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taxotere(docetaxel) injection, solution, concentrateforintra

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HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use taxotere safely and effectively. See full prescribing information for taxotere.
taxotere(docetaxel) injection, solution, concentrate for intravenous use
Initial U.S. Approval: 1996
WARNING
See full prescribing information for completeboxed warning
Treatment-related mortality increases with abnormal liver function,at higher doses, and in patients with NSCLC and prior platinum-basedtherapy receiving TAXOTERE at 100 mg/m2 ( 5.1)
Should not be given if bilirubin > ULN, or if SGOT and/or SGPT> 1.5 × ULN concomitant with alkaline phosphatase > 2.5 ×ULN. LFT elevations increase risk of severe or life-threatening complications.Obtain LFTs before each treatment cycle ( 8.6)
Should not be given if neutrophil counts are < 1500 cells/mm3. Obtain frequent blood counts to monitor for neutropenia( 4)
Severe hypersensitivity, including very rare fatal anaphylaxis,has been reported in patients who received dexamethasone premedication.Severe reactions require immediate discontinuation of TAXOTERE andadministration of appropriate therapy ( 5.3)
Contraindicated if history of severe hypersensitivity reactionsto TAXOTERE or to drugs formulated with polysorbate 80 ( 4)
Severe fluid retention may occur despite dexamethasone ( 5.10)
RECENT MAJOR CHANGES
Indications andusage ( 1), dosage and administration( 2), warnings and precautions ( 5), adverse reactions( 6), 09/2007
INDICATIONS AND USAGE
Taxotere is a microtubuleinhibitor used for:
BreastCancer (BC): single agent for locally advanced or metastaticBC after chemotherapy failure; and with doxorubicin and cyclophosphamideas adjuvant treatment of operable node-positive BC ( 1.1)
Non-SmallCell Lung Cancer (NSCLC): single agent for locally advancedor metastatic NSCLC after platinum therapy failure; and with cisplatinfor unresectable, locally advanced or metastatic untreated NSCLC ( 1.2)
HormoneRefractory Prostate Cancer (HRPC): with prednisone in androgenindependent (hormone refractory) metastatic prostate cancer ( 1.3)
GastricAdenocarcinoma (GC): with cisplatin and fluorouracil foruntreated, advanced GC, including the gastroesophageal junction ( 1.4)
SquamousCell Carcinoma of the Head and Neck Cancer (SCCHN): withcisplatin and fluorouracil for induction treatment of locally advancedSCCHN ( 1.5)
DOSAGE AND ADMINISTRATION
Administer undersupervision of qualified physicians experienced in using antineoplasticagents. Facilities to manage possible complications must be available.
Administer IV over 1hr every 3 weeks. PVC equipment is not recommended.
BC: locally advanced or metastatic: 60–100 mg/m2 single agent ( 2.1)
BC adjuvant: 75 mg/m2 administered 1 hour after doxorubicin50 mg/m2 and cyclophosphamide 500 mg/m2 every3 weeks for 6 cycles ( 2.1)
NSCLC: after platinum therapy failure: 75 mg/m2 singleagent ( 2.2)
NSCLC: chemotherapy-naive: 75 mg/m2 followed by cisplatin75 mg/m2 ( 2.2)
HRPC: 75 mg/m2 with 5 mg prednisone twice a day continuously( 2.3)
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 cisplatininfusion ( 2.4)
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 cisplatininfusion; for 4 cycles ( 2.5)
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 ( 2.5)
Premedication Regimen ( 2.6)
Oral corticosteroids such as dexamethasone 16 mg per day (e.g., 8 mg twice a day) for 3 days starting1 day before administration
HRPC: oral dexamethasone 8 mg, at 12, 3, and 1 hrs before treatment
Dosage adjustments during treatment seefull prescribing information ( 2.7)
DOSAGE FORMS AND STRENGTHS
Single dose vial 80 mg/2 mL and diluent, 20 mg/0.5 mL and diluent( 3)
CONTRAINDICATIONS
Hypersensitivity to Taxotere or polysorbate 80 ( 4)
Neutrophil counts of < 1500 cells/mm3 ( 4)
WARNINGS AND PRECAUTIONS
Acute myeloid leukemia ( 5.6)
Fetal harm can occur when administered to a pregnant woman. Women of childbearing potential should be advised not to become pregnantwhen taking TAXOTERE ( 5.7)
Asthenia ( 5.12)
ADVERSE REACTIONS
Most common adversereactions are infections, neutropenia, anemia, febrile neutropenia,hypersensitivity, thrombocytopenia, neuropathy, dysgeusia, dyspnea,constipation, anorexia, nail disorders, fluid retention, asthenia,pain, nausea, diarrhea, vomiting, mucositis, alopecia, skin reactions,myalgia ( 6)
Other adverse reactions, including serious adverse reactions havebeen reported ( 6)
To report SUSPECTED ADVERSE REACTIONS, contact sanofi-aventis U.S. LLC at1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
DRUG INTERACTIONS
Compounds that induce, inhibit, or are metabolized by P450-3A4( 7)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling
Revised: 07/2008
Back to Highlights and TabsFULL PRESCRIBING INFORMATION: CONTENTS*
*Sections or subsections omitted from the full prescribing information are not listed
WARNING
1. INDICATIONS AND USAGE
1.1 Breast Cancer
1.2 Non-Small Cell Lung Cancer
1.3 Prostate Cancer
1.4 Gastric Adenocarcinoma
1.5 Head and Neck Cancer
2. DOSAGE AND ADMINISTRATION
2.1 Breast Cancer
2.2 Non-Small Cell Lung Cancer
2.3 Prostate cancer
2.4 Gastric adenocarcinoma
2.5 Head and Neck Cancer
2.6 Premedication Regimen
2.7 Dosage Adjustments During Treatment
2.8 Administration Precautions
2.9 Preparation and Administration
2.10Stability
3. DOSAGE FORMS AND STRENGTHS
4. CONTRAINDICATIONS
5. WARNINGS AND PRECAUTIONS
5.1 Toxic Deaths
5.2 Premedication Regimen
5.3 Hypersensitivity Reactions
5.4 Hematologic Effects
5.5 Hepatic Impairment
5.6 Acute Myeloid Leukemia
5.7 Pregnancy
5.8 General
5.9 Cutaneous
5.10Fluid Retention
5.11Neurologic
5.12Asthenia
6. ADVERSE REACTIONS
6.1 Clinical Trial Experience
6.2 Post-marketing Experiences
7. DRUG INTERACTIONS
8. USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Hepatic Impairment
10. OVERDOSAGE
11. DESCRIPTION
12. CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.3 Human Pharmacokinetics
13. NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14. CLINICAL STUDIES
14.1Breast Cancer
14.2Adjuvant Treatment of Breast Cancer
14.3Non-Small Cell Lung Cancer (NSCLC)
14.4 Prostate Cancer
14.5 Gastric Adenocarcinoma
14.6Head and Neck Cancer
15. REFERENCES
16. HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
16.2Storage
16.3Handling and Disposal
17. PATIENT COUNSELING INFORMATION
*Sections or subsections omitted from the full prescribing information are not listed
FULL PRESCRIBING INFORMATION

WARNING

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

TAXOTERE should generally notbe given to patients with bilirubin > upper limit of normal (ULN),or to patients with SGOT and/or SGPT >1.5 × ULN concomitant withalkaline phosphatase >2.5 × ULN. Patients with elevations ofbilirubin or abnormalities of transaminase concurrent with alkalinephosphatase 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 elevationsof transaminase >1.5 × ULN also had a higher rate of febrileneutropenia grade 4 but did not have an increased incidence of toxicdeath. Bilirubin, SGOT or SGPT, and alkaline phosphatase values shouldbe obtained prior to each cycle of TAXOTERE therapy and reviewed bythe treating physician.

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

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

Severe fluid retention occurred in 6.5% (6/92) of patients despiteuse of a 3-day dexamethasone premedication regimen. It was characterizedby one or more of the following events: poorly tolerated peripheraledema, 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)].

1. INDICATIONS AND USAGE

1.1 Breast Cancer

TAXOTERE is indicated for the treatment of patients with locallyadvanced or metastatic breast cancer after failure of prior chemotherapy.
TAXOTERE in combination with doxorubicin and cyclophosphamideis indicated for the adjuvant treatment of patients with operablenode-positive breast cancer.

1.2 Non-Small Cell Lung Cancer

TAXOTERE as a single agent is indicated for the treatment ofpatients with locally advanced or metastatic non-small cell lung cancerafter failure of prior platinum-based chemotherapy.
TAXOTERE in combination with cisplatin is indicated for thetreatment of patients with unresectable, locally advanced or metastaticnon-small cell lung cancer who have not previously received chemotherapyfor this condition.

1.3 Prostate Cancer

TAXOTERE in combination with prednisone is indicated for thetreatment of patients with androgen independent (hormone refractory)metastatic prostate cancer.

1.4 Gastric Adenocarcinoma

TAXOTERE in combination with cisplatin and fluorouracil is indicatedfor the treatment of patients with advanced gastric adenocarcinoma,including adenocarcinoma of the gastroesophageal junction, who havenot received prior chemotherapy for advanced disease.

1.5 Head and Neck Cancer

TAXOTERE in combination with cisplatinand fluorouracil is indicated for the induction treatment of patientswith locally advanced squamous cell carcinoma of the head and neck(SCCHN).

2. DOSAGE AND ADMINISTRATION

TAXOTERE (docetaxel) InjectionConcentrate should be administered under the supervision of a qualifiedphysician experienced in the use of antineoplastic agents. Appropriatemanagement of complications is possible only when adequate diagnosticand 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 administered1-hour after doxorubicin 50 mg/m2 and cyclophosphamide500 mg/m2 every 3 weeks for 6 courses. Prophylactic G-CSFmay be used to mitigate the risk of hematological toxicities [see Dosage AdjustmentsDuring Treatment (2.7)].

2.2 Non-Small Cell Lung Cancer

For treatment after failure of prior platinum-based chemotherapy,TAXOTERE was eva luated as monotherapy, and the recommended dose is75 mg/m2 administered intravenously over 1 hour every 3weeks. A dose of 100 mg/m2 in patients previously treatedwith chemotherapy was associated with increased hematologic toxicity,infection, and treatment-related mortality in randomized, controlledtrials [see Boxed Warning, Dosage AdjustmentsDuring Treatment (2.7), Warnings andPrecautions (5), Clinical Studies(14)].
For chemotherapy-naïve patients, TAXOTERE was eva luatedin combination with cisplatin. The recommended dose of TAXOTERE is75 mg/m2 administered intravenously over 1 hour immediatelyfollowed by cisplatin 75 mg/m2 over 30–60 minutesevery 3 weeks [see Dosage Adjustments During Treatment (2.7)].

2.3 Prostate cancer

For hormone-refractory metastatic prostate cancer, the recommendeddose of TAXOTERE is 75 mg/m2 every 3 weeks as a 1 hourintravenous infusion. Prednisone 5 mg orally twice daily is administeredcontinuously [see Dosage Adjustments During Treatment (2.7)].

2.4 Gastric adenocarcinoma

For gastric adenocarcinoma, the recommended dose of TAXOTEREis 75 mg/m2 as a 1 hour intravenous infusion, followedby 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 5days, starting at the end of the cisplatin infusion. Treatment isrepeated every three weeks. Patients must receive premedication withantiemetics and appropriate hydration for cisplatin administration [see Dosage AdjustmentsDuring 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. Allpatients treated on the TAXOTERE containing arms of the TAX323 andTAX324 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 hourintravenous infusion followed by cisplatin 75 mg/m2 intravenouslyover 1 hour, on day one, followed by fluorouracil as a continuousintravenous infusion at 750 mg/m2 per day for five days. This regimen is administered every 3 weeks for 4 cycles. Followingchemotherapy, patients should receive radiotherapy. [see Dosage AdjustmentsDuring Treatment (2.7)].

Induction chemotherapy followed by chemoradiotherapy (TAX324)
For the induction treatment of patientswith locally advanced (unresectable, low surgical cure, or organ preservation)SCCHN, the recommended dose of TAXOTERE is 75 mg/m2 asa 1 hour intravenous infusion on day 1, followed by cisplatin 100mg/m2 administered as a 30-minute to 3 hour infusion, followedby fluorouracil 1000 mg/m2/day as a continuous infusionfrom day 1 to day 4. This regimen is administered every 3 weeks for3 cycles. Following chemotherapy, patients should receive chemoradiotherapy [see Dosage AdjustmentsDuring Treatment (2.7)].

2.6 Premedication Regimen

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 administrationin order to reduce the incidence and severity of fluid retention aswell as the severity of hypersensitivity reactions [see Boxed Warning, Warnings and Precautions (5)].
For hormone-refractory metastatic prostate cancer, given theconcurrent use of prednisone, the recommended premedication regimenis oral dexamethasone 8 mg, at 12 hours, 3 hours and 1 hour beforethe TAXOTERE infusion [see Warnings and Precautions (5)].

2.7 Dosage Adjustments During Treatment

Breast Cancer

Patientswho are dosed initially at 100 mg/m2 and who experienceeither febrile neutropenia, neutrophils <500 cells/mm3 for more than 1 week, or severe or cumulative cutaneous reactionsduring TAXOTERE therapy should have the dosage adjusted from 100 mg/m2 to 75 mg/m2. If the patient continues to experiencethese 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 <500cells/mm3 for more than 1 week, severe or cumulative cutaneousreactions, or severe peripheral neuropathy during TAXOTERE therapymay tolerate higher doses. Patients who develop ≥grade 3 peripheralneuropathy should have TAXOTERE treatment discontinued entirely.

Combination Therapy with TAXOTERE in the Adjuvant Treatmentof Breast Cancer

TAXOTEREin combination with doxorubicin and cyclophosphamide should be administeredwhen the neutrophil count is ≥1,500 cells/mm3. Patients who experience febrile neutropenia should receive G-CSF inall subsequent cycles. Patients who continue to experience this reactionshould remain on G-CSF and have their TAXOTERE dose reduced to 60mg/m2. Patients who experience Grade 3 or 4 stomatitisshould have their TAXOTERE dose decreased to 60 mg/m2.Patients who experience severe or cumulative cutaneous reactions ormoderate neurosensory signs and/or symptoms during TAXOTERE therapyshould have their dosage of TAXOTERE reduced from 75 to 60 mg/m2. If the patient continues to experience these reactionsat 60 mg/m2, treatment should be discontinued.

Non-Small Cell Lung Cancer

Monotherapy with TAXOTERE for NSCLC treatmentafter failure of prior platinum-based chemotherapy

Patientswho are dosed initially at 75 mg/m2 and who experienceeither 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 treatmentshould have treatment withheld until resolution of the toxicity andthen resumed at 55 mg/m2. Patients who develop ≥grade3 peripheral neuropathy should have TAXOTERE treatment discontinuedentirely.

Combination therapy with TAXOTERE for chemotherapy-naïveNSCLC

For patientswho are dosed initially at TAXOTERE 75 mg/m2 in combinationwith cisplatin, and whose nadir of platelet count during the previouscourse of therapy is <25,000 cells/mm3, in patientswho experience febrile neutropenia, and in patients with serious non-hematologictoxicities, the TAXOTERE dosage in subsequent cycles should be reducedto 65 mg/m2. In patients who require a further dose reduction,a dose of 50 mg/m2 is recommended. For cisplatin dosageadjustments, see manufacturers' prescribing information.