ETOPOPHOS Powder for solution for injection Ref.[8157] Active ingredients: Etoposide

ETOPOPHOS should only be administered and monitored under the supervision of a qualified physician experienced in the use of anti-neoplastic medicinal products (see section 4.4).

Adult population

The recommended dose of ETOPOPHOS in adult patients is 50 to 100 mg/m²/day (etoposide equivalent) on days 1 to 5 or 100 to 120 mg/m² on days 1, 3, and 5 every 3 to 4 weeks in combination with other drugs indicated in the disease to be treated.

Dosage should be modified to take into account the myelosuppressive effects of other drugs in the combination or the effects of prior radiotherapy or chemotherapy (see section 4.4) which may have compromised bone marrow reserve. The doses after the initial dose should be adjusted if neutrophil count is below 500 cells/mm³ for more than 5 days. In addition the dose should be adjusted in case of occurrence of fever, infections, or at a thrombocyte count below 25,000 cells/mm³, which is not caused by the disease. Follow up doses should be adjusted in case of occurrence of grade 3 or 4 toxicities or if renal creatinine clearance is below 50 ml/min. At decreased creatinine clearance of 15 to 50 mL/min a dose reduction by 25% is recommended.

Administration Precautions: As with other potentially toxic compounds, caution should be exercised in handling and preparing the solution of ETOPOPHOS. Skin reactions associated with accidental exposure to ETOPOPHOS may occur. The use of gloves is recommended. If ETOPOPHOS solution contacts the skin or mucosa, immediately wash the skin with soap and water and flush the mucosa with water (see section 6.6).

Elderly population

No dosage adjustment is necessary in elderly patients (age >65 years old), other than based on renal function (see section 5.2).

Paediatric population

Hodgkin’s lymphoma; non-Hodgkin’s lymphoma; acute myeloid leukaemia

ETOPOPHOS in paediatric patients has been used in the range of 75 to 150 mg/m²/day (etoposide equivalent) for 2 to 5 days in combination with other antineoplastic agents. The treatment regimen should be chosen according to the local standard of care.

Ovarian cancer; small cell lung cancer; gestational trophoblastic neoplasia; testicular cancer

The safety and efficacy of ETOPOPHOS below 18 years of age have not been established. Currently available data are described in section 5.2 but no recommendation on a posology can be made.

Renal Impairment

In patients with impaired renal function, the following initial dose modification should be considered based on measured creatinine clearance.

In patients with creatinine clearance less than 15 mL/min and on dialysis further dose reduction is likely to be required as etoposide clearance is further reduced in these patients (see section 4.4). Subsequent dosing in moderate and severe renal impairment should be based on patient tolerance and clinical effect (see section 4.4). Since etoposide and its metabolites are not dialyzable, it can be administered pre- and post-haemodialysis (see section 4.9).

Method of administration

Etoposide phosphate is administered by slow intravenous infusion (usually over a 30 to 60 minute period) (see section 4.4).

For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.

Total doses of 2.4 g/m² to 3.5 g/m² administered intravenously over three days have resulted in severe mucositis and myelotoxicity. Metabolic acidosis and cases of serious hepatic toxicity have been reported in patients receiving higher than recommended intravenous doses of etoposide. Similar toxicities can be expected with oral formulation. A specific antidote is not available. Treatment should therefore be symptomatic and supportive, and patients should be closely monitored. Etoposide and its metabolites are not dialyzable.

3 Years.

Storage conditions after reconstitution of the medicinal product

After reconstitution: chemical and physical in-use stability has been demonstrated for 24 hours at 15 to 30°C and for 7 days at 2 to 8°C. From a microbiological point of view, the reconstituted solution should immediately be used undiluted or should be diluted. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 7 days at 2 to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

After dilution: when the reconstituted solution is diluted immediately, the chemical and physical in-use stability of the diluted infusion solution has been demonstrated for 24 hours at 15 to 30°C and for 7 days at 2° to 8°C. From a microbiological point of view, the product should be used immediately.

Store in a refrigerator (2 to 8°C).

Store in the original package in order to protect from light.

Type I glass vial with a butyl rubber stopper and flip-off aluminium seal. Packs of 1, 5, 10, 20, 25 vials.

Not all pack sizes may be marketed.

Procedures for proper handling and disposal of anti-cancer drugs should be followed.

Care must be taken whenever handling cytostatic products. Always take steps to prevent exposure. As with other potentially toxic compounds, caution should be exercised in handling and preparing ETOPOPHOS solutions. Skin reactions associated with accidental exposure to ETOPOPHOS may occur. The use of gloves is recommended. If etoposide phosphate should contact the skin or mucosa, immediately wash the skin with soap and water and flush the mucosa with water.

ETOPOPHOS solutions must be prepared under aseptic conditions.

Preparation of ETOPOPHOS 100 mg powder for solution for infusion

Before use the content of each vial must be reconstituted with 5 ml or 10 ml of:

• water for injections or,
• 5% glucose solution or,
• 0.9% sodium chloride solution.

This will yield a reconstituted stock solution containing 20 mg/ml or 10 mg/ml etoposide.

After reconstitution, the solution can be administered without further dilution or it can be further diluted with 5% glucose solution or 0.9% sodium chloride solution to obtain concentrations as low as 0.1 mg/ml etoposide.

The products administered by parenteral route must be visually examined to check for any particulates or discoloration prior to administration. If any discolouration or particulate matter is observed, the reconstituted solution must be discarded.

ETOPOPHOS is for single use only. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.