VEPESID Capsule, soft Ref.[8156] Active ingredients: Etoposide

VEPESID capsules 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).

Posology

The dose of VEPESID capsules is based on the recommended intravenous dose taking into account the dose-dependent bioavailability of VEPESID capsules. A 100 mg oral dose would be comparable to a 75 mg intravenous dose; a 400 mg oral dose would be comparable to a 200 mg intravenous dose. Within-patient variability in exposure (i.e. between cycles) is larger with oral administration than after intravenous administration (see section 4.4 and 5.2).

Monotherapy

The usual dose of VEPESID administered orally is 100 to 200 mg/m²/day on days 1 to 5 or 200 mg/m²/day on days 1, 3 and 5 every 3 to 4 weeks. Daily doses greater than 200 mg should be divided and given twice per day.

Combination therapy

The usual dose of VEPESID administered orally is 100 to 200 mg/m²/day on days 1 to 5 or 200 mg/m²/day on days 1, 3 and 5 every 3 to 4 weeks in combination with other drugs approved for use 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.

Alternative dosage schedule

An alternative dosage schedule for VEPESID capsules is 50 mg/m²/day for 2 to 3 weeks, with courses repeated after a one week rest period or upon recovery from myelosuppression.

Neutropenia and thrombocytopenia

Patients should not begin a new cycle of treatment with VEPESID 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.

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

The safety and efficacy of VEPESID in children 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. 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

Capsules should be taken on an empty stomach.

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.

Do not store above 25°C.

Store in the original package.

Do not open any blister in which there is evidence of capsule leakage.

Pack of 20, 50 Capsules, softgels.

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. This includes appropriate equipment, such as wearing gloves and washing hands with soap and water after handling such products. If etoposide should contact the skin, mucosa or eyes, immediately wash the skin with soap and water and flush the mucosa or eyes with water.

Do not open any blister in which there is evidence of capsule leakage.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.