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EMEND(fosaprepitant dimeglumine) injection, powder, lyophili

2014-01-15 16:00:40 来源: 作者: 【大中小】浏览:302次评论:0条

HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use EMEND safely and effectively. See full prescribing information for EMEND. EMEND (fosaprepitant dimeglumine) for Injection, for intravenous use Initial U.S. Approval: 2008
RECENT MAJOR CHANGES
Dosage and Administration, HEC (2.1) 11/2010 Dosage and Administration, MEC (2.2) 11/2010 Dosage and Administration, Preparation (2.3) 11/2010 Dosage and Administration, Administration with Food (2) removal 11/2010
INDICATIONS AND USAGE
EMEND for Injection is a substance P/neurokinin-1 (NK1) receptor antagonist, in combination with other antiemetic agents, is indicated in adults for the (1): prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) Limitations of Use (1) Chronic continuous administration is not recommended.
DOSAGE AND ADMINISTRATION
HEC (Single Dose Regimen): EMEND for Injection (150mg) is administered on Day 1 only as an infusion over 20-30 minutes initiated approximately 30 minutes prior to chemotherapy. No capsules of EMEND are administered on Days 2 and 3. EMEND for Injection is part of a regimen to prevent nausea and vomiting induced by HEC that includes a corticosteroid and a 5-HT3 antagonist. (2.1) HEC and MEC (3-Day Dosing Regimen): EMEND for Injection (115mg) is administered on Day 1 as an infusion over 15 minutes initiated approximately 30 minutes prior to chemotherapy. EMEND capsules (80mg) are given orally on Days 2 and 3. EMEND for Injection and EMEND capsules are part of a regimen to prevent nausea and vomiting induced by HEC or MEC that includes a corticosteroid and a 5-HT3 antagonist. (2.1, 2.2).
DOSAGE FORMS AND STRENGTHS
One single dose glass vial supplied as sterile lyophilized powder for intravenous use only after reconstitution and dilution: 150 mg and 115mg (3)
CONTRAINDICATIONS
Known hypersensitivity to any component of this drug. (4) Do not use concurrently with pimozide or cisapride, since inhibition of CYP3A4 by aprepitant may result in elevated plasma concentrations of these drugs, potentially causing serious or life-threatening reactions. (4)
WARNINGS AND PRECAUTIONS
Fosaprepitant should be used with caution in patients receiving concomitant medications that are primarily metabolized through CYP3A4. (5.1) Immediate hypersensitivity reactions may occur during infusion. Patients have generally responded to discontinuation. It is not recommended to reinitiate the infusion. (5.2) Coadministration of fosaprepitant or aprepitant with warfarin (a CYP2C9 substrate) may result in a clinically significant decrease in International Normalized Ratio (INR) of prothrombin time. (5.3) The efficacy of hormonal contraceptives during and for 28days following the last dose of fosaprepitant or aprepitant may be reduced. Alternative or back-up methods of contraception should be used. (5.4)
ADVERSE REACTIONS
Adverse reactions for the CINV oral aprepitant regimen in conjunction with highly and moderately emetogenic chemotherapy (incidence ≥1% and greater than standard therapy) are: hiccups, asthenia/fatigue, AST/ALT increased, headache, constipation, anorexia, dyspepsia, diarrhea, eructation. (6.1) Adverse reactions reported for EMEND for Injection were generally similar to that seen in prior HEC studies with oral aprepitant. In addition, infusion site reactions (3%) occurred with EMEND for Injection. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
Coadministration of fosaprepitant or aprepitant with drugs that inhibit or induce CYP3A4 activity may result in increased or reduced plasma concentrations of aprepitant, respectively. (7.1, 7.2) Coadministration of EMEND for Injection with drugs that are metabolized by CYP2C9 (e.g. warfarin, tolbutamide), may result in lower plasma concentrations of these drugs. (7.1)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling
Revised: 03/2011

Back to Highlights and Tabs

FULL PRESCRIBING INFORMATION: CONTENTS*

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

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.1 Prevention of Nausea and Vomiting Associated with Highly Emetogenic Chemotherapy (HEC)

2.2 Prevention of Nausea and Vomiting Associated with Moderately Emetogenic Chemotherapy (MEC)

2.3 Preparation of EMEND for Injection

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

4.1 Hypersensitivity

4.2 Concomitant Use with Pimozide or Cisapride

5 WARNINGS AND PRECAUTIONS

5.1 CYP3A4 Interactions

5.2 Hypersensitivity Reactions

5.3 Coadministration with Warfarin (a CYP2C9 substrate)

5.4 Coadministration with Hormonal Contraceptives

5.5 Chronic Continuous Use

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Effect of Fosaprepitant/Aprepitant on the Pharmacokinetics of Other Agents

7.2 Effect of Other Agents on the Pharmacokinetics of Aprepitant

7.3 Additional Interactions

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Patients with Severe Hepatic 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

14.1 Highly Emetogenic Chemotherapy (HEC)

14.2 Moderately Emetogenic Chemotherapy (MEC)

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

EMEND for Injection is a substance P/neurokinin-1 (NK1) receptor antagonist indicated in adults for use in combination with other antiemetic agents for the:

prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin [see Dosage and Administration (2.1)]
prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) [see Dosage and Administration (2.2)].

Limitations of Use

EMEND for Injection has not been studied for the treatment of established nausea and vomiting.

Chronic continuous administration is not recommended [see Warnings and Precautions (5.5)].

2 DOSAGE AND ADMINISTRATION

2.1 Prevention of Nausea and Vomiting Associated with Highly Emetogenic Chemotherapy (HEC)

EMEND for Injection 150mg (Single Dose Regimen of EMEND):

EMEND for Injection 150mg is administered intravenously on Day 1 only as an infusion over 20-30 minutes initiated approximately 30 minutes prior to chemotherapy. No capsules of EMEND are administered on Days 2 and 3. EMEND for Injection should be administered in conjunction with a corticosteroid and a 5-HT3 antagonist as specified in Table 1. The recommended dosage of dexamethasone with EMEND for Injection 150mg differs from the recommended dosage of dexamethasone with EMEND for Injection 115mg on Days 3 and 4.

Table 1: Recommended dosing (Single Dose Regimen of EMEND) for the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy
	Day 1	Day 2	Day 3	Day 4
* Dexamethasone should be administered 30 minutes prior to chemotherapy treatment on Day 1 and in the morning on Days 2 through 4. The dose of dexamethasone accounts for drug interactions. † Ondansetron should be administered 30 minutes prior to chemotherapy treatment on Day 1.
EMEND	150 mg intravenous	none	none	none
Dexamethasone*	12 mg orally	8 mg orally	8 mg orally twice daily	8 mg orally twice daily
Ondansetron†	32 mg intravenous	none	none	none

EMEND for Injection 115mg (3-Day Dosing Regimen of EMEND):

EMEND for Injection 115mg is administered on Day 1 only as an infusion over 15 minutes initiated 30minutes prior to chemotherapy. Capsules of EMEND 80mg should be administered on Days 2 and 3. EMEND for Injection 115mg should be administered in conjunction with a corticosteroid and a 5-HT3 antagonist as specified in Table 2. The recommended dosage of dexamethasone with EMEND for Injection 115mg differs from the recommended dosage of dexamethasone with EMEND for Injection 150mg on Days 3 and 4.

Capsules of EMEND 125mg may be substituted for EMEND for Injection 115mg on Day 1.

Table 2: Recommended dosing (3-Day Dosing Regimen of EMEND) for the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy
	Day 1	Day 2	Day 3	Day 4
* Dexamethasone should be administered 30 minutes prior to chemotherapy treatment on Day 1 and in the morning on Days 2 through 4. The dose of dexamethasone accounts for drug interactions. † Ondansetron should be administered 30 minutes prior to chemotherapy treatment on Day 1.
EMEND	115 mg intravenous	80 mg orally	80 mg orally	none
Dexamethasone*	12 mg orally	8 mg orally	8 mg orally once daily	8 mg orally once daily
Ondansetron†	32 mg intravenous	none	none	none

2.2 Prevention of Nausea and Vomiting Associated with Moderately Emetogenic Chemotherapy (MEC)

EMEND for Injection 115mg (3-Day Dosing Regimen of EMEND):

EMEND for Injection 115mg is administered on Day 1 only as an infusion over 15 minutes initiated 30minutes prior to chemotherapy. Capsules of EMEND 80mg should be administered on Days 2 and 3. EMEND for Injection 115mg should be administered in conjunction with a corticosteroid and a 5-HT3 antagonist as specified in Table 3. The recommended dosage of dexamethasone with EMEND for Injection 115mg differs from the recommended dosage of dexamethasone with EMEND for Injection 150mg on Days 3 and 4.

Capsules of EMEND 125mg may be substituted for EMEND for Injection 115mg on Day 1.

Table 3: Recommended dosing (3-Day Dosing Regimen of EMEND) for the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy
* Dexamethasone should be administered 30 minutes prior to chemotherapy treatment on Day 1. The dose of dexamethasone accounts for drug interactions. † Ondansetron 8-mg capsule should be administered 30 to 60 minutes prior to chemotherapy treatment and one 8-mg capsule should be administered 8 hours after the first dose on Day 1.
	Day 1	Day 2	Day 3
EMEND	115 mg intravenous	80 mg orally	80 mg orally
Dexamethasone*	12 mg orally	none	none
Ondansetron†	8 mg orally twice daily	none	none

2.3 Preparation of EMEND for Injection

Table 4: Preparation Instructions for EMEND for Injection (115-mg and 150-mg)
	115 mg	150 mg
Step 1	Aseptically inject 5 mL 0.9% Sodium Chloride for Injection (normal saline) into the vial. Assure that normal saline is added to the vial along the vial wall in order to prevent foaming. Swirl the vial gently. Avoid shaking and jetting saline into the vial.	Aseptically inject 5 mL 0.9% Sodium Chloride for Injection (normal saline) into the vial. Assure that normal saline is added to the vial along the vial wall in order to prevent foaming. Swirl the vial gently. Avoid shaking and jetting saline into the vial.
Step 2	Aseptically prepare an infusion bag filled with 110mL of normal saline.	Aseptically prepare an infusion bag filled with 145mL of normal saline.
Step 3	Aseptically withdraw the entire volume from the vial and transfer it into the infusion bag containing 110mL of normal saline to yield a total volume of 115mL and a final concentration of 1mg/1mL.	Aseptically withdraw the entire volume from the vial and transfer it into the infusion bag containing 145mL of normal saline to yield a total volume of 150mL and a final concentration of 1mg/1mL.
Step 4	Gently invert the bag 2-3 times.	Gently invert the bag 2-3 times.
	Note: The differences in preparation for each dose are displayed as bolded text.

The reconstituted final drug solution is stable for 24 hours at ambient room temperature (at or below 25°C).

Parenteral drug products should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit.

Caution: EMEND for Injection should not be mixed or reconstituted with solutions for which physical and chemical compatibility have not been established. EMEND for Injection is incompatible with any solutions containing divalent cations (e.g., Ca2+, Mg2+), including Lactated Ringer’s Solution and Hartmann's Solution.

3 DOSAGE FORMS AND STRENGTHS

One 150mg single dose glass vial: White to off-white lyophilized solid (Sterile lyophilized powder for intravenous use only after reconstitution and dilution).

One 115mg single dose glass via