Drug Class Description
Podophyllotoxin derivatives (cytotoxics).

Generic Name
Etoposide

Drug Description
Each vial contains etoposide phosphate equivalent to 100 mg etoposide.Each vial also contains 7.64 mg (0.33mmol) sodium

Presentation
Powder for solution for injection.White to off-white lyophilised powder.

Indications
Etopophos is an anti-neoplastic drug for intravenous use, which can be used alone or in combination with other cytotoxic drugs.Present data indicate that Etopophos is applicable in the therapy of: small cell lung cancer, resistant non-seminomatous testicular carcinoma.

Adult Dosage
Etopophos should be administered by individuals experienced in the use of anti-neoplastic therapy.The recommended course of Etopophos Injection is 60-120 mg/m², (etoposide equivalent) i.v daily for five consecutive days. As Etopophos produces myelosuppression, courses should not be repeated more frequently than at 21 day intervals. In any case, repeat courses of Etopophos should not be given until the blood picture has been checked for evidence of myelosuppression and found to be satisfactory.When used as part of combination therapy, the dosage should be reduced toward the lower end of the dosage range to take into account the myelosuppressive effects of radiation therapy or chemotherapy which may have compromised bone marrow reserve.Immediately prior to administration, the content of each vial must be reconstituted with either 5 ml or 10 ml Water for Injections B.P., 5% Glucose Intravenous Infusion B.P. or 0.9% Sodium Chloride Intravenous Infusion B.P. to a concentration equivalent to 20 mg/ml or 10 mg/ml etoposide (22.7 mg/ml or 11.4 mg/ml etoposide phosphate) respectively. Following reconstitution the solution may be administered without further dilution or it can be further diluted to concentrations as low as 0.1 mg/ml etoposide (0.14 mg/ml etoposide phosphate) with either 5% Glucose Intravenous Infusion B.P. or 0.9% Sodium Chloride Intravenous Infusion B.P.Etopophos solutions may be infused over 5 minutes to 3.5 hours.Care should be taken to avoid extravasation. Occasionally following extravasation of etoposide, soft tissue irritation and inflammation has occurred, ulceration was generally not seen.Elderly:No dosage adjustment is necessary.Paediatric use:Safety and effectiveness in children have not been established. Until further data are available, Etopophos should not be given to children under 12 years of age.

Child Dosage
Under 12 years, not recommended.

Contra Indications
Etopophos is contra-indicated in patients with severe hepatic dysfunction or in those patients who have demonstrated hypersensitivity to etoposide, etoposide phosphate or any other component of the formulation.

Special Precautions
Since etoposide phosphate is rapidly and completely converted to etoposide, the WARNINGS and PRECAUTIONS that are considered when prescribing etoposide should be considered when prescribing Etopophos.When Etopophos is administered intravenously care should be taken to avoid extravasation.If radiotherapy and/or chemotherapy has been given prior to starting Etopophos treatment, an adequate interval should be allowed to enable the bone marrow to recover. If the leucocyte count falls below 2,000/mm³, treatment should be suspended until the circulating blood elements have returned to acceptable levels (platelets above 100,000/mm³, leucocytes above 4,000/mm³), this is usually within 10 days.Peripheral blood counts and liver function should be monitored.Bacterial infections should be brought under control before treatment with Etopophos commences.No data are available on the use of Etopophos in patients with renal and hepatic impairment.The occurrence of acute leukaemia, which can occur with or without myelodysplasia has been reported rarely in patients treated with etoposide containing regimens.

Interactions
Caution should be exercised when administering Etopophos with drugs that are known to inhibit phosphatase activities (e.g., levamisole hydrochloride). High dose cyclosporin (resulting in concentrations >2000 ng/ml) administered with oral etoposide has led to an 80% increase in etoposide exposure (AUC) with a 38% decrease in total body clearance of etoposide, compared to etoposide alone.In children, elevated SGPT levels are associated with reduced drug total body clearance. Prior use of cisplatin may also result in a decrease of etoposide total body clearance in children.

Adverse Reactions
In clinical studies with Etopophos the most frequent clinically significant adverse experiences were leucopenia and neutropenia which occurred in almost all patients. The leucopenia was severe in approximately 20% of the patients, with neutropenia severe in about one third. Thrombocytopenia was reported in about a quarter of the patients and was severe in about 10% of the cases. Anaemia was observed in about three quarters of the patients and was severe in about 20%. Gastrointestinal adverse events were usually mild to moderate. Nausea and/or vomiting was seen in about a third of the patients. Anorexia and mucositis was reported by 10-20% of the patients and constipation, abdominal pain, diarrhoea and taste alteration was seen in between 5 to 10%. Asthenia or malaise affected about a third of the patients. Alopecia was also observed in a third of the patients. Chills and/or fever were reported in a quarter of the patients, dizziness and extravasation/phlebitis in about 5% of the patients. No cardiovascular symptoms including hypotension, have been observed during administration of 5 minute infusions of Etopophos.Since etoposide phosphate is converted to etoposide, the adverse experiences reported below that are associated with etoposide may occur with Etopophos.The following data on adverse reactions are based on both oral and intravenous administration of etoposide.Haematological:The dose limiting toxicity of etoposide is myelosuppression, predominantly leucopenia and thrombocytopenia. Anaemia occurs infrequently.The leucocyte count nadir occurs approximately 21 days after treatment.Alopecia:Alopecia occurs in approximately two-thirds of patients and is reversible on cessation of therapy.Gastrointestinal:Nausea and vomiting are the major gastrointestinal toxicities and occur in over one-third of patients. Anti-emetics are useful in controlling these side effects. Abdominal pain, anorexia, diarrhoea, oesophagitis and stomatitis occur infrequently.Other Toxicities:Hypotension may occur following an excessively rapid infusion of etoposide and may be reversed by slowing the infusion rate. Symptomatic hypotension has not been seen with Etopophos.Anaphylactoid reactions have been reported following administration of etoposide. Higher rates of anaphylactoid reactions have been reported in children who received infusions at concentrations higher than those recommended. The role that concentration of infusion (or rate of infusion) plays in the development of anaphylactoid reactions is uncertain. These reactions have usually responded to cessation of therapy and administration of pressor agents, corticosteroids, antihistamines or volume expanders as appropriate.Apnoea with spontaneous resumption of breathing following discontinuation of etoposide injection has been reported. Sudden fatal reactions associated with bronchospasm have been reported. Hypertension and/or flushing have also been reported. Blood pressure usually returns to normal within a few hours after cessation of the infusion.The use of etoposide has been reported infrequently to cause peripheral neuropathy.Etoposide has been shown to reach high concentrations in the liver and kidney, thus presenting a potential for accumulation in cases of functional impairment.Somnolence, fatigue, aftertaste, fever, rash, pigmentation, pruritus, urticaria, dysphagia, transient cortical blindness and a single case of radiation recall dermatitis have also been reported following the administration of etoposide

Manufacturer
Bristol-Myers Squibb Pharmaceuticals Ltd

Drug Availability
(POM)

Updated
13 May 2009