Special Warning : אזהרת שימוש

4.4    Special warnings and precautions for use


Haematological toxicity is dose-related and full blood count including platelets should be monitored regularly (see section 4.2).

As with other cytotoxic medicinal products, topotecan can cause severe myelosuppression.
Myelosuppression leading to sepsis and fatalities due to sepsis have been reported in patients treated with topotecan (see section 4.8).

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.

Topotecan has been associated with reports of interstitial lung disease, some of which have been fatal (see section 4.8). Underlying risk factors include history of ILD, pulmonary fibrosis, lung cancer, thoracic exposure to radiation and use of pneumotoxic drugs and/or colony stimulating factors. Patients should be monitored for pulmonary symptoms indicative of interstitial lung disease (e.g. cough, fever, dyspnoea and/or hypoxia), and topotecan should be discontinued if a new diagnosis of ILD is confirmed.

Topotecan montherapy and topotecan in combination with cisplatin are commonly associated with clinically relevant thrombocytopenia. This should be taken into account, e.g. in case patients at increased risk of tumour bleeds are considered for therapy.

As expected, patients with poor performance status (PS>1) have a lower response rate and an increased incidence of complications such as fever, infection and sepsis (see section 4.8). 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.

A small number of hepatically impaired patients (serum bilirubin between 1.5 and 10 mg/dl) were given 1.5 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.

Effects on Driving

4.7    Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.
However, caution should be observed when driving or operating machines if fatigue and asthenia persist.