ANZATAX INJECTION CONCENTRATE 6 MG/ML [SIN09539P]

Product Info

ANZATAX INJECTION CONCENTRATE 6 MG/ML

[SIN09539P]

4.1 Therapeutic indications

Anzatax Injection Concentrate is indicated for the first-line therapy of advanced metastatic ovarian cancer in combination with a platinum agent.

Anzatax Injection Concentrate is indicated for the treatment of metastatic ovarian cancer and metastatic breast cancer, after failure of standard therapy.

Anzatax Injection Concentrate is indicated for the first-line therapy in combination with a platinum compound or as a single agent for the treatment of non-small cell lung cancer (NSCLC) in patients who are not candidates for potentially curative surgery and/or radiation therapy.

Anzatax Injection Concentrate is indicated for adjuvant treatment of node positive breast cancer administered sequentially to doxorubicin and cyclophosphamide.

Anzatax Injection Concentrate is indicated for the first-line therapy of metastatic cancer of the breast, in combination with trastuzumab (Herceptin), in patients who have tumors that over-express HER-2.

4.2 Dose and method of administration

Dosage

All patients should be premedicated before paclitaxel is administered to prevent severe hypersensitivity reactions (see Section 4.4 Special warnings and precautions for use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Before every treatment cycle, patients should be premedicated with:

• dexamethasone 20 mg orally 12 hours and 6 hours prior to starting the paclitaxel infusion.

• promethazine 25 mg to 50 mg intravenously or other suitable H₁-antagonist, 30 minutes prior to starting the paclitaxel infusion.

• cimetidine 300 mg or ranitidine 50 mg by intravenous infusion over 15 minutes, starting 30 minutes prior to the paclitaxel infusion.

For primary treatment of ovarian cancer, it is recommended that paclitaxel be used at a dose of:

• 175 mg/m², administered intravenously over 3 hours, followed by cisplatin 75 mg/m². The infusion should be repeated every three weeks.

• 135 mg/m², administered intravenously over 24 hours, followed by cisplatin 75 mg/m². The infusion should be repeated every three weeks.

For the treatment of metastatic ovarian cancer or metastatic breast cancer, it is recommended that paclitaxel be used as a single agent at a dose of 175 mg/m². Paclitaxel should be administered as an intravenous infusion over 3 hours. The infusion should be repeated every 3 weeks as tolerated. Patients have tolerated treatment with up to 9 cycles of paclitaxel therapy, but the optimal course of therapy remains to be established.

For primary or secondary treatment of NSCLC, the recommended dose of paclitaxel is 175 mg/m² administered intravenously over 3 hours with a 3-week interval between courses.

For node positive breast cancer, the recommended dose of paclitaxel is 175 mg/m² administered intravenously over 3 hours every 3 weeks for four courses following doxorubicin and cyclophosphamide combination therapy.

For over-expression of HER-2 breast cancer, paclitaxel 175 mg/m² administered intravenously over 3 hours with a 3-week interval between courses. Paclitaxel may be started the day following the first dose of trastuzumab or immediately after the subsequent doses of trastuzumab if the preceding dose of trastuzumab was well tolerated.

Method of administration

Dilution

Anzatax Injection Concentrate MUST BE DILUTED PRIOR TO INTRAVENOUS INFUSION. It should be diluted in 5% glucose or 0.9% sodium chloride intravenous infusion.

Dilution should be made to a final concentration of 0.3 to 1.2 mg/mL.

After the final dilution of Anzatax Injection Concentrate, the bottle should be swirled gently to disperse the paclitaxel. DO NOT SHAKE.

Avoid contact of paclitaxel solutions with plasticised polyvinyl chloride (PVC) equipment, infusion lines or devices used when preparing infusion solutions. Prepare and store diluted paclitaxel solutions in glass bottles or non-PVC infusion bags. These precautions are to avoid leaching of the plasticiser DEHP (di-[2-ethylhexyl] phthalate) from PVC infusion bags or sets. Paclitaxel solutions should be administered through polyethylene lined administration sets (e.g., Gemini 20 giving set), using an IMED® pump.

Although solutions of paclitaxel for infusion prepared as outlined above are chemically stable for 3 days at room temperature (25°C) and 14 days at 2°C to 8°C, it is recommended that the solution for infusion should be administered immediately after preparation as it does not contain an antimicrobial agent. The infusion should be completed within 24 hours of preparation of the solution and any residue discarded, according to the guidelines for the disposal of cytotoxic drugs (see Section 6.6 Special precautions for disposal – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Use in one patient on one occasion only.

Compounding centres which:

1. are licensed by the TGA to reconstitute and/or further dilute cytotoxic products; and

2. have validated aseptic procedure and regular monitoring of aseptic technique may apply the following shelf lives when stored under the specified conditions:

Solutions prepared this way have been shown to be chemically stable for these periods. Administration should be completed within 24 hours of the start of the infusion and any residue discarded according to the guidelines for the disposal of cytotoxic drugs. Do not use paclitaxel if any precipitation forms or if the diluted solution appears cloudy.

Filtration

A microporous membrane of 0.22 microns or less in size is recommended as the in-line filter for all infusions of paclitaxel. The IMED® 0.2 micron add on filter set composed of polysulfone and the IVEX™ II 0.2 micron filter composed of cellulose have both been found to be suitable for Anzatax Injection Concentrate.

Paclitaxel is a cytotoxic anticancer drug and as with other potentially toxic compounds, caution should be exercised in handling paclitaxel. The use of gloves is recommended. Following topical exposure, tingling, burning, redness have been observed. If paclitaxel solution contacts the skin, wash the skin immediately and thoroughly with soap and water. If paclitaxel contacts mucous membranes, the membranes should be flushed thoroughly with water. Upon inhalation, dyspnoea, chest pain, burning eyes, sore throat and nausea have been reported. Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration.

The published guidelines related to procedures for the proper handling and disposal of cytotoxic drugs should be followed.

Care must be taken whenever handling cytotoxic products. Always take steps to prevent exposure. This included appropriate equipment, such as wearing gloves and washing hands with soap and water after handling such products.

Dosage adjustment

Subsequent doses of paclitaxel should be administered according to individual patient tolerance. Repetition of a course of paclitaxel is not recommended until the patient’s neutrophil count is at least 1.5 x 10⁹ cells/L (1,500 cells/mm³) and the platelet count is at least 100 x 10⁹ cells/L (100,000 cells/mm³). If there is severe neutropenia (neutrophil count less than 0.5 x 10⁹ cells/L for a minimum of 7 days) or severe peripheral neuropathy or severe mucositis during paclitaxel therapy, the dose of paclitaxel in subsequent courses should be reduced by 20% (see Section 4.4 Special warnings and precautions for use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). The incidence of neurotoxicity and the severity of neutropenia increase with dose within a regime.

Hepatic impairment

Patients with hepatic impairment may be at increased risk of toxicity, particularly grade III–IV myelosuppression. Dose adjustment is recommended, as shown in Table 2 for both 3- and 24-hour infusions. Patients should be monitored closely for the development of profound myelosuppression.

Paediatric population

Paclitaxel is not recommended for use in children below 18 years due to lack of data on safety and efficacy.

4.3 Contraindications

Anzatax Injection Concentrate must not be used in patients who have exhibited hypersensitivity reactions to paclitaxel or other taxanes.

Anzatax Injection Concentrate must not be used in patients who have a history of hypersensitivity reactions to PEG 35 castor oil or drugs formulated in PEG 35 castor oil (e.g., ciclosporin for injection concentrate and teniposide for injection concentrate) or any of the other excipients.

Anzatax Injection Concentrate should not be administered in patients who have a baseline neutrophil counts of <1.5x10⁹ cells/L.

Patients with severe hepatic impairment must not be treated with paclitaxel.