Topotecan Actavis

6). Posology When used in combination with cisplatin, the full prescribing information for cisplatin should be consulted. 5 x 109/l, a platelet count of ≥ 100 x 109/l and a haemoglobin level of ≥ 9 g/dl (after transfusion if necessary).

5 mg/m2 body surface area/day administered by intravenous infusion over 30 minutes daily for five consecutive days with a three week interval between the startMedicinal product no longer authorised 3 of each course. 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).

g. G-CSF) or to dose reduce to maintain neutrophil counts. 0 mg/m2/day if necessary). Doses should be similarly reduced if the platelet count falls below 25 x 109/l. 0 mg/m2 and a further dose reduction was required to manage adverse effects.

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 six courses or until progressive disease.

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). g. G-CSF) or to dose reduce to maintain neutrophil counts. 45 mg/m2/day if necessary).

Doses should be similarly reduced if the platelet count falls below 25 x 109/l. Dosage in renally impaired patients Monotherapy (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. 75 mg/m2/day for five consecutive days. 5 mg/dl. Medicinal product no longer authorised 4 If cisplatin is discontinued, there are insufficient data regarding continuing monotherapy with topotecan in patients with cervical cancer.

2). Method of administration Topotecan Actavis is for intravenous infusion after reconstitution and dilution. 6). Precautions to be taken before handling or administering the medicinal product Reconstitution and dilution of the medicinal product must be performed by trained personnel.

Summary of the safety profile In dose-finding trials involving 523 patients with relapsed ovarian cancer and 631 patients with relapsed small cell lung cancer, the dose limiting toxicity of topotecan monotherapy was found to be haematological.

Toxicity was predictable and reversible. There were no signs of cumulative haematological or non-haematological toxicity. The adverse event profile for topotecan when given in combination with cisplatin in the cervical cancer clinical trials is consistent with that seen with topotecan monotherapy.

The overall haematological toxicity is lower in patients treated with topotecan in combination with cisplatin compared to topotecan monotherapy, but higher than with cisplatin alone. Additional adverse events were seen when topotecan was given in combination with cisplatin, however, these events were seen with cisplatin monotherapy and not attributable to topotecan.

The prescribing information for cisplatin should be consulted for a full list of adverse events associated cisplatin use. The integrated safety data for topotecan monotherapy are presented below. Tabulated list of adverse reactions Adverse reactions are listed below, by system organ class and absolute frequency (all reported events).

Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000), including isolated reports and not known (cannot be estimated from the available data).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 4). Hepatobiliary disorders Common: hyperbilirubinaemia Skin and subcutaneous tissue disorders Very common: alopecia Common: pruritus General disorders and administration site conditions Very common: pyrexia asthenia fatigue Common: malaise Very rare: extravasation3 3Extravasation has been reported very rarely.

2). As with other cytotoxic medicinal products, topotecan can cause severe myelosuppression. 8). Topotecan-induced neutropenia can cause neutropenic colitis. Fatalities due to neutropenic colitis have been reported in clinical trials with topotecan.

In patients presenting with fever, neutropenia, and a compatible pattern of abdominal pain, the possibility of neutropenic colitis should be considered. 8). Underlying risk factors include history of ILD, pulmonary fibrosis, lung cancer, thoracic exposure to radiation and use of pneumotoxic substances and/or colony stimulating factors.

g. cough, fever, dyspnoea and/or hypoxia), and topotecan should be discontinued if a new diagnosis of ILD is confirmed. Topotecan monotherapy and topotecan in combination with cisplatin are commonly associated with clinically relevant thrombocytopenia.

g. 8). Accurate assessment of performance status at the time therapy is given is important, to ensure that patients have not deteriorated to performance status 3. There is insufficient experience of the use of topotecan in patients with severely impaired renal function (creatinine clearance < 20 ml/min) or severely impaired hepatic function (serum bilirubin ≥ 10 mg/dl) due to cirrhosis.

Topotecan is not recommended to be used in these patient groups. 5 mg/m2 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.

e. essentially ‘sodium- free’.

5 x 109/l and/or a platelet count of < 100 x 109/l.