A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Taxotere Indications, Dosage, Storage, Stability - Docetaxel
Taxotere Indications, Dosage, Storage, Stability - Docetaxel
INDICATIONS AND USAGE
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.
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.
Prostate Cancer: TAXOTERE in combination with prednisone
is indicated for the treatment of patients with androgen independent (hormone
refractory) metastatic prostate cancer.
DOSAGE AND ADMINISTRATION
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 also Dosage Adjustments).
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, WARNINGS
and CLINICAL STUDIES sections).
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.
Prostate cancer: For hormone-refractory metastatic prostate
cancer, the recommended dose of TAXOTERE is 75 mg/m2 every 3 weeks
as a 1 hour infusion. Prednisone 5 mg orally twice daily is administered continuously.
Premedication Regimen: All patients should be premedicated
with oral corticosteroids (see below for prostate cancer) such as dexametha-sone
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
sections).
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
sections).
Dosage Adjustments During Treatment
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 therapymay tolerate higher doses. Patients who develop >
grade 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 > 1,500 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
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 = grade 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’
Combination Therapy with TAXOTERE for Hormone-Refractory Metastatic
Prostate Cancer
TAXOTERE should be administered when the neutrophil count is
> 1,500 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.
Special Populations
Hepatic Impairment: Patients with bilirubin > ULN should
generally not receive TAXOTERE. Also, patients with SGOT and/or SGPT > 1.5
x ULN concomitant with alkaline phosphatase > 2.5 x ULN should generally
not receive TAXOTERE.
Children: The safety and effectiveness of docetaxel in pediatric
patients below the age of 16 years have not been established.
Elderly: See Precautions,
Geriatric Use. In general, dose selection for an elderly patient should
be cautious, reflecting the greater frequency of decreased hepatic, renal, or
cardiac function and of concomitant disease or other drug therapy in elderly
patients.
PREPARATION AND ADMINISTRATION
Administration Precautions
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 section.
If TAXOTERE Injection Concentrate, initial diluted solution,
or final dilution for infusion should come into contact with the skin, immediately
and thoroughly wash with soap and water.
If TAXOTERE Injection Concentrate, initial diluted solution,
or final dilution for 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.
|
Product
|
Diluent13% (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
|
Preparation and Administration
A. Initial Diluted Solution
1.TAXOTERE vials should be stored between 2 and 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 10mg 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 injectinto
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 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.
Stability
TAXOTERE infusion solution, if stored between 2 and (36 and
77°F) 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).
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 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 published1-7. There is no general agreement
that all of the procedures recommended in the guidelines are necessary or appropriate.
REFERENCES
1.OSHA Work-Practice Guidelines for Controlling Occupational
Exposure to Hazardous Drugs. Am J Health-Syst Pharm. 1996; 53: 1669-1685.
2.American Society of Hospital Pharmacists Technical Assistance
Bulletin on Handling Cytotoxic and Hazardous Drugs. Am J Hosp Pharm. 1990;
47(95): 1033-1049.
3.AMA Council Report. Guidelines for Handling Parenteral Antineoplastics.
JAMA. 1985; 253(11): 1590-1592.
4.Recommendations for the Safe Handling of Parenteral Antineoplastic
Drugs. NIH Publication No. 83-2621. For sale by the Superintendent of Documents,
US Government Printing Office, Washington, DC 20402.
5.National Study Commission on Cytotoxic Exposure -Recommendations
for Handling Cytotoxic Agents. Available from Louis P. Jeffry, Chairman, National
Study Commission on Cytotoxic Exposure. Massachusetts College of Pharmacy and
Allied Health Sciences, 179 Longwood Avenue, Boston, MA 02115.
6.Clinical Oncological Society of Australia. Guidelines and
Recommendations for Safe Handling of Antineoplastic Agents. Med J Austr.
1983; 426-428.
7.Jones, RB, et al. Safe Handling of Chemotherapeutic Agents:
A Report from the Mt. Sinai Medical Center. CA-A Cancer Journal for Clinicians.
1983; Sept/Oct: 258-263.
Prescribing Information as of August 2004 Manufactured
by Aventis Pharma Ltd. Dagenham, Essex RM10 7XS, United Kingdom Manufactured
for: Aventis Pharmaceuticals Inc., Bridgewater, NJ 08807 USA www.aventis-us.com
©2004 Aventis Pharmaceuticals TAX-AUG04-F-A,
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