Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use

Paclitaxel should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Since significant hypersensitivity reactions may occur, appropriate supportive equipment should be available.

Patients must be pretreated with corticosteroids, antihistamines and H2 antagonists (see 4.2).

Paclitaxel should be given before cisplatin when used in combination (see 4.5).

Significant hypersensitivity reactions characterised by dyspnoea and hypotension requiring treatment, angioedema and generalised urticaria have occurred in < 1% of patients receiving paclitaxel after adequate premedication. These reactions are probably histamine-mediated. In the case of severe hypersensitivity reactions, paclitaxel should be discontinued immediately, symptomatic therapy should be initiated and the patient should not be rechallenged with the drug.


Bone marrow suppression (primarily neutropenia) is the dose-limiting toxicity.
Frequent monitoring of blood counts should be instituted. Patients should not be retreated until neutrophils recover to 1,500/mm³ ( 1,000/mm³ for KS patients) and platelets recover to 100,000/mm³ ( 75,000/mm³ for KS patients). In the KS clinical study, the majority of patients were receiving granulocyte colony stimulating factor (G-CSF).


Severe cardiac conduction abnormalities have been reported rarely with single agent paclitaxel. If patients develop significant conduction abnormalities during paclitaxel administration, appropriate therapy should be administered and continuous cardiac monitoring should be performed during subsequent therapy with paclitaxel.
Hypotension, hypertension, and bradycardia have been observed during paclitaxel administration; patients are usually asymptomatic and generally do not require treatment. Frequent vital sign monitoring, particularly during the first hour of paclitaxel infusion, is recommended. Severe cardiovascular events were observed more frequently in patients with NSCLC than in those with breast or ovarian carcinoma. A single case of heart failure related to paclitaxel was seen in the AIDS- KS clinical study.


When paclitaxel is used in combination with doxorubucin or trastuzumab for initial treatment of metastatic breast cancer, attention should be placed on the monitoring of cardiac function. When patients are candidates for treatment with paclitaxel in these combinations, they should undergo baseline cardiac assessment including history, physical examination, ECG, echocardiogram, and/or MUGA scan. Cardiac function should be further monitored during treatment (e.g. every three months). Monitoring may help to identify patients who develop cardiac dysfunction and treating physicians should carefully assess the cumulative dose (mg/m2) of anthracycline administered when making decisions regarding frequency of ventricular function assessment.
When testing indicates deterioration in cardiac function, even asymptomatic, treating physicians should carefully assess the clinical benefits of further therapy against the potential for producing cardiac damage, including potentially irreversible damage. If further treatment is administered, monitoring of cardiac function should be more frequent (e.g. every 1-2 cycles). For more details see Summary of Product Characteristics of trastuzumab or doxorubicin.


Although the occurrence of peripheral neuropathy is frequent, the development of severe symptoms is rare. In severe cases, a dose reduction of 20% (25% for KS patients) for all subsequent courses of paclitaxel is recommended. In NSCLC patients and in ovarian cancer patients treated in the first-line setting, the administration of paclitaxel as a three hour infusion in combination with cisplatin, resulted in a greater incidence of severe neurotoxicity than both single agent paclitaxel and cyclophosphamide followed by cisplatin.


Patients with hepatic impairment may be at increased risk of toxicity, particularly grade III-IV myelosuppression. There is no evidence that the toxicity of paclitaxel is increased when given as a three-hour infusion to patients with mildly abnormal liver function. When paclitaxel is given as a longer infusion, increased myelosuppression may be seen in patients with moderate to severe hepatic impairment. Patients should be monitored closely for the development of profound myelosuppression (see 4.2).
Inadequate data are available to recommend dosage alterations in patients with mild to moderate hepatic impairments (see 5.2).


No data are available for patients with severe baseline cholestasis. Patients with severe hepatic impairment should not be treated with paclitaxel.


Since paclitaxel 6mg/ml infusion contains ethanol anhydrous (401.66 mg/ml), consideration should be given to possible CNS and other effects.


Special care should be taken to avoid intra-arterial application of paclitaxel, since in animal studies testing for local tolerance severe tissue reactions were observed after intra-arterial application.
Pseudomembranous colitis has been rarely reported including cases in patients who have not been concomitantly treated with antibiotics. This reaction should be considered in the differential diagnosis of cases of severe or persistent diarrhoea occurring during or shortly after treatment with paclitaxel.
Paclitaxel in combination with radiation of the lung, irrespective of their chronological order, may contribute to the development of interstitial pneumonitis.


In KS patients, severe mucositis is rare. If severe reactions occur, the paclitaxel dose should be reduced by 25%.


This product contains polyxolyl castor oil (macrogol glycerol ricinolate) which may cause severe allergic reactions.

Effects on Driving

4.7 Effects on ability to drive and use machines
Paclitaxel has not been demonstrated to interfere with this ability. However, it should be noted that the formulation contains alcohol (see 4.4 and 6.1).