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HALAVEN (eribulin mesylate) Injection

2015-12-01 05:02:30 来源: 作者: 【大中小】浏览:396次评论:0条

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use HALAVEN ® safely and effectively. See full prescribing information for HALAVEN.
HALAVEN ® (eribulin mesylate) Injection
For intravenous administration
Initial U.S. Approval: 2010
RECENT MAJOR CHANGES

Dosage and Administration, Recommended Dose (2.1) 12/2014

Dosage and Administration, Dose Modification (2.2) 12/2014

INDICATIONS AND USAGE

HALAVEN is a microtubule inhibitor indicated for the treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting (1)
DOSAGE AND ADMINISTRATION

Administer 1.4 mg/m2 intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle (2.1)
Reduce dose in patients with hepatic impairment or with moderate or severe renal impairment (2.1)
Do not mix with other drugs or administer with dextrose-containing solutions (2.3)

DOSAGE FORMS AND STRENGTHS

Intravenous administration (3)

Eribulin mesylate injection, 1 mg per 2 mL (0.5 mg per mL) (3)
CONTRAINDICATIONS

None. (4)
WARNINGS AND PRECAUTIONS

Neutropenia: Monitor peripheral blood cell counts and adjust dose as appropriate (2.2, 5.1, 6)
Peripheral Neuropathy: Monitor for signs of neuropathy. Manage with dose delay and adjustment (2.2, 5.2, 6)
Embryo-Fetal Toxicity: Fetal harm can occur when administered to a pregnant woman (5.3) (8.1)
QT Prolongation: Monitor for prolonged QT intervals in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, and electrolyte abnormalities. Avoid in patients with congenital long QT syndrome (5.4)

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥25%) were neutropenia, anemia, asthenia/fatigue, alopecia, peripheral neuropathy, nausea, and constipation (6)

To report SUSPECTED ADVERSE REACTIONS, contact Eisai Inc. at (1-877-873-4724) or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

USE IN SPECIFIC POPULATIONS

Nursing Mothers: Discontinue drug or nursing, taking into consideration the importance of the drug to the mother (8.3)
Hepatic Impairment: A lower starting dose is recommended for patients with mild (Child-Pugh A) and moderate (Child-Pugh B) hepatic impairment. Patients with severe hepatic impairment (Child-Pugh C) were not studied (8.6)
Renal Impairment: A lower starting dose is recommended for patients with moderate (CrCl 30-49 mL/min) or severe (CrCl 15-29 mL/min) renal impairment (8.7)

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 10/2015

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dose

2.2 Dose Modification

2.3 Instructions for Preparation and Administration

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Neutropenia

5.2 Peripheral Neuropathy

5.3 Embryo-Fetal Toxicity

5.4 QT Prolongation

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6. 2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Effects of Other Drugs on HALAVEN

7.2 Effect of HALAVEN on Other Drugs

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy Category D

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

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

*: Sections or subsections omitted from the full prescribing information are not listed.

1 INDICATIONS AND USAGE

HALAVEN is indicated for the treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dose

The recommended dose of HALAVEN is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.

The recommended dose of HALAVEN in patients with mild hepatic impairment (Child-Pugh A) is 1.1 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle [see Use in Specific Populations (8.6)].

The recommended dose of HALAVEN in patients with moderate hepatic impairment (Child-Pugh B) is 0.7 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle [see Use in Specific Populations (8.6)].

The recommended dose of HALAVEN in patients with moderate or severe renal impairment (creatinine clearance (CrCl) 15-49 mL/min) is 1.1 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle [see Use in Specific Populations (8.7)].

2.2 Dose Modification

Assess for peripheral neuropathy and obtain complete blood cell counts prior to each dose.

Recommended dose delays

• Do not administer HALAVEN on Day 1 or Day 8 for any of the following:
      ¯ ANC < 1,000/mm3
      ¯ Platelets < 75,000/mm3
      ¯ Grade 3 or 4 non-hematological toxicities.

• The Day 8 dose may be delayed for a maximum of 1 week.
¯ If toxicities do not resolve or improve to ≤ Grade 2 severity by Day 15, omit the dose.
¯ If toxicities resolve or improve to ≤ Grade 2 severity by Day 15, administer HALAVEN at a reduced dose and initiate the next cycle no sooner than 2 weeks later.

Recommended dose reductions

If a dose has been delayed for toxicity and toxicities have recovered to Grade 2 severity or less, resume HALAVEN at a reduced dose as set out in Table 1.
Do not re-escalate HALAVEN dose after it has been reduced.

Table 1 Recommended Dose Reductions
Event Description	Recommended HALAVEN Dose
Permanently reduce the 1.4 mg/m2 HALAVEN dose for any of the following:
ANC <500/mm3 for >7 days
ANC <1,000 /mm3 with fever or infection
Platelets <25,000/mm3	1.1 mg/m2
Platelets <50,000/mm3 requiring transfusion
Non-hematologic Grade 3 or 4 toxicities
Omission or delay of Day 8 HALAVEN dose in previous cycle for toxicity
Occurrence of any event requiring permanent dose reduction while receiving 1.1 mg/m2	0.7 mg/m2
Occurrence of any event requiring permanent dose reduction while receiving 0.7 mg/m2	Discontinue HALAVEN
ANC = absolute neutrophil count. Toxicities graded in accordance with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

2.3 Instructions for Preparation and Administration

Aseptically withdraw the required amount of HALAVEN from the single-use vial and administer undiluted or diluted in 100 mL of 0.9% Sodium Chloride Injection, USP.

Do not dilute in or administer through an intravenous line containing solutions with dextrose. Do not administer in the same intravenous line concurrent with the other medicinal products.

Store undiluted HALAVEN in the syringe for up to 4 hours at room temperature or for up to 24 hours under refrigeration (40°F or/ 4°C). Store diluted solutions of HALAVEN for up to 4 hours at room temperature or up to 24 hours under refrigeration.

Discard unused portions of the vial.

3 DOSAGE FORMS AND STRENGTHS

HALAVEN (eribulin mesylate) Injection, 1 mg/2 mL (0.5 mg/mL).

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Neutropenia

Severe neutropenia (ANC < 500/mm3) lasting more than one week occurred in 12% (62/503) of patients in Study 1, leading to discontinuation in <1% of patients [see Adverse Reactions (6)]. Patients with alanine aminotransferase or aspartate aminotransferase > 3 × ULN (upper limit of normal) experienced a higher incidence of Grade 4 neutropenia and febrile neutropenia than patients with normal aminotransferase levels. Patients with bilirubin > 1.5 × ULN also had a higher incidence of Grade 4 neutropenia and febrile neutropenia.

Monitor complete blood counts prior to each dose; increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. Delay administration of HALAVEN and reduce subsequent dose