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FASLODEX(fulvestrant)injection
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HIGHLIGHTS OF PRESCRIBING INFORMATION |
These highlights do not include all the information needed to use FASLODEX® safely and effectively. See full prescribing information for FASLODEX.
FASLODEX® (fulvestrant) injection
INITIAL U.S. APPROVAL: 2002
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INDICATIONS AND USAGE
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FASLODEX is an estrogen receptor antagonist indicated for the:
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DOSAGE AND ADMINISTRATION
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FASLODEX 500 mg should be administered intramuscularly into the buttocks slowly (1 - 2 minutes per injection) as two 5 mL injections, one in each buttock, on days 1, 15, 29 and once monthly thereafter. (2.1, 14)
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A dose of 250 mg is recommended in patients with moderate hepatic impairment to be administered intramuscularly into the buttock slowly (1 - 2 minutes) as one 5 mL injection on days 1, 15, 29 and once monthly thereafter. (2.2, 5.2, 8.6)
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DOSAGE FORMS AND STRENGTHS
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FASLODEX, an injection for intramuscular administration, is supplied as 50 mg/mL fulvestrant. (3)
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CONTRAINDICATIONS
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WARNINGS AND PRECAUTIONS
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Blood Disorders: Should be used with caution in patients with bleeding diatheses, thrombocytopenia, or anticoagulant use. (5.1)
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Hepatic Impairment: A 250 mg dose is recommended in patients with moderate hepatic impairment (2.2, 5.2, 8.6)
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Pregnancy: Fetal harm can occur when administered to a pregnant woman. Women should be advised of the potential hazard to the fetus and to avoid becoming pregnant while receiving FASLODEX. (5.3)
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ADVERSE REACTIONS
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The most common, clinically significant adverse reactions occurring in ≥ 5% of patients receiving FASLODEX 500 mg were: injection site pain, nausea, bone pain, arthralgia, headache, back pain, fatigue, pain in extremity, hot flash, vomiting, anorexia, asthenia, musculoskeletal pain, cough, dyspnea, and constipation. (6.1)
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Increased hepatic enzymes (ALT, AST, ALP) occurred in >15% of FASLODEX patients and were not dose-dependent.
To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch for voluntary reporting of adverse reactions
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DRUG INTERACTIONS
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USE IN SPECIFIC POPULATIONS
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Nursing Mothers: discontinue drug or nursing taking into account the importance of drug to the mother. (8.3)
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Pediatric Patients: efficacy has not been demonstrated in girls with McCune-Albright Syndrome and progressive precocious puberty. (8.4)
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See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling |
Revised: 09/2011 |
Back to Highlights and Tabs
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FULL PRESCRIBING INFORMATION: CONTENTS* |
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1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dose
2.2 Dose Modification
2.3 Administration Technique
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Blood Disorders
5.2 Hepatic Impairment
5.3 Use in Pregnancy
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Post-Marketing Experience
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
8.7 Renal Impairment
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
FDA-APPROVED PATIENT LABELING
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
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FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
FASLODEX is indicated for the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy.
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dose
The recommended dose is 500 mg to be administered intramuscularly into the buttocks slowly (1 - 2 minutes per injection) as two 5 mL injections, one in each buttock, on days 1, 15, 29 and once monthly thereafter [see Clinical Studies (14)].
2.2 Dose Modification
Hepatic Impairment:
A dose of 250 mg is recommended for patients with moderate hepatic impairment (Child-Pugh class B) to be administered intramuscularly into the buttock slowly (1 - 2 minutes) as one 5 mL injection on days 1, 15, 29 and once monthly thereafter.
FASLODEX has not been eva luated in patients with severe hepatic impairment (Child-Pugh class C) [see Warnings and Precautions (5.2) and Use in Specific Populations (8.6)].
2.3 Administration Technique
The proper method of administration of FASLODEX for intramuscular use is described in the instructions that follow:
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Remove glass syringe barrel from tray and check that it is not damaged.
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Remove perforated patient record label from syringe.
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Peel open the safety needle (SafetyGlide™) outer packaging. For complete SafetyGlide™ instructions refer below to the "Directions for Use of SafetyGlide™".
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Break the seal of the white plastic cover on the syringe luer connector to remove the cover with the attached rubber tip cap (see Figure 1).
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Twist to lock the needle to the luer connector.
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Remove needle sheath.
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Remove excess gas from the syringe (a small gas bubble may remain).
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Administer intramuscularly slowly in the buttock.
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Immediately activate needle protection device upon withdrawal from patient by pushing lever arm completely forward until needle tip is fully covered (see Figure 2).
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Visually confirm that the lever arm has fully advanced and the needle tip is covered. If unable to activate, discard immediately into an approved sharps collector.
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Repeat steps 1 through 10 for second syringe.
How To Use FASLODEX.
For the 2 x 5 mL syringe package, the contents of both syringes must be injected to receive the 500 mg recommended dose.
SAFETYGLIDE™ INSTRUCTIONS FROM BECTON DICKINSON
SafetyGlide™ is a trademark of Becton Dickinson and Company
Reorder number 305917
CAUTION CONCERNING SAFETYGLIDE™
Federal (USA) law restricts this device to sale by or on the order of a physician. To help avoid HIV (AIDS), HBV (Hepatitis), and other infectious diseases due to accidental needlesticks, contaminated needles should not be recapped or removed, unless there is no alternative or that such action is required by a specific medical procedure.
WARNING CONCERNING SAFETYGLIDE™
Do not autoclave SafetyGlide™ Needle before use. Hands must remain behind the needle at all times during use and disposal.
DIRECTIONS FOR USE OF SAFETYGLIDE™
For each syringe:
Remove glass syringe barrel from tray and check that it is not damaged.
Peel apart packaging of the SafetyGlide™, break the seal of the white plastic cover on the syringe Luer connector and attach the SafetyGlide™ needle to the Luer Lock of the syringe by twisting.
Transport filled syringe to point of administration.
Pull shield straight off needle to avoid damaging needle point.
Administer injection following package instruction.
For user convenience, the needle ‘bevel up’ position is orientated to the lever arm, as shown in Figure 3.
Immediately activate needle protection device upon withdrawal from patient by pushing lever arm completely forward until needle tip is fully covered (Figure 2).
Visually confirm that the lever arm has fully advanced and the needle tip is covered. If unable to activate, discard immediately into an approved sharps collector.
Activation of the protective mechanism may cause minimal splatter of fluid that may remain on the needle after injection.
For greatest safety, use a one-handed technique and activate away from self and others.
After single use, discard in an approved sharps collector in accordance with applicable regulations and institutional policy.
Becton Dickinson guarantees the contents of their unopened or undamaged packages to be sterile, non-toxic and non-pyrogenic.
Figure 1
Figure 2
Figure 3
3 DOSAGE FORMS AND STRENGTHS
FASLODEX, an injection for intramuscular administration, is supplied as 5-mL prefilled syringes containing 50 mg/mL fulvestrant.
4 CONTRAINDICATIONS
FASLODEX is contraindicated in patients with a known hypersensitivity to the drug or to any of its components. Hypersensitivity reactions, including urticaria and angioedema, have been reported in association with FASLODEX.
5 WARNINGS AND PRECAUTIONS
5.1 Blood Disorders
Because FASLODEX is administered intramuscularly, it should be used with caution in patients with bleeding diatheses, thrombocytopenia, or anticoagulant use.
5.2 Hepatic Impairment
The safety and pharmacokinetics of FASLODEX were eva luated in a study in seven subjects with moderate hepatic impairment (Child-Pugh class B) and seven subjects with normal hepatic function. Exposure was increased in patients with moderate hepatic impairment, therefore a dose of 250 mg is recommended [see Dosage and Administration (2.2)].
FASLODEX has not been studied in patients with severe hepatic impairment (Child-Pugh class C) [see Use in Specific Populations (8.6)].
5.3 Use in Pregnancy
Based on its mechanism of action and findings in animals, FASLODEX can cause fetal harm when administered to a pregnant woman. Fulvestrant caused fetal loss or abnormalities in animals when administered during the period of organogenesis at doses significantly smaller than the maximum recommended human dose based on the body surface area. There are no adequate and well-controlled studies in pregnant women using FASLODEX. Women of childbearing potential should be advised not to become pregnant while receiving FASLODEX. If FASLODEX is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1)].
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other trials and may not reflect the rates observed in clinical practice.
Comparison of FASLODEX 500 mg and FASLODEX 250 mg
The following frequency categories for adverse reactions (ARs) were calculated based on the safety analysis of Study 1 that compared FASLODEX 500 mg with FASLODEX 250 mg. The most frequently reported adverse reactions in the fulvestrant 500 mg group were injection site pain (11.6% of patients), nausea (9.7% of patients) and bone pain (9.4% of patients); the most frequently reported adverse reactions in the fulvestrant 250 mg group were nausea (13.6% of patients), back pain (10.7% of patients) and injection site pain (9.1% of patients).
Table 1 lists adverse reactions reported with an incidence of 5% or greater, regardless of assessed causality, from the controlled clinical trial Study 1 comparing the administration of FASLODEX 500 mg intramuscularly once a month with FASLODEX 250 mg intramuscularly once a month.
Table 1: Summary of Most Commonly Reported Adverse Reactions in Study 1 (≥ 5% in either treatment group): Safety Population
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Body System
and Adverse Reaction
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Number (%) of Patients
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Fulvestrant 500 mg
N=361
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Fulvestrant 250 mg
N=374
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Body as a Whole
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Injection Site Pain
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42 (11.6)
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34 (9.1)
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Headache
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28 (7.8)
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25 (6.7)
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Back Pain
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27 (7.5)
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40 (10.7)
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Fatigue
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27 (7.5)
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24 (6.4)
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Pain in Extremity
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25 (6.9)
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26 (7.0)
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Asthenia
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21 (5.8)
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23 (6.1)
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Vascular System
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Hot Flash
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24 (6.6)
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22 (5.9)
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Digestive System
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Nausea
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35 (9.7)
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51 (13.6)
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Vomiting
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22 (6.1)
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21 (5.6)
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Anorexia
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22 (6.1)
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14 (3.7)
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Constipation
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18 (5.0)
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13 (3.5)
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Musculoskeletal System
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Bone Pain
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34 (9.4)
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28 (7.5)
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Arthralgia
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29 (8.0)
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29 (7.8)
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Musculoskeletal Pain
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20 (5.5)
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12 (3.2)
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Respiratory System
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Cough
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19 (5.3)
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20 (5.3)
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Dyspnea
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16 (4.4)
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19 (5.1)
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In the pooled safety population (N=1127) from clinical trials comparing FASLODEX 500 mg to FASLODEX 250 mg, post-baseline increases of ≥1 CTC grade in either AST, ALT, or alkaline phosphatase were observed in > 15% of patients receiving FASLODEX. Grade 3-4 increases were observed in 1-2% of patients. The incidence and severity of increased hepatic enzymes (ALT, AST, ALP) did not differ between the 250 mg and the 500 mg FASLODEX arms.
Comparison of FASLODEX 250 mg and Anastrozole 1 mg in Combined Trials (Studies 2 and 3)
The most commonly reported adverse reactions in the FASLODEX and anastrozole treatment groups, regardless of the investigator’s assessment of causality, were gastrointestinal symptoms (including nausea, vomiting, constipation, diarrhea and abdominal pain), headache, back pain, vasodilatation (hot flashes), and pharyngitis.
Injection site reactions with mild transient pain and inflammation were seen with FASLODEX and occurred in 7% of patients (1% of treatments) given the single 5 mL injection (predominantly European Trial Study 3) and in 27% of patients (4.6% of treatments) given the 2 x 2.5 mL injections (North American Trial Study 2).
Table 2 lists adverse reactions reported with an incidence of 5% or greater, regardless of assessed causality, from the two controlled clinical trials comparing the administration of FASLODEX 250 mg intramuscularly once a month with anastrozole 1 mg orally once a day.
Table 2: Combined Data from Studies 2 and 3, Adverse Reactions ≥ 5%
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Body System and Adverse Reaction* |
FASLODEX 250 mg
N=423
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Anastrozole 1 mg
N=423
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Body as a Whole
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68.3
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67.6
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| 以下是“全球医药”详细资料 |
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