Drugs List

Therapeutic Indications

Uses

High grade malignant glioma: Adjunctive treatment
Recurrent glioblastoma multiforme: Adjunctive treatment

Administration

For intralesional use

Contraindications

Breastfeeding
Pregnancy

Precautions and Warnings

Porphyria

Avoid communication between resection cavity and ventricular system
Staff: Not to be handled by pregnant staff
Monitor for cerebral oedema
Monitor for intracranial hypertension
Monitor for known complications of craniotomy
Development of brain oedema may require the removal of the implants
Oedema or inflammation may occur around resection cavity area
Female: Ensure adequate contraception during treatment
Driving or operating machinery not advisable following treatment

Communication between the surgical resection cavity and the ventricular system should be avoided to prevent the implants from migrating into the ventricular system and possibly causing obstructive hydrocephalous. If a communication exists that is larger than an implant, it should be closed prior to carmustine implantation.

Computer tomography and magnetic resonance imaging may demonstrate enhancement in the brain tissue surrounding the resection cavity after placement of carmustine implants.
This enhancement may represent oedema and inflammation caused by carmustine implant or tumour progression.

Alkylating agents are normally considered unsafe for use in porphyria.

Pregnancy and Lactation

Pregnancy

Carmustine is contraindicated during pregnancy.

There are no studies assessing the reproductive toxicity of carmustine, or the use of carmustine in pregnant women. Animal studies have shown carmustine to be mutagenic, embryotoxic and teratogenic.

If an inadvertent pregnancy occurs, the woman should be advised of the possible risk for severe adverse effects in the embryo and foetus.

The effect of concurrent therapies must also be considered.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Carmustine is contraindicated during breastfeeding.

It is not known if carmustine is excreted in human breast milk. Some sources consider it likely based on molecular weight, solubility and lack of ionisation at physiological pH.

The effect of concurrent therapies must also be considered.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal thinking
Abnormal vision
Abscess
Accidental injury
Allergic reaction
Alopecia
Amnesia
Anaemia
Anxiety
Aphasia
Aspiration pneumonia
Asthenia
Ataxia
Back pain
Cerebral haemorrhage
Cerebral infarct
Cerebrospinal fluid leaks
Chest pain
Coma
Confusion
Conjunctival oedema
Constipation
Convulsions
Deep vein thrombosis (DVT)
Depression
Diabetes
Diarrhoea
Diplopia
Dizziness
Dysphagia
Eye pain
Facial nerve paresis
Facial oedema
Faecal incontinence
Fever
Gait abnormality
Gastro-intestinal haemorrhage
Grand mal seizure
Haemorrhage
Hallucinations
Headache
Hemiplegia
Hydrocephalus
Hyperglycaemia
Hypertension
Hypoesthesia
Hypokalaemia
Hyponatraemia
Hypotension
Impaired healing
Infections
Insomnia
Intracranial hypertension
Leukocytosis
Meningitis
Nausea
Neck pain
Neuropathy
Oedema
Pain
Paraesthesia
Paranoid delusions
Peripheral oedema
Personality disorder
Pneumonia
Pulmonary embolism
Rash
Sepsis
Somnolence
Speech disturbances
Stupor
Thrombocytopenia
Tremor
Urinary incontinence
Urinary tract infections
Visual field defects
Vomiting

Presentation

Carmustine implant

Drugs List

Therapeutic Indications

Uses

High grade malignant glioma: Adjunctive treatment
Recurrent glioblastoma multiforme: Adjunctive treatment

Dosage

Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

Adults

Administration

For intralesional use

Contraindications

Breastfeeding
Pregnancy

Precautions and Warnings

Porphyria

Avoid communication between resection cavity and ventricular system
Staff: Not to be handled by pregnant staff
Monitor for cerebral oedema
Monitor for intracranial hypertension
Monitor for known complications of craniotomy
Development of brain oedema may require the removal of the implants
Oedema or inflammation may occur around resection cavity area
Female: Ensure adequate contraception during treatment
Driving or operating machinery not advisable following treatment

Communication between the surgical resection cavity and the ventricular system should be avoided to prevent the implants from migrating into the ventricular system and possibly causing obstructive hydrocephalous. If a communication exists that is larger than an implant, it should be closed prior to carmustine implantation.

Computer tomography and magnetic resonance imaging may demonstrate enhancement in the brain tissue surrounding the resection cavity after placement of carmustine implants.
This enhancement may represent oedema and inflammation caused by carmustine implant or tumour progression.

Alkylating agents are normally considered unsafe for use in porphyria.

Pregnancy and Lactation

Pregnancy

Carmustine is contraindicated during pregnancy.

There are no studies assessing the reproductive toxicity of carmustine, or the use of carmustine in pregnant women. Animal studies have shown carmustine to be mutagenic, embryotoxic and teratogenic.

If an inadvertent pregnancy occurs, the woman should be advised of the possible risk for severe adverse effects in the embryo and foetus.

The effect of concurrent therapies must also be considered.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Carmustine is contraindicated during breastfeeding.

It is not known if carmustine is excreted in human breast milk. Some sources consider it likely based on molecular weight, solubility and lack of ionisation at physiological pH.

The effect of concurrent therapies must also be considered.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal thinking
Abnormal vision
Abscess
Accidental injury
Allergic reaction
Alopecia
Amnesia
Anaemia
Anxiety
Aphasia
Aspiration pneumonia
Asthenia
Ataxia
Back pain
Cerebral haemorrhage
Cerebral infarct
Cerebrospinal fluid leaks
Chest pain
Coma
Confusion
Conjunctival oedema
Constipation
Convulsions
Deep vein thrombosis (DVT)
Depression
Diabetes
Diarrhoea
Diplopia
Dizziness
Dysphagia
Eye pain
Facial nerve paresis
Facial oedema
Faecal incontinence
Fever
Gait abnormality
Gastro-intestinal haemorrhage
Grand mal seizure
Haemorrhage
Hallucinations
Headache
Hemiplegia
Hydrocephalus
Hyperglycaemia
Hypertension
Hypoesthesia
Hypokalaemia
Hyponatraemia
Hypotension
Impaired healing
Infections
Insomnia
Intracranial hypertension
Leukocytosis
Meningitis
Nausea
Neck pain
Neuropathy
Oedema
Pain
Paraesthesia
Paranoid delusions
Peripheral oedema
Personality disorder
Pneumonia
Pulmonary embolism
Rash
Sepsis
Somnolence
Speech disturbances
Stupor
Thrombocytopenia
Tremor
Urinary incontinence
Urinary tract infections
Visual field defects
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full review Date: July 2013

Reference Sources

British National Formulary, 65th Edition (2013) Pharmaceutical Press, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Summary of Product Characteristics: Gliadel 7.7 mg implant. Archimedes Pharma UK. Revised December 2011.