Etoposide

Registered South African indications:

• Testicular tumour
• Refractory testicular tumours
• Small cell anaplastic lung tumours
• Malignant (Non-Hodgkin's) lymphomas, especially of the histiocytic (large cell diffuse) variety

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Severe hepatic dysfunction
• Severely impaired medullary haematopoiesis (particularly after extensive radio- and/or chemotherapy or secondary to neoplastic infiltration). This may be evidenced by mild to marked leukopenia and/or thrombocytopenia
• Chickenpox, existing or recent (including recent exposure)
• Herpes zoster
• Bone marrow depression
• Concomitant use of yellow fever vaccine or other live vaccines is contraindicated in immunosuppressed patients
• Pregnancy
• Lactation

Contraindications registered in other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients
• Concomitant use of yellow fever vaccine or other live vaccines is contraindicated in immunosuppressed patients
• Lactation

• Pregnancy (Recommendations in other jurisdictions)
• Women of childbearing potential during treatment and up to 6 months after ending treatment
• Renal impairment
• Mild to moderate hepatic impairment (South African recommendations)
• Hepatic impairment (Recommendations in other jurisdictions)
• Males of reproductive potential
• Rapid administration
• Low serum albumin 
• Myelosuppression
• Secondary leukaemia
• Hypotension
• History of tumour lysis syndrome

Forms avail. in SA and covered in this monograph: inj, inf

South African registered indications and dosages

Testicular tumour
- First line in combination with other approved chemotherapeutic medicines
Refractory testicular tumours
- In combination with other approved medicines, for those with refractory testicular tumours who have already received appropriate surgical, chemotherapeutic and radiotherapeutic treatment
Small cell anaplastic lung tumours
- In combination with other approved chemotherapeutic medicines for small cell anaplastic lung tumours
Malignant (Non-Hodgkin's) lymphomas, especially of the histiocytic (large cell diffuse) variety
- In combination with other approved chemotherapeutic medicines

• IV: 50-100mg/m²/day for days 1-5 OR 100mg/m²/day on days 1, 3 and 5; In both regimens, give as a slow infusion over 30-60min; These regimens are given every 3-4 weeks in combination with other approved relevant medicines

Dosage should be adjusted according to the individual requirements of each patient, based on clinical response and the appearance or severity of toxicity. Patients should be carefully monitored for signs of toxicity, such as myelosuppression

The dosage may also need to be adjusted if the patient has received radiation or other chemotherapy

Hypotension following rapid IV administration of etoposide has been reported. Hypotension usually responds to cessation of infusion and/or other supportive therapy as appropriate

When restarting the infusion, a slower rate of administration should be used. During intravenous infusion, great care must be taken to ensure the catheter stays in the vein, as leakage into surrounding tissue is highly irritant. Etoposide should not be administered intra-arterially, intrapleurally, or intra-peritoneally

Etoposide should not be given by rapid intravenous push

Caution should be exercised with handling and preparation of etoposide (see additional prescribing points)

Not established for use in children

Pregnancy

South African recommendations

• Contraindicated
• Safety and efficacy in pregnancy has not been established
• Etoposide can cause foetal harm when administered during pregnancy. If this medicine is used during pregnancy, or if a woman falls pregnant on treatment, she should be advised of possible danger to the foetus
• Women of childbearing age should be advised not to fall pregnant while using etoposide. Women of childbearing potential should use appropriate contraceptive measures to avoid pregnancy during etoposide therapy
• Etoposide has been shown to be teratogenic in mice and rats. Given the mutagenic potential of etoposide, an effective contraceptive is required for both male and female patients during treatment and up to 6 months after ending treatment
• Genetic consultation is recommended if the patient wishes to have children after ending treatment

Recommendations in other jurisdictions

• Caution; positive evidence of risk in animal studies
• There are no or limited amount of data from the use of etoposide phosphate in pregnant women
• Studies in animals have shown reproductive toxicity
• In general etoposide can cause foetal harm when administered to pregnant women. Etoposide should not be used during pregnancy unless the clinical condition of the woman requires treatment with etoposide
• Women of childbearing potential should be advised to avoid becoming pregnant. Women of childbearing potential have to use effective contraception during and up to 6 months after treatment
• Etoposide has been shown to be teratogenic in mice and rats
• If this medicinal product is used during pregnancy, or if the patient becomes pregnant while receiving this medicinal product, the patient should be informed of the potential hazard to the foetus
• Genetic consultation is recommended if the patient wishes to have children after ending the treatment

Breastfeeding

Recommendations below are applicable to South Africa and other jurisdictions

• Contraindicated
• Etoposide is excreted in human milk. There is the potential for serious adverse reactions in nursing infants from etoposide
• A decision must be made whether to discontinue breastfeeding or to discontinue etoposide, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman

Fertility

Recommendations below are applicable to South Africa and other jurisdictions

• As etoposide may decrease male fertility, preservation of sperm may be considered for the purpose of later fatherhood

Recommendations below are applicable to South Africa and other jurisdictions

• CrCl>50ml/min: Caution; no dose adjustment recommended
• CrCl≤50ml/min: Caution; dose adjustment recommended

In patients with CrCl<15ml/min and on dialysis further dose reduction is likely to be required as etoposide clearance is further reduced in these patients. Subsequent dosing in moderate and severe renal impairment should be based on patient tolerance and clinical effect. Since etoposide and its metabolites are not dialyzable, it can be administered pre- and post-haemodialysis (Recommendations in other jurisdictions)

South African recommendations

• Mild to moderate: Caution; no dose adjustment recommended
  Patients with impaired hepatic function should regularly have their hepatic function monitored due to the risk of accumulation
• Severe: Contraindicated

Recommendations in other jurisdictions

• Caution; no dose adjustment recommended
  Patients with impaired hepatic function should regularly have their hepatic function monitored due to the risk of accumulation

• No dose adjustment recommended

Central Nervous System Disorders

• Dizziness
• Peripheral neuropathy
• Seizures
• Optic neuritis
• Cortical blindness
• Somnolence
• Fatigue
• Asthenia

Cardiovascular Disorders

• Myocardial infarction 
• Arrhythmia
• Transient hypotension
• Hypertension
• Hypotension

Respiratory Disorders

• Pulmonary fibrosis
• Interstitial pneumonitis

Gastrointestinal Disorders

• Abdominal pain
• Constipation
• Nausea and vomiting
• Anorexia
• Stomatitis 
• Oesophagitis
• Diarrhea
• Dysphagia
• Dysgeusia

Hepatobiliary Disorders

• Hepatotoxicity

Skin and Subcutaneous Tissue Disorders

• Alopecia
• Pigmentation
• Rash
• Urticaria
• Pruritus
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Radiation recall dermatitis

Immune, Blood and Lymphatic System Disorders

• Secondary leukaemia
• Myelosuppression
• Leukopenia
• Thrombocytopenia
• Neutropenia
• Anaemia
• Anaphylactic-type reactions

Others

• Extravasation
• Phlebitis

• Cisplatin
• Phenytoin
• Warfarin
• Yellow fever vaccine
• Live vaccines
• Myelosuppressant agents
• Phenylbutazone 
• Sodium salicylate
• Aspirin
• Anthracyclines
• Ciclosporin

• Full blood count
• Hepatic function
• Albumin
• Renal function

Preparation for intravenous infusion

• Hard plastic devices made from acrylic or ABS (a polymer of acrylonitrile, butadiene, and styrene) can crack or leak when used for undiluted etoposide injection
• The cracking or leaking effect has not been reported with the diluted form of etoposide
• Etoposide can be diluted with 5% dextrose water or 0.9% sodium chloride solution, resulting in a final concentration of 0.2-0.4mg/ml
• Solutions more concentrated than this may lead to crystal formation within 5 minutes; such solutions should not be administered intravenously
• If a 0.4mg/ml solution of etoposide is passed through tubing connected to a peristaltic pump, it might precipitate out
• The final mixture of etoposide for parenteral use should be visually inspected for particulate matter and discoloration before administration

Handling and disposal

• Procedures for the proper handling and disposal of anti-cancer medicines should be adhered to
• Care is essential when handling cytostatic products; steps to prevent exposure should always be taken
• Caution is required in both handling and preparing etoposide solutions
• Any unused product or waste material should be disposed of in accordance with local requirements

Accidental exposure

• Skin reactions can occur if there's accidental exposure to etoposide
• The use of gloves is recommended during handling
• If etoposide should come into contact with the skin or mucosa, the affected area should be immediately washed with soap and water. Mucosa should be flushed with water

Preparation conditions

• Etoposide solutions must be prepared under aseptic conditions

Etoposide is a semi-synthetic derivative of podophyllotoxin. Experimental data indicate that etoposide arrests the cell cycle in the G² phase. Etoposide differs from the vinca alkaloids in that it does not cause an accumulation of cells in metaphase, but prevents cells from entering mitosis or destroys cells in the G² phase. The incorporation of thymidine into DNA is inhibited in vitro by etoposide.

Injection (per 5ml) 100mg

• Aspen etoposide (Pharmacare)
• Eposin (Teva)
• Etoposide-hexal (Sandoz)
• P&U etoposide CSV (Pfizer) originator (Discontinued: 20/06/2022)