- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Oral formulations of etoposide
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.
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.
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
The recommended oral dose of etoposide is 120mg to 240mg per square metre of body surface area per day for five consecutive days. Doses over 200mg should be divided and given twice daily.
Courses may be repeated at minimum of twenty one day intervals.
A repeat course should not be given until the blood picture has been checked for evidence of myelosuppression and found to be satisfactory.
Patients with Renal Impairment
Creatinine clearance of 15 to 50ml/minute: Initial dose should be reduced to 75% of the initial recommended dose.
Creatinine clearance less than 15ml/minute: Manufacturer suggests a further dose reduction based on tolerance and clinical effect.
The Renal Drug Handbook suggests the following reductions:
GFR 60ml/minute: 85% of normal dose.
GFR 45 to 60ml/minute: 80% of normal dose.
GFR 30 to 45ml/minute: 75% of normal dose.
GFR less than 30ml/minute: 50% of normal dose, based on clinical response.
Additional Dosage Information
Oral dosing recommendations are based on the parenteral dose with adjustment made for the lower bioavailability from oral administration.
Bioavailability of the capsules appears to be dependent on the dose administered, and varies from patient to patient. In view of the significant patient to patient variability, dose adjustment may be required in order to achieve a therapeutic effect.
Suspend therapy if leucocytes fall below 2,000/cubic millimetre until levels of leucocytes are above 4,000/cubic millimetre and platelets are above 100,000/cubic millimetre (usually about 10 days)
For oral administration.
The capsules should be taken on an empty stomach (1 hour before food or two hours after food).
Severe hepatic impairment
Precautions and Warnings
Children under 18 years
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
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 oral anti-cancer drugs
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
Suspend treatment if leucocytes fall below 2,000/cubic mm
Not licensed for use in children under 18 years
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
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 ).
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
Altered liver function tests
Cortical blindness (transient)
Hypersensitivity reactions including anaphylaxis
Increased susceptibility to infection
Radiation recall dermatitis
Toxic epidermal necrolysis
Tumour lysis syndrome
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 ).
Last Full Review Date: March 2016
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: Vepesid. Bristol-Myers Squibb Pharmaceuticals Ltd. Revised February 2016.
Summary of Product Characteristics: Eposin. Medac GmbH. Revised May 2005.
Summary of Product Characteristics: Etopophos Injection. Bristol- Myers Squibb Pharmaceuticals Ltd. Revised February 2016.
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: 04 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
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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