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Drug:   Docetaxel - Taxotere®

Usual Diluents

D5W,    NS

Dilution Data

Preparation: [ note:  two formulations are available.  One requires reconstitution - listed below (first entry), and the alternative formulation is available as a solution (20mg/ml) - Docetaxel Injection Concentrate requires NO prior dilution with a diluent and is ready to add to the infusion solution.. ]


A.  Formulation requiring reconstitution:
  1. TAXOTERE vials should be stored between 2 and 25°C (36 and 77°F). If the vials are stored under refrigeration, allow the appropriate number of vials of TAXOTERE Injection Concentrate and diluent (13% ethanol in water for injection) vials to stand at room temperature for approximately 5 minutes.
  2. Aseptically withdraw the entire contents of the appropriate diluent vial (approximately 1.8 mL for TAXOTERE 20 mg and approximately 7.1 mL for TAXOTERE 80 mg) into a syringe by partially inverting the vial, and transfer it to the appropriate vial of TAXOTERE Injection Concentrate. If the procedure is followed as described, an initial diluted solution of 10 mg docetaxel/mL will result.
  3. Mix the initial diluted solution by repeated inversions for at least 45 seconds to assure full mixture of the concentrate and diluent. Do not shake.
  4. The initial diluted TAXOTERE solution (10 mg docetaxel/mL) should be clear; however, there may be some foam on top of the solution due to the polysorbate 80. Allow the solution to stand for a few minutes to allow any foam to dissipate. It is not required that all foam dissipate prior to continuing the preparation process.
    The initial diluted solution may be used immediately or stored either in the refrigerator or at room temperature for a maximum of 8 hours.
B. Final Dilution for Infusion
  1. Aseptically withdraw the required amount of initial diluted TAXOTERE solution (10 mg docetaxel/mL) with a calibrated syringe and inject 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 to 0.74 mg/mL.
    If a dose greater than 200 mg of TAXOTERE is required, use a larger volume of the infusion vehicle so that a concentration of 0.74 mg/mL TAXOTERE is not exceeded.
  2. Thoroughly mix the infusion by manual rotation.
  3. As with all parenteral products, TAXOTERE should be inspected visually for particulate matter or discoloration prior to administration whenever the solution and container permit. If the TAXOTERE initial diluted solution or final dilution for intravenous infusion is not clear or appears to have precipitation, these should be discarded.
The final TAXOTERE dilution for infusion should be administered intravenously as a 1-hour infusion under ambient room temperature and lighting conditions.

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Stability
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TAXOTERE infusion solution, if stored between 2 and 25°C (36 and 77°F) is stable for 4 hours. Fully prepared TAXOTERE infusion solution (in either 0.9% Sodium Chloride solution or 5% Dextrose solution) should be used within 4 hours (including the 1 hour i.v. administration).


Preparation of DOCETAXEL injection, solution, concentrate -Docetaxel 20 mg/mL:
One-vial Docetaxel (Injection Concentrate):  Docetaxel Injection Concentrate requires NO prior dilution with a diluent and is ready to add to the infusion solution.

Please follow the preparation instructions provided below.
Preparation and Administration:----------------------------------------------------------
DO NOT use the two-vial formulation (Injection Concentrate and diluent) with the one-vial formulation.

One-vial Docetaxel (Injection Concentrate):
Docetaxel Injection Concentrate (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 from the vial because larger bore needles (e.g., 18 and 19 gauge) may result in stopper coring and rubber particulates.

  1. Docetaxel vials should be stored between 2 and 25°C (36 and 77°F). If the vials are stored under refrigeration, allow the appropriate number of vials of Docetaxel Injection Concentrate vials 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 concentrate (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 is required, use a larger volume of the infusion vehicle so that a concentration of 0.74 mg/mL docetaxel is not exceeded.
  3. Thoroughly mix the infusion by gentle manual rotation.
  4. As with all parenteral products, docetaxel should be inspected visually for particulate matter or discoloration prior to administration whenever the solution and container permit. If the docetaxel dilution for intravenous infusion is not clear or appears to have precipitation, it should be discarded.
  5. Docetaxel 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 dilution for infusion should be administered intravenously as a 1-hour infusion under ambient room temperature (below 25°C) and lighting conditions.
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Stability
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Docetaxel final dilution for infusion, if stored between 2°C and 25°C (36°F and 77°F) is stable for 6 hours. Docetaxel 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 and 46°F).

DOSAGE FORMS AND STRENGTHS:
One-vial Docetaxel (Injection Concentrate)
Docetaxel 20 mg/mL
Docetaxel Injection Concentrate 20 mg/1 mL: 20 mg docetaxel in 1 mL in 50/50 (v/v) ratio polysorbate 80/dehydrated alcohol.

Docetaxel 80 mg/4 mL
Docetaxel Injection Concentrate 80 mg/4 mL: 80 mg docetaxel in 4 mL 50/50 (v/v) ratio polysorbate 80/dehydrated alcohol.

Docetaxel 160 mg/8 mL
Docetaxel Injection Concentrate 160 mg/8 mL: 160 mg docetaxel in 8 mL 50/50 (v/v) ratio polysorbate 80/dehydrated alcohol.

Additional information can be found in the official nomograph.

Stability / Miscellaneous

WARNINGS CLINICAL PHARMACOLOGY INDICATIONS
CONTRAINDICATIONS DOSAGE AND ADMINISTRATION RECONSTITUTION / DILUTION
  HOW SUPPLIED  
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DOSAGE AND ADMINISTRATION SUMMARY [Details below].
Administer under supervision of qualified physicians experienced in using antineoplastic agents. Facilities to manage possible complications must be available.

Administer IV over 1 hr every 3 weeks. PVC equipment is not recommended.

-BC: locally advanced or metastatic: 60–100 mg/m2 single agent.
-BC adjuvant: 75 mg/m2 administered 1 hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 3 weeks for 6 cycles.
-NSCLC: after platinum therapy failure: 75 mg/m2 single agent .
-NSCLC: chemotherapy-naive: 75 mg/m2 followed by cisplatin 75 mg/m2.
-HRPC: 75 mg/m2 with 5 mg prednisone twice a day continuously.
-GC: 75 mg/m2 followed by cisplatin 75 mg/m2 (both on day 1 only) followed by fluorouracil 750 mg/m2 per day as a 24-hr IV (days 1–5), starting at end of cisplatin infusion .
-SCCHN: 75 mg/m2 followed by cisplatin 75 mg/m2 IV (day 1), followed by fluorouracil 750 mg/m2 per day as a 24-hr IV (days 1–5), starting at end of cisplatin infusion; for 4 cycles.
-SCCHN: 75 mg/m2 followed by cisplatin 100 mg/m2 IV (day 1), followed by fluorouracil 1000 mg/m2 per day as a 24-hr IV (days 1–4); for 3 cycles .


Premedication Regimen:
Oral corticosteroids such as dexamethasone 16 mg per day (e.g., 8 mg twice a day) for 3 days starting 1 day before administration.
HRPC: oral dexamethasone 8 mg, at 12, 3, and 1 hrs before treatment.



WARNINGS
The incidence of treatment-related mortality associated with TAXOTERE therapy is increased in patients with abnormal liver function, in patients receiving higher doses, and in patients with non-small cell lung carcinoma and a history of prior treatment with platinum-based chemotherapy who receive TAXOTERE as a single agent at a dose of 100 mg/m2[see Warnings and Precautions (5.1)].

TAXOTERE should generally not be given to patients with bilirubin > upper limit of normal (ULN), or to patients with SGOT and/or SGPT >1.5 × ULN concomitant with alkaline phosphatase >2.5 × ULN. Patients with elevations of bilirubin or abnormalities of transaminase concurrent with alkaline phosphatase are at increased risk for the development of grade 4 neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death. Patients with isolated elevations of transaminase >1.5 × ULN also had a higher rate of febrile neutropenia grade 4 but did not have an increased incidence of toxic death. Bilirubin, SGOT or SGPT, and alkaline phosphatase values should be obtained prior to each cycle of TAXOTERE therapy and reviewed by the treating physician.

TAXOTERE therapy should not be given to patients with neutrophil counts of <1500 cells/mm3. In order to monitor the occurrence of neutropenia, which may be severe and result in infection, frequent blood cell counts should be performed on all patients receiving TAXOTERE.

Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension and/or bronchospasm, or very rarely fatal anaphylaxis, have been reported in patients who received the recommended 3-day dexamethasone premedication. Hypersensitivity reactions require immediate discontinuation of the TAXOTERE infusion and administration of appropriate therapy [see Warnings and Precautions (5.2)]. TAXOTERE must not be given to patients who have a history of severe hypersensitivity reactions to TAXOTERE or to other drugs formulated with polysorbate 80 [see Contraindications (4)].

Severe fluid retention occurred in 6.5% (6/92) of patients despite use of a 3-day dexamethasone premedication regimen. It was characterized by one or more of the following events: poorly tolerated peripheral edema, generalized edema, pleural effusion requiring urgent drainage, dyspnea at rest, cardiac tamponade, or pronounced abdominal distention (due to ascites) [see Warnings and Precautions (5.10)].





CLINICAL PHARMACOLOGY
Mechanism of Action
Docetaxel is an antineoplastic agent that acts by disrupting the microtubular network in cells that is essential for mitotic and interphase cellular functions. Docetaxel binds to free tubulin and promotes the assembly of tubulin into stable microtubules while simultaneously inhibiting their disassembly. This leads to the production of microtubule bundles without normal function and to the stabilization of microtubules, which results in the inhibition of mitosis in cells. Docetaxel's binding to microtubules does not alter the number of protofilaments in the bound microtubules, a feature which differs from most spindle poisons currently in clinical use.




1. INDICATIONS AND USAGE

1.1 Breast Cancer
TAXOTERE is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy.
TAXOTERE in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer.

1.2 Non-Small Cell Lung Cancer
TAXOTERE as a single agent is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy.
TAXOTERE in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer who have not previously received chemotherapy for this condition.

1.3 Prostate Cancer
TAXOTERE in combination with prednisone is indicated for the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer.

1.4 Gastric Adenocarcinoma
TAXOTERE in combination with cisplatin and fluorouracil is indicated for the treatment of patients with advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for advanced disease.

1.5 Head and Neck Cancer
TAXOTERE in combination with cisplatin and fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).



2. DOSAGE AND ADMINISTRATION
TAXOTERE (docetaxel) Injection Concentrate should be administered under the supervision of a qualified physician experienced in the use of antineoplastic agents. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available.


2.1 Breast Cancer
The recommended dose of TAXOTERE is 60–100 mg/m2 administered intravenously over 1 hour every 3 weeks.
In the adjuvant treatment of operable node-positive breast cancer, the recommended TAXOTERE dose is 75 mg/m2 administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 3 weeks for 6 courses. Prophylactic G-CSF may be used to mitigate the risk of hematological toxicities [see Dosage Adjustments During Treatment (2.7)].

2.2 Non-Small Cell Lung Cancer
For treatment after failure of prior platinum-based chemotherapy, TAXOTERE was evaluated as monotherapy, and the recommended dose is 75 mg/m2 administered intravenously over 1 hour every 3 weeks. A dose of 100 mg/m2 in patients previously treated with chemotherapy was associated with increased hematologic toxicity, infection, and treatment-related mortality in randomized, controlled trials [see Boxed Warning, Dosage Adjustments During Treatment (2.7), Warnings and Precautions (5), Clinical Studies (14)].
For chemotherapy-naïve patients, TAXOTERE was evaluated in combination with cisplatin. The recommended dose of TAXOTERE is 75 mg/m2 administered intravenously over 1 hour immediately followed by cisplatin 75 mg/m2 over 30–60 minutes every 3 weeks [see Dosage Adjustments During Treatment (2.7)].

2.3 Prostate cancer
For hormone-refractory metastatic prostate cancer, the recommended dose of TAXOTERE is 75 mg/m2 every 3 weeks as a 1 hour intravenous infusion. Prednisone 5 mg orally twice daily is administered continuously [see Dosage Adjustments During Treatment (2.7)].

2.4 Gastric adenocarcinoma
For gastric adenocarcinoma, the recommended dose of TAXOTERE is 75 mg/m2 as a 1 hour intravenous infusion, followed by cisplatin 75 mg/m2, as a 1 to 3 hour intravenous infusion (both on day 1 only), followed by fluorouracil 750 mg/m2 per day given as a 24-hour continuous intravenous infusion for 5 days, starting at the end of the cisplatin infusion. Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and appropriate hydration for cisplatin administration [see Dosage Adjustments During Treatment (2.7)].

2.5 Head and Neck Cancer
Patients must receive premedication with antiemetics, and appropriate hydration (prior to and after cisplatin administration). Prophylaxis for neutropenic infections should be administered. All patients treated on the TAXOTERE containing arms of the TAX323 and TAX324 studies received prophylactic antibiotics.

Induction chemotherapy followed by radiotherapy (TAX323)
For the induction treatment of locally advanced inoperable SCCHN, the recommended dose of TAXOTERE is 75 mg/m2 as a 1 hour intravenous infusion followed by cisplatin 75 mg/m2 intravenously over 1 hour, on day one, followed by fluorouracil as a continuous intravenous infusion at 750 mg/m2 per day for five days. This regimen is administered every 3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy. [see Dosage Adjustments During Treatment (2.7)].
Induction chemotherapy followed by chemoradiotherapy (TAX324)
For the induction treatment of patients with locally advanced (unresectable, low surgical cure, or organ preservation) SCCHN, the recommended dose of TAXOTERE is 75 mg/m2 as a 1 hour intravenous infusion on day 1, followed by cisplatin 100 mg/m2 administered as a 30-minute to 3 hour infusion, followed by fluorouracil 1000 mg/m2/day as a continuous infusion from day 1 to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, patients should receive chemoradiotherapy [see Dosage Adjustments During Treatment (2.7)].

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2.6 Premedication Regimen
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All patients should be premedicated with oral corticosteroids (see below for prostate cancer) such as dexamethasone 16 mg per day (e.g., 8 mg BID) for 3 days starting 1 day prior to TAXOTERE administration in order to reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions [see Boxed Warning, Warnings and Precautions (5)].
For hormone-refractory metastatic prostate cancer, given the concurrent use of prednisone, the recommended premedication regimen is oral dexamethasone 8 mg, at 12 hours, 3 hours and 1 hour before the TAXOTERE infusion [see Warnings and Precautions (5)].

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2.7 Dosage Adjustments During Treatment
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Breast Cancer
Patients who are dosed initially at 100 mg/m2 and who experience either febrile neutropenia, neutrophils <500 cells/mm3 for more than 1 week, or severe or cumulative cutaneous reactions during TAXOTERE therapy should have the dosage adjusted from 100 mg/m2 to 75 mg/m2. If the patient continues to experience these reactions, the dosage should either be decreased from 75 mg/m2 to 55 mg/m2 or the treatment should be discontinued. Conversely, patients who are dosed initially at 60 mg/m2 and who do not experience febrile neutropenia, neutrophils <500 cells/mm3 for more than 1 week, severe or cumulative cutaneous reactions, or severe peripheral neuropathy during TAXOTERE therapy may tolerate higher doses. Patients who develop greater than or equalgrade 3 peripheral neuropathy should have TAXOTERE treatment discontinued entirely.


Combination Therapy with TAXOTERE in the Adjuvant Treatment of Breast Cancer
TAXOTERE in combination with doxorubicin and cyclophosphamide should be administered when the neutrophil count is geq1,500 cells/mm3. Patients who experience febrile neutropenia should receive G-CSF in all subsequent cycles. Patients who continue to experience this reaction should remain on G-CSF and have their TAXOTERE dose reduced to 60 mg/m2. Patients who experience Grade 3 or 4 stomatitis should have their TAXOTERE dose decreased to 60 mg/m2. Patients who experience severe or cumulative cutaneous reactions or moderate neurosensory signs and/or symptoms during TAXOTERE therapy should have their dosage of TAXOTERE reduced from 75 to 60 mg/m2. If the patient continues to experience these reactions at 60 mg/m2, treatment should be discontinued.


Non-Small Cell Lung Cancer
Monotherapy with TAXOTERE for NSCLC treatment after failure of prior platinum-based chemotherapy

Patients who are dosed initially at 75 mg/m2 and who experience either febrile neutropenia, neutrophils <500 cells/mm3 for more than one week, severe or cumulative cutaneous reactions, or other grade 3/4 non-hematological toxicities during TAXOTERE treatment should have treatment withheld until resolution of the toxicity and then resumed at 55 mg/m2. Patients who develop geqgrade 3 peripheral neuropathy should have TAXOTERE treatment discontinued entirely.


Combination therapy with TAXOTERE for chemotherapy-naïve NSCLC
For patients who are dosed initially at TAXOTERE 75 mg/m2 in combination with cisplatin, and whose nadir of platelet count during the previous course of therapy is <25,000 cells/mm3, in patients who experience febrile neutropenia, and in patients with serious non-hematologic toxicities, the TAXOTERE dosage in subsequent cycles should be reduced to 65 mg/m2. In patients who require a further dose reduction, a dose of 50 mg/m2 is recommended. For cisplatin dosage adjustments, see manufacturers' prescribing information.


Prostate Cancer
Combination therapy with TAXOTERE for hormone-refractory metastatic prostate cancer

TAXOTERE should be administered when the neutrophil count is geq1,500 cells/mm3. Patients who experience either febrile neutropenia,neutrophils <500 cells/mm3 for more than one week, severe or cumulative cutaneous reactions or moderate neurosensory signs and/or symptoms during TAXOTERE therapy should have the dosage of TAXOTERE reduced from 75 to 60 mg/m2. If the patient continues to experience these reactions at 60 mg/m2, the treatment should be discontinued.


Gastric or Head and Neck Cancer
TAXOTERE in combination with cisplatin and fluorouracil in gastric cancer or head and neck cancer

Patients treated with TAXOTERE in combination with cisplatin and fluorouracil must receive antiemetics and appropriate hydration according to current institutional guidelines. In both studies, G-CSF was recommended during the second and/or subsequent cycles in case of febrile neutropenia, or documented infection with neutropenia, or neutropenia lasting more than 7 days. If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite G-CSF use, the TAXOTERE dose should be reduced from 75 to 60 mg/m2. If subsequent episodes of complicated neutropenia occur the TAXOTERE dose should be reduced from 60 to 45 mg/m2. In case of Grade 4 thrombocytopenia the TAXOTERE dose should be reduced from 75 to 60 mg/m2. Patients should not be retreated with subsequent cycles of TAXOTERE until neutrophils recover to a level >1,500 cells/mm3 and platelets recover to a level >100,000 cells/mm3. Discontinue treatment if these toxicities persist. [see PACKAGE INSERT FOR Warnings and Precautions (5)].

Recommended dose modifications for toxicities in patients treated with TAXOTERE in combination with cisplatin and fluorouracil are shown in Table 1

Table 1 - Recommended Dose Modifications for Toxicities in Patients Treated with TAXOTERE in Combination with Cisplatin and Fluorouracil
Toxicity Dosage adjustment
Diarrhea grade 3 First episode: reduce fluorouracil dose by 20%.
Second episode: then reduce TAXOTERE dose by 20%.
Diarrhea grade 4 First episode: reduce TAXOTERE and fluorouracil doses by 20%.
Second episode: discontinue treatment.
Stomatitis/mucositis
grade 3
First episode: reduce fluorouracil dose by 20%.
Second episode: stop fluorouracil only, at all subsequent cycles.
Third episode: reduce TAXOTERE dose by 20%.
Stomatitis/mucositis
grade 4
First episode: stop fluorouracil only, at all subsequent cycles.
Second episode: reduce TAXOTERE dose by 20%.


Liver dysfunction:
In case of AST/ALT >2.5 to leq5 × UNL and AP leq2.5× UNL, or AST/ALT >1.5 to leq5 × UNL and AP >2.5 to  leq5 × UNL, TAXOTERE should be reduced by 20%.

In case of AST/ALT >5 × UNL and/or AP >5 × UNL TAXOTERE should be stopped.



The dose modifications for cisplatin and fluorouracil in the gastric cancer study are provided below:

Cisplatin dose modifications and delays

Peripheral neuropathy: A neurological examination should be performed before entry into the study, and then at least every 2 cycles and at the end of treatment. In the case of neurological signs or symptoms, more frequent examinations should be performed and the following dose modifications can be made according to NCIC-CTC grade:

• Grade 2: Reduce cisplatin dose by 20%.

• Grade 3: Discontinue treatment.

Ototoxicity: In the case of grade 3 toxicity, discontinue treatment.

Nephrotoxicity: In the event of a rise in serum creatinine geqgrade 2 (>1.5 × normal value) despite adequate rehydration, CrCl should be determined before each subsequent cycle and the following dose reductions should be considered (see Table 2).

For other cisplatin dosage adjustments, also refer to the manufacturers' prescribing information.

Table 2 – Dose Reductions for Evaluation of Creatinine Clearance
 Creatinine clearance result before next cycle Cisplatin dose next cycle
CrCl = Creatinine clearance
CrCl geq60 mL/min Full dose of cisplatin was given. CrCl was to be repeated before each treatment cycle.
CrCl between 40 and 59 mL/min Dose of cisplatin was reduced by 50% at subsequent cycle. If CrCl was >60 mL/min at end of cycle, full cisplatin dose was reinstituted at the next cycle.
  If no recovery was observed, then cisplatin was omitted from the next treatment cycle.
CrCl <40 mL/min Dose of cisplatin was omitted in that treatment cycle only.
  If CrCl was still <40 mL/min at the end of cycle, cisplatin was discontinued.
  If CrCl was >40 and <60 mL/min at end of cycle, a 50% cisplatin dose was given at the next cycle.

  If CrCl was >60 mL/min at end of cycle, full cisplatin dose was given at next cycle.


Fluorouracil dose modifications and treatment delays

For diarrhea and stomatitis, see Table 1.

In the event of grade 2 or greater plantar-palmar toxicity, fluorouracil should be stopped until recovery. The fluorouracil dosage should be reduced by 20%.

For other greater than grade 3 toxicities, except alopecia and anemia, chemotherapy should be delayed (for a maximum of 2 weeks from the planned date of infusion) until resolution to grade leq1 and then recommenced, if medically appropriate.

For other fluorouracil dosage adjustments, also refer to the manufacturers' prescribing information.

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2.8 Administration Precautions
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TAXOTERE is a cytotoxic anticancer drug and, as with other potentially toxic compounds, caution should be exercised when handling and preparing TAXOTERE solutions. The use of gloves is recommended. Please refer to Handling and Disposal.

If TAXOTERE Injection Concentrate, initial diluted solution, or final dilution for intravenous infusion should come into contact with the skin, immediately and thoroughly wash with soap and water. If TAXOTERE Injection Concentrate, initialdiluted solution, or final dilution for intravenous infusion should come into contact with mucosa, immediately and thoroughly wash with water.

Contact of the TAXOTERE concentrate 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 TAXOTERE dilution for infusion should be stored in bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administered through polyethylene-lined administration sets.

TAXOTERE Injection Concentrate requires two dilutions prior to administration. Please follow the preparation instructions provided below. Note: Both the TAXOTERE Injection Concentrate and the diluent vials contain an overfill to compensate for liquid loss during preparation. This overfill ensures that after dilution with the entire contents of the accompanying diluent, there is an initial diluted solution containing 10 mg/mL docetaxel.

The table below provides the fill range of the diluent, the approximate extractable volume of diluent when the entire contents of the diluent vial are withdrawn, and the concentration of the initial diluted solution for TAXOTERE 20 mg and TAXOTERE 80 mg (see Table 3).

Table 3 – Initial Dilution of TAXOTERE Injection Concentrate
Product Diluent 13% (w/w) ethanol in water for injection
Fill Range
(mL)
Approximate extractable volume of diluent when entire contents are withdrawn
(mL)
Concentration of the initial diluted solution
(mg/mL docetaxel)
Taxotere®
20 mg/0.5 mL
1.88 – 2.08 mL 1.8 mL 10 mg/mL
Taxotere®
80 mg/2 mL
6.96 – 7.70 mL 7.1 mL 10 mg/mL

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2.9 Preparation and Administration    [Note if using prediluted solution - see above]
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A.  Initial Diluted Solution
  1. TAXOTERE vials should be stored between 2 and 25°C (36 and 77°F). If the vials are stored under refrigeration, allow the appropriate number of vials of TAXOTERE Injection Concentrate and diluent (13% ethanol in water for injection) vials to stand at room temperature for approximately 5 minutes.
  2. Aseptically withdraw the entire contents of the appropriate diluent vial (approximately 1.8 mL for TAXOTERE 20 mg and approximately 7.1 mL for TAXOTERE 80 mg) into a syringe by partially inverting the vial, and transfer it to the appropriate vial of TAXOTERE Injection Concentrate. If the procedure is followed as described, an initial diluted solution of 10 mg docetaxel/mL will result.
  3. Mix the initial diluted solution by repeated inversions for at least 45 seconds to assure full mixture of the concentrate and diluent. Do not shake.
  4. The initial diluted TAXOTERE solution (10 mg docetaxel/mL) should be clear; however, there may be some foam on top of the solution due to the polysorbate 80. Allow the solution to stand for a few minutes to allow any foam to dissipate. It is not required that all foam dissipate prior to continuing the preparation process.
    The initial diluted solution may be used immediately or stored either in the refrigerator or at room temperature for a maximum of 8 hours.
B. Final Dilution for Infusion
  1. Aseptically withdraw the required amount of initial diluted TAXOTERE solution (10 mg docetaxel/mL) with a calibrated syringe and inject 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 to 0.74 mg/mL.
    If a dose greater than 200 mg of TAXOTERE is required, use a larger volume of the infusion vehicle so that a concentration of 0.74 mg/mL TAXOTERE is not exceeded.
  2. Thoroughly mix the infusion by manual rotation.
  3. As with all parenteral products, TAXOTERE should be inspected visually for particulate matter or discoloration prior to administration whenever the solution and container permit. If the TAXOTERE initial diluted solution or final dilution for intravenous infusion is not clear or appears to have precipitation, these should be discarded.
The final TAXOTERE dilution for infusion should be administered intravenously as a 1-hour infusion under ambient room temperature and lighting conditions.

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2.10   Stability
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TAXOTERE infusion solution, if stored between 2 and 25°C (36 and 77°F) is stable for 4 hours. Fully prepared TAXOTERE infusion solution (in either 0.9% Sodium Chloride solution or 5% Dextrose solution) should be used within 4 hours (including the 1 hour i.v. administration).


3. DOSAGE FORMS AND STRENGTHS

TAXOTERE 80 mg/2 mL

TAXOTERE (docetaxel) Injection Concentrate 80 mg/2 mL: 80 mg docetaxel in 2 mL polysorbate 80 and Diluent for TAXOTERE 80 mg (13% (w/w) ethanol in water for injection). Both items are in a blister pack in one carton.


TAXOTERE 20 mg/0.5 mL

TAXOTERE (docetaxel) Injection Concentrate 20 mg/0.5 mL: 20 mg docetaxel in 0.5 mL polysorbate 80 and Diluent for TAXOTERE 20 mg (13% (w/w) ethanol in water for injection). Both items are in a blister pack in one carton.


4. CONTRAINDICATIONS
TAXOTERE is contraindicated in patients who have a history of severe hypersensitivity reactions to docetaxel or to other drugs formulated with polysorbate 80.

TAXOTERE should not be used in patients with neutrophil counts of <1500 cells/mm3.




HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
TAXOTERE Injection Concentrate is supplied in a single-dose vial as a sterile, pyrogen-free, non-aqueous, viscous solution with an accompanying sterile, non-pyrogenic, Diluent (13% ethanol in water for injection) vial. The following strengths are available:

TAXOTERE 80 mg/2 mL (NDC 0075-8001-80)

TAXOTERE (docetaxel) Injection Concentrate 80 mg/2 mL: 80 mg docetaxel in 2 mL polysorbate 80 and Diluent for TAXOTERE 80 mg (13% (w/w) ethanol in water for injection). Both items are in a blister pack in one carton.

TAXOTERE 20 mg/0.5 mL (NDC 0075-8001-20)

TAXOTERE (docetaxel) Injection Concentrate 20 mg/0.5 mL: 20 mg docetaxel in 0.5 mL polysorbate 80 and Diluent for TAXOTERE 20 mg (13% (w/w) ethanol in water for injection). Both items are in a blister pack in one carton.


Storage
Store between 2 and 25°C (36 and 77°F). Retain in the original package to protect from bright light. Freezing does not adversely affect the product.


Handling and Disposal
Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published1–4.


Reference(s)

PRIMARY:
 [PACKAGE INSERT DATA] : cytarabine (CYTARABINE) injection, solution. Mayne Pharma (USA) Inc. Paramus, NJ 07652. Revision Date January 2004.



Handling and Disposal:
  1. NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165.
  2. OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999. http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html
  3. American Society of Health-System Pharmacists. (2006) ASHP Guidelines on Handling Hazardous Drugs. Am J Health-Syst Pharm. 2006;63:1172–1193
  4. Polovich, M., White, J. M., & Kelleher, L.O. (eds.) 2005. Chemotherapy and biotherapy guidelines and recommendations for practice (2nd. ed.) Pittsburgh, PA: Oncology Nursing Society.

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