Gliadel

Sections of the PIL

Changes/updates

Section 2  What you need to know before you receive Gliadel Implants

The following information was added under subsection ‘Warnings and precautions’

            ‘Following surgery to remove the brain tumour and insert the GLIADEL Implants, your doctor or surgeon will monitor you closely for known complications. In some cases your surgeon may need to re-operate (due to complications or recurrence of the tumour).   Complications include:

-  Convulsions (seizures)

-  Infections in the brain (infections within the skull)

-  Swelling of the brain due to accumulation of fluid

-  Brain fluid leak

-  Wound healing problems

            Your doctor will monitor you closely in case you are taking steroids due to swelling or high fluid pressure in the brain.

            Prior to inserting the implants your surgeon may need to close a canal in your brain to avoid the implants passing through  it which could cause an accumulation of fluids within the skull.

            After insertion of Gliadel Implants, medical imaging may detect swelling of the brain due to accumulation of fluid and inflammation caused by Gliadel Implants or tumour progression.’

In addition, under the subsection: ‘Pregnancy and breast-feeding’ the text was slightly amended to:

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before receiving this medicine’

Section 4 Possible side effects

• Very common wording changed from ‘Very common side effects ( > 10 patients in every 100)’ to ‘Very common: may affect more than 1 in 10 people’

1) ‘Metabolism & nutrition disorders’ subsection was removed and the following very common side effect ‘abnormal (slow) healing of the surgical wound’ was moved to ‘General disorders and administration side conditions’;

2) A new subsection was created under very common side effects: ‘Psychiatric disorders’ and ‘depression’ was moved from ‘Nervous system disorders’ to this section.

3) ‘Headache’ was listed as a very common side effect in ‘Nervous System Disorders’

• Common wording changed from ‘Common side effects (between 1 and 10 patients in every 100)’ to ‘Common: may affect up to 1 in 10 people’

1) ‘High blood sugar levels’ was added as a common side effect to ‘Metabolism & nutrition disorders’

• Three subsections were added under ‘common’:

1) ‘Psychiatric disorders’ and the following side effects events: ‘Changes in your personality; excessive anxiety; abnormal thinking; hallucinations; insomnia (little or poor sleep)’ were moved from ‘Nervous system disorders’;

2) ‘Vascular disorders’ and the following side effects were added: ‘Bleeding; high or low blood pressure’;

3) ‘Skin and subcutaneous (tissue under the skin) disorders’ and the following was added: ‘rash’

Finally, under subsection: ‘Renal (kidney) and urinary disorders’ ‘urinary incontinence’ changed to ‘urinary infections: urinary incontinence’

• ‘Uncommon side effects (between 1 and 10 patients in every 1000)’ section was added, as well as a subsection named: ‘Injury, poisoning and procedural complications’ and a new side effect: Pneumocephalus (air accumulation at the implant site)’

Section 6 Contents of the pack and other information

The wording in subsection ‘What GLIADEL Implants contain’ changed slightly.

Manufacturer 1 changed from IDIS limited to Almac Pharma.

Please refer to the PIL for full information.

The date of revision of text has been updated to November 2019

Sections of the SmPC

Changes/updates

4.1 Therapeutic indications

Indication was updated to include specificity that: ‘Gliadel implant is indicated for the treatment of adult patients’ and ‘Gliadel Implant is indicated as an adjunct to surgery for the treatment of adult patients’ (this information was moved from posology section 4.2)

4.2 Posology and method of administration

Information added:

‘Paediatric population

The safety and efficacy of GLIADEL Implant in children under 18 years of age have not been established. No data are available.’

4.4 Special warnings and precautions for use

Pneumocephalus included as a complication of craniotomy.

The following text was also added under section 4.4:

‘Changes of wall 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. Gliadel wafers implantation adjacent to large cerebral vessels should be avoided.’

4.6 Fertility, pregnancy and lactation

Information on fertility was added as below:

‘Fertility:

No impairment of fertility studies have been conducted with GLIADEL Implants.’

4.7 Effects on ability to drive and use machines

Section updated to:

‘GLIADEL Implant has no influence on the ability to drive and use machines. However, craniotomy and GLIADEL Implant may cause nervous system and vision abnormalities. Therefore patient should be warned of the potential effect of these events on the ability to drive or to use machines.’

4.8 Undesirable effects

‘Adverse events’ wording was replaced throughout the document by ‘adverse reactions’.

Within the table ‘Common Adverse Reactions Observed in ≥ 5% of Patients Receiving GLIADEL Implant at Initial Surgery’ the following changes occurred:

• Several adverse reactions moved across the table to different subsections. Please refer to the SmPC for the full changes in this section.
• ‘Metabolism and nutrition disorders’ is now named ‘Psychiatric disorders’. ‘Depression’ was moved from a very common side effect listed within ‘Nervous systems disorders’ to a very common side effect listed in ‘Psychiatric disorders'.
• In addition, the following adverse reactions were added under ‘Psychiatric disorders’ as common side effects: ‘Personality disorder, anxiety, thinking abnormal, hallucinations, insomnia’
• Under sub-section ‘Nervous System Disorders’, ‘intracranial hypertension’ was replaced by ‘intracranial pressure increased’
• ‘Cardiac disorders’ was replaced by ‘Vascular disorders’ and within this section ‘Deep thrombophlebitis was replaced by ‘Thrombophlebitis’ as a very common side effect;
• A new sub-section was created ‘Infections and infestations’ and ‘Pneumonia’ was moved to this section as a common side effect.

Under the table ‘Common Adverse Reactions Observed in ≥4% of Patients Receiving GLIADEL Implant at Initial Surgery’ the following changes occurred:

• Several adverse reactions moved across the table to different subsections. Please refer to the SmPC for the full changes in this section.
• Under sub-section ‘Nervous System Disorders’, ‘intracranial hypertension’ was replaced by ‘intracranial pressure increased’
•  ‘Cardiac disorders’ was replaced by ‘Vascular disorders’ and within this section ‘Deep thrombophlebitis was replaced by ‘Thrombophlebitis’ as a common side effect;
• A new sub-section was created ‘Infections and infestations’ and ‘Pneumonia’ was moved to this section as a common side effect
• ‘Oral moniliasis’ was removed as a common side effect in ‘Gastrointestinal disorders’ and ‘oral candidias’ was added as a common side effect in ‘Infections and infestations’

The table named ‘Common Adverse Events in 1% to 4% of Patients Receiving GLIADEL Implant‘ was changed to ‘Adverse Reactions in Patients Receiving GLIADEL Implant’ The following changes occurred:

• A new subsection was created called ‘Psychiatric disorders’ and the following common adverse reactions were moved from ‘nervous system disorders’: ‘Depression, abnormal thinking, insomnia, paranoid reaction’;
• Another new subsection was created and named ‘Injury, poisoning and procedural complications’ and ‘pneumocephalus’ was added as uncommon side effect.

In this section, the following text was also added after the last table ‘Cases of air accumulation at the implant site, sometimes associated with neurological symptoms (hemiplegia, aphasia, seizures) have been reported with Gliadel.’

Section 6.6 Special precautions for disposal and other handling

In the end of the text in the first paragraph, the following was added: ‘for cytotoxic agents.’

Section 10 Date of Revision of the Text

Date of revision of text has been updated to November 2019