotoxic Agents. Available from Louis P. Jeffrey, ScD., Chairman,

National Study Commission on Cytotoxic Exposure, Massachusetts College of

Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston,

Massachusetts 02115.

Clinical Oncological Society of Australia, Guidelines and Recommendations for Safe

Handling of Antineoplastic Agents. Med J Australia, 1983; 1:426-428.

Jones RB, et al: Safe Handling of Chemotherapeutic Agents: A Report from the

Mount Sinai Medical Center. CA -- A Cancer Journal for Clinicians, 1983;

(Sept/Oct) 258-263.

American Society of Hospital Pharmacists Technical Assistance Bulletin on Handling

Cytotoxic and Hazardous Drugs. Am J. Hosp Pharm, 1990; 47:1033-1049.

OSHA Work-Practice Guidelines for Personnel Dealing with Cytotoxic

(Antineoplastic) Drugs. Am J Hosp Pharm, 1986; 43:1193-1204.

MANUFACTURER

Eisai Inc.

Woodcliff Lake, NJ 07677

LICENSE HOLDER

Megapharm Ltd P.O.B 519,

Hod Hasharon 4510501.

ISRAEL LICENSE NUMBER

110-34-29392-00

DATE OF REVISION OF THE TEXT

Rev. 04/2010

The format of this leaflet was determined by the ministry of health and its content was checked and

approved in May 2013.

GLIAD SPC 052013 P.1