Posology : מינונים

4.2       Posology and method of administration

Method of administration
The use of topotecan should be confined to units specialised in the administration of cytotoxic chemotherapy and should only be administered under the supervision of a physician experienced in the use of chemotherapy (see section 6.6).

Topotecan must be further diluted before use (see section 6.6).

Posology

When used in combination with cisplatin, the full prescribing information for cisplatin should be consulted.

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

Ovarian and Small Cell Lung Carcinoma

Initial dose
The recommended dose of topotecan is 1.5 mg/m2 body surface area/day administered by intravenous infusion over 30 minutes daily for 5 consecutive days with a 3 week interval between the start of each course. If well tolerated, treatment may continue until disease progession (see sections 4.8 and 5.1).

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 medications (e.g. G-CSF) or to dose reduce to maintain neutrophil counts.

If dose reduction is chosen for patients who experience severe neutropenia (neutrophil count < 0.5 x 109/l) for 7 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 0.25 mg/m2/day to 1.25 mg/m2/day (or subsequently down to 1.0 mg/m2/day if necessary).

Doses should be similarly reduced if the platelet count falls below 25 x 109/l. In clinical trials, topotecan was discontinued if the dose has been reduced to 1.0 mg/m2 and a further dose reduction was required to manage adverse effects.

Cervical Carcinoma

Initial dose
The recommended dose of topotecan is 0.75 mg/m2/day administered as 30 minute intravenous infusion daily on days 1, 2 and 3. Cisplatin is administered as an intravenous infusion on day 1 at a dose of 50 mg/m2/day and following the topotecan dose. This treatment schedule is repeated every 21 days for 6 courses or until progressive disease.

Subsequent doses
Topotecan should not be re-administered unless the neutrophil count is more than or equal to 1.5 x 109/l, the platelet count is more than or equal to 100 x 109/l, and the haemoglobin level is more than or equal to 9 g/dl (after transfusion if necessary).


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

If dose reduction is chosen for patients who experience severe neutropenia (neutrophil count less than 0.5 x 109/l) for 7 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 20% to 0.60 mg/m2/day for subsequent courses (or subsequently down to 0.45 mg/m2/day if necessary).

Doses should be similarly reduced if the platelet count falls below 25 x 109/l.

Special populations

Patients with renal impairment
Monotherapy (Ovarian and Small cell lung carcinoma)
Insufficient data are available to make a recommendation for patients with a creatinine clearance < 20 ml/min. Limited data indicate that the dose should be reduced in patients with moderate renal impairment. The recommended monotherapy dose of topotecan in patients with ovarian and small cell lung carcinoma and a creatinine clearance between 20 and 39 ml/min is 0.75 mg/m2/day for 5 consecutive days.


Combination therapy (Cervical carcinoma)
In clinical studies with topotecan in combination with cisplatin for the treatment of cervical cancer, therapy was only initiated in patients with serum creatinine less than or equal to 1.5 mg/dl. If, during topotecan/cisplatin combination therapy serum creatinine exceeds 1.5 mg/dl, it is recommended that the full prescribing information be consulted for any advice on cisplatin dose reduction/continuation. If cisplatin is discontinued, there are insufficient data regarding continuing monotherapy with topotecan in patients with cervical cancer.


Paediatric Population
The experience in children is limited, therefore no recommendation for treatment of paediatric patients with topotecan can be given (see sections 5.1 and 5.2).