Posology : מינונים

4.2 Posology and method of administration

HYCAMTIN capsules should only be prescribed and therapy supervised by a physician experienced in the use of chemotherapeutic agents.

Posology
Prior to administration of the first course of topotecan, patients must have a baseline neutrophil count of ≥1.5 x 109/l, a platelet count of ≥100 x 109/l and a haemoglobin level of ≥9 g/dl (after transfusion if necessary).


Initial dose
The recommended dose of HYCAMTIN capsules is 2.3 mg/m2 body surface area per day administered for five consecutive days with a three week interval between the start of each course. If well tolerated, treatment may continue until disease progression (see sections 4.8 and 5.1).

The capsule(s) must be swallowed whole, and must not be chewed crushed or divided.
Hycamtin capsules may be taken with or without food (see section 5.2).
Subsequent doses
Topotecan should not be re-administered unless the neutrophil count is ≥ 1 x 109/l, the platelet count is ≥ 100 x 109/l, and the haemoglobin level is ≥ 9 g/dl (after transfusion if necessary).

Standard oncology practice for the management of neutropenia is either to administer topotecan with other medicinal products (e.g. G-CSF) or to reduce the dose to maintain neutrophil counts.

If dose reduction is chosen for patients who experience severe neutropenia (neutrophil count < 0.5 x 109/l) for seven days or more, or severe neutropenia associated with fever or infection, or who have had treatment delayed due to neutropenia, the dose should be reduced by 0.4 mg/m2/day to 1.9 mg/m2/day (or subsequently down to 1.5 mg/m2/day if necessary).

Doses should be similarly reduced if the platelet count falls below 25 x 109/l. In clinical studies, topotecan was discontinued if the dose needed to be reduced below 1.5 mg/m2 /day.

For patients who experience Grade 3 or 4 diarrhoea, the dose should be reduced by 0.4 mg/m2/day for subsequent courses (see section 4.4). Patients with Grade 2 diarrhoea may need to follow the same dose modification guidelines.

Proactive management of diarrhoea with anti-diarrhoeal agents is important. Severe cases of diarrhoea may require administration of oral or intravenous electrolytes and fluids, and interruption of topotecan therapy (see sections 4.4 and 4.8).

Special populations
Patients with renal impairment
The recommended monotherapy dose of oral topotecan in patients with small cell lung carcinoma with creatinine clearance between 30 and 49 ml/min is 1.9 mg/m2/day for five consecutive days. If well tolerated, the dose may be increased to 2.3 mg/m2/day in subsequent cycles (see section 5.2).

Limited data in Korean patients with creatinine clearance less than 50 ml/min suggest a further lowering of dose may be required (see section 5.2).

Insufficient data are available to make a recommendation for patients with a creatinine clearance < 30 ml/min.

Patients with hepatic impairment
Pharmacokinetics of HYCAMTIN capsules have not been specifically studied in patients with impaired hepatic function. There are insufficient data available with HYCAMTIN capsules to make a dose recommendation for this patient group (see section 4.4).

Paediatric population
Currently available data are described in sections 5.1 and 5.2 but no recommendation on a posology can be made.

Elderly No overall differences in effectiveness were observed between patients aged over 65 years and younger adult patients. However in the two studies in which both oral and intravenous topotecan were administered, patients over 65 years old receiving oral topotecan experienced an increase in drug related diarrhoea compared to those younger than 65 years of age (see section 4.4 and 4.8).