Drugs List

Therapeutic Indications

Uses

Idiopathic thrombocytopenic purpura
Leukaemia
Lymphoma
Myeloma - multiple
Tumours - solid

Vincristine is used alone or in conjunction with other oncolytic drugs for the treatment of:

Leukaemias including acute lymphocytic leukaemia, chronic lymphocytic leukaemia, acute myelogenous leukaemia and blastic crisis of chronic myelogenous leukaemia

Malignant lymphomas including Hodgkin's disease and non-Hodgkin's lymphomas

Multiple myeloma

Solid tumours including breast carcinoma, small cell bronchogenic carcinoma, head and neck carcinoma and soft tissue sarcomas

Paediatric solid tumours, including Ewing's sarcoma, embryonal rhabdomyosarcoma, neuroblastoma, Wilm's tumour, retinoblastoma and medulloblastoma

Idiopathic thrombocytopenic purpura (ITP). Patients with true ITP refractory to splenectomy and short-term treatment with adrenocortical steroids may respond to vincristine but the drug is not recommended as primary treatment of this disorder.

Administration

For Intravenous use only. Fatal if given by all other routes.

The NPSA issued the following guidance in August 2008

When vinca alkaloids are prescribed, dispensed or administered in adult or adolescent units:

Doses in syringes should no longer be used.

The prescribed dose should be supplied from the hospital pharmacy ready to administer in a 50ml minibag of sodium chloride 0.9%.

The following warning should be prominently displayed on the label of all vinca alkaloid doses 'For Intravenous Use Only - Fatal if Administered by Other Routes'

There should be judicious use of colour and design on the label, outer packaging and delivery bags to further differentiate minibags containing vinca alkaloids from other minibag infusions.

The vinca alkaloid should be infused intravenously over 5 to 10 minutes and the patient closely monitored for signs of extravasation. Incidents of extravasation should be reported and shared via the National Extravasation Information Service ( www.extravasation.org.uk )

NB. The use of minibags to administer vinca alkaloids to children in paediatric units is not recommended. Local protocols should be consulted for information regarding the volume and method of administration in such patients.

Contraindications

Hypersensitivity to benzyl alcohol
Breastfeeding
Demyelinating Charcot-Marie-Tooth syndrome
Pregnancy
Severe hepatic impairment

Precautions and Warnings

Children under 3 years
Concurrent radiotherapy to the liver
Constipation
Elderly
Infection
Spinal cord irradiation
Decreased gastrointestinal motility
Hepatic impairment
Ischaemic heart disease
Myelosuppression
Neurological disorder
Neuromuscular disorder
Pulmonary disease

Advise ability to drive/operate machinery may be affected by side effects
Give pre-treatment counselling and consideration of sperm cryopreservation
Previous/Concurrent medicine consider washout period: See prescribing info
Treatment to be prescribed under the supervision of a specialist
Some presentations may contain benzyl alcohol
For intravenous use only
If extravasation occurs follow local policy & seek expert help immediately
Perform full blood count before each treatment cycle
Monitor for constipation; give laxatives as required
Monitor uric acid levels
Advise patient to report symptoms of infection immediately
Discontinue if bronchospasm or decreased respiratory function occur
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
Male & female: Contraception required during & for 6 months after treatment

The neurotoxic effect of vincristine may be additive with other neurotoxic agents or increased by spinal cord irradiation and neurological disease.

Vincristine should not be re-administered in patients who experience acute dyspnoea and/or severe bronchospasm. These reactions have most commonly been reported when used in conjunction with Mitomycin-C and may be more serious in patients with pre-existing pulmonary dysfunction. Reactions may occur within minutes and up to 2 weeks following vincristine administration. Progressive dyspnoea requiring chronic therapy may occur.

Routine prophylactic regimen against constipation is recommended. Some manufacturers contraindicate vincristine in patients with impending ileus and/or constipation, especially in children.

If central nervous system leukaemia is diagnosed, additional agents may be required as vincristine does not appear to cross the blood-brain barrier in adequate amounts.

Some brands of vincristine contain benzyl alcohol which may cause toxic reactions and anaphylactoid reactions in infants and children up to 3 years old.

Pregnancy and Lactation

Pregnancy

Vincristine is contraindicated in pregnancy.

Reports of development toxicity including; neonatal pancytopenia, intrauterine growth retardation and foetal death have been reported when vincristine was used in human pregnancy.

Animal studies have shown embryocidal and teratogenic effects.

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 to 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

Vincristine is contraindicated in breastfeeding.

It is unknown whether vincristine sulfate is excreted in human breast milk. Due to the potential for adverse reactions vincristine should not be used.

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 cramps
Agitation
Alopecia
Amenorrhoea
Anaemia
Anaphylaxis
Anorexia
Ataxia
Azoospermia
Back pain
Blindness
Bone marrow depression
Bone pain
Bronchospasm
Cellulitis
Coma
Confusion
Constipation
Convulsions
Coronary artery disorder
Cortical blindness (transient)
Cranial nerve palsies
Deafness
Depression
Diarrhoea
Difficulty in walking
Dizziness
Double vision
Dyspnoea
Dysuria
Fever
Foot drop
Gait abnormality
Gastro-intestinal perforation
Hallucinations
Headache
Hepatic veno-occlusive disease
Hoarseness
Hypertension
Hyperuricaemia
Hyponatraemia
Hypotension
Inappropriate secretion of antidiuretic hormone
Incontinence
Infertility
Injection site reactions
Intestinal necrosis
Jaw pain
Leucopenia
Limb pain
Loss of balance
Loss of deep tendon reflexes
Mouth ulcers
Muscle wasting
Muscle weakness
Myalgia
Myocardial infarction
Nausea
Necrosis (injection site)
Neuritic pain
Neuropathy
Nystagmus
Oedema
Optic atrophy
Pain in parotid gland
Pancreatitis
Paraesthesia
Paralytic ileus
Paresis
Pharyngeal pain
Phlebitis
Polyuria
Psychoses
Ptosis
Rash
Sensory disturbances
Sleeplessness
Testicular pain
Thrombocytopenia
Thrombocytosis
Urinary retention
Vertigo
Vomiting
Weight loss

Presentation

Infusions of vincristine sulphate

Drugs List

Therapeutic Indications

Uses

Idiopathic thrombocytopenic purpura
Leukaemia
Lymphoma
Myeloma - multiple
Tumours - solid

Vincristine is used alone or in conjunction with other oncolytic drugs for the treatment of:

Leukaemias including acute lymphocytic leukaemia, chronic lymphocytic leukaemia, acute myelogenous leukaemia and blastic crisis of chronic myelogenous leukaemia

Malignant lymphomas including Hodgkin's disease and non-Hodgkin's lymphomas

Multiple myeloma

Solid tumours including breast carcinoma, small cell bronchogenic carcinoma, head and neck carcinoma and soft tissue sarcomas

Paediatric solid tumours, including Ewing's sarcoma, embryonal rhabdomyosarcoma, neuroblastoma, Wilm's tumour, retinoblastoma and medulloblastoma

Idiopathic thrombocytopenic purpura (ITP). Patients with true ITP refractory to splenectomy and short-term treatment with adrenocortical steroids may respond to vincristine but the drug is not recommended as primary treatment of this disorder.

Dosage

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

Vincristine sulfate is for intravenous administration only. Fatal if given by other routes.

Great care should be taken in calculating the dose as overdosage may be extremely serious or even fatal. The dose should be calculated on an individual basis and should not be increased beyond the level which produces therapeutic benefit.

Adults

Elderly

Children

Patients with Hepatic Impairment

Administration

For Intravenous use only. Fatal if given by all other routes.

The NPSA issued the following guidance in August 2008

When vinca alkaloids are prescribed, dispensed or administered in adult or adolescent units:

Doses in syringes should no longer be used.

The prescribed dose should be supplied from the hospital pharmacy ready to administer in a 50ml minibag of sodium chloride 0.9%.

The following warning should be prominently displayed on the label of all vinca alkaloid doses 'For Intravenous Use Only - Fatal if Administered by Other Routes'

There should be judicious use of colour and design on the label, outer packaging and delivery bags to further differentiate minibags containing vinca alkaloids from other minibag infusions.

The vinca alkaloid should be infused intravenously over 5 to 10 minutes and the patient closely monitored for signs of extravasation. Incidents of extravasation should be reported and shared via the National Extravasation Information Service ( www.extravasation.org.uk )

NB. The use of minibags to administer vinca alkaloids to children in paediatric units is not recommended. Local protocols should be consulted for information regarding the volume and method of administration in such patients.

Contraindications

Hypersensitivity to benzyl alcohol
Breastfeeding
Demyelinating Charcot-Marie-Tooth syndrome
Pregnancy
Severe hepatic impairment

Precautions and Warnings

Children under 3 years
Concurrent radiotherapy to the liver
Constipation
Elderly
Infection
Spinal cord irradiation
Decreased gastrointestinal motility
Hepatic impairment
Ischaemic heart disease
Myelosuppression
Neurological disorder
Neuromuscular disorder
Pulmonary disease

Advise ability to drive/operate machinery may be affected by side effects
Give pre-treatment counselling and consideration of sperm cryopreservation
Previous/Concurrent medicine consider washout period: See prescribing info
Treatment to be prescribed under the supervision of a specialist
Some presentations may contain benzyl alcohol
For intravenous use only
If extravasation occurs follow local policy & seek expert help immediately
Perform full blood count before each treatment cycle
Monitor for constipation; give laxatives as required
Monitor uric acid levels
Advise patient to report symptoms of infection immediately
Discontinue if bronchospasm or decreased respiratory function occur
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
Male & female: Contraception required during & for 6 months after treatment

The neurotoxic effect of vincristine may be additive with other neurotoxic agents or increased by spinal cord irradiation and neurological disease.

Vincristine should not be re-administered in patients who experience acute dyspnoea and/or severe bronchospasm. These reactions have most commonly been reported when used in conjunction with Mitomycin-C and may be more serious in patients with pre-existing pulmonary dysfunction. Reactions may occur within minutes and up to 2 weeks following vincristine administration. Progressive dyspnoea requiring chronic therapy may occur.

Routine prophylactic regimen against constipation is recommended. Some manufacturers contraindicate vincristine in patients with impending ileus and/or constipation, especially in children.

If central nervous system leukaemia is diagnosed, additional agents may be required as vincristine does not appear to cross the blood-brain barrier in adequate amounts.

Some brands of vincristine contain benzyl alcohol which may cause toxic reactions and anaphylactoid reactions in infants and children up to 3 years old.

Pregnancy and Lactation

Pregnancy

Vincristine is contraindicated in pregnancy.

Reports of development toxicity including; neonatal pancytopenia, intrauterine growth retardation and foetal death have been reported when vincristine was used in human pregnancy.

Animal studies have shown embryocidal and teratogenic effects.

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 to 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

Vincristine is contraindicated in breastfeeding.

It is unknown whether vincristine sulfate is excreted in human breast milk. Due to the potential for adverse reactions vincristine should not be used.

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 cramps
Agitation
Alopecia
Amenorrhoea
Anaemia
Anaphylaxis
Anorexia
Ataxia
Azoospermia
Back pain
Blindness
Bone marrow depression
Bone pain
Bronchospasm
Cellulitis
Coma
Confusion
Constipation
Convulsions
Coronary artery disorder
Cortical blindness (transient)
Cranial nerve palsies
Deafness
Depression
Diarrhoea
Difficulty in walking
Dizziness
Double vision
Dyspnoea
Dysuria
Fever
Foot drop
Gait abnormality
Gastro-intestinal perforation
Hallucinations
Headache
Hepatic veno-occlusive disease
Hoarseness
Hypertension
Hyperuricaemia
Hyponatraemia
Hypotension
Inappropriate secretion of antidiuretic hormone
Incontinence
Infertility
Injection site reactions
Intestinal necrosis
Jaw pain
Leucopenia
Limb pain
Loss of balance
Loss of deep tendon reflexes
Mouth ulcers
Muscle wasting
Muscle weakness
Myalgia
Myocardial infarction
Nausea
Necrosis (injection site)
Neuritic pain
Neuropathy
Nystagmus
Oedema
Optic atrophy
Pain in parotid gland
Pancreatitis
Paraesthesia
Paralytic ileus
Paresis
Pharyngeal pain
Phlebitis
Polyuria
Psychoses
Ptosis
Rash
Sensory disturbances
Sleeplessness
Testicular pain
Thrombocytopenia
Thrombocytosis
Urinary retention
Vertigo
Vomiting
Weight loss

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: May 2015

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, 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.

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. Accessed on 8 May 2015.

Martindale: The Complete Drug Reference (online) London: Brayfield A (ed). Pharmaceutical Press. Accessed on 8 May 2015.

Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications. Accessed on 8 May 2015.

Summary of Product Characteristics: Oncovin. Genus. Revised October 2014.

Summary of Product Characteristics: Vincristine Sulfate. Hospira UK Ltd. Revised December 2008.

Summary of Product Characteristics: Vincristine Sulfate. Teva. Revised October 2010.