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EMEND(aprepitant)for oral suspension

2016-06-12 12:23:22 来源: 作者: 【大中小】浏览:305次评论:0条

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use EMEND CAPSULES and EMEND FOR ORAL SUSPENSION safely and effectively. See full prescribing information for EMEND CAPSULES and EMEND FOR ORAL SUSPENSION.
EMEND (aprepitant) capsules, for oral use
EMEND (aprepitant) for oral suspension
Initial U.S. Approval: 2003
RECENT MAJOR CHANGES

Indications and Usage (1.1)	12/2015
Dosage and Administration
Prevention of CINV (2.1)	12/2015
Preparation Instructions (2.3)	12/2015
Administration Instructions (2.4)	12/2015

INDICATIONS AND USAGE

EMEND® is a substance P/neurokinin 1 (NK1) receptor antagonist.

EMEND for oral suspension is indicated

in combination with other antiemetic agents, in patients 6 months of age and older for prevention of:
- acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin (1.1)
- nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) (1.1)

EMEND capsules is indicated

in combination with other antiemetic agents, in patients 12 years of age and older for prevention of:
- acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin (1.1)
- nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) (1.1)
for prevention of postoperative nausea and vomiting (PONV) in adults (1.2)

Limitations of Use: (1.3)

EMEND has not been studied for treatment of established nausea and vomiting.
Chronic continuous administration of EMEND is not recommended.

DOSAGE AND ADMINISTRATION

Recommended Dosage for Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) (2.1)

EMEND capsules in adults and pediatric patients 12 years of age and older: is 125 mg on Day 1 and 80 mg on Days 2 and 3.
EMEND for oral suspension in pediatric patients 6 months to less than 12 years of age or pediatric and adult patients unable to swallow capsules: see dosing recommendations in Table 3 in the Full Prescribing Information.
Administer EMEND 1 hour prior to chemotherapy on Days 1, 2, and 3. If no chemotherapy is given on Days 2 and 3, administer EMEND in morning.
See Full Prescribing Information for recommended dosages of concomitant dexamethasone and 5-HT3 antagonist for HEC and MEC.

Recommended Dosage for PONV (2.2)

Adults: 40 mg EMEND capsules within 3 hours prior to induction of anesthesia.

Preparation and Administration (2.3, 2.4)

EMEND capsules and EMEND for oral suspension can be administered with or without food.
Swallow EMEND capsules whole.
EMEND for oral suspension should be prepared by healthcare provider. Once prepared, it may be administered either by a healthcare provider, patient, or caregiver.
For details on preparation see Full Prescribing Information.

DOSAGE FORMS AND STRENGTHS

EMEND capsules: 40 mg; 80 mg; 125 mg (3)

EMEND for oral suspension: 125 mg (3)

CONTRAINDICATIONS

Known hypersensitivity to any component of this drug. (4)
Concurrent use with pimozide. (4)

WARNINGS AND PRECAUTIONS

CYP3A4 Interactions: Aprepitant is a substrate, weak-to-moderate inhibitor and inducer of CYP3A4; See Full Prescribing Information for recommendations regarding contraindications, risk of adverse reactions, and dosage adjustments of EMEND and concomitant drugs. (4, 5.1, 7.1, 7.2)
Warfarin (a CYP2C9 substrate): Risk of decreased INR of prothrombin time; monitor INR in 2-week period, particularly at 7 to 10 days, following initiation of EMEND. (5.2, 7.1)
Hormonal Contraceptives: Efficacy of contraceptives may be reduced during administration of and for 28 days following the last dose of EMEND. Use effective alternative or back-up methods of contraception. (5.3, 7.1, 8.3)

ADVERSE REACTIONS

Most common adverse reactions are (6.1):

Prevention of Chemotherapy Induced Nausea and Vomiting (CINV)

Adults (≥3%): fatigue, diarrhea, asthenia, dyspepsia, abdominal pain, hiccups, white blood cell count decreased, dehydration, and alanine aminotransferase increased.
Pediatrics (≥3%): neutropenia, headache, diarrhea, decreased appetite, cough, fatigue, hemoglobin decreased, dizziness, and hiccups.

PONV

Adults (≥3%): constipation and hypotension.

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

See Full Prescribing Information for a list of clinically significant drug interactions. (4, 5.1, 5.2, 5.3, 7.1, 7.2)

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

Revised: 12/2015

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

1.1 Prevention of Chemotherapy Induced Nausea and Vomiting (CINV)

1.2 Prevention of Postoperative Nausea and Vomiting (PONV)

1.3 Limitations of Use

2 DOSAGE AND ADMINISTRATION

2.1 Prevention of Chemotherapy Induced Nausea and Vomiting (CINV)

2.2 Prevention of Postoperative Nausea and Vomiting (PONV)

2.3 Preparation Instructions for EMEND for Oral Suspension -- for Healthcare Providers

2.4 Administration Instructions

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Clinically Significant CYP3A4 Drug Interactions

5.2 Decrease in INR with Concomitant Warfarin

5.3 Risk of Reduced Efficacy of Hormonal Contraceptives

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Effect of Aprepitant on the Pharmacokinetics of Other Drugs

7.2 Effect of Other Drugs on the Pharmacokinetics of Aprepitant

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.3 Females and Males of Reproductive Potential

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Patients with Renal Impairment

8.7 Patients with 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 Prevention of Nausea and Vomiting Associated with HEC in Adults

14.2 Prevention of Nausea and Vomiting Associated with MEC in Adults

14.3 Prevention of Nausea and Vomiting Associated with HEC or MEC in Pediatric Patients

14.4 Prevention of PONV in Adults

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

1.1 Prevention of Chemotherapy Induced Nausea and Vomiting (CINV)

EMEND® for oral suspension, in combination with other antiemetic agents, is indicated in patients 6 months of age and older 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.
nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC).

EMEND® capsules, in combination with other antiemetic agents, is indicated in patients 12 years of age and older 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.
nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC).

1.2 Prevention of Postoperative Nausea and Vomiting (PONV)

EMEND capsules are indicated in adults for the prevention of postoperative nausea and vomiting.

1.3 Limitations of Use

EMEND has not been studied for the treatment of established nausea and vomiting.
Chronic continuous administration of EMEND is not recommended because it has not been studied, and because the drug interaction profile may change during chronic continuous use.

2 DOSAGE AND ADMINISTRATION

2.1 Prevention of Chemotherapy Induced Nausea and Vomiting (CINV)

Adults and Pediatric Patients 12 Years of Age and Older

The recommended oral dosage of EMEND capsules, dexamethasone, and a 5-HT3 antagonist in adults and pediatric patients 12 years of age and older who can swallow oral capsules, for the prevention of nausea and vomiting associated with administration of HEC or MEC is shown in Table 1 or Table 2, respectively. For patients who cannot swallow oral capsules, EMEND for oral suspension can be used instead of EMEND capsules as shown in Table 3.

Table 1: Recommended Dosing for the Prevention of Nausea and Vomiting Associated with HEC
	Population	Day 1	Day 2	Day 3	Day 4
* Administer EMEND capsules 1 hour prior to chemotherapy treatment on Days 1, 2, and 3. If no chemotherapy is given on Days 2 and 3, administer EMEND capsules in the morning. † Administer dexamethasone 30 minutes prior to chemotherapy treatment on Day 1 and in the morning on Days 2 through 4. A 50% dosage reduction of dexamethasone is recommended to account for a drug interaction with EMEND [see Clinical Pharmacology (12.3)].
EMEND capsules*	Adults and Pediatric Patients 12 Years and Older	125 mg orally	80 mg orally	80 mg orally	none
Dexamethasone	Adults	12 mg orally	8 mg orally	8 mg orally	8 mg orally
Dexamethasone	Pediatric Patients 12 Years and Older	If a corticosteroid, such as dexamethasone, is co-administered, administer 50% of the recommended corticosteroid dose on Days 1 through 4 [see Clinical Studies (14.3)].†
5-HT3 antagonist	Adults and Pediatric Patients 12 Years and Older	See selected 5-HT3 antagonist prescribing information for the recommended dosage	none	none	none

Table 2: Recommended Dosing for the Prevention of Nausea and Vomiting Associated with MEC
	Population	Day 1	Day 2	Day 3
* Administer EMEND capsules 1 hour prior to chemotherapy treatment on Days 1, 2, and 3. If no chemotherapy is given on Days 2 and 3, administer EMEND capsules in the morning. † Administer dexamethasone 30 minutes prior to chemotherapy treatment on Day 1. A 50% dosage reduction of dexamethasone is recommended to account for a drug interaction with EMEND [see Clinical Pharmacology (12.3)].
EMEND capsules*	Adults and Pediatric Patients 12 Years and Older	125 mg orally	80 mg orally	80 mg orally
Dexamethasone	Adults	12 mg orally	none	none
Dexamethasone	Pediatric Patients 12 Years and Older	If a corticosteroid, such as dexamethasone, is co-administered, administer 50% of the recommended corticosteroid dose on Days 1 through 4 [see Clinical Studies (14.3)].†
5-HT3 antagonist	Adults and Pediatric Patients 12 Years and Older	See the selected 5-HT3 antagonist prescribing information for recommended dosage	none	none

Pediatric Patients 6 Months to less than 12 Years of Age or Pediatric and Adult Patients Unable to Swallow Capsules

The recommended dose of EMEND for oral suspension to be administered with a 5-HT3 antagonist, with or without a corticosteroid, for the prevention of nausea and vomiting associated with administration of HEC or MEC is specified in Table 3. Dosing of EMEND for oral suspension is based on weight, to a maximum of 125 mg on Day 1 and 80 mg on Days 2 and 3. Dosing in pediatric patients less than 6 kg is not recommended.

Table 3: Recommended Dosing in Pediatric Patients 6 Months to Less than 12 Years of Age or Pediatric and Adult Patients Unable to Swallow Capsules
	Population	Day 1	Day 2	Day 3	Day 4
* After preparation, the final concentration of EMEND for oral suspension is 25 mg/mL [see Dosage and Administration (2.3)]. Administer EMEND for oral suspension 1 hour prior to chemotherapy treatment on Days 1, 2, and 3. If no chemotherapy is given on Days 2 and 3, administer EMEND for oral suspension in the morning. † Administer dexamethasone 30 minutes prior to chemotherapy treatment on Day 1. A 50% dosage reduction of dexamethasone is recommended to account for a drug interaction with EMEND [see Clinical Pharmacology (12.3)].
EMEND for oral suspension*	Pediatric Patients 6 Months to Less than12 Years or Pediatric and Adult Patients Unable to Swallow Capsules	3 mg/kg orally Maximum dose 125 mg	2 mg/kg orally Maximum dose 80 mg	2 mg/kg orally Maximum dose 80 mg	none
Dexamethasone	Adults Unable to Swallow Capsules	See Table 1 or 2	See Table 1 or 2	See Table 1 or 2	See Table 1 or 2
Dexamethasone	Pediatric Patients 6 Months to Less than12 Years or Pediatric Patients Unable to Swallow Capsules	If a corticosteroid, such as dexamethasone, is co-administered, administer 50% of the recommended corticosteroid dose on Days 1 through 4 [see Clinical Studies (14.3)].†
5-HT3 antagonist	Pediatric Patients 6 Months to Less than12 Years or Pediatric and Adult Patients Unable to Swallow Capsules	See selected 5-HT3 antagonist prescribing information for the recommended dosage	none	none	none

2.2 Prevention of Postoperative Nausea and Vomiting (PONV)

The recommended oral dosage of EMEND capsules in adults is 40 mg within 3 hours prior to induction of anesthesia.

2.3 Preparation Instructions for EMEND for Oral Suspension -- for Healthcare Providers

EMEND for oral suspension should be prepared by a healthcare provider.

Once prepared, it may be administered either by a healthcare provider, patient, or caregiver.

Before you prepare EMEND:

Do not open the pouch of EMEND until ready to prepare the medicine.
Store the pouch at room temperature [between 68°F-77°F (20°C-25°C)].

Table 4: Instructions for Healthcare Providers on How to Prepare EMEND for Oral Suspension
EMEND for oral suspension is packaged as a kit with one 1 mL oral dosing dispenser, one 5 mL oral dosing dispenser, one cap and one mixing cup.
1. Fill the mixing cup with room temperature drinking water.
2. Fill the 5 mL oral dosing dispenser with 4.6 mL of water from the mixing cup. Make sure no air is in the dispenser - if air is present, remove.
3. Discard all the unused water remaining in the mixing cup.
4. Add the 4.6 mL of water from the dispenser back into the mixing cup.
5. Each pouch of EMEND for oral suspension contains 125 mg of aprepitant which is to be suspended in 4.6 mL of water giving a final concentration of 25 mg/mL. Hold the EMEND for oral suspension pouch upright and shake the contents to the bottom before opening the pouch. 6. Pour the entire contents of the pouch into the 4.6 mL of water in the mixing cup and snap the lid shut.
7. Mix the EMEND suspension gently by swirling 20 times; then gently invert the mixing cup 5 times. To prevent foaming, do not shake the mixing cup. The mixture will be cloudy pink to light pink.
8. Check the EMEND mixture for any clumps or foaming: If any clumps are present, repeat Step 7 until there are no clumps. If there is any foam, wait for the foam to disappear before going on to Step 9.
9. Fill the dispenser with the prescribed dose shown above in Table 3. Choose the dispenser based on dose: Use 1 mL dispenser if dose is 1 mL or less. Use 5 mL dispenser if dose is more than 1 mL. Fill the dispenser with the prescribed dose from the cup. If the dose is less than 1 mL round to the nearest 0.1 mL. If the dose is more than 1 mL round to the nearest 0.2 mL. It is common to have medicine leftover in the cup. Make sure no air is in the dispenser - if air is present, remove. Make sure the dispenser contains the prescribed dose.
10. Place the cap on the dispenser until it clicks. 11. If the dose is not administered immediately after measuring, store filled oral dosing dispenser(s) in the refrigerator [between 36°F-46°F (2°C-8°C)] for up to 72 hours prior to use. When dispensing dose(s) to the patient or caregiver, instruct them to refrigerate the oral dosing dispenser(s) until they are ready to administer the dose. 12. When ready to use, the mixture can be kept at room temperature [between 68°F-77°F (20°C-25°C)] for up to 3 hours.
13. Discard the mixing cup along with any remaining suspension.

2.4 Administration Instructions

EMEND capsules and EMEND for oral suspension can be administered with or without food.

EMEND capsules

Swallow capsules whole.

EMEND for oral suspension

The dose will be prepared by the healthcare provider and dispensed to the patient or caregiver in an oral dispenser.
Keep the dispenser in the refrigerator until administered to the patient. The dose can be stored at room temperature for up to 3 hours before use.
When ready to use, take the cap off the dispenser, place the dispenser in the patient's mouth along the inner cheek on either the right or left side. Slowly dispense the medicine.
The dose must be used within 72 hours of preparation.
Discard any doses remaining after 72 hours.

3 DOSAGE FORMS AND STRENGTHS

EMEND capsules:

40 mg: white body and mustard yellow cap with "464" and "40 mg" printed radially in black ink on the body.
80 mg: white body and cap with "461" and "80 mg" printed radially in black ink on the body.
125 mg: white body and pink cap with "462" and "125 mg" printed radially in black ink on the body.

EMEND for oral suspension:

125 mg as a pink to light pink powder in a single-use pouch with one 1 mL oral dosing dispenser, one 5 mL oral dosing dispenser, one cap and mixing cup.

4 CONTRAINDICATIONS

EMEND is contraindicated in patients:

who are hypersensitive to any component of the product. Hypersensitivity reactions including anaphylactic reactions have been reported [see Adverse Reactions (6.2)].
taking pimozide. Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of this drug which is a CYP3A4 substrate, potentially causing serious or life-threatening reactions, such as QT prolongation, a known adverse reaction of pimozide [see Warnings and Precautions (5.1)].

5 WARNINGS AND PRECAUTIONS

5.1 Clinically Significant CYP3A4 Drug Interactions

Aprepitant is a substrate, a weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4.

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