Drugs List

Therapeutic Indications

Uses

Advanced/metastatic breast cancer resistant to anthracycline chemotherapy
First line treatment of stage 3 or 4 non-small cell lung cancer

Administration

For intravenous use only. Fatal if given by 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% (or 5% glucose).

- 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.

The majority of manufacturers recommend that administration should always be followed by at least 250ml of sodium chloride 0.9% infusion to flush the vein.

Contraindications

Children under 18 years
Infection within the last 2 weeks
Neutrophil count below 1.5 x 10 to the power of 9 / L
Platelet count below 100 x 10 to the power of 9/ L
Breastfeeding
Pregnancy

Precautions and Warnings

Females of childbearing potential
Hepatic metastases
History of ischaemic heart disease
Ischaemic heart disease
Severe hepatic impairment

Administration of live vaccines is not recommended
Avoid concurrent liver radiotherapy
Advise ability to drive/operate machinery may be affected by side effects
Give pre-treatment counselling and consideration of sperm cryopreservation
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of anti-cancer drugs
Dilute and use as an infusion
For intravenous use only
If extravasation occurs follow local policy & seek expert help immediately
Staff: Not to be handled by pregnant staff
Investigate signs and symptoms suggesting an infection
Monitor hepatic function
Monitor platelets, leucocytes and granulocytes before each dose
Advise patient to report breathlessness or cough immediately
Advise patient to report symptoms of infection immediately
Consider the use of anti-emetics before and during therapy
Suspend treatment if neutrophil count is less than 1,500/cubic mm
Suspend treatment if platelets fall below 100,000/cubic mm
Consider dose reduction in severe hepatic impairment
Advise patient not to take St John's wort concurrently
Female: Contraception required during and for 3 months after treatment
Male: Contraception required during and for 6 months after treatment

Close haematological checks are necessary during treatment (measurement of haemoglobin level, leucocyte, neutrophil and platelet counts before each administration). Treatment limiting toxicity is mainly neutropenia. This effect is non-cumulative, having its nadir between 7 and 14 days after the administration and is rapidly reversible within 5 to 7 days.

If extravasation occurs, administration should be stopped, the vein flushed with 0.9 % sodium chloride solution and the remaining dose administered in another vein. Always follow local protocols for the management of extravasation. The appropriate management of such events is contentious but may include glucocorticosteroid to reduce risk of phlebitis.

To avoid the risk of bronchospasm - especially in combination therapy with mitomycin C appropriate prophylaxis may be considered.

Pregnancy and Lactation

Pregnancy

Vinorelbine is contraindicated in pregnancy.

There is insufficient evidence of safety in humans, vinorelbine is suspected to cause serious birth defects when administered during pregnancy. It is unclear if vinorelbine crosses the placental barrier, molecular weight suggests that transmission may be inhibited but not prevented. There have been a small number of cases in which vinorelbine was used and from these, oligohydramnios (attributed to a concomitant cytotoxic) and transient neonatal anaemia have been reported.

However, Briggs concludes that as the indications can be fatal, if a woman requires treatment with this agent and informed consent is obtained, treatment should not be withheld because of pregnancy. If an inadvertent pregnancy occurs, the woman should be advised of the possible risk for severe adverse effects in the embryo and foetus.

Animal (mice and rabbit) studies have shown embryo- and foetotoxicity with intrauterine growth retardation and delayed ossification.

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

Vinorelbine is contraindicated in breastfeeding.

At the time of writing there are no data on the excretion of vinorelbine into breast milk. Due to the potential for serious adverse reactions in the nursing infant, it should not be given to nursing mothers. Schaefer (2007) advises that breastfeeding should not take place until 30 days after the treatment has stopped, due to the long and variable half life of vinorelbine.

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

Alopecia
Anaemia
Angina pectoris
Angioedema
Anorexia
Arrhythmias
Arthralgia
Asthenia
Bronchospasm
Burning pain at injection site
Cardiac disorders
Chest pain
Collapse
Constipation
Diarrhoea
Dyspnoea
ECG changes
Erythema
Erythema at injection site
Fatigue
Febrile neutropenia
Fever
Flushing
Granulocytopenia
Guillain-Barre syndrome
Hypersensitivity reactions including anaphylaxis
Hypertension
Hyponatraemia
Hypotension
Inappropriate secretion of antidiuretic hormone
Increase in alkaline phosphatase
Increase in creatinine
Increase in serum ALT/AST
Infections
Injection site reactions
Interstitial pneumopathies
Jaw pain
Leucopenia
Loss of deep tendon reflexes
Motor disturbances
Myalgia
Myelosuppression
Myocardial infarction
Nausea
Necrosis (injection site)
Neurological disorders
Neuropathy
Neutropenia
Neutropenic sepsis
Oesophagitis
Pain
Palpitations
Pancreatitis
Paraesthesia
Paralytic ileus
Peripheral coldness
Phlebitis (injection site)
Pruritus
Rash
Respiratory insufficiency
Sensory disturbances
Septicaemia
Serum bilirubin increased
Skin reactions
Stomatitis
Tachycardia
Thrombocytopenia
Tumour pain
Urticaria
Vein discolouration
Vomiting
Weakness of legs

Presentation

Vinorelbine (as tartrate) parenteral formulations

Drugs List

Therapeutic Indications

Uses

Advanced/metastatic breast cancer resistant to anthracycline chemotherapy
First line treatment of stage 3 or 4 non-small cell lung cancer

Dosage

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

This preparation is for intravenous use only. Fatal if given by other routes.

Adults

Patients with Hepatic Impairment

Administration

For intravenous use only. Fatal if given by 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% (or 5% glucose).

- 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.

The majority of manufacturers recommend that administration should always be followed by at least 250ml of sodium chloride 0.9% infusion to flush the vein.

Contraindications

Children under 18 years
Infection within the last 2 weeks
Neutrophil count below 1.5 x 10 to the power of 9 / L
Platelet count below 100 x 10 to the power of 9/ L
Breastfeeding
Pregnancy

Precautions and Warnings

Females of childbearing potential
Hepatic metastases
History of ischaemic heart disease
Ischaemic heart disease
Severe hepatic impairment

Administration of live vaccines is not recommended
Avoid concurrent liver radiotherapy
Advise ability to drive/operate machinery may be affected by side effects
Give pre-treatment counselling and consideration of sperm cryopreservation
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of anti-cancer drugs
Dilute and use as an infusion
For intravenous use only
If extravasation occurs follow local policy & seek expert help immediately
Staff: Not to be handled by pregnant staff
Investigate signs and symptoms suggesting an infection
Monitor hepatic function
Monitor platelets, leucocytes and granulocytes before each dose
Advise patient to report breathlessness or cough immediately
Advise patient to report symptoms of infection immediately
Consider the use of anti-emetics before and during therapy
Suspend treatment if neutrophil count is less than 1,500/cubic mm
Suspend treatment if platelets fall below 100,000/cubic mm
Consider dose reduction in severe hepatic impairment
Advise patient not to take St John's wort concurrently
Female: Contraception required during and for 3 months after treatment
Male: Contraception required during and for 6 months after treatment

Close haematological checks are necessary during treatment (measurement of haemoglobin level, leucocyte, neutrophil and platelet counts before each administration). Treatment limiting toxicity is mainly neutropenia. This effect is non-cumulative, having its nadir between 7 and 14 days after the administration and is rapidly reversible within 5 to 7 days.

If extravasation occurs, administration should be stopped, the vein flushed with 0.9 % sodium chloride solution and the remaining dose administered in another vein. Always follow local protocols for the management of extravasation. The appropriate management of such events is contentious but may include glucocorticosteroid to reduce risk of phlebitis.

To avoid the risk of bronchospasm - especially in combination therapy with mitomycin C appropriate prophylaxis may be considered.

Pregnancy and Lactation

Pregnancy

Vinorelbine is contraindicated in pregnancy.

There is insufficient evidence of safety in humans, vinorelbine is suspected to cause serious birth defects when administered during pregnancy. It is unclear if vinorelbine crosses the placental barrier, molecular weight suggests that transmission may be inhibited but not prevented. There have been a small number of cases in which vinorelbine was used and from these, oligohydramnios (attributed to a concomitant cytotoxic) and transient neonatal anaemia have been reported.

However, Briggs concludes that as the indications can be fatal, if a woman requires treatment with this agent and informed consent is obtained, treatment should not be withheld because of pregnancy. If an inadvertent pregnancy occurs, the woman should be advised of the possible risk for severe adverse effects in the embryo and foetus.

Animal (mice and rabbit) studies have shown embryo- and foetotoxicity with intrauterine growth retardation and delayed ossification.

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

Vinorelbine is contraindicated in breastfeeding.

At the time of writing there are no data on the excretion of vinorelbine into breast milk. Due to the potential for serious adverse reactions in the nursing infant, it should not be given to nursing mothers. Schaefer (2007) advises that breastfeeding should not take place until 30 days after the treatment has stopped, due to the long and variable half life of vinorelbine.

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

Alopecia
Anaemia
Angina pectoris
Angioedema
Anorexia
Arrhythmias
Arthralgia
Asthenia
Bronchospasm
Burning pain at injection site
Cardiac disorders
Chest pain
Collapse
Constipation
Diarrhoea
Dyspnoea
ECG changes
Erythema
Erythema at injection site
Fatigue
Febrile neutropenia
Fever
Flushing
Granulocytopenia
Guillain-Barre syndrome
Hypersensitivity reactions including anaphylaxis
Hypertension
Hyponatraemia
Hypotension
Inappropriate secretion of antidiuretic hormone
Increase in alkaline phosphatase
Increase in creatinine
Increase in serum ALT/AST
Infections
Injection site reactions
Interstitial pneumopathies
Jaw pain
Leucopenia
Loss of deep tendon reflexes
Motor disturbances
Myalgia
Myelosuppression
Myocardial infarction
Nausea
Necrosis (injection site)
Neurological disorders
Neuropathy
Neutropenia
Neutropenic sepsis
Oesophagitis
Pain
Palpitations
Pancreatitis
Paraesthesia
Paralytic ileus
Peripheral coldness
Phlebitis (injection site)
Pruritus
Rash
Respiratory insufficiency
Sensory disturbances
Septicaemia
Serum bilirubin increased
Skin reactions
Stomatitis
Tachycardia
Thrombocytopenia
Tumour pain
Urticaria
Vein discolouration
Vomiting
Weakness of legs

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 2014

Reference Sources

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.

Drugs during Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd Edition, ed. Schaefer, Peters & Miller, Elsevier Academic Press, London 2007.

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com [Accessed on May 23, 2014].

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

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Navelbine. Pierre Fabre Ltd. Revised July 2011.
Summary of Product Characteristics: Vinorelbine. Medac GmbH. Revised February 2014.
Summary of Product Characteristics: Vinorelbine. Actavis. Revised April 2014.

NPSA Rapid Response Report 11 August 2008. Using Vinca Alkaloid Minibags (Adult/Adolescent Units).
Available at: https://www.nrls.npsa.nhs.uk/alerts/?entryid45=59890
Last accessed: 18 July 2014.