Topoccord 1/Topoccord 4 Dosage/Direction for Use

The use of topotecan should be confined to units specialized in the administration of cytotoxic chemotherapy. Topotecan should only be administered under the supervision of a physician experienced in the use of chemotherapy (see Special precautions for disposal and other handling under Cautions for Usage).
Posology: When topotecan is 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, 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 progression (see Adverse Reactions and Pharmacology: Pharmacodynamics under Actions).
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 dose 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 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 studies, topotecan was discontinued if the dose had 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 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 ≥1.5 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 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): There is insufficient experience with the use of topotecan in patients with severely impaired renal function (creatinine clearance <20 ml/min). Use of topotecan in this group of patients is not recommended (see Precautions).
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 or 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.
Patients with hepatic impairment: A small number of hepatically impaired patients (serum bilirubin between 1.5 and 10 mg/dl) were given intravenous topotecan at 1.5 mg/m²/day for five days every three weeks. A reduction in topotecan clearance was observed. However, there are insufficient data available to make a dose recommendation for this patient group (see Precautions).
There is insufficient experience with the use of topotecan in patients with severely impaired hepatic function (serum bilirubin ≥10 mg/dl) due to cirrhosis. Topotecan is not recommended to be used in this patient group (see Precautions).
Paediatric population: Currently available data are described in Pharmacodynamics and Pharmacokinetics but no recommendation on a posology can be made.
Method of Administration: Topotecan must be further diluted before use (see Special precautions for disposal and other handling under Cautions for Usage).