Consumer medicine information

GLIADEL Implants

Carmustine

BRAND INFORMATION

Brand name

Gliadel Implant

Active ingredient

Carmustine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using GLIADEL Implants.

WHAT IS IN THIS LEAFLET

This leaflet answers some common questions about GLIADEL. It does not contain all the available information that is known about GLIADEL. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of treatment with GLIADEL against the benefits they expect it will have for you.

If you have any concerns about treatment with this medicine, ask your doctor or pharmacist.

Keep this leaflet as you may want to read it again after your GLIADEL treatment.

WHAT GLIADEL IS USED FOR

GLIADEL is used to treat some types of brain cancers after removal by surgery.

GLIADEL works by killing cancer cells and/or stopping cancer cells from growing and multiplying.

GLIADEL belongs to a group of medicines called antineoplastic or cytotoxic medicines. You may also hear these being called chemotherapy medicines.

Ask your doctor if you have any questions about why GLIADEL treatment has been prescribed for you.

GLIADEL is not addictive.

BEFORE YOU ARE GIVEN GLIADEL

When you must not be given it

You must not be given GLIADEL if you are breastfeeding or plan to breastfeed.

It is recommended that you do not breast-feed while undergoing GLIADEL treatment, as it may pass into the breast milk and therefore there is a possibility that the breast-fed baby may be affected.

Do not use GLIADEL to treat children.

There is no experience with the use of GLIADEL in children.

If you are not sure whether you should have GLIADEL, talk to your doctor or pharmacist.

Before you are given it

Tell your doctor or pharmacist if you have any allergies to:

  • any other medicines
  • any other substances, such as foods, preservatives or dyes.

Tell your doctor if you are pregnant or intend to become pregnant.

Like most medicines used to treat cancer, GLIADEL is not recommended for use during pregnancy. If there is need to consider GLIADEL during your pregnancy, your doctor will discuss with you the benefits and risks of using it.

If you have not told your doctor about any of the above, tell them before you have GLIADEL.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

HOW GLIADEL IS GIVEN

How much is given

Your doctor will decide what dose you will receive. This will depend on your condition and other factors.

Ask your doctor if you want to know more about the dose of GLIADEL you receive.

How it is given

The GLIADEL Implants are placed inside your head during the surgery to remove your tumor. The usual number of implants is up to eight (61.6 mg of carmustine), however this number may be reduced by your doctor depending on your tumor size.

How long is it given

You are only given GLIADEL Implants once when your tumor is removed during surgery. The implants will then slowly dissolve away.

If you are given too much (overdose)

Your doctor will know the correct dose for you, so the chances of overdose are highly unlikely.

AFTER YOU HAVE BEEN GIVEN GLIADEL

Things you must do

If you become pregnant after being given GLIADEL tell you doctor immediately.

If you are about to be started on any new medicine tell your doctor that you have had GLIADEL implanted.

Tell any other doctors, dentists and pharmacists who are treating you that you have had GLIADEL Implants.

In particular, GLIADEL Implants will be seen on brain scans so warn any doctors before you have any brain scans after the GLIADEL has been implanted.

If you are about to be started on any new medicine, tell your doctor, dentist or pharmacist that you have had GLIADEL implanted.

SIDE EFFECTS

Tell your doctor, nurse or pharmacist as soon as possible if you do not feel well after being given GLIADEL Implants.

GLIADEL helps most people with brain tumors, but like other chemotherapeutic medicines, it may have unwanted side effects. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have

If any of the following happen, tell your doctor or pharmacist immediately:

  • high temperature
  • pain – head, neck, chest or back
  • headache
  • confusion or stupor
  • fits or seizures
  • weakness or paralysis of one side of the body
  • unusual tiredness, sleepiness or weakness
  • nausea or vomiting
  • pain or burning feeling when urinating
  • shortness of breath or difficulty in breathing
  • oral thrush – sore creamy yellow raised patches in the mouth
  • rash
  • difficulty in talking
  • diarrhoea or constipation
  • difficulty swallowing
  • problems seeing
  • dizziness
  • depression, problems sleeping, abnormal thinking
  • clumsiness and lack of coordination

Most of these side effects are usually mild to moderate. However, they may also be signs of a more serious side effect. You may need medical attention

If any of the following happen, tell your doctor or pharmacist immediately or go to Accident and Emergency at your nearest hospital:

  • pneumonia – chest infection with cough and yellow/green sputum
  • a blood clot in your leg or severe chest pain with a shortness of breath
  • decreased level of consciousness
  • coma

These are serious side effects. You may need urgent medical attention or hospitalisation. These side effects are rare.

Other side effects not listed above may also occur in some patients. Tell your doctor if you notice anything else that is making you feel unwell.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

STORAGE

GLIADEL implants are stored in the freezer at or below -20°C in the pharmacy department of your hospital.

GLIADEL DESCRIPTION

What it looks like

GLIADEL Implants are an off-white to pale yellow flat disc approximately 1.45 cm in diameter and 1 mm thick.

Active Ingredients

GLIADEL Implants contain 7.7 mg of carmustine as the active ingredient.

Other Ingredients

The other ingredient in GLIADEL Implants is an inactive copolymer called Polifeprosan 20. This copolymer consists of two polymers - carboxypropane and sebacic acid.

Sponsor

Eisai Australia Pty. Ltd.
Level 2, 437 St. Kilda Rd.
Melbourne, VIC, 3004 Australia

ARTG Number 77283

Date of revision: 5 November 2015

BRAND INFORMATION

Brand name

Gliadel Implant

Active ingredient

Carmustine

Schedule

S4

 

1 Name of Medicine

Carmustine.

6.7 Physicochemical Properties

Carmustine is a light yellow powder. It is highly soluble in alcohol and lipids and is poorly soluble in water. Its melting point range is 29.5-32.0°C and it has a molecular weight of 214.06.
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.
Carmustine is a nitrosourea. The chemical name of carmustine is 1,3-bis (2-chloroethyl)-1-nitrosourea (or BCNU).

Chemical structure.

The structural formula for carmustine is:

CAS number.

154-93-8.

2 Qualitative and Quantitative Composition

Each Gliadel implant contains 7.7 mg of carmustine.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Implant.
Gliadel Implants are sterile, off-white to pale yellow implants approximately 1.45 cm in diameter and 1 mm thick.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Gliadel is designed to deliver carmustine directly into the surgical cavity created after tumour resection. On exposure to the aqueous environment of the cavity, the anhydride bonds in the copolymer are hydrolysed, releasing carmustine, carboxyphenoxypropane, and sebacic acid. The carmustine released from Gliadel diffuses into the surrounding brain tissue and produces an antineoplastic effect by alkylating DNA and RNA.
Carmustine has been shown to degrade both spontaneously and metabolically. The production of an alkylating moiety, hypothesised to be chloroethyl carbonium ion, leads to the formation of DNA cross-links.
The tumouricidal activity of Gliadel is dependent on release of carmustine to the tumour 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 predominantly eliminated by the kidney and sebacic acid (an endogenous fatty acid) is metabolised by the liver and expired as CO2 in animals.

Clinical trials.

Primary surgery.

A randomised, double blind, placebo controlled clinical trial was conducted in adult patients with newly diagnosed high grade malignant glioma undergoing initial craniotomy for tumour resection. The trial determined the safety and efficacy of Gliadel 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 tumour 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 were implanted in 120 patients. The majority of patients received 6-8 wafers. The majority of patients (93/120, 77.5% in the Gliadel group and 98/120, 81.7% in the placebo group) with newly diagnosed malignant glioma received a standard course of radiotherapy (55 to 60 Gy) typically starting 3 weeks after surgery. There were 17 patients (14.2%) in the Gliadel 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 Gliadel 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 13.9 months with Gliadel (p-value < 0.05, log rank test). The hazard ratio for Gliadel treatment was 0.73 (95% CI: 0.56-0.95). (See Figure 1.)
When only patients with glioblastoma multiforme were included in the analysis, the hazard ratio with Gliadel treatment was 0.78 (95% CI: 0.59-1.03, p = 0.08, log-rank test).

Surgery for recurrent disease.

A randomised, double blind, placebo controlled clinical trial was conducted in adult patients with recurrent malignant glioma. This trial determined the safety and efficacy of Gliadel implants plus surgery compared to placebo implants plus surgery. Ninety-five percent of the patients treated with Gliadel had 7-8 wafers implanted. Chemotherapy was withheld at least four weeks (six weeks for nitrosoureas) prior to and two weeks after surgery in patients undergoing reoperation for malignant glioma.
In 222 patients with recurrent malignant glioma 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. Median survival increased by 33%, from 24 weeks (5.5 months) with placebo to 32 weeks (7.4 months) with Gliadel 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 treatment. In patients with pathologic diagnoses other than GBM at the time of surgery for tumour recurrence, Gliadel produced no survival prolongation. (See Figures 2 and 3.)

5.2 Pharmacokinetic Properties

The absorption, distribution, metabolism, and excretion of the copolymer in humans are unknown. Carmustine concentrations delivered by Gliadel in human brain tissue have not been determined. Plasma levels of carmustine after Gliadel implantation were not determined. Animal studies suggest that nearly all the carmustine in the implants is released within 7 days of implantation.
Following an intravenous infusion of carmustine at doses ranging from 30 to 170 mg/m2, 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/m2 dose of 14C-carmustine was excreted in the urine over 96 hours and 6% was expired as CO2.
Gliadel implants are biodegradable in the human brain when placed into the cavity after tumour resection. The rate of biodegradation is variable from patient to patient. During the biodegradation process, an implant remnant may be observed on brain imaging scans or at reoperation even though extensive degradation of all components has occurred. Data obtained from review of CT scans obtained 49 days after implantation of Gliadel demonstrated that images consistent with implants were visible to varying degrees in the scans of 11 of 18 patients. Data obtained at reoperation and autopsies have demonstrated implant remnants up to 232 days after Gliadel implantation.
Implant remnants removed at reoperation from two patients with recurrent malignant glioma, one at 64 days and the second at 92 days after implantation, were analysed for content. Table 3 presents the results of analyses completed on these remnants.
The implant remnants consisted mostly of water and monomeric components with minimal detectable carmustine present.

5.3 Preclinical Safety Data

Genotoxicity.

No mutagenicity studies have been conducted with Gliadel. However, such studies have been conducted with carmustine, the active component of Gliadel, when administered systemically. Carmustine was mutagenic in vitro and clastogenic in vitro and in vivo.

Carcinogenicity.

No carcinogenicity studies have been conducted with Gliadel. However, such studies have been conducted with carmustine, the active component of Gliadel, when administered systemically. Carcinogenicity studies were conducted in rats and mice, with the data indicating an increased incidence of pulmonary neoplasms in rats and possible tumorigenic activity in mice.

4 Clinical Particulars

4.1 Therapeutic Indications

Gliadel is indicated in newly-diagnosed high-grade malignant glioma patients as an adjunct to surgery and radiation.
Gliadel is also indicated for use as adjunct to surgery to prolong survival in patients with recurrent glioblastoma multiforme (GBM) for whom surgical resection is indicated.

4.3 Contraindications

Gliadel is contraindicated in patients with a history of hypersensitivity to carmustine or any of the excipients of Gliadel (see Section 6.1 List of Excipients).
Gliadel Implant is also contraindicated in breastfeeding mothers.

4.4 Special Warnings and Precautions for Use

Surgery.

Patients undergoing craniotomy for malignant glioma and implantation of Gliadel should be monitored closely for known complications of craniotomy which include seizures/ convulsions, intra-cranial infections, abnormal wound healing and brain oedema (see Section 4.8 Adverse Effects (Undesirable Effects)). Cases of intracerebral mass effect unresponsive to corticosteroids have been described in patients treated with Gliadel, including one case leading to brain herniation. Pneumocephalus has been reported, commonly, following surgery involving Gliadel administration.
Changes of the walls of cerebral blood vessels located close to Gliadel wafer, including cases of aneurysms leading to cerebral bleeding several months after Gliadel wafer implantation, have been described. Implantation of Gliadel wafers adjacent to large cerebral vessels should be avoided.
Communication between the surgical resection cavity and the ventricular system should be avoided to prevent the implants 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 at operation prior to implantation.

Imaging studies.

Computed tomography (CT) and magnetic resonance imaging (MRI) of the head may demonstrate enhancement in the brain tissue surrounding the resection cavity after placement of Gliadel implants. This enhancement may represent oedema and inflammation caused by Gliadel or tumour progression.

Recommendations for safe handling.

Implants should 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 dedicated biohazard waste container after use. A surgical instrument dedicated to the handling of the implants should be used for implant placement. If repeat neurosurgical intervention is required, any implant or implant remnant should be handled as a potentially cytotoxic agent and discarded into the biohazard container.
Each implant is wrapped in a double foil system for use in operating theatres, with the outer sachet acting as a nonsterile overwrap and the inner sachet only being sterile.

Use in the elderly.

Limited data are available in patients aged ≥ 75 years. Gliadel should be used with caution in such patients.

Paediatric use.

The safety and efficacy of Gliadel in children has not been established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Interactions of Gliadel with other drugs have not been formally evaluated.
The short and long-term toxicity profiles of Gliadel when given in conjunction with chemotherapy have not been fully explored. Gliadel, when given in conjunction with radiotherapy, does not appear to have any short-term or chronic toxicities.

Systemic chemotherapy.

Some patients (n = 6) in the clinical trials have received systemic chemotherapy. Chemotherapy was withheld at least four weeks (six weeks for nitrosoureas) prior to and two weeks after surgery in patients undergoing reoperation for malignant glioma.

Radiotherapy.

Some patients in the clinical trials have received external beam radiation therapy (n = 36). External beam radiation therapy was initiated no sooner than three weeks after Gliadel implantation. Of the 36 patients who received Gliadel at initial surgery for newly diagnosed malignant glioma followed by external beam radiation therapy, 3/15 (20%) in one study and 11/21 (52%) in the other study experienced new or worsened seizures.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No impairment of fertility studies have been conducted with Gliadel.
However, such studies have been conducted with carmustine, the active component of Gliadel, when administered systemically. Carmustine has been shown to affect fertility in male rats, with conception rate being reduced in females mated to treated males, as carmustine can cause testicular degeneration.
(Category D)
There are no studies in either pregnant women or laboratory animals on Gliadel, but the active component, carmustine, when administered systemically, can cause foetal harm when administered to a pregnant woman and has been shown to be embryotoxic in rats and rabbits and teratogenic in rats.
Although it is preferable that Gliadel is not used in pregnancy, if it is, or if the patient becomes pregnant after Gliadel implantation, the patient must be warned of the potential hazard to the foetus.
It is not known if either carmustine, carboxyphenoxypropane or sebacic acid are excreted in human milk. Since some drugs are excreted in human milk and because of the potential for serious adverse reactions from carmustine in nursing infants, women being treated with Gliadel should not breastfeed their infants. For women who wish to breastfeed their infants, Gliadel is contraindicated.

4.8 Adverse Effects (Undesirable Effects)

Clinical trials.

Adverse reactions for the trials are described in Tables 1 and 2.

Primary surgery.

The following data are some of the most frequently occurring adverse events observed in 5% or more of the newly diagnosed malignant glioma patients during the trial. (See Table 1.)

Surgery for recurrent disease.

The following postoperative adverse events were observed in 4% or more of the patients receiving Gliadel at recurrent 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 group are listed. These adverse events were either not present preoperatively or worsened postoperatively during the follow-up period. The follow-up period was up to 71 months. (See Table 2.)
The following four categories of adverse events are possibly related to treatment with Gliadel. The frequency with which they occurred in the randomised 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 and 37.5% in patients receiving placebo. Grand mal seizures occurred in 5% of Gliadel-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 group and 4.2% in the placebo group. The time from surgery to the onset of the first postoperative seizure did not differ between the Gliadel and placebo treated patients.
In the surgery for recurrent disease trial, the incidence of postoperative seizures was 19% in both patients receiving Gliadel and placebo. In this study, 12/22 (54%) of patients treated with Gliadel and 2/22 (9%) of placebo patients experienced the first new or worsened seizure within the first five postoperative days. The median time to onset of the first new or worsened postoperative seizure was 3.5 days in patients treated with Gliadel and 61 days in placebo patients.

2. Brain oedema.

In the initial surgery trial, brain oedema was noted in 22.5% of patients treated with Gliadel and in 19.2% of patients treated with placebo. Development of brain oedema with mass effect (due to tumour recurrence, intracranial infection or necrosis) may necessitate reoperation and, in some cases, removal of Gliadel or its remnants.

3. Healing abnormalities.

The following healing abnormalities have been reported in clinical trials of Gliadel: 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-treated patients and in 11.7% of placebo recipients. Cerebrospinal fluid leaks occurred in 5% of Gliadel recipients and 0.8% of those given placebo.
During surgery, a water-tight dural closure should be obtained to minimise the risk of cerebrospinal fluid leak.
In the surgery for recurrent disease trial, the incidence of healing abnormalities was 14% in Gliadel-treated patients and 5% in patients receiving placebo.

4. Intracranial infection.

In the initial surgery trial, the incidence of brain abscess or meningitis was 5% in patients treated with Gliadel and 6% in patients receiving placebo. In the recurrent setting, the incidence of brain abscess or meningitis was 4% in patients treated with Gliadel and 1% in patients receiving placebo.
The following adverse events, not listed in Tables 1 to 2 above, were reported in less than 4% but at least 1% of patients treated with Gliadel in all studies. The events listed were either not present preoperatively or worsened postoperatively. Whether Gliadel caused these events cannot be determined.

Body as a whole.

Peripheral oedema (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.

Diarrhoea (2%); constipation (2%); dysphagia (1%); gastrointestinal haemorrhage (1%); faecal incontinence (1%).

Haemic and lymphatic system.

Thrombocytopaenia (1%); leukocytosis (1%).

Metabolic and nutritional disorders.

Hyponatraemia (3%); hyperglycaemia (3%); hypokalaemia (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 haemorrhage and cerebral infarct were each reported in less than 1% of patients treated with Gliadel.

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%).
In a published clinical study, cyst formation after Gliadel Implant treatment has been reported. This reaction occurred in 10% of the patients observed in the study, however, the formation of cyst is possible after resection of a malignant glioma.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important.
It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at http://www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Each Gliadel implant contains 7.7 mg of carmustine, resulting in a dose of 61.6 mg when eight implants are placed in the tumour resection cavity. It is recommended that a maximum of eight implants be placed if the size and shape of the resection cavity allows it. Otherwise, use the maximum number of implants possible. No more than eight implants should be used per surgical procedure, as there is no clinical experience with this dose.

Handling and disposal.

Gliadel implants should be handled with care (see Section 4.4 Special Warnings and Precautions for Use on safe handling).
The sachets containing Gliadel should be delivered to the operating room and remain unopened until ready to place the implants into the resection cavity. The outside surface of the outer foil sachet is not sterile and must be removed under sterile conditions from the sterile inner sachet prior to implantation.

Instructions for opening sachet containing Gliadel Implant.

1. To remove the sterile inner sachet from the outer sachet, locate the folded corner and slowly pull in an outward motion.
2. Do not pull in a downward motion rolling knuckles over the sachet. This may exert pressure on the implant and cause it to break.
3. Remove the inner sachet by grabbing hold of the crimped edge and pulling upward.
4. To open the inner sachet, gently hold the crimped edge and cut in an arc-like fashion around the implant.
5. To remove the Gliadel implant, gently grasp the implant with the aid of forceps and place it onto a designated sterile field.
Once the tumour is resected, tumour pathology is confirmed and haemostasis is obtained, up to eight Gliadel Implants may be placed to cover as much of the resection cavity as possible. Slight overlapping of the implants is acceptable. Implants broken in half may be used, but implants broken in more than two pieces should be discarded in a biohazard container.
Oxidised regenerated cellulose (Surgicel) may be placed over the implants to secure them against the cavity surface. After placement of the implants, the resection cavity should be irrigated and the dura closed in a water-tight fashion.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.9 Overdose

For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).
There is no clinical experience with use of more than eight Gliadel implants per surgical procedure.

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

The implants contain 192.3 mg of a biodegradable polyanhydride copolymer (Polifeprosan 20).

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Gliadel must be stored at or below -20°C (deep freeze). Gliadel implants have been demonstrated to be stable at either -18°C or -20°C.
Unopened outer sachets may be kept at a temperature of not more than 22°C for a maximum of six hours. Refreezing of sachets is allowed if they have not been opened and have been kept for a maximum of 6 hours at a temperature of not more than 22°C. Gliadel Implants should be used within 30 days when refrozen.

6.5 Nature and Contents of Container

Each implant is packaged in two aluminium foil laminate sachets. The inner sachet is sterile and is designed to maintain product sterility and protect the product from moisture. The outer sachet is a peelable overwrap.
The outside surface of the outer sachet is not sterile.
Each box of Gliadel contains eight implants representing a single dose.

6.6 Special Precautions for Disposal

Any unused implants or implant remnant should be handled as a potentially cytotoxic agent and discarded into a biohazard container.

Summary Table of Changes