Docetaxel (Page 3 of 11)

2.8 Administration Precautions

Docetaxel injection is a cytotoxic anticancer drug and, as with other potentially toxic compounds, caution should be exercised when handling and preparing docetaxel injection solutions. The use of gloves is recommended [see How Supplied/ Storage and Handling ( 16.3)].

If docetaxel injection initial diluted solution, or final dilution for infusion should come into contact with the skin, immediately and thoroughly wash with soap and water.

If docetaxel injection initial diluted solution, or final dilution for infusion should come into contact with mucosa, immediately and thoroughly wash with water.

Contact of the docetaxel injection with plasticized PVC equipment or devices used to prepare solutions for infusion is not recommended. In order to minimize patient exposure to the plasticizer DEHP (di-2-ethylhexyl phthalate), which may be leached from PVC infusion bags or sets, the final docetaxel injection dilution for infusion should be stored in bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administered through polyethylene-lined administration sets.

One-vial Docetaxel Injection (Injection)

Docetaxel injection requires NO prior dilution with a diluent and is ready to add to the infusion solution.

Please follow the preparation instructions provided below.

2.9 Preparation and Administration

DO NOT use the two-vial formulation (Injection Concentrate and diluent) with the one-vial formulation.

One-vial Docetaxel Injection (Injection)

Docetaxel injection (20 mg/mL) requires NO prior dilution with a diluent and is ready to add to the infusion solution. Use only a 21 gauge needle to withdraw docetaxel injection from the vial because larger bore needles (e.g., 18 and 19 gauge) may result in stopper coring and rubber particulates.

  1. Docetaxel injection vials should be stored between 2°C and 25°C (36°F and 77°F). If the vials are stored under refrigeration, allow the appropriate number of vials of docetaxel injection to stand at room temperature for approximately 5 minutes before use.
  2. Using only a 21 gauge needle, aseptically withdraw the required amount of docetaxel injection (20 mg docetaxel/mL) with a calibrated syringe and inject via a single injection (one shot) into a 250 mL infusion bag or bottle of either 0.9% Sodium Chloride solution or 5% Dextrose solution to produce a final concentration of 0.3 mg/mL to 0.74 mg/mL.
    If a dose greater than 200 mg of docetaxel injection is required, use a larger volume of the infusion vehicle so that a concentration of 0.74 mg/mL docetaxel injection is not exceeded.
  3. Thoroughly mix the infusion by gentle manual rotation.
  4. As with all parenteral products, docetaxel injection should be inspected visually for particulate matter or discoloration prior to administration whenever the solution and container permit. If the docetaxel injection dilution for intravenous infusion is not clear or appears to have precipitation, it should be discarded.
  5. Docetaxel injection infusion solution is supersaturated, therefore may crystallize over time. If crystals appear, the solution must no longer be used and shall be discarded.

The docetaxel injection dilution for infusion should be administered intravenously as a 1-hour infusion under ambient room temperature (below 25°C) and lighting conditions.

2.10 Stability

Docetaxel injection final dilution for infusion, if stored between 2°C and 25°C (36°F and 77°F) is stable for 6 hours. Docetaxel injection final dilution for infusion (in either 0.9% Sodium Chloride solution or 5% Dextrose solution) should be used within 6 hours (including the 1 hour intravenous administration).

In addition, physical and chemical in-use stability of the infusion solution prepared as recommended has been demonstrated in non-PVC bags up to 48 hours when stored between 2°C and 8°C (36°F and 46°F).

3 DOSAGE FORMS AND STRENGTHS

One-vial Docetaxel Injection USP

Docetaxel Injection USP 20 mg/mL

Docetaxel Injection USP 20 mg/1 mL single-dose vial: 20 mg docetaxel in 1 mL in 50/50 (v/v) ratio polysorbate 80/dehydrated alcohol.

Docetaxel Injection USP 80 mg/4 mL

Docetaxel Injection USP 80 mg/4 mL single-dose vial: 80 mg docetaxel in 4 mL 50/50 (v/v) ratio polysorbate 80/dehydrated alcohol.

​Docetaxel Injection USP 160 mg/8 mL

Docetaxel Injection USP 160 mg/8 mL single-dose vial: 160 mg docetaxel in 8 mL 50/50 (v/v) ratio polysorbate 80/dehydrated alcohol.

4 CONTRAINDICATIONS

Docetaxel is contraindicated in patients with:

  • neutrophil counts of <1500 cells/mm3 [see Warnings and Precautions ( 5.3)].
  • a history of severe hypersensitivity reactions to docetaxel or to other drugs formulated with polysorbate 80. Severe reactions, including anaphylaxis, have occurred [see Warnings and Precautions ( 5.5)] .

5 WARNINGS AND PRECAUTIONS

5.1 Toxic Deaths

Breast Cancer

Docetaxel administered at 100 mg/m 2 was associated with deaths considered possibly or probably related to treatment in 2.0% (19/965) of metastatic breast cancer patients, both previously treated and untreated, with normal baseline liver function and in 11.5% (7/61) of patients with various tumor types who had abnormal baseline liver function (AST and/or ALT >1.5 times ULN together with AP >2.5 times ULN). Among patients dosed at 60 mg/m 2 , mortality related to treatment occurred in 0.6% (3/481) of patients with normal liver function, and in 3 of 7 patients with abnormal liver function. Approximately half of these deaths occurred during the first cycle. Sepsis accounted for the majority of the deaths.

Non-small Cell Lung Cancer

Docetaxel administered at a dose of 100 mg/m 2 in patients with locally advanced or metastatic non-small cell lung cancer who had a history of prior platinum-based chemotherapy was associated with increased treatment-related mortality (14% and 5% in two randomized, controlled studies). There were 2.8% treatment-related deaths among the 176 patients treated at the 75 mg/m 2 dose in the randomized trials. Among patients who experienced treatment-related mortality at the 75 mg/m 2 dose level, 3 of 5 patients had an ECOG PS of 2 at study entry [see Dosage and Administration ( 2.2), Clinical Studies ( 14)].

5.2 Hepatic Impairment

Patients with elevations of bilirubin or abnormalities of transaminase concurrent with alkaline phosphatase are at increased risk for the development of severe neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death.

Avoid docetaxel in patients with bilirubin > upper limit of normal (ULN), or to patients with AST and/or ALT >1.5 × ULN concomitant with alkaline phosphatase >2.5 × ULN [see Warnings and Precautions ( 5.1)].

For patients with isolated elevations of transaminase >1.5 × ULN, consider docetaxel dose modifications [see Dosage and Administration ( 2.7)]. Measure bilirubin, AST or ALT, and alkaline phosphatase prior to each cycle of docetaxel therapy.

5.3 Hematologic Effects

Perform frequent peripheral blood cell counts on all patients receiving docetaxel. Do not retreat patients with subsequent cycles of docetaxel until neutrophils recover to a level >1500 cells/mm 3 [see Contraindications (4)]. Avoid retreating patients until platelets recover to a level > 100,000 cells/mm 3.

A 25% reduction in the dose of docetaxel is recommended during subsequent cycles following severe neutropenia (<500 cells/mm 3) lasting 7 days or more, febrile neutropenia, or a grade 4 infection in a docetaxel cycle [see Dosage and Administration ( 2.7)].

Neutropenia (<2000 neutrophils/mm 3) occurs in virtually all patients given 60 mg/m 2 to 100 mg/m 2 of docetaxel and grade 4 neutropenia (<500 cells/mm 3) occurs in 85% of patients given 100 mg/m 2 and 75% of patients given 60 mg/m 2. Frequent monitoring of blood counts is, therefore, essential so that dose can be adjusted. Docetaxel should not be administered to patients with neutrophils <1500 cells/mm 3.

Febrile neutropenia occurred in about 12% of patients given 100 mg/m 2 but was very uncommon in patients given 60 mg/m 2. Hematologic responses, febrile reactions and infections, and rates of septic death for different regimens are dose related [see Adverse Reactions ( 6.1), Clinical Studies ( 14)].

Three breast cancer patients with severe liver impairment (bilirubin >1.7 times ULN) developed fatal gastrointestinal bleeding associated with severe drug-induced thrombocytopenia. In gastric cancer patients treated with docetaxel in combination with cisplatin and fluorouracil (TCF), febrile neutropenia and/or neutropenic infection occurred in 12% of patients receiving G-CSF compared to 28% who did not. Patients receiving TCF should be closely monitored during the first and subsequent cycles for febrile neutropenia and neutropenic infection [see Dosage and Administration ( 2.7), Adverse Reactions ( 6)].

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