Drugs List

Therapeutic Indications

Uses

Small cell lung cancer
Testicular carcinoma - non-seminomatous

Treatment of small cell lung cancer and resistant non-seminomatous testicular carcinoma alone or in combination with other cytotoxic drugs.

Unlicensed Uses

Childhood rhabdomyosarcoma
Neuroblastoma in childhood
Soft tissue tumours of childhood

In paediatric patients:
Acute lymphoblastic leukaemia, acute myeloid leukaemia, Ewing tumour, germ-cell tumours, neuroectodermal tumours, non-Hodgkin's lymphoma, relapsed Hodgkin's disease, rhabdomyosarcoma, soft tissue sarcoma, stage 4 neuroblastoma.

Administration

For slow intravenous infusion, between 30 and 60 minutes

Contraindications

Children under 12 years
Breastfeeding
Pregnancy
Severe hepatic impairment

Precautions and Warnings

Children under 18 years
Herpes zoster
Hypoalbuminaemia
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
Dehydration
Hepatic impairment
Renal impairment - creatinine clearance below 50ml/minute

Administration of live vaccines is not recommended
Reduce dose in patients with creatinine clearance below 50ml/min
Advise ability to drive/operate machinery may be affected by side effects
Give pre-treatment counselling and consideration of sperm cryopreservation
Maintain adequate hydration of patient prior / during treatment
Treat and control infections prior to commencing therapy
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of anti-cancer drugs
For intravenous use only
If extravasation occurs follow local policy & seek expert help immediately
Interrupt treatment if infusion reaction occurs & monitor until resolution
Resuscitation facilities must be immediately available
Staff: Not to be handled by pregnant staff
Monitor hepatic function before treatment and regularly during treatment
Monitor renal function before treatment and regularly during treatment
Monitor complete blood counts before each dose
Monitor patients for signs of tumour lysis syndrome
Restart therapy when platelets>100,000/cubic mm & leucocytes>4,000/cubic mm
Advise patient to report symptoms of infection immediately
Discontinue if thrombocytopenia occurs
May cause anaphylactic / anaphylactoid reactions
Potentially leukaemogenic
Interrupt treatment and/or reduce dose for any grade 3 toxicity
Reduce dose if neutrophil count <0.5x10 to the power 9/L for 5 days or more
Reduce dose if neutrophils < 0.5 x 10 to the power 9/L with fever/infection
Suspend treatment if leucocytes fall below 2,000/cubic mm
Reduce dose if platelets <25 x 10 to the power of 9/L
Male & female: Contraception required during & for 6 months after treatment

Acute leukaemia, which can occur with or without a preleukaemic phase, has been reported rarely in patient treated with etoposide in combination with other anti-neoplastic drugs. The predisposing factors have not been identified.

A new treatment cycle should only be started if neutrophil count is greater than 1.5 x 10 to the power of 9/L and platelet count is greater than 100 x 10 to the power 9/L unless caused by malignant disease.

If severe reactions occur the dose should be reduced or discontinued and appropriate corrective measures initiated. Re-initiation of etoposide should be carried out with caution and consideration to the risks versus the benefits.

Pregnancy and Lactation

Pregnancy

Etoposide is contraindicated during pregnancy.

Growth restriction and severe myelosuppression has been observed in newborns of pregnant women using etoposide during the 2nd and 3rd trimester.

Studies in rats and mice have shown teratogenic effects.

The effects 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 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

Etoposide is contraindicated in breastfeeding.

Etoposide is excreted into human breast milk and there is a potential for severe toxicity in the nursing infant. Briggs suggests that breastfeeding should be stopped for at least 55 hours after the last dose of etoposide, based on its half life, while Schaefer suggests 24 to 36 hours.

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
Acute leukaemia
Alopecia
Altered liver function tests
Anaemia
Anaphylactoid-like reaction
Anorexia
Apnoea
Arrhythmias
Asthenia
Bronchospasm
Constipation
Convulsions
Cortical blindness (transient)
Cough
Cyanosis
Diarrhoea
Dizziness
Dysphagia
Extravasation
Fatigue
Fever
Flushing
Haemorrhage
Hepatic impairment
Hypersensitivity reactions including anaphylaxis
Hypertension
Hypotension (transient)
Increased susceptibility to infection
Interstitial pneumonitis
Laryngospasm
Leucopenia
Malaise
Mucositis
Myelosuppression
Myocardial infarction
Nausea
Neutropenia
Oesophagitis
Optic neuritis
Peripheral neuropathy
Phlebitis (injection site)
Pruritus
Pulmonary fibrosis
Radiation recall dermatitis
Rash
Renal impairment
Skin discolouration
Somnolence
Stevens-Johnson syndrome
Stomatitis
Tachycardia
Taste disturbances
Thrombocytopenia
Toxic epidermal necrolysis
Tumour lysis syndrome
Urticaria
Vomiting

Presentation

Etoposide phosphate lyophilised powder for injection.

Drugs List

Therapeutic Indications

Uses

Small cell lung cancer
Testicular carcinoma - non-seminomatous

Treatment of small cell lung cancer and resistant non-seminomatous testicular carcinoma alone or in combination with other cytotoxic drugs.

Unlicensed Uses

Childhood rhabdomyosarcoma
Neuroblastoma in childhood
Soft tissue tumours of childhood

In paediatric patients:
Acute lymphoblastic leukaemia, acute myeloid leukaemia, Ewing tumour, germ-cell tumours, neuroectodermal tumours, non-Hodgkin's lymphoma, relapsed Hodgkin's disease, rhabdomyosarcoma, soft tissue sarcoma, stage 4 neuroblastoma.

Dosage

Due to the complexity and specialist nature of dosage regimens for the treatment of malignant disease, specific dosing information on this agent is not included.
Doses may vary significantly if this agent is used as monotherapy or different combinations.
When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.

Patients with Renal Impairment

Administration

For slow intravenous infusion, between 30 and 60 minutes

Contraindications

Children under 12 years
Breastfeeding
Pregnancy
Severe hepatic impairment

Precautions and Warnings

Children under 18 years
Herpes zoster
Hypoalbuminaemia
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
Dehydration
Hepatic impairment
Renal impairment - creatinine clearance below 50ml/minute

Administration of live vaccines is not recommended
Reduce dose in patients with creatinine clearance below 50ml/min
Advise ability to drive/operate machinery may be affected by side effects
Give pre-treatment counselling and consideration of sperm cryopreservation
Maintain adequate hydration of patient prior / during treatment
Treat and control infections prior to commencing therapy
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of anti-cancer drugs
For intravenous use only
If extravasation occurs follow local policy & seek expert help immediately
Interrupt treatment if infusion reaction occurs & monitor until resolution
Resuscitation facilities must be immediately available
Staff: Not to be handled by pregnant staff
Monitor hepatic function before treatment and regularly during treatment
Monitor renal function before treatment and regularly during treatment
Monitor complete blood counts before each dose
Monitor patients for signs of tumour lysis syndrome
Restart therapy when platelets>100,000/cubic mm & leucocytes>4,000/cubic mm
Advise patient to report symptoms of infection immediately
Discontinue if thrombocytopenia occurs
May cause anaphylactic / anaphylactoid reactions
Potentially leukaemogenic
Interrupt treatment and/or reduce dose for any grade 3 toxicity
Reduce dose if neutrophil count <0.5x10 to the power 9/L for 5 days or more
Reduce dose if neutrophils < 0.5 x 10 to the power 9/L with fever/infection
Suspend treatment if leucocytes fall below 2,000/cubic mm
Reduce dose if platelets <25 x 10 to the power of 9/L
Male & female: Contraception required during & for 6 months after treatment

Acute leukaemia, which can occur with or without a preleukaemic phase, has been reported rarely in patient treated with etoposide in combination with other anti-neoplastic drugs. The predisposing factors have not been identified.

A new treatment cycle should only be started if neutrophil count is greater than 1.5 x 10 to the power of 9/L and platelet count is greater than 100 x 10 to the power 9/L unless caused by malignant disease.

If severe reactions occur the dose should be reduced or discontinued and appropriate corrective measures initiated. Re-initiation of etoposide should be carried out with caution and consideration to the risks versus the benefits.

Pregnancy and Lactation

Pregnancy

Etoposide is contraindicated during pregnancy.

Growth restriction and severe myelosuppression has been observed in newborns of pregnant women using etoposide during the 2nd and 3rd trimester.

Studies in rats and mice have shown teratogenic effects.

The effects 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 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

Etoposide is contraindicated in breastfeeding.

Etoposide is excreted into human breast milk and there is a potential for severe toxicity in the nursing infant. Briggs suggests that breastfeeding should be stopped for at least 55 hours after the last dose of etoposide, based on its half life, while Schaefer suggests 24 to 36 hours.

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
Acute leukaemia
Alopecia
Altered liver function tests
Anaemia
Anaphylactoid-like reaction
Anorexia
Apnoea
Arrhythmias
Asthenia
Bronchospasm
Constipation
Convulsions
Cortical blindness (transient)
Cough
Cyanosis
Diarrhoea
Dizziness
Dysphagia
Extravasation
Fatigue
Fever
Flushing
Haemorrhage
Hepatic impairment
Hypersensitivity reactions including anaphylaxis
Hypertension
Hypotension (transient)
Increased susceptibility to infection
Interstitial pneumonitis
Laryngospasm
Leucopenia
Malaise
Mucositis
Myelosuppression
Myocardial infarction
Nausea
Neutropenia
Oesophagitis
Optic neuritis
Peripheral neuropathy
Phlebitis (injection site)
Pruritus
Pulmonary fibrosis
Radiation recall dermatitis
Rash
Renal impairment
Skin discolouration
Somnolence
Stevens-Johnson syndrome
Stomatitis
Tachycardia
Taste disturbances
Thrombocytopenia
Toxic epidermal necrolysis
Tumour lysis syndrome
Urticaria
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: March 2016

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 (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Summary of Product Characteristics: Etopophos Injection. Bristol- Myers Squibb Pharmaceuticals Ltd. Revised February 2016
Summary of Product Characteristics: Eposin. medac GmbH. Revised July 2015.
Summary of Product Characteristics: Etoposide 20mg/ml. Teva. Revised December 2014.

The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 05 July 2017

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Etoposide Last revised: November 1, 2010
Last accessed: 3rd October 2014