Posology : מינונים

4.2   Posology and method of administration
Etoposide must not be given by intra-cavity injection.
Dose adjustments
Dosage of etoposide should be modified to take into account the myelosuppressive effects of other drugs in the combination or the effects of prior X-ray therapy or chemotherapy which may have compromised bone marrow reserve.
Etoposide is administered by slow intravenous infusion. ETOPOSIDE SHOULD NOT BE ADMINISTERED BY RAPID INTRAVENOUS INJECTION.
Hypotension following rapid intravenous administration of etoposide has been reported. Therefore, it is recommended that the etoposide injection be administered by slow I.V. infusion over a 30- to 60-minute period.
Longer infusion times may be required based on patient tolerance. As with other potentially toxic compounds, caution should be exercised in handling and preparing the solution of etoposide. Skin reactions associated with accidental exposure to etoposide may occur. The use of gloves is recommended. If etoposide solution contacts the skin or mucosa, immediately wash the skin or mucosa thoroughly with soap and water.
Patients should not begin a new cycle of treatment with etoposide if the neutrophil count is less than 1,500 cells/mm3 or the platelet count is less than 100,000 cells/mm3, unless caused by malignant disease.

Doses subsequent to the initial dose should be adjusted if neutrophil count less than 500 cells/mm3 occurs for more than 5 days or is associated with fever or infection, if platelet count less than 25,000 cells/mm3 occurs, if any other grade 3 or 4 toxicity develops or if renal clearance is less than 50 ml/min.

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

Measured Creatinine Clearance                            Dose of Etoposide Phosphate >50 mL/min                                               100% of dose 15-50 mL/min                                              75% of dose 
Subsequent dosing should be based on patient tolerance and clinical effect. Data are not available in patients with creatinine clearance <15 mL/min and further dose reductions should be considered in these patients. Subsequent etoposide dosing should be based on patient tolerance and clinical effect.

Testicular Tumours, Hodgkin’s Disease, Malignant (non-Hodgkin’s) Lymphomas-Especially of the Histiocytic Variety, Acute Non-Lymphocytic Leukemia
The usual dose of etoposide, in combination with other approved chemotherapeutic agents, ranges from 50-100 mg/m2/day on days 1 through 5 to 100 mg/m2/day on days 1, 3, and 5.

Small Cell Lung Cancer
The usual dose of etoposide, in combination with other approved chemotherapeutic drugs, ranges from 35 mg/m2/day for 4 days to 50 mg/m2/day for 5 days.
Chemotherapy courses should be repeated at 3- to 4-week intervals after adequate recovery from any toxicity.
The dosage should be modified to take into account the myelosuppressive effects of other drugs in the combination, or the effects of prior X-ray therapy or chemotherapy which may have compromised bone marrow reserve.