Anzatax Special Precautions





Zuellig Pharma


Full Prescribing Info
Special Precautions
Generally the prescribing of paclitaxel should be restricted to medical staff experienced in the use of cancer chemotherapeutic agents.
Premedication: In order to minimise the possibility of hypersensitivity reactions due to histamine release, patients should be premedicated before every treatment cycle of paclitaxel. Premedication should include corticosteroids (e.g. dexamethasone), antihistamines (e.g. diphenhydramine or promethazine) and an H2-receptor antagonist (e.g. cimetidine or ranitidine) (see Dosage & Administration). The characteristic symptoms of hypersensitivity reactions are dyspnoea and hypotension both requiring treatment, angioedema and widespread urticaria. In clinical trials, 2% of patients treated with paclitaxel experienced severe hypersensitivity. One of these reactions was fatal in a patient treated without premedication. Anzatax Injection Concentrate must not be used in patients who have exhibited hypersensitivity reactions to paclitaxel.
Neutropenia (see Adverse Reactions): As the dose limiting toxicity of paclitaxel is dose related bone marrow suppression (primarily neutropenia), paclitaxel should be given with extreme caution to patients with a pre-treatment neutrophil count of less than 1.5 x 109 cells/L (1,500 cells/mm3). Blood counts should be frequently monitored during treatment with paclitaxel. Further cycles of paclitaxel should not be administered until the patient's neutrophil count is greater than 1.5 x 109 cells/L (1,500 cells/mm3) and the platelet count is greater than 100 x 109 cells/L (100,000 cells/mm3).
If there is severe neutropenia during a course of paclitaxel (i.e. neutrophil count less than 0.5 x 109 cells/L [500 cells/mm3] for 7 or more days), the dose of paclitaxel in subsequent cycles should be reduced by 20%. Previous radiation therapy may induce more severe myelosuppression. There is little information available from such patients at doses above 135 mg/m2.
Conduction abnormalities: Severe conduction abnormalities have occurred rarely in patients receiving paclitaxel. One patient required the insertion of a temporary pacemaker. If significant conduction abnormalities develop during paclitaxel infusions, the patient should be closely monitored and treated as required. Any subsequent treatment of the patient with paclitaxel should be accompanied by continuous cardiac monitoring. Severe cardiovascular events have been observed more frequently in patients with NSCLC than breast or ovarian cancer.
Gastrointestinal: In patients receiving paclitaxel who complain of abdominal pain with other signs and symptoms, bowel perforation should be excluded.
Carcinogenesis, mutagenesis, impairment of fertility: No studies have examined the carcinogenic potential of paclitaxel, however, drugs similar to paclitaxel are carcinogens. In vitro studies (chromosome abnormalities in human lymphocytes) and in vivo (micronucleus test using mice) mammalian test systems have shown paclitaxel to be mutagenic. When testing using the Ames test or the CHO/HGPRT gene mutation assay, paclitaxel did not induce mutagenicity. Following treatment with intravenous paclitaxel at a dose of 1 mg/kg (6 mg/m2), rats showed decreased fertility and toxicity in unborn offspring. Paclitaxel administered intravenously to rabbits during organogenesis at a dose of 3 mg/kg (33 mg/m2) was toxic to both mother and foetus.
Administration: Paclitaxel is administered by intravenous infusion only; it must not be administered by the intracerebral, intrapleural or intraperitoneal routes. Anzatax Injection Concentrate must be diluted before intravenous infusion. Prior to intravenous infusion of paclitaxel, it must be ensured that the indwelling catheter is in the correct position as extravasation, necrosis and/or thrombophlebitis may result with incorrect administration (see Dosage & Administration).
Patients receiving paclitaxel should be under continuous observation for at least the first 30 minutes following the start of the infusion and frequently thereafter. In case of a severe hypersensitivity reaction, paclitaxel infusion should be discontinued immediately and appropriate treatment given as indicated for anaphylaxis. The patient should not be rechallenged with the drug. Minor hypersensitivity reactions such as flushing, skin reactions, etc. do not require interruption of therapy (see also Adverse Reactions). In some patients, temporary discontinuation of the infusion is sufficient to resolve the symptoms. Other patients may require therapy with bronchodilators, adrenaline, antihistamines and corticosteroids, either alone or in combination.
Renal and hepatic impairment: The effect of renal and/or hepatic impairment on the pharmacokinetics of paclitaxel has not been established. However, as the liver is thought to be the primary site for metabolism of the drug, paclitaxel should be given cautiously to patients with decreased liver function. Paclitaxel has been shown to cause a dose related elevation of liver enzymes.
When paclitaxel is given as a 24 hour infusion to patients with moderate to severe hepatic impairment, increased myelosuppression may be seen as compared to patients with mildly elevated liver function tests given 24 hour infusions.
Hypotension and bradycardia: Patients may develop hypotension and bradycardia during paclitaxel treatment, but generally not to a level requiring treatment. Vital signs should be monitored frequently, particularly during the first hour of paclitaxel infusion. Only patients with serious conduction abnormalities require continuous cardiac monitoring (see Precautions and Adverse Reactions).
Nervous system: Patients with pre-existing neuropathy should be carefully monitored. Peripheral neuropathy is commonly reported in patients receiving paclitaxel and the severity is dose dependent. A 20% reduction in paclitaxel dose is recommended for patients who develop peripheral neuropathy during therapy (see Adverse Reactions).
In NSCLC patients, the administration of paclitaxel in combination with cisplatin resulted in a greater incidence of neurotoxicity than usually seen in patients receiving single agent paclitaxel.
Use in pregnancy Category D: Studies have shown paclitaxel to be toxic to embryos and foetuses in rabbits at an intravenous dose of 3 mg/kg (33 mg/m2) given during organogenesis. Paclitaxel is toxic to rat foetuses at a dose of 1 mg/kg (6 mg/m2). Examination revealed that no gross external, soft tissue or skeletal alterations occurred.
Category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects.
Use in lactation: The evidence from many drugs would suggest that paclitaxel could be excreted in breast milk, though this is not known. Because infants receiving the drug could experience serious adverse effects, breastfeeding should be discontinued while the mother is undergoing treatment.
Use in children: The safety and effectiveness of Anzatax Injection Concentrate in children has not been established. It should be noted that children may be more sensitive than adults to the effects of ethanol.
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