DOCEFREZ description, usages, side effects, indications, overdosage, supplying and lots more!

DOCEFREZ

Sun Pharma Global FZE

  • Description
  • Clinical Pharmacology
  • Indications & Usage
  • Contraindications
  • Warnings
  • Precautions
  • Side Effects
  • Overdosage
  • Dosage & Administration
  • How Supplied
  • Patient Counseling Information
  • Supplemental Patient Material
  • Boxed Warning
  • Patient Package Insert
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use DOCEFREZ safely and effectively. See full prescribing information for DOCEFREZ. DOCEFREZ (docetaxel) for Injection, Intravenous InfusionInitial U.S. Approval: 1996

RECENT MAJOR CHANGES

  • Dosage and administration (2.9) 07/2012

BOXED WARNING


WARNING: TOXIC DEATHS, HEPATOTOXICITY, NEUTROPENIA, HYPERSENSITIVITY REACTIONS, and FLUID RETENTION
See full prescribing information for complete boxed warning
  • Treatment-related mortality increases with abnormal liver function, at higher doses, and in patients with NSCLC and prior platinum-based therapy receiving docetaxel at 100 mg/m2 (5.1)
  • Should not be given if bilirubin > ULN, or if AST and/or ALT > 1.5 x ULN concomitant with alkaline phosphatase > 2.5 x 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 DOCEFREZ and administration of appropriate therapy (5.4)
  • Contraindicated if history of severe hypersensitivity reactions to docetaxel or to drugs formulated with polysorbate 80 (4)
  • Severe fluid retention may occur despite dexamethasone (5.5)

INDICATIONS AND USAGE

  • Breast Cancer (BC): single agent for locally advanced or metastatic BC after chemotherapy failure (1.1)
  • Non-Small Cell Lung Cancer (NSCLC): single agent for locally advanced or metastatic NSCLC after platinum therapy failure (1.2)
  • Hormone Refractory Prostate Cancer (HRPC): with prednisone in androgen independent (hormone refractory) metastatic prostate cancer (1.3)

DOSAGE AND ADMINISTRATION

  • BC locally advanced or metastatic: 60 mg/m2 to 100 mg/m2 single agent (2.1)
  • NSCLC: after platinum therapy failure: 75 mg/m2 single agent (2.2)
  • HRPC: 75 mg/m2 with 5 mg prednisone twice a day continuously (2.3)
For all patients:
  • Premedicate with oral corticosteroids (2.6)
  • Adjust dose as needed (2.7)

DOSAGE FORMS AND STRENGTHS

  • Single use vial 80 mg docetaxel and Diluent for 80 mg (3)
  • Single use vial 20 mg docetaxel and Diluent for 20 mg (3)

CONTRAINDICATIONS

  • Hypersensitivity to docetaxel or polysorbate 80 (4)
  • Neutrophil counts of < 1500 cells/mm3 (4)

WARNINGS AND PRECAUTIONS

  • Acute myeloid leukemia: In patients who received docetaxel, doxorubicin and cyclophosphamide, monitor for delayed myelodysplasia or myeloid leukemia (5.6)
  • Cutaneous reactions:  Reactions including erythema of the extremities with edema followed by desquamation may occur. Severe skin toxicity may require dose adjustment (5.7)
  • Neurologic reactions: Reactions including. paresthesia, dysesthesia, and pain may occur.  Severe neurosensory symptoms require dose adjustment or discontinuation if persistent. (5.8)
  • Asthenia: Severe asthenia may occur and may require treatment discontinuation. (5.9)
  • Pregnancy: Fetal harm can occur when administered to a pregnant woman. Women of childbearing potential should be advised not to become pregnant when receiving DOCEFREZ (5.10, 8.1)

Side Effects

6

To report SUSPECTED ADVERSE REACTIONS, contact Caraco Pharmaceutical Laboratories, Ltd. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

DRUG INTERACTIONS

  • Cytochrome P450 3A4 inducers, inhibitors, or substrates: May alter docetaxel metabolism. (7)

FULL PRESCRIBING INFORMATION: CONTENTS*




FULL PRESCRIBING INFORMATION

WARNING: TOXIC DEATHS, HEPATOTOXICITY, NEUTROPENIA, HYPERSENSITIVITY REACTIONS, and FLUID RETENTION


The incidence of treatment-related mortality associated with docetaxel 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 docetaxel as a single agent at a dose of 100 mg/m2   [see Warnings and Precautions (5.1)].

DOCEFREZ should not be given to patients with bilirubin > upper limit of normal (ULN), or to patients with AST and/or ALT >1.5 x ULN concomitant with alkaline phosphatase >2.5 x 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 x ULN also had a higher rate of febrile neutropenia grade 4 but did not have an increased incidence of toxic death. Bilirubin, AST or ALT, and alkaline phosphatase values should be obtained prior to each cycle of DOCEFREZ therapy [see Warnings and Precautions (5.2)].
 
DOCEFREZ 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 DOCEFREZ [see Warnings and Precautions (5.3)].
 
Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension and/or bronchospasm, or very rarely fatal anaphylaxis, have been reported in patients who received a 3-day dexamethasone premedication. Hypersensitivity reactions require immediate discontinuation of the DOCEFREZ infusion and administration of appropriate therapy [see Warnings and Precautions (5.4)]. DOCEFREZ must not be given to patients who have a history of severe hypersensitivity reactions to docetaxel 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 (5.5)].

1 INDICATIONS AND USAGE

1.1 Breast Cancer


1.2 Non-Small Cell Lung Cancer


1.3 Prostate Cancer


2 DOSAGE AND ADMINISTRATION


[see Dosage and Administration (2.7)].

2.1 Breast Cancer

  • For locally advanced or metastatic breast cancer after failure of prior chemotherapy, the recommended dose of DOCEFREZ is 60 mg/mto 100 mg/madministered intravenously over 1 hour every 3 weeks.

2.2 Non-Small Cell Lung Cancer

  • For treatment after failure of prior platinum-based chemotherapy, docetaxel 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/min patients previously treated with chemotherapy was associated with increased hematologic toxicity, infection, and treatment-related mortality in randomized, controlled trials [see Boxed Warning, Dosage and Administration (2.7), Warnings and Precautions (5), Clinical Studies (14)].

2.3 Prostate Cancer

  • For hormone-refractory metastatic prostate cancer, the recommended dose of DOCEFREZ is 75 mg/mevery 3 weeks as a 1 hour intravenous infusion. Prednisone 5 mg orally twice daily is administered continuously [see Dosage and Administration (2.7)].

2.6 Premedication Regimen


[see Boxed Warning, Warnings and Precautions (5.4)]. 2

[see Warnings and Precautions (5.4)]

2.7 Dosage Adjustments During Treatment


Breast Cancer

3 2 22 2 3

Non-Small Cell Lung Cancer

Monotherapy with DOCEFREZ for NSCLC treatment after failure of prior platinum-based chemotherapy


23 2

Prostate Cancer

Combination therapy with DOCEFREZ  for hormone-refractory metastatic prostate cancer


33



[see Drug Interactions (7), Clinical Pharmacology (12.3)]

2.8 Administration Precautions


. [see How Supplied/ Storage and Handling (16.3)].





DOCEFREZ (Lyophilized Powder for Injection and Diluent)





Table 1- Reconstitution of DOCEFREZ (docetaxel) for Injection
Product Fill Range of the Diluent (35.4% w/w ethanol in polysorbate 80) Volume of Diluent to be added for the reconstitution Concentration of the reconstituted solution
Docetaxel 20 mg vial
1.10 – 1.15 mL
1 mL
20 mg/0.8 mL
Docetaxel 80 mg vial
4.13 – 4.29 mL
4 mL
24 mg/mL

2.9 Preparation and Administration


DOCEFREZ (Lyophilized Powder for Injection and Diluent)
  • DOCEFREZ vials should be stored between 2°C and 8°C (36°F and 46°F). Allow the appropriate number of vials of DOCEFREZ (docetaxel) for Injection and diluent (35.4% ethanol in polysorbate 80) vials to stand at room temperature for approximately 5 minutes.
  • a) For DOCEFREZ 20: Use 1 mL syringe with needle of 18- to 21-gauge, 1½-inch for withdrawing diluent for DOCEFREZ 20.
    b) For DOCEFREZ 80: Use 4 mL syringe with needle of 18- to 21-gauge, 1½-inch for withdrawing diluent for DOCEFREZ 80.
  • a) For DOCEFREZ 20: Aseptically withdraw 1 mL from the diluent vial into a syringe by partially inverting the vial, and transfer it to product vial of DOCEFREZ (docetaxel) for Injection.
    b) For DOCEFREZ 80:  Aseptically withdraw 4 mL from the diluent vial into a syringe by partially inverting the vial, and transfer it to product vial of DOCEFREZ (docetaxel) for Injection.
  • Shake the reconstituted vial well in order to completely dissolve the docetaxel powder present in the vial. For the 20 mg vial, the resultant concentration is 20 mg/0.8 mL. For the 80 mg vial, the resultant concentration is 24 mg/mL.




  • Aseptically withdraw the required amount of reconstituted DOCEFREZ solution 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 DOCEFREZ is required, use a larger volume of the infusion vehicle so that a concentration of 0.74 mg/mL docetaxel is not exceeded.
  • Thoroughly mix the infusion by manual rotation.
  • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If the DOCEFREZ reconstituted solution or infusion solution is not clear or appears to have precipitation, these should be discarded.

The final DOCEFREZ infusion solution should be administered intravenously as a 1-hour infusion under ambient room temperature and lighting conditions.

2.10 Stability


3 DOSAGE FORMS AND STRENGTHS


DOCEFREZ (Lyophilized Powder for Injection and Diluent)

DOCEFREZ 80 mg



 
DOCEFREZ 20 mg

4 CONTRAINDICATIONS

  • DOCEFREZ is contraindicated in patients who have 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 (5.4)]. 
  • DOCEFREZ should not be used in patients with neutrophil counts of <1500 cells/mm3.

5 WARNINGS AND PRECAUTIONS

5.1 Toxic Deaths


Breast Cancer

2 2

Non-Small Cell Lung Cancer

222[see Dosage and Administration (2.2), Clinical Studies (14)].

5.2 Hepatic Impairment


[see Boxed Warning, Use in Specific Populations (8.6), Clinical studies (14)].

5.3 Hematologic Effects


33

3[see Dosage and Administration (2.7)].

3223223

22[see Adverse Reactions (6.1), Clinical Studies (14)].

[see Dosage and Administration (2.7), Adverse Reactions (6)]

5.4 Hypersensitivity Reactions




[see Dosage and Administration (2.6)].

5.5 Fluid Retention


[see Dosage and Administration (2.6)]



22

e.g

5.6 Acute Myeloid Leukemia


5.7 Cutaneous Reactions


[see Dosage and Administration (2.7)]

5.8 Neurologic Reactions


e.g[see Dosage and Administration (2.7)].

5.9 Asthenia


5.10 Use in Pregnancy




[see Use in Specific Populations (8.1)]

6 ADVERSE REACTIONS


  • Toxic Deaths [see Boxed Warning, Warnings and Precautions (5.1)]
  • Hepatotoxicity [see Boxed Warning, Warnings and Precautions (5.2)]
  • Neutropenia [see Boxed Warning, Warnings and Precautions (5.3)]
  • Hypersensitivity [see Boxed Warning, Warnings and Precautions (5.4)]
  • Fluid Retention [see Boxed Warning, Warnings and Precautions (5.5)]




6.1 Clinical Trials Experience


Breast Cancer

Monotherapy with docetaxel for locally advanced or metastatic breast cancer after failure of prior chemotherapy


2
Table 2 - Summary of Adverse Reactions in Patients Receiving Docetaxel at 100 mg/m2
Adverse Reaction All Tumor Types Normal LFTsNormal Baseline LFTs: Transaminases ≤1.5 times ULN or alkaline phosphatase ≤ 2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN
n=2045
%
All Tumor Types Elevated LFTsElevated Baseline LFTs: AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase > 2.5 times ULN
n=61
%
Breast Cancer Normal LFTsNormal Baseline LFTs: Transaminases ≤1.5 times ULN or alkaline phosphatase ≤ 2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN
n=965
%
Hematologic
Neutropenia
<2000 cells/mm3
96
96
99
<500 cells/mm3
75
88
86
Leukopenia
<4000 cells/mm3
96
98
99
<1000 cells/mm3
32
47
44
Thrombocytopenia
<100,000 cells/mm3
8
25
9
Anemia
<11 g/dL
90
92
94
<8 g/dL
9
31
8
Febrile NeutropeniaFebrile Neutropenia: ANC grade 4 with fever >38oC with intravenous antibiotics and/or hospitalization
11
26
12
Septic Death
2
5
1
Non-Septic Death
1
7
1
Infections
Any
22
33
22
Severe
6
16
6
Fever in Absence of Infection
Any
31
41
35
Severe
2
8
2
Hypersensitivity Reactions
Regardless of Premedication
Any
21
20
18
Severe
4
10
3
With 3-day Premedication
n=92
n=3
n=92
Any
15
33
15
Severe
2
0
2
Fluid Retention
Regardless of Premedication
Any
47
39
60
Severe
7
8
9
With 3-day Premedication
n=92
n=3
n=92
Any
64
67
64
Severe
7
33
7
Neurosensory
Any
49
34
58
Severe
4
0
6
Cutaneous
Any
48
54
47
Severe
5
10
5
Nail Changes
Any
31
23
41
Severe
3
5
4
Gastrointestinal
Nausea
39
38
42
Vomiting
22
23
23
Diarrhea
39
33
43
Severe
5
5
6
Stomatitis
Any
42
49
52
Severe
6
13
7
Alopecia
76
62
74
Asthenia
Any
62
53
66
Severe
13
25
15
Myalgia
Any
19
16
21
Severe
2
2
2
Arthralgia
9
7
8
Infusion Site Reactions
4
3
4
Hematologic Reactions

[see Warnings and Precautions (5.3)]. 3

3



3

Hypersensitivity Reactions

[see Boxed Warning, Warnings and Precautions (5.4)]

Fluid Retention

[see Boxed Warning, Dosage and Administration (2.6), Warnings and Precautions (5.5)]

Cutaneous Reactions

[see Warnings and Precautions (5.7)].



Neurologic Reactions

[ see Warnings and Precautions (5.8)].

Gastrointestinal Reactions





Cardiovascular Reactions

2

Infusion Site Reactions



Hepatic Reactions



Hematologic and Other Toxicity: Relation to dose and baseline liver chemistry abnormalities

22

Table 3 - Hematologic Adverse Reactions in Breast Cancer Patients Previously Treated with Chemotherapy Treated at Docetaxel 100 mg/m2 with Normal or Elevated Liver Function Tests or 60 mg/m2 with Normal Liver Function Tests
Adverse Reaction Docetaxel 100 mg/m2 Docetaxel 60 mg/m2
Normal LFTsNormal Baseline LFTs: Transaminases ≤ 1.5 times ULN or alkaline phosphatase ≤ 2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN
n=730
%
Elevated LFTsElevated Baseline LFTs: AST and/or ALT > 1.5 times ULN concurrent with alkaline phosphatase > 2.5 times ULN
n=18
%
Normal LFTsNormal Baseline LFTs: Transaminases ≤ 1.5 times ULN or alkaline phosphatase ≤ 2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN
n=174
%
Neutropenia
Any <2000 cells/mm3
98
100
95
Grade 4 <500 cells/mm3
84
94
75
Thrombocytopenia
Any <100,000 cells/mm3
11
44
14
Grade 4 <20,000 cells/mm3
1
17
1
Anemia <11 g/dL
95
94
65
Infection Incidence of infection requiring hospitalization and/or intravenous antibiotics was 8.5% (n=62) among the 730 patients with normal LFTs at baseline; 7 patients had concurrent grade 3 neutropenia, and 46 patients had grade 4 neutropenia.
Any
23
39
1
Grade 3 and 4
7
33
0
Febrile Neutropenia Febrile Neutropenia: For 100 mg/m2, ANC grade 4 and fever > 38°C with intravenous antibiotics and/or hospitalization; for 60 mg/m2, ANC grade 3/4 and fever > 38.1°C
By Patient
12
33
0
By Course
2
9
0
Septic Death
2
6
1
Non-Septic Death
1
11
0

Table 4 - Non-Hematologic Adverse Reactions in Breast Cancer Patients Previously Treated with Chemotherapy Treated at Docetaxel 100 mg/m2 with Normal or Elevated Liver Function Tests or 60 mg/m2 with Normal Liver Function Tests
Adverse Reaction Docetaxel 100 mg/m2 Docetaxel 60 mg/m2
Normal LFTsNormal Baseline LFTs: Transaminases ≤ 1.5 times ULN or alkaline phosphatase ≤ 2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN
n=730
%
Elevated LFTsElevated Baseline Liver Function: AST and/or ALT > 1.5 times ULN concurrent with alkaline phosphatase > 2.5 times ULN
n=18
%
Normal LFTsNormal Baseline LFTs: Transaminases ≤ 1.5 times ULN or alkaline phosphatase ≤ 2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN
n=174
%
NA = not available
Acute Hypersensitivity Reaction
Regardless of Premedication
Any
13
6
1
Severe
1
0
0
Fluid RetentionFluid Retention includes (by COSTART): edema (peripheral, localized, generalized, lymphedema, pulmonary edema, and edema otherwise not specified) and effusion (pleural, pericardial, and ascites); no premedication given with the 60 mg/m2 dose
Regardless of Premedication
Any
56
61
13
Severe
8
17
0
Neurosensory
Any
57
50
20
Severe
6
0
0
Myalgia
23
33
3
Cutaneous
Any
45
61
31
Severe
5
17
0
Asthenia
Any
65
44
66
Severe
17
22
0
Diarrhea
Any
42
28
NA
Severe
6
11
Stomatitis
Any
53
67
19
Severe
8
39
1
222222222222

222

Lung Cancer

Monotherapy with docetaxel for unresectable, locally advanced or metastatic NSCLC previously treated with platinum-based chemotherapy

2

Table 5- Treatment Emergent Adverse Reactions Regardless of Relationship to Treatment in Patients Receiving Docetaxel as Monotherapy for Non-Small Cell Lung Cancer Previously Treated with Platinum-Based ChemotherapyNormal Baseline LFTs: Transaminases ≤ 1.5 times ULN or alkaline phosphatase ≤ 2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN
Adverse Reaction Docetaxel 75 mg/m2
n=176
%
Best Supportive Care
n=49
%
Vinorelbine/Ifosfamide
n=119
%
Neutropenia
Any
84
14
83
Grade 3/4
65
12
57
Leukopenia
Any
84
6
89
Grade 3/4
49
0
43
Thrombocytopenia
Any
8
0
8
Grade 3/4
3
0
2
Anemia
Any
91
55
91
Grade 3/4
9
12
14
Febrile NeutropeniaFebrile Neutropenia: ANC grade 4 with fever >38°C with intravenous antibiotics and/or hospitalization
6
NANot Applicable
1
Infection
Any
34
29
30
Grade 3/4
10
6
9
Treatment Related Mortality
3
NANot Applicable
3
Hypersensitivity Reactions
Any
6
0
1
Grade 3/4
3
0
0
Fluid Retention
Any
34
NDNot Done
23
Severe
3
3
Neurosensory
Any
23
14
29
Grade 3/4
2
6
5
Neuromotor
Any
16
8
10
Grade 3/4
5
6
3
Skin
Any
20
6
17
Grade 3/4
1
2
1
Gastrointestinal
Nausea
Any
34
31
31
Grade 3/4
5
4
8
Vomiting
Any
22
27
22
Grade 3/4
3
2
6
Diarrhea
Any
23
6
12
Grade 3/4
3
0
4
Alopecia
56
35
50
Asthenia
Any
53
57
54
SevereCOSTART term and grading system
18
39
23
Stomatitis
Any
26
6
8
Grade 3/4
2
0
1
Pulmonary
Any
41
49
45
Grade 3/4
21
29
19
Nail Disorder
Any
11
0
2
SevereCOSTART term and grading system
1
0
0
Myalgia
Any
6
0
3
SevereCOSTART term and grading system
0
0
0
Arthralgia
Any
3
2
2
SevereCOSTART term and grading system
0
0
1
Taste Perversion
Any
6
0
0
SevereCOSTART term and grading system
1
0
0
Prostate Cancer

Combination therapy with docetaxel in patients with prostate cancer


Table 6- Clinically Important Treatment Emergent Adverse Reactions (Regardless of Relationship) in Patients with Prostate Cancer who Received Docetaxel in Combination with Prednisone (TAX327)
Docetaxel 75 mg/m2 every 3 weeks +
prednisone 5 mg twice daily
n=332
%
Mitoxantrone 12 mg/m2 every 3 weeks +
prednisone 5 mg twice daily
n=335
%
Adverse Reaction Any Grade 3/4 Any Grade 3/4
Anemia
67
5
58
2
Neutropenia
41
32
48
22
Thrombocytopenia
3
1
8
1
Febrile neutropenia
3
N/A
2
N/A
Infection
32
6
20
4
Epistaxis
6
0
2
0
Allergic Reactions
8
1
1
0
Fluid RetentionRelated to treatment
Weight GainRelated to treatment
Peripheral EdemaRelated to treatment
24
8
18
1
0
0
5
3
2
0
0
0
Neuropathy Sensory
30
2
7
0
Neuropathy Motor
7
2
3
1
Rash/Desquamation
6
0
3
1
Alopecia
65
N/A
13
N/A
Nail Changes
30
0
8
0
Nausea
41
3
36
2
Diarrhea
32
2
10
1
Stomatitis/Pharyngitis
20
1
8
0
Taste Disturbance
18
0
7
0
Vomiting
17
2
14
2
Anorexia
17
1
14
0
Cough
12
0
8
0
Dyspnea
15
3
9
1
Cardiac left ventricular function
10
0
22
1
Fatigue
53
5
35
5
Myalgia
15
0
13
1
Tearing
10
1
2
0
Arthralgia
8
1
5
1

6.2 Post-marketing Experiences




Body as a whole

Cardiovascular

Cutaneous

Gastrointestinal

Hematologic

Hypersensitivity

Hepatic

Neurologic

Ophthalmologic

Hearing

Respiratory

Renal

7 DRUG INTERACTIONS


In vitro

In vivo[see Dosage and Administration (2.7) and Clinical Pharmacology (12.3)]

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy


[see ‘Warnings and Precautions’ section]



2

8.3 Nursing Mothers


8.4 Pediatric Use


8.5 Geriatric Use




Prostate Cancer

8.6 Hepatic Impairment


[see Boxed Warning, Warnings and Precautions (5.2), Clinical Pharmacology (12.3)].

10 OVERDOSAGE




22

22222

11 DESCRIPTION


tert
11 DESCRIPTION435314

DOCEFREZ (Lyophilized Powder for Injection and Diluent)



12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.3 Pharmacokinetics


Absorption:22222

Distribution:In vitro1in vitro

Metabolism:In vitro[see Drug Interactions (7)]

Elimination:14tert

Effect of Age:2

Effect of Gender:

Hepatic Impairment:[see Warnings and Precautions (5.2) and Use in Specific Populations (8.6)].

Effect of Race:222

Effect of Ketoconazole[see Dosage and Administration (2.7) and Drug-Drug Interactions (7)]

Effect of Combination Therapies:

Dexamethasone

Prednisone

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility




in vitro1in vivothth2

th2rdth2

14 CLINICAL STUDIES

14.1 Locally Advanced or Metastatic Breast Cancer




Randomized Trials


222
Table 7- Efficacy of Docetaxel in the Treatment of Breast Cancer Patients Previously Treated with an Anthracycline-Containing Regimen (Intent-to-Treat Analysis)
Efficacy Parameter
Docetaxel
(n=203)
Mitomycin/
Vinblastine
(n=189)
p-value
Median Survival
11.4 months
8.7 months
p=0.01
Log Rank
Risk RatioFor the risk ratio, a value less than 1.00 favors docetaxel., Mortality (Docetaxel: Control)
95% CI (Risk Ratio)
0.73
0.58-0.93
Median Time to Progression
4.3 months
2.5 months
p=0.01
Log Rank
Risk RatioFor the risk ratio, a value less than 1.00 favors docetaxel., Progression (Docetaxel: Control)
95% CI (Risk Ratio)
0.75
0.61-0.94
Overall Response Rate
Complete Response Rate
28.1%
3.4%
9.5%
1.6%
p<0.0001
Chi Square
22
Table 8- Efficacy of Docetaxel in the Treatment of Breast Cancer Patients Previously Treated with an Alkylating-Containing Regimen (Intent-to-Treat Analysis)
Efficacy Parameter Docetaxel (n=161) Doxorubicin (n=165) p-value
Median Survival
14.7 months
14.3 months
p=0.39
Log Rank
Risk RatioFor the risk ratio, a value less than 1.00 favors docetaxel., Mortality (Docetaxel: Control)
95% CI (Risk Ratio)
0.89
0.68-1.16
Median Time to Progression
6.5 months
5.3 months
p=0.45
Log Rank
Risk RatioFor the risk ratio, a value less than 1.00 favors docetaxel., Progression (Docetaxel: Control)
95% CI (Risk Ratio)
0.93
0.71-1.16
Overall Response Rate
Complete Response Rate
45.3%
6.8%
29.7%
4.2%
p=0.004
Chi Square
22222222

Single Arm Studies

2

22

14.3 Non-Small Cell Lung Cancer (NSCLC)




Monotherapy with Docetaxel for NSCLC Previously Treated with Platinum-Based Chemotherapy

22 Boxed Warning, Dosage and Administration (2.7), Warnings and Precautions (5.3)]

222
22222
Table 9- Efficacy of Docetaxel in the Treatment of Non-Small Cell Lung Cancer Patients Previously Treated with a Platinum-Based Chemotherapy Regimen (Intent-to-Treat Analysis)
  TAX317 TAX320
Docetaxel
75 mg/m2
n=55
Best Supportive Care
n=49
Docetaxel
75 mg/m2
n=125
Control
(V/IVinorelbine/Ifosfamide)
n=123
Overall Survival Log-rank Test
p=0.01
p=0.13
Risk Ratioa value less than 1.00 favors docetaxel., Mortality (Docetaxel: Control)
95% CI (Risk Ratio)
0.56
(0.35, 0.88)
0.82
(0.63, 1.06)
Median Survival
95% CI
7.5 monthsp≤0.05
(5.5, 12.8)
4.6 months
(3.7, 6.1)
5.7 months
(5.1, 7.1)
5.6 months
(4.4, 7.9)
% 1-year Survival
95% CI
37%p≤0.05 uncorrected for multiple comparisons
(24, 50)
12%
(2, 23)
30%p≤0.05 uncorrected for multiple comparisons
(22, 39)
20%
(13, 27)
Time to Progression
95% CI
12.3 weeksp≤0.05
(9.0, 18.3)
7.0 weeks
(6.0, 9.3)
8.3 weeks
(7.0, 11.7)
7.6 weeks
(6.7, 10.1)
Response Rate
95% CI
5.5%
(1.1, 15.1)
Not Applicable
5.7%
(2.3, 11.3)
0.8%
(0.0, 4.5)
2

Figure 1- TAX317 Survival K-M Curves - Docetaxel 75 mg/m2 vs. Best Supportive Care
14.3 Non-Small Cell Lung Cancer (NSCLC)

Figure 2 - TAX320 Survival K-M Curves – Docetaxel 75 mg/m2 vs. Vinorelbine or Ifosfamide Control
14.3 Non-Small Cell Lung Cancer (NSCLC)
2

14.4 Hormone Refractory Prostate Cancer


  • Docetaxel 75 mg/m2 every 3 weeks for 10 cycles.
  • Docetaxel 30 mg/m2 administered weekly for the first 5 weeks in a 6-week cycle for 5 cycles.
  • Mitoxantrone 12 mg/m2 every 3 weeks for 10 cycles.

Table 10- Efficacy of Docetaxel in the Treatment of Patients with Androgen Independent (Hormone Refractory) Metastatic Prostate Cancer (Intent-to-Treat Analysis)
  Docetaxel+Prednisone
every 3 weeks
Mitoxantrone+Prednisone
every 3 weeks
Number of patients
Median survival (months)
95% CI
Hazard ratio
95% CI
p-valueStratified log rank test. Threshold for statistical significance = 0.0175 because of 3 arms.
335
18.9
(17.0-21.2)
0.761
(0.619-0.936)
0.0094
337
16.5
(14.4-18.6)
--
--
--
Figure 3- TAX327 Survival K-M Curves
14.4 Hormone Refractory Prostate Cancer

15 REFERENCES

  • 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.
  • 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
  • American Society of Health-System Pharmacists. (2006) ASHP Guidelines on Handling Hazardous Drugs. Am J Health-Syst Pharm. 2006;63:1172-1193
  • 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.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied


DOCEFREZ (Lyophilized Powder for Injection and Diluent)







16.2 Storage


16.3 Handling and Disposal


[see References (15)]

17 PATIENT COUNSELING INFORMATION


See FDA-Approved Patient Labeling
  • DOCEFREZ may cause fetal harm. Advise patients to avoid becoming pregnant while receiving this drug. Women of childbearing potential should use effective contraceptives if receiving DOCEFREZ [see Warnings and Precautions (5.10) and Use in Specific Populations (8.1)].
  • Obtain detailed allergy and concomitant drug information from the patient prior to DOCEFREZ administration.
  • Explain the significance of oral corticosteroids such as dexamethasone administration to the patient to help facilitate compliance. Instruct patients to report if they were not compliant with oral corticosteroid regimen.
  • Instruct patients to immediately report signs of a hypersensitivity reaction.
  • Tell patients to watch for signs of fluid retention such as peripheral edema in the lower extremities, weight gain and dyspnea.
  • Explain the significance of routine blood cell counts. Instruct patients to monitor their temperature frequently and immediately report any occurrence of fever.
  • Instruct patients to report myalgia, cutaneous, or neurologic reactions.
  • Explain to patients that side effects such as nausea, vomiting, diarrhea, constipation, fatigue, excessive tearing, infusion site reactions, and hair loss are associated with docetaxel administration.

Patient Information


DOCEFREZ™ (‘dō-sə-‘frāz)
(docetaxel)
for Injection



What is the most important information I should know about DOCEFREZ?

DOCEFREZ can cause serious side effects, including death.
  • The chance of death in people who receive DOCEFREZ is higher if you:
    • have liver problems
    • receive high doses of DOCEFREZ
    • have non-small cell lung cancer and have been treated with chemotherapy medicines that contain platinum
  • DOCEFREZ can affect your blood cells.  Your doctor should do routine blood tests during treatment with DOCEFREZ. This will include regular checks of your white blood cell counts. If your white blood cells are too low, your doctor may not treat you with DOCEFREZ until you have enough white blood cells. People with low white blood counts can develop life-threatening infections. The earliest sign of infection may be fever. Follow your doctor’s instructions for how often to take your temperature while taking DOCEFREZ. Call your doctor right away if you have a fever.
  • Serious allergic reactions can happen in people who take DOCEFREZ. Serious allergic reactions are medical emergencies that can lead to death and must be treated right away. Tell your doctor right away if you have any of these signs of a serious allergic reaction:
    • trouble breathing
    • sudden swelling of your face, lips, tongue, throat, or trouble swallowing
    • hives (raised bumps), rash, or redness all over your body
  • Your body may hold too much fluid (severe fluid retention) during treatment with DOCEFREZ.  This can be life threatening. To decrease the chance of this happening, you must take another medicine, a corticosteroid, before each DOCEFREZ treatment. You must take the corticosteroid exactly as your doctor tells you. Tell your doctor or nurse before your DOCEFREZ treatment if you forget to take corticosteroid dose or do not take it as your doctor tells you.
What is DOCEFREZ?
 
DOCEFREZ
  • breast cancer
  • non-small cell lung cancer
  • prostate cancer


Who should not take DOCEFREZ?


  • have had a severe allergic reaction to:
    • docetaxel, the active ingredient in DOCEFREZ, or
    • any other medicines that contain polysorbate 80.  Ask your doctor or pharmacist if you are not sure.

See “What is the most important information I should know about DOCEFREZ?” for the signs and symptoms of a severe allergic reaction.

  • have a low white blood cell count.
What should I tell my doctor before receiving DOCEFREZ?

  • are allergic to any medicines. See “Who should not take DOCEFREZ?” Also, see the end of this leaflet for a list of the ingredients in DOCEFREZ.
  • have liver problems
  • have any other medical conditions
  • are pregnant or plan to become pregnant. DOCEFREZ can harm your unborn baby.
  • are breast-feeding or plan to breast-feed. It is not known if DOCEFREZ passes into your breast milk. You and your doctor should decide if you will take DOCEFREZ or breast-feed.




How will I receive
DOCEFREZ?
  • DOCEFREZ will be given to you as an intravenous injection into your vein, usually over 1 hour.
  • DOCEFREZ is usually given every 3 weeks.
  • Your doctor will decide how long you will receive treatment with DOCEFREZ
  • Your doctor will check your blood cell counts and other blood tests during your treatment with DOCEFREZ to check for side effects of DOCEFREZ.
  • Your doctor may stop your treatment, change the timing of your treatment, or change the dose of your treatment if you have certain side effects while taking DOCEFREZ.
What are the possible side effects of DOCEFREZ?

DOCEFREZ may cause serious side effects including death.
  • See “What is the most important information I should know about DOCEFREZ?”
  • Acute Myeloid Leukemia (AML), a type of blood cancer, can happen in people who take DOCEFREZ  along with certain other medicines. Tell your doctor about all the medicines you take.
  • Other Blood Disorders – Changes in blood counts due to leukemia and other blood disorders may occur years after treatment with Docefrez.
  • Skin Reactions including redness and swelling of your arms and legs with peeling of your skin.
  • Neurologic Symptoms including numbness, tingling, or burning in your hands and feet.
  • changes in your sense of taste
  • feeling short of breath
  • constipation
  • decreased appetite
  • changes in your fingernails or toenails
  • swelling of your hands, face or feet
  • feeling weak or tired
  • joint and muscle pain
  • nausea and vomiting
  • diarrhea
  • mouth or lips sores
  • hair loss
  • rash
  • redness of the eye, excess tearing
  • skin reactions at the site of DOCEFREZ administration such as increased skin pigmentation, redness, tenderness, swelling, warmth or dryness of the skin.
  • tissue damage if DOCEFREZ leaks out of the vein into the tissues






General information about DOCEFREZ




 
What are the ingredients in DOCEFREZ?



Every three-week injection of DOCEFREZ for breast, and non-small cell lung cancers
 
Take your oral corticosteroid medicine as your doctor tells you.
 
Oral corticosteroid dosing:
 
Day 1 Date:_________ Time:______AM _______PM
 
Day 2 Date:_________ Time:______AM _______PM
(DOCEFREZ Treatment Day)
 
Day 3 Date:_________ Time:______AM _______PM
 
 
Every three-week injection of DOCEFREZ for prostate cancer
 
Take your oral corticosteroid medicine as your doctor tells you.
 
Oral corticosteroid dosing:
 
Date:___________      Time:___________
 
Date:___________      Time:___________
(DOCEFREZ Treatment Day)
 
                                 Time:___________
 


Sun Pharmaceutical Ind. Ltd.




Caraco Pharmaceutical Laboratories, Ltd.




PACKAGE LABEL.PRINCIPAL DISPLAY PANEL-DOCEFREZ-20MG-LABEL


NDC 47335-285-40
DocefrezTM
(Docetaxel) for Injection
20 mg
For Intravenous Infusion Only
Each Docefrez for Injection vial contains a slight overfill to deliver 20 mg of Docetaxel per 0.8 mL after reconstitution
Rx ONLY
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL-DOCEFREZ-20MG-LABEL

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL-DOCEFREZ-20MG-CARTON



NDC 47335-285-41
DocefrezTM
(Docetaxel) for Injection
20 mg*
For Intravenous Infusion Only
*Each Docefrez for Injection vial contains a slight overfill to deliver 20 mg of Docetaxel per 0.8 mL after reconstitution
Each carton contains:
One vial of Docefrez (docetaxel) for Injection 20 mg
One vial of DILUENT for Docefrez 20 mg

Rx ONLY
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL-DOCEFREZ-20MG-CARTON

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL-DILUENT-20MG-LABEL


NDC 47335-287-40
DILUENT for DocefrezTM 20 mg
1.13 mL
Single Use Vial-Discard Unused Portion.
Rx ONLY
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL-DILUENT-20MG-LABEL

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL-DOCEFREZ-80MG-LABEL


NDC 47335-286-40
DocefrezTM
(Docetaxel) for Injection
80 mg
For Intravenous Infusion Only
Each Docefrez for Injection vial contains a slight overfill to deliver 80 mg of Docetaxel
(24 mg/mL after reconstitution)
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL-DOCEFREZ-80MG-LABEL

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL-DOCEFREZ-80MG-CARTON



NDC 47335-286-41
DocefrezTM
(Docetaxel) for Injection
80 mg*
For Intravenous Infusion Only
*Each Docefrez for Injection vial contains a slight overfill to deliver 80 mg of Docetaxel (24 mg/mL after reconstitution)
Each carton contains:
One vial of Docefrez (docetaxel) for Injection 80 mg
One vial of DILUENT for Docefrez 80 mg
Rx ONLY
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL-DOCEFREZ-80MG-CARTON

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL-DILUENT-80MG-LABEL


NDC 47335-288-40
DILUENT for DocefrezTM 80 mg
4.21 mL
Rx ONLY
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL-DILUENT-80MG-LABEL

DOCEFREZ

docetaxel anhydrous KIT

Product Information

Product Type Human prescription drug label Item Code (Source) NDC:47335-285
Route of Administration DEA Schedule

Packaging

# Item Code Package Description Marketing Start Date Marketing End Date
1 NDC:47335-285-41 1 in 1 CARTON

Marketing Information

Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA022534 2011-05-03


DOCEFREZ

docetaxel anhydrous KIT

Product Information

Product Type Human prescription drug label Item Code (Source) NDC:47335-286
Route of Administration DEA Schedule

Packaging

# Item Code Package Description Marketing Start Date Marketing End Date
1 NDC:47335-286-41 1 in 1 CARTON

Marketing Information

Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA022534 2011-05-03


PLEASE, BE CAREFUL!
Be sure to consult your doctor before taking any medication!
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