aprepitant (oral), Emend fosaprepitant (injection), Emend

 Indications

PO, IV: Prevention of: Acute and delayed nausea and

vomiting associated with initial and repeat courses of

highly emetogenic chemotherapy, Nausea and vomiting

associated with initial and repeat courses of moderately

emetogenic chemotherapy. PO: Prevention of postoperative

nausea and vomiting.

Action

Acts as a selective antagonist at substance P/neurokinin

1 (NK1) receptors in the brain. Therapeutic Effects:

Decreased nausea and vomiting associated with

chemotherapy. Augments the antiemetic effects of dexamethasone

and 5-HT3 antagonists (ondansetron).

Pharmacokinetics

Absorption: 60–65% absorbed following oral administration.

Following IV administration, fosaprepitant

is rapidly converted to aprepitant, the active component.

Distribution: Crosses the blood brain barrier; remainder

of distribution unknown.

Metabolism and Excretion: Mostly metabolized

by the liver (CYP3A4 enzyme system); not renally excreted.

Half-life: Aprepitant—9–13 hr.

TIME/ACTION PROFILE (antiemetic effect)

ROUTE ONSET PEAK DURATION

PO 1 hr 4 hr* 24 hr

IV rapid end of infusion*

24 hr

*Blood level.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Concurrent

use with pimozide (risk of life-threatening adverse cardiovascular

reactions); Lactation: May cause unwanted

effects in nursing infants.

Use Cautiously in: Concurrent use with any agents

metabolized by CYP3A4; OB: Use only if clearly needed;

Children 18 yr (IV) and 6 mo (PO) (safety and effectiveness

not established). 

CV: dizziness, fatigue, weakness. Derm: STEVENSJOHNSON

SYNDROME. GI: diarrhea. Misc: hiccups, hypersensitivity

reaction (flushing, erythema, dyspnea)

(IV).

Interactions

Drug-Drug: Aprepitant inhibits, induces, and is metabolized

by the CYP3A4 enzyme system; it also induces

the CYP2C9 system. Concurrent use with other medications

that are metabolized by CYP3A4 may result inq

toxicity from these agents including docetaxel, paclitaxel,

etoposide, irinotecan, ifosfamide, imatinib,

vinorelbine, vinblastine, vincristine, midazolam,

triazolam, and alprazolam; concurrent use should

be undertaken with caution. Concurrent use with

drugs that significantly inhibit the CYP3A4 enzyme

system (including ketoconazole, itraconazole,

nefazodone, clarithromycin, ritonavir, nelfinavir,

and diltiazem) mayqblood levels and effects

of aprepitant. Concurrent use with drugs that induce

the CYP3A4 enzyme system including rifampin,

carbamazepine, and phenytoin maypblood levels

and effects of aprepitant.qblood levels and effects of

dexamethasone (regimen reflects a 50% dosep); a

similar effect occurs with methylprednisolone (pIV

dose by 25%,pPO dose by 50% when used concurrently).

Maypthe effects of warfarin (careful monitoring

for 2 wk recommended), oral contraceptives

(use alternate method), and phenytoin.

Route/Dosage

Prevention of Nausea and Vomiting Associated

with Highly Emetogenic Chemotherapy

PO (Adults): Capsules or suspension—125 mg

given 1 hr prior to chemotherapy (Day 1) (with dexamethasone

12 mg PO given 30 min prior to chemotherapy

and a 5-HT3 antagonist given prior to chemotherapy),

then 80 mg once daily for 2 days (Days 2 and 3)

(with dexamethasone 8 mg once daily for 3 days [Days

2–4]).

IV (Adults): 150 mg given 30 min prior to chemotherapy

on Day 1 (with dexamethasone 12 mg PO given 30

min prior to chemotherapy and a 5-HT3 antagonist

given prior to chemotherapy). Continue dexamethasone

on Days 2–4 (8 mg PO on Day 2, 8 mg twice daily

on Days 3 and 4).

PO (Children 12 yr): Capsules—125 mg given 1

hr prior to chemotherapy (Day 1) (with PO dexamethasone

at 50% of recommended dose given 30 min prior

to chemotherapy and a 5-HT3 antagonist given prior to

chemotherapy), then 80 mg once daily for 2 days (Days

2 and 3) (with PO dexamethasone at 50% of recommended

dose once daily for 3 days [Days 2–4]).

PO (Children 6 mo–12 yr and 6 kg): Suspension—

3 mg/kg (max dose125 mg) given 1 hr

prior to chemotherapy (Day 1) (with PO dexamethasone

at 50% of recommended dose given 30 min prior

to chemotherapy and a 5-HT3 antagonist given prior to

chemotherapy), then 2 mg/kg (max dose80 mg)

once daily for 2 days (Days 2 and 3) (with PO dexamethasone

at 50% of recommended dose once daily for 3

days [Days 2–4]).

Prevention of Nausea and Vomiting Associated

with Moderately Emetogenic

Chemotherapy

PO (Adults): Capsules or suspension—125 mg

given 1 hr prior to chemotherapy (Day 1) (with dexamethasone

12 mg PO given 30 min prior to chemotherapy

and a 5-HT3 antagonist), then 80 mg once daily for

2 days (Days 2 and 3).

IV (Adults): 150 mg given 30 min prior to chemotherapy

on Day 1 (with dexamethasone 12 mg PO given 30

min prior to chemotherapy and a 5-HT3 antagonist).

PO (Children 12 yr): Capsules—125 mg given 1

hr prior to chemotherapy (Day 1) (with PO dexamethasone

at 50% of recommended dose given 30 min prior

to chemotherapy and a 5-HT3 antagonist), then 80 mg

once daily for 2 days (Days 2 and 3).

PO (Children 6 mo–12 yr and 6 kg): Suspension—

3 mg/kg (max dose125 mg) given 1 hr

prior to chemotherapy (Day 1) (with PO dexamethasone

at 50% of recommended dose given 30 min prior

to chemotherapy and a 5-HT3 antagonist given prior to

chemotherapy), then 2 mg/kg (max dose80 mg)

once daily for 2 days (Days 2 and 3) (with PO dexamethasone

at 50% of recommended dose once daily for 3

days [Days 2–4]).

Prevention of Postoperative Nausea and

Vomiting

PO (Adults): 40 mg given within 3 hr prior to induction

of anesthesia.

Availability (generic available)

Capsules: 40 mg, 80 mg, 125 mg. Lyophilized powder:

150 mg/vial. Powder for oral suspension (requires

reconstitution): 125 mg/pouch.