Emend

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

 



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1. NAME OF THE MEDICINAL PRODUCT

EMEND 40 mg hard capsules

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains 40 mg of aprepitant.

Excipient with known effect
Each capsule contains 40 mg of sucrose.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Hard capsule.

Capsules are opaque with a white body and mustard yellow cap with “464” and “40 mg” printed 
radially in black ink on the body.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

EMEND 40 mg is indicated for the prevention of postoperative nausea and vomiting (PONV) in 
adults.

4.2 Posology and method of administration

Posology
Clinical treatment guidelines should be considered as regards the need for prophylactic treatment 
against postoperative nausea and vomiting (PONV).

The recommended oral dose of EMEND is a single 40 mg dose within 3 hours prior to induction of 
anaesthesia.

Special populations
Elderly ( 65 years)
No dose adjustment is necessary for the elderly (see section 5.2).

Gender
No dose adjustment is necessary based on gender (see section 5.2).

Renal impairment
No dose adjustment is necessary for patients with renal impairment or for patients with end stage renal 
disease undergoing haemodialysis (see section 5.2).

Hepatic impairment
No dose adjustment is necessary for patients with mild hepatic impairment. There are limited data in 
patients with moderate hepatic impairment and no data in patients with severe hepatic impairment. 
Aprepitant should be used with caution in these patients (see sections 4.4 and 5.2).

 



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Paediatric population
The safety and efficacy of EMEND 40 mg in children and adolescents below 18 years of age has not 
yet been established. Currently available data are described in sections 5.1 and 5.2, but no 
recommendation on a posology can be made.

Method of administration
The hard capsule should be swallowed whole.
EMEND may be taken with or without food.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Patients with moderate to severe hepatic impairment
There are limited data in patients with moderate hepatic impairment and no data in patients with 
severe hepatic impairment. EMEND should be used with caution in these patients (see section 5.2).

CYP3A4 interactions
EMEND (40 mg) should be used with caution in patients receiving concomitant administration of 
pimozide, terfenadine, astemizole, cisapride or ergot alkaloid derivatives. Inhibition of cytochrome 
P450 isoenzyme 3A4 (CYP3A4) by aprepitant could result in elevated plasma concentrations of these 
active substances, potentially causing serious adverse reactions (see section 4.5).

Co-administration with hormonal contraceptives
The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration 
of EMEND. Alternative non-hormonal back-up methods of contraception should be used during 
treatment with EMEND and for 2 months following the last dose of EMEND (see section 4.5).

For further information on interaction potential of aprepitant at higher and multiple doses, please refer 
to the Summary of Product Characteristics for EMEND 80 mg hard capsules and EMEND 125 mg 
hard capsules.

Excipients
EMEND capsules contain sucrose. Patients with rare hereditary problems of fructose intolerance, 
glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Aprepitant is a substrate, and a dose-dependent inhibitor, and an inducer of CYP3A4. Aprepitant is 
also an inducer of CYP2C9. During treatment, the single 40 mg dose of aprepitant recommended for 
PONV results in a weak inhibition of CYP3A4. After the treatment, EMEND causes a transient mild 
induction of CYP2C9, CYP3A4 and glucuronidation. Aprepitant has been studied at higher doses. 
During treatment for chemotherapy induced nausea and vomiting (CINV), the 3-day 125 mg/80 mg 
regimen of aprepitant is a moderate inhibitor of CYP3A4. Aprepitant does not seem to interact with 
the P-glycoprotein transporter, as suggested by the lack of interaction of aprepitant with digoxin.

Effect of aprepitant on the pharmacokinetics of other active substances
CYP3A4 inhibition
As a weak inhibitor of CYP3A4, aprepitant (40 mg) can increase plasma concentrations of orally 
co-administered active substances that are metabolised through CYP3A4. The total exposure of orally 
administered CYP3A4 substrates may increase up to approximately 1.5-fold after a single 40 mg dose 
of aprepitant; the effect of aprepitant on the plasma concentrations of intravenously administered 
CYP3A4 substrates is expected to be smaller.

 



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EMEND 40 mg should be used with caution in patients receiving pimozide, terfenadine, astemizole, 
cisapride, or ergot alkaloid derivatives. Inhibition of CYP3A4 by aprepitant could result in elevated 
plasma concentrations of these active substances, potentially causing serious reactions.

Corticosteroids 
Dexamethasone: A single 40 mg dose of aprepitant, when co-administered with a single oral dose of 
dexamethasone 20 mg, increased the AUC of dexamethasone by 1.45-fold. No dose adjustment is 
recommended.

Methylprednisolone: Although the concomitant administration of methylprednisolone with the single 
40 mg dose of aprepitant has not been studied, a single 40 mg dose of aprepitant produces a weak 
inhibition of CYP3A4 and it is not expected to alter the plasma concentrations of methylprednisolone 
to a clinically significant degree. Therefore, no dose adjustment is recommended. 

Midazolam
The AUC of orally administrated midazolam increased by 1.2-fold when a single dose of 40 mg 
aprepitant was co-administered with a single oral dose of 2 mg midazolam; this effect was not 
considered clinically important.

Induction
As a mild inducer of CYP2C9, CYP3A4 and glucuronidation, aprepitant can decrease plasma 
concentrations of substrates eliminated by these routes within two weeks following initiation of 
treatment. For CYP2C9 and CYP3A4 substrates the induction is transient with a maximum effect 
reached after 3-5 days. The effect may be maintained for a few days, and is expected to be clinically 
insignificant by two weeks after the end of treatment with EMEND. Data are lacking regarding effects 
of CYP2C8 and CYP2C19. Co-administration of EMEND with active substances that are known to be 
metabolized by CYP2C9 (e.g., phenytoin, warfarin), may result in lower plasma concentrations of 
these active substances. Based on interaction studies with tolbutamide and oral contraceptives, total 
exposure of concomitantly administered active substances metabolised by CYP2C9 or CYP3A4 may 
be reduced up to 15-30 %.

Hormonal contraceptives
The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration 
of EMEND. Alternative non-hormonal back-up methods of contraception should be used during 
treatment with EMEND and for 2 months following the last dose of EMEND. 

5-HT3 antagonists
In clinical interaction studies, aprepitant did not have clinically important effects on the 
pharmacokinetics of ondansetron, granisetron, or hydrodolasetron (the active metabolite of 
dolasetron).

Effect of other medicinal products on the pharmacokinetics of aprepitant
Concomitant administration of EMEND with active substances that inhibit CYP3A4 activity (e.g., 
ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone, 
and protease inhibitors) should be approached cautiously, as the combination is expected to result in 
several-fold increased plasma concentrations of aprepitant (see section 4.4).

Concomitant administration of EMEND with active substances that strongly induce CYP3A4 activity 
(e.g., rifampicin, phenytoin, carbamazepine, phenobarbital) should be avoided as the combination 
results in reductions of the plasma concentrations of aprepitant that may result in decreased efficacy of 
EMEND. Concomitant administration of EMEND with herbal preparations containing St. John’s Wort 
(Hypericum perforatum) is not recommended.

Ketoconazole 
When a single 125 mg dose of aprepitant was administered on Day 5 of a 10-day regimen of 
400 mg/day of ketoconazole, a strong CYP3A4 inhibitor, the AUC of aprepitant increased 
approximately 5-fold and the mean terminal half-life of aprepitant increased approximately 3-fold.

 



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Rifampicin
When a single 375 mg dose of aprepitant was administered on Day 9 of a 14-day regimen of 
600 mg/day of rifampicin, a strong CYP3A4 inducer, the AUC of aprepitant decreased 91 % and the 
mean terminal half-life decreased 68 %. 

4.6 Fertility, pregnancy and lactation

Contraception in males and females
The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration 
of EMEND. Alternative non-hormonal back-up methods of contraception should be used during 
treatment with EMEND and for 2 months following the last dose of EMEND (see sections 4.4 and 
4.5).

Pregnancy
For aprepitant no clinical data on exposed pregnancies are available. In animal studies there was no 
indication of direct or indirect harmful effects with respect to pregnancy, embryonal/foetal 
development, parturition or postnatal development (see section 5.3). The potential effects on 
reproduction of alterations in neurokinin regulation are unknown. EMEND should not be used during 
pregnancy unless clearly necessary.

Breast-feeding
Aprepitant is excreted in the milk of lactating rats. It is not known whether aprepitant is excreted in 
human milk; therefore, breast-feeding is not recommended during treatment with EMEND.

Fertility
Fertility studies did not indicate direct or indirect harmful effects with respect to mating performance, 
fertility, embryonic/foetal development, or sperm count and motility (see section 5.3).

4.7 Effects on ability to drive and use machines

EMEND may have minor influence on the ability to drive and use machines. Dizziness and fatigue 
may occur following administration of EMEND (see section 4.8).

4.8 Undesirable effects

Summary of the safety profile
The safety profile of aprepitant was evaluated in approximately 6,500 adults.

Adverse reactions were reported in approximately 4 % of adults treated with 40 mg aprepitant 
compared with approximately 6 % of patients treated with 4 mg ondansetron intravenously. In 
controlled clinical studies in adults receiving general anaesthesia, 564 patients were administered 
40 mg aprepitant orally and 538 patients were administered 4 mg ondansetron intravenously. Most 
adverse reactions reported in these clinical studies were described as mild to moderate in intensity. 

The most common adverse reaction reported at a greater incidence in adults treated with 40 mg 
aprepitant (1.1 %) than with ondansetron (1.0 %) was ALT increased.

Tabulated list of adverse reactions
The following adverse reactions were observed in PONV studies in adults treated with aprepitant at a 
greater incidence than with ondansetron or in postmarketing use:

Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon 
(≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000) and very rare (< 1/10,000), not known (cannot 
be estimated from the available data).

 



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System organ class Adverse reaction Frequency
Immune system disorders hypersensitivity reactions including 

anaphylactic reactions
not known

Psychiatric disorders insomnia uncommon
Nervous system disorders dysarthria, hypoaesthesia, sensory disturbance uncommon
Eye disorders miosis, visual acuity reduced uncommon
Cardiac disorders bradycardia uncommon
Respiratory, thoracic and 
mediastinal disorders

dyspnoea, wheezing uncommon

Gastrointestinal disorders abdominal pain upper, bowel sounds 
abnormal, dry mouth, nausea, stomach 
discomfort, constipation*, sub-ileus*

uncommon

Skin and subcutaneous tissue 
disorders

pruritus, rash, urticaria, Stevens-Johnson 
syndrome/toxic epidermal necrolysis

not known

Investigations ALT increased common
*Reported in patients taking a higher dose of aprepitant.

Description of selected adverse reactions
Additional adverse reactions were observed in adults treated with the aprepitant (125 mg/80 mg) 
regimen for chemotherapy induced nausea and vomiting (CINV) and at a greater incidence than with 
standard therapy: abdominal distension, abdominal pain, acne, anaemia, anxiety, AST increased, 
asthenia, blood alkaline phosphatase increased, blood sodium decreased, candidiasis, cardiovascular 
disorder, chest discomfort, cognitive disorder, conjunctivitis, cough, decreased appetite, disorientation, 
dizziness, duodenal ulcer perforation, dysgeusia, dyspepsia, dysuria, eructation, euphoric mood, faeces 
hard, fatigue, febrile neutropenia, flatulence, gait disturbance, gastroesophageal reflux disease, glucose 
urine present, hiccups, hot flush, hyperhidrosis, lethargy, malaise, muscle spasms, muscular weakness, 
nausea*, neutropenic colitis, neutrophil count decreased, oedema, oropharyngeal pain, palpitations, 
photosensitivity reaction, pollakiuria, polydipsia, postnasal drip, rash pruritic, red blood cells urine 
positive, seborrhoea, skin lesion, sneezing, somnolence, staphylococcal infection, stomatitis, throat 
irritation, tinnitus, urine output increased, vomiting*, weight decreased.
*Nausea and vomiting were efficacy parameters in the first 5 days of post-chemotherapy treatment and were 
reported as reactions only thereafter.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

In the event of overdose, EMEND should be discontinued and general supportive treatment and 
monitoring should be provided. Because of the antiemetic activity of aprepitant, emesis induced by a 
medicinal product may not be effective.

Aprepitant cannot be removed by haemodialysis.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antiemetics and antinauseants, ATC code: A04AD12

Aprepitant is a selective high-affinity antagonist at human substance P neurokinin 1 (NK1) receptors.

 

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In 2 multicentre, randomised, double-blind, active comparator-controlled, parallel-group phase III 
clinical studies in adults, aprepitant was compared with ondansetron for the prevention of PONV in 
1,658 patients undergoing open abdominal surgery. The majority of adults were women (> 90 %), 
mainly undergoing gynaecological surgery. Patients were randomised to receive 40 mg aprepitant, 
125 mg aprepitant, or 4 mg ondansetron. Aprepitant was given orally with 50 mL of water 1 to 3 hours 
before anaesthesia. Ondansetron was given intravenously immediately before induction of anaesthesia. 
The antiemetic activity of aprepitant was evaluated during the 0 to 48 hour period following the end of 
surgery.

The results show that a higher percentage of post-surgical adults experienced complete response (no 
emesis and no use of rescue) with aprepitant 40 mg than with ondansetron 4 mg (lower bound of C.I. 
is 0.0 indicating borderline significance) as described in Table 1.

Table 1
Percent of post-operative adults responding by treatment group

Combined results from 2 Phase III trials

Aprepitant
40 mg orally

(N=541)

Ondansetron
4 mg intravenously

(N=526)

Percentage point
difference (%) §

and 95 % C.I. #

n/m (%) n/m (%) % 95 % C.I.

Complete response (0-24 
hours) †

298/541 (55.1) 258/526 (49.0) 5.9 (0.0, 11.8)

† Complete response: No emesis and no use of rescue
§ Difference (%) calculated as Aprepitant 40 mg minus Ondansetron 4 mg
# Difference (%) and 95 % C.I. calculated using stratified Miettinen-Nurminen method using Cochran-

Mantel-Haenszel weights

The reduction in risk for a vomiting episode over the 0 to 24 hour period with aprepitant 40 mg 
relative to ondansetron 4 mg was 53.3 % (95 % C.I.: 35.3 to 66.3) in an analysis that censors patients 
at the time of rescue use.

Paediatric population
The safety and exploratory efficacy of aprepitant were evaluated in a Phase I clinical study (n=50) 
using a 40 mg powder for oral suspension. The percentage of subjects reporting no vomiting over the 
first 24 hours following surgery was similar for subjects receiving aprepitant versus ondansetron. No 
new safety concerns were identified. However, the data from this small study do not support a 
conclusion on the optimal dosing regimen. Further studies evaluating the use of aprepitant in 
paediatric patients are on-going (see section 4.2 for information on paediatric use).

5.2 Pharmacokinetic properties

Aprepitant displays non-linear pharmacokinetics. Both clearance and absolute bioavailability decrease 
with increasing dose.

Absorption
The mean absolute oral bioavailability of aprepitant is 67 % for the 80 mg capsule and 59 % for the 
125 mg capsule. The mean peak plasma concentration (Cmax) of aprepitant occurred at approximately 
4 hours (tmax).

Following oral administration of a single 40 mg dose of EMEND in the fasted state, the AUC0-
(mean ± SD) was 8.0 ± 2.1 µg  h/mL and the Cmax was 0.7 ± 0.24 µg/mL. The median tmax was 
3.0 hours.

Concomitant intake of a 40 mg dose with a standard breakfast decreased the aprepitant Cmax by 18 % 
but did not affect AUC. This is not considered to be clinically important.

 



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Distribution
Aprepitant is highly protein bound, with a mean of 97 %. The geometric mean apparent volume of 
distribution at steady state (Vdss) is approximately 66 L in humans.

Biotransformation
Aprepitant undergoes extensive metabolism. In healthy young adults, aprepitant accounts for 
approximately 19 % of the radioactivity in plasma over 72 hours following a single intravenous 
administration 100 mg dose of [14C]-fosaprepitant, a prodrug for aprepitant, indicating a substantial 
presence of metabolites in the plasma. Twelve metabolites of aprepitant have been identified in human 
plasma. The metabolism of aprepitant occurs largely via oxidation at the morpholine ring and its side 
chains and the resultant metabolites were only weakly active. In vitro studies using human liver 
microsomes indicate that aprepitant is metabolised primarily by CYP3A4 and potentially with minor 
contribution by CYP1A2 and CYP2C19.

Elimination
Aprepitant is not excreted unchanged in urine. Metabolites are excreted in urine and via biliary 
excretion in faeces. Following a single intravenously administered 100 mg dose of [14C]-fosaprepitant, 
a prodrug for aprepitant to healthy subjects, 57 % of the radioactivity was recovered in urine and 45 % 
in faeces.

The plasma clearance of aprepitant is dose-dependent, decreasing with increased dose and ranged from 
approximately 60 to 72 mL/min in the therapeutic dose range. The terminal half-life is approximately 
9 hours after administration of a single 40 mg dose.

Pharmacokinetics in special populations
Elderly: Following oral administration of a single 125 mg dose of aprepitant on Day 1 and 80 mg once 
daily on Days 2 through 5, the AUC0-24hr of aprepitant was 21 % higher on Day 1 and 36 % higher on 
Day 5 in elderly ( 65 years) relative to younger adults. The Cmax was 10 % higher on Day 1 and 24 % 
higher on Day 5 in elderly relative to younger adults. These differences are not considered clinically 
meaningful. No dose adjustment for EMEND is necessary in elderly patients.

Gender: Following oral administration of a single 125 mg dose of aprepitant, the Cmax for aprepitant is 
16 % higher in females as compared with males. The half-life of aprepitant is 25 % lower in females 
as compared with males and its tmax occurs at approximately the same time. These differences are not 
considered clinically meaningful. No dose adjustment for EMEND is necessary based on gender.

Hepatic impairment: Mild hepatic impairment (Child-Pugh class A) does not affect the 
pharmacokinetics of aprepitant to a clinically relevant extent. No dose adjustment is necessary for 
patients with mild hepatic impairment. Conclusions regarding the influence of moderate hepatic 
impairment (Child-Pugh class B) on aprepitant pharmacokinetics cannot be drawn from available data. 
There are no clinical or pharmacokinetic data in patients with severe hepatic impairment (Child-Pugh 
class C).

Renal impairment: A single 240 mg dose of aprepitant was administered to patients with severe renal 
impairment (CrCl < 30 mL/min) and to patients with end stage renal disease (ESRD) requiring 
haemodialysis.

In patients with severe renal impairment, the AUC0- of total aprepitant (unbound and protein bound) 
decreased by 21 % and Cmax decreased by 32 %, relative to healthy subjects. In patients with ESRD 
undergoing haemodialysis, the AUC0- of total aprepitant decreased by 42 % and Cmax decreased by 
32 %. Due to modest decreases in protein binding of aprepitant in patients with renal disease, the AUC 
of pharmacologically active unbound aprepitant was not significantly affected in patients with renal 
impairment compared with healthy subjects. Haemodialysis conducted 4 or 48 hours after dosing had 
no significant effect on the pharmacokinetics of aprepitant; less than 0.2 % of the dose was recovered 
in the dialysate.

 



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No dose adjustment for EMEND is necessary for patients with renal impairment or for patients with 
ESRD undergoing haemodialysis.

Paediatric population: In a study using a powder for oral suspension formulation, a single dose of 
40 mg aprepitant administered to adolescent patients (aged 12 through 17 years) resulted in a mean 
AUC0-48hr of 6 µg/mL with a mean peak plasma concentration (Cmax) of 0.5 µg/mL occurring at 
approximately 4 hours. Administration of body surface area adjusted doses to patients 6 months to less 
than 12 years achieved a mean AUC0-48hr above 4 µg/mL with a mean Cmax above 0.5 µg/mL occurring 
at approximately 3 hours.

Relationship between concentration and effect
Using a highly specific NK1-receptor tracer, positron emission tomography (PET) studies in healthy 
young men have shown that aprepitant penetrates into the brain and occupies NK1 receptors in a dose-
and plasma-concentration-dependent manner. Aprepitant plasma concentrations achieved with the 
3-day regimen of EMEND are predicted to provide greater than 95 % occupancy of brain NK1
receptors.

5.3 Preclinical safety data

Pre-clinical data reveal no special hazard for humans based on conventional studies of single and 
repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and development. 
It should be noted that systemic exposure in adult male rats was lower than the therapeutic exposure in 
humans at 40 mg. Consequently, no adequate assessment of potential effects on male fertility in rats 
can be made. However, in a 9 month study in dogs, no organ weight changes nor gross or 
histomorphologic findings were present in male reproductive organs at systemic exposures 35-fold 
above the therapeutic exposure in humans at 40 mg. Although no adverse effects were noted in 
reproduction studies when adult female animals were exposed 3.5-to 4-fold above the therapeutic 
exposure in humans at 40 mg, the potential effects on reproduction of alterations in neurokinin 
regulation are unknown.

In a juvenile toxicity study in rats treated from post natal day 10 to day 63 aprepitant led to an earlier
vaginal opening in females from 250 mg/kg b.i.d. and to a delayed preputial separation in males, from
10 mg/kg b.i.d. There were no margins to clinically relevant exposure. There were no 
treatment-related effects on mating, fertility or embryonic/foetal survival, and no pathological changes 
in the reproductive organs. In a juvenile toxicity study in dogs treated from post natal day 14 to 
day 42, a decreased testicular weight and Leydig cell size were seen in the males at 6 mg/kg/day and 
increased uterine weight, hypertrophy of the uterus and cervix, and oedema of vaginal tissues were 
seen in females from 4 mg/kg/day. There were no margins to clinically relevant exposure of 
aprepitant. For short term treatment according to recommended dose regimen these findings are
considered unlikely to be clinically relevant.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Capsule content
Sucrose
Microcrystalline cellulose (E 460)
Hydroxypropylcellulose (E 463)
Sodium laurilsulfate

Capsule shell
Gelatin
Titanium dioxide (E 171)
Yellow iron oxide (E 172)

 



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Printing ink
Shellac
Potassium hydroxide
Black iron oxide (E 172)

6.2 Incompatibilities

Not applicable.

6.3 Shelf-life

4 years

6.4 Special precautions for storage

Store in the original package in order to protect from moisture.

6.5 Nature and contents of container

Different pack sizes are available:

Aluminium blister containing one 40 mg capsule.
5 Aluminium blisters each containing one 40 mg capsule.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements for disposal.

7. MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

8. MARKETING AUTHORISATION NUMBER

EU/1/03/262/007
EU/1/03/262/008

9. DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION

Date of first authorisation: 11 November 2003
Date of latest renewal: 22 September 2008

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.

 



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1. NAME OF THE MEDICINAL PRODUCT

EMEND 165 mg hard capsules

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains 165 mg of aprepitant.

Excipient with known effect
Each capsule contains 165 mg of sucrose.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Hard capsule.

Capsules are opaque with a light blue cap and a white body with “466” and “165 mg” printed radially 
in black ink on one side of the body and the Merck logo on the other side.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Prevention of acute and delayed nausea and vomiting associated with highly emetogenic 
cisplatin-based cancer chemotherapy in adults. 

Prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy in 
adults.

EMEND 165 mg is given as part of combination therapy (see section 4.2).

4.2 Posology and method of administration

Posology
EMEND 165 mg is given on Day 1 only, approximately one hour before the start of chemotherapy, as 
part of a regimen that includes a corticosteroid and a 5-HT3 antagonist. 

The following regimens are recommended in adults for the prevention of nausea and vomiting 
associated with emetogenic cancer chemotherapy:

 



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Highly Emetogenic Chemotherapy Regimen
Day 1 Day 2 Day 3 Day 4

EMEND 165 mg orally none none none
Dexamethasone 12 mg orally 8 mg orally 8 mg orally 

twice daily
8 mg orally 
twice daily

5-HT3 antagonists Standard dose of 
5-HT3 antagonists.

See the product 
information for the 

selected 5-HT3
antagonist for the 
appropriate dosing 

information

none none none

Dexamethasone should be administered 30 minutes prior to chemotherapy treatment on Day 1 and in 
the morning on Days 2 to 4. Dexamethasone should also be administered in the evenings on Days 3 
and 4. The dose of dexamethasone accounts for active substance interactions.

Moderately Emetogenic Chemotherapy Regimen
Day 1

EMEND 165 mg orally
Dexamethasone 12 mg orally

5-HT3 antagonists Standard dose of 5-HT3
antagonists. See the

product information for 
the selected 5-HT3
antagonist for the 
appropriate dosing 

information

Dexamethasone should be administered 30 minutes prior to chemotherapy treatment on Day 1. The 
dose of dexamethasone accounts for active substance interactions.

Efficacy data in combination with other corticosteroids and 5-HT3 antagonists are limited. For 
additional information on the co-administration with corticosteroids, see section 4.5. Please refer to the 
Summary of Product Characteristics of co-administered 5-HT3 antagonist medicinal products.

Fosaprepitant 150 mg, a lyophilised prodrug of aprepitant for intravenous administration, is also 
available as a single dose and may be used as an alternative to oral EMEND 165 mg.

Special populations
Elderly ( 65 years)
No dose adjustment is necessary for the elderly (see section 5.2).

Gender
No dose adjustment is necessary based on gender (see section 5.2).

Renal impairment
No dose adjustment is necessary for patients with renal impairment or for patients with end stage renal 
disease undergoing haemodialysis (see section 5.2).

Hepatic impairment
No dose adjustment is necessary for patients with mild hepatic impairment. There are limited data in 
patients with moderate hepatic impairment and no data in patients with severe hepatic impairment. 
Aprepitant should be used with caution in these patients (see sections 4.4 and 5.2).

 



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Paediatric population
The safety and efficacy of EMEND 165 mg in children and adolescents below 18 years of age has not 
been established. No data are available. Other pharmaceutical forms/strengths may be more 
appropriate for administration to this population.

Method of administration
The hard capsule should be swallowed whole.
EMEND may be taken with or without food.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Co-administration with pimozide, terfenadine, astemizole or cisapride (see section 4.5).

4.4 Special warnings and precautions for use

Patients with moderate to severe hepatic impairment
There are limited data in patients with moderate hepatic impairment and no data in patients with 
severe hepatic impairment. EMEND should be used with caution in these patients (see section 5.2).

CYP3A4 interactions
EMEND should be used with caution in patients receiving concomitant active substances that are 
metabolised primarily through CYP3A4 and with a narrow therapeutic range, such as cyclosporine, 
tacrolimus, sirolimus, everolimus, alfentanil, ergot alkaloid derivatives, fentanyl, and quinidine (see 
section 4.5). Additionally, concomitant administration with irinotecan should be approached with 
particular caution as the combination might result in increased toxicity.

Co-administration with warfarin (a CYP2C9 substrate)
In patients on chronic warfarin therapy, the International Normalised Ratio (INR) should be monitored 
closely during treatment with EMEND and for 14 days following the use of EMEND (see section 4.5).

Co-administration with hormonal contraceptives
The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration 
of EMEND. Alternative non-hormonal back-up methods of contraception should be used during 
treatment with EMEND and for 2 months following the last dose of EMEND (see section 4.5).

Excipients
EMEND capsules contain sucrose. Patients with rare hereditary problems of fructose intolerance, 
glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Aprepitant is a substrate, a moderate inhibitor, and an inducer of CYP3A4. Aprepitant is also an 
inducer of CYP2C9. During treatment with EMEND, CYP3A4 is inhibited for up to 4 days. EMEND 
causes a transient mild induction of CYP2C9, CYP3A4 and glucuronidation approximately one week 
after treatment. Aprepitant does not seem to interact with the P-glycoprotein transporter, as suggested 
by the lack of interaction of aprepitant with digoxin.

Effect of aprepitant on the pharmacokinetics of other active substances
CYP3A4 inhibition
As a moderate inhibitor of CYP3A4, aprepitant can increase plasma concentrations of co-administered 
active substances that are metabolised through CYP3A4. The total exposure of orally administered
CYP3A4 substrates may increase up to approximately 3-fold for 2 days following a single 165 mg 
dose of EMEND and decreasing to baseline approximately 4 days after dosing of 165 mg EMEND. 
The effect of aprepitant on the plasma concentrations of intravenously administered CYP3A4 
substrates is expected to be smaller. EMEND must not be used concurrently with pimozide, 

 



14

terfenadine, astemizole, or cisapride (see section 4.3). Inhibition of CYP3A4 by aprepitant could result 
in elevated plasma concentrations of these active substances, potentially causing serious or life-
threatening reactions. Caution is advised during concomitant administration of EMEND and active 
substances that are metabolised primarily through CYP3A4 and with a narrow therapeutic range, such 
as cyclosporine, tacrolimus, sirolimus, everolimus, alfentanil, diergotamine, ergotamine, fentanyl, and 
quinidine (see section 4.4).

Corticosteroids
Dexamethasone: Interaction studies with aprepitant 165 mg and dexamethasone have not been 
conducted; however, the following study with 200 mg of aprepitant should be considered when using 
EMEND 165 mg with oral dexamethasone. Aprepitant, when given as a single dose of 200 mg in the 
fed state (standard light breakfast) on Day 1 with oral dexamethasone, co-administered orally as 12 mg 
on Day 1 and 8 mg on Days 2 through 4, increased the AUC0-24hr of dexamethasone by 2.1- and 
2.3-fold on Days 1 and 2, to a lesser extent (1.4-fold increase) on Day 3, and had no effect on Day 4 
(1.1-fold). The daily dose of dexamethasone on Days 1 and 2 should be reduced by approximately 
50 % when co-administered with EMEND 165 mg on Day 1 to achieve exposures of dexamethasone 
similar to those obtained when given without EMEND 165 mg.

Methylprednisolone: Interaction studies with aprepitant 165 mg and methylprednisolone have not 
been conducted; however, the following study with the aprepitant 125 mg/80 mg regimen should be 
considered when using EMEND 165 mg with methylprednisolone. EMEND, when given as a regimen 
of 125 mg on Day 1 and 80 mg/day on Days 2 and 3, increased the AUC of methylprednisolone, a 
CYP3A4 substrate, by 1.3-fold on Day 1 and by 2.5-fold on Day 3, when methylprednisolone was 
co-administered intravenously as 125 mg on Day 1 and orally as 40 mg on Days 2 and 3. 

During continuous treatment with methylprednisolone, the AUC of methylprednisolone may decrease 
at later time points within 14 days following initiation of the EMEND dose, due to the inducing effect 
of aprepitant on CYP3A4. This effect may be expected to be more pronounced for orally administered 
methylprednisolone.

Chemotherapeutic medicinal products
Interaction studies with aprepitant 165 mg and chemotherapeutic medicinal products have not been 
conducted; however, based on studies with 3-day regimen of oral aprepitant and docetaxel and 
vinorelbine, EMEND 165 mg is not expected to have a clinically relevant interaction with 
intravenously administered docetaxel and vinorelbine. In pharmacokinetic studies, EMEND, when 
given as a regimen of 125 mg on Day 1 and 80 mg/day on Days 2 and 3, did not influence the 
pharmacokinetics of docetaxel administered intravenously on Day 1 or vinorelbine administered 
intravenously on Day 1 or Day 8. Because the effect of EMEND on the pharmacokinetics of orally 
administered CYP3A4 substrates is greater than the effect of EMEND on the pharmacokinetics of 
intravenously administered CYP3A4 substrates, an interaction with orally administered 
chemotherapeutic medicinal products metabolised primarily or partly by CYP3A4 (e.g., etoposide, 
vinorelbine) cannot be excluded. Caution is advised and additional monitoring may be appropriate in 
patients receiving medicinal products metabolized primarily or partly by CYP3A4 (see section 4.4). 
Post-marketing events of neurotoxicity, a potential adverse reaction of ifosfamide, have been reported 
after aprepitant and ifosfamide co-administration.

Immunosuppressants
Following a single 165 mg aprepitant dose, a transient moderate increase for two days possibly 
followed by a mild decrease in exposure of immunosuppressants metabolised by CYP3A4 (e.g.,
cyclosporine, tacrolimus, everolimus and sirolimus) is expected. Given the short duration of increased 
exposure, dose reduction of the immunosuppressant based on Therapeutic Dose Monitoring is not 
recommended on the day of and the day after administration of EMEND 165 mg.

Midazolam
Interaction studies with aprepitant 165 mg and midazolam have not been conducted; however, the 
following study with 200 mg of aprepitant should be considered when using EMEND 165 mg with 
medicinal products metabolised via CYP3A4. In a study with 2 mg midazolam orally co-administered 

 



15

with 200 mg aprepitant in the fed state (standard light breakfast), the AUC0-∞ of midazolam, a 
sensitive CYP3A4 substrate, was increased 3.2-fold on Day 1. No clinically important effect resulted 
on Day 4 (midazolam AUC0-∞ 1.2-fold increase) and a slight change in midazolam AUC0-∞ was 
observed on Day 8 (35 % decrease).

The potential effects of increased plasma concentrations of midazolam or other benzodiazepines 
metabolised via CYP3A4 (alprazolam, triazolam) should be considered when co-administering these 
medicinal products with EMEND 165 mg.

Induction
As a mild inducer of CYP2C9, CYP3A4 and glucuronidation, aprepitant can decrease plasma 
concentrations of substrates eliminated by these routes. This effect may become apparent 
approximately 7 days following the single dose administration of EMEND 165 mg. The effect is 
maintained for a few days, thereafter slowly declines and is clinically insignificant within 14 days after 
end of EMEND treatment. A single dose of aprepitant 200 mg on Day 1 co-administered with 
midazolam, a sensitive CYP3A4 substrate, on Days 1, 4 and 8 resulted in a 35 % reduction of 
midazolam AUC0-∞ on Day 8. It is anticipated that EMEND 165 mg would cause similar induction of 
CYP2C9, CYP3A4, and glucuronidation than that caused by the administration of the 3-day oral 
aprepitant regimen, for which a transient induction with its maximum effect 6 to 8 days after first 
aprepitant dose has been observed. The 3-day oral aprepitant regimen resulted in an about 30-35 % 
reduction in AUC of CYP2C9 substrates and up to a 64 % decrease in ethinyl estradiol trough 
concentrations. Data are lacking regarding effects on CYP2C8 and CYP2C19. Caution is advised 
when warfarin, acenocoumarol, tolbutamide, phenytoin or other active substances that are known to be 
metabolised by CYP2C9 are administered with EMEND 165 mg.

Warfarin
In patients on chronic warfarin therapy, the prothrombin time (INR) should be monitored closely 
during treatment and for 14 days following the use of EMEND 165 mg for chemotherapy induced 
nausea and vomiting (see section 4.4). When a single 125 mg dose of EMEND was administered on 
Day 1 and 80 mg/day on Days 2 and 3 to healthy subjects who were stabilised on chronic warfarin 
therapy, there was no effect of EMEND on the plasma AUC of R(+) or S(-) warfarin determined on 
Day 3; however, there was a 34 % decrease in S(-) warfarin (a CYP2C9 substrate) trough 
concentration accompanied by a 14 % decrease in INR 5 days after completion of EMEND. 

Tolbutamide
EMEND, when given as 125 mg on Day 1 and 80 mg/day on Days 2 and 3, decreased the AUC of 
tolbutamide (a CYP2C9 substrate) by 23 % on Day 4, 28 % on Day 8, and 15 % on Day 15, when a 
single dose of tolbutamide 500 mg was administered orally prior to the administration of the 3-day 
regimen of EMEND and on Days 4, 8, and 15.

Hormonal contraceptives
The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration 
of EMEND. Alternative non-hormonal back-up methods of contraception should be used during 
treatment with EMEND and for 2 months following the last dose of EMEND. 

In a clinical study, single doses of an oral contraceptive containing ethinyl estradiol and norethindrone 
were administered on Days 1 through 21 with EMEND, given as a regimen of 125 mg on Day 8 and 
80 mg/day on Days 9 and 10 with ondansetron 32 mg intravenously on Day 8 and oral dexamethasone 
given as 12 mg on Day 8 and 8 mg/day on Days 9, 10, and 11. During days 9 through 21 in this study, 
there was as much as a 64 % decrease in ethinyl estradiol trough concentrations and as much as a 60 % 
decrease in norethindrone trough concentrations. 

5-HT3 antagonists
In clinical interaction studies, aprepitant, when given as a regimen of 125 mg on Day 1 and 80 mg on 
Days 2 and 3, did not have clinically important effects on the pharmacokinetics of ondansetron, 
granisetron, or hydrodolasetron (the active metabolite of dolasetron).

 



16

Effect of other medicinal products on the pharmacokinetics of aprepitant
Concomitant administration of EMEND with active substances that inhibit CYP3A4 activity (e.g., 
ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone, 
and protease inhibitors) should be approached cautiously, as the combination is expected to result in 
several-fold increased plasma concentrations of aprepitant (see section 4.4). 

Concomitant administration of EMEND with active substances that strongly induce CYP3A4 activity 
(e.g., rifampicin, phenytoin, carbamazepine, phenobarbital) should be avoided as the combination 
results in reductions of the plasma concentrations of aprepitant that may result in decreased efficacy of 
EMEND. Concomitant administration of EMEND with herbal preparations containing St. John’s Wort 
(Hypericum perforatum) is not recommended.

Ketoconazole
When a single 125 mg dose of aprepitant was administered on Day 5 of a 10-day regimen of 
400 mg/day of ketoconazole, a strong CYP3A4 inhibitor, the AUC of aprepitant increased 
approximately 5-fold and the mean terminal half-life of aprepitant increased approximately 3-fold.

Rifampicin
When a single 375 mg dose of aprepitant was administered on Day 9 of a 14-day regimen of 
600 mg/day of rifampicin, a strong CYP3A4 inducer, the AUC of aprepitant decreased 91 % and the 
mean terminal half-life decreased 68 %. 

4.6 Fertility, pregnancy and lactation

Contraception in males and females
The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration 
of EMEND. Alternative non-hormonal back-up methods of contraception should be used during 
treatment with EMEND and for 2 months following the last dose of EMEND (see sections 4.4 and 
4.5).

Pregnancy
For aprepitant no clinical data on exposed pregnancies are available. The potential for reproductive 
toxicity of aprepitant has not been fully characterised, since exposure levels above the therapeutic 
exposure in humans at the 125 mg/80 mg and 165 mg doses could not be attained in animal studies. 
These studies did not indicate direct or indirect harmful effects with respect to pregnancy, 
embryonal/foetal development, parturition or postnatal development (see section 5.3). The potential 
effects on reproduction of alterations in neurokinin regulation are unknown. EMEND should not be 
used during pregnancy unless clearly necessary.

Breast-feeding
Aprepitant is excreted in the milk of lactating rats. It is not known whether aprepitant is excreted in 
human milk; therefore, breast-feeding is not recommended during treatment with EMEND.

Fertility
The potential for effects of aprepitant on fertility has not been fully characterised because exposure 
levels above the therapeutic exposure in humans could not be attained in animal studies. These fertility 
studies did not indicate direct or indirect harmful effects with respect to mating performance, fertility, 
embryonic/foetal development, or sperm count and motility (see section 5.3).

4.7 Effects on ability to drive and use machines

EMEND may have minor influence on the ability to drive and use machines. Dizziness and fatigue 
may occur following administration of EMEND (see section 4.8).

 



17

4.8 Undesirable effects

Summary of the safety profile
The safety profile of aprepitant was evaluated in approximately 6,500 adults.

Based on a comparable pharmacokinetic/pharmacodynamic profile, the 1-day oral regimen of 
EMEND 165 mg is anticipated to have a similar safety and tolerability profile to that of the 1-day 
regimen of fosaprepitant 150 mg and the 3-day oral aprepitant regimen in chemotherapy patients (see 
section 5.2).

The most common adverse reactions reported at a greater incidence in adults treated with the 3-day 
oral aprepitant regimen than with standard therapy in patients receiving Highly Emetogenic 
Chemotherapy (HEC) were: hiccups (4.6 % versus 2.9 %), alanine aminotransferase (ALT) increased 
(2.8 % versus 1.1 %), dyspepsia (2.6 % versus 2.0 %), constipation (2.4 % versus 2.0 %), headache 
(2.0 % versus 1.8 %), and decreased appetite (2.0 % versus 0.5 %). The most common adverse 
reaction reported at a greater incidence in patients treated with the 3-day oral aprepitant regimen than 
with standard therapy in patients receiving Moderately Emetogenic Chemotherapy (MEC) was fatigue 
(1.4 % versus 0.9 %).

Tabulated list of adverse reactions
The following adverse reactions were observed in a pooled analysis of the HEC and MEC studies at a 
greater incidence with aprepitant than with standard therapy in adults or postmarketing use:

Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon 
(≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000) and very rare (< 1/10,000), not known (cannot 
be estimated from the available data).

System organ class Adverse reaction Frequency
Infection and infestations candidiasis, staphylococcal infection rare
Blood and lymphatic system 
disorders

febrile neutropenia, anaemia uncommon

Immune system disorders hypersensitivity reactions including 
anaphylactic reactions

not known

Metabolism and nutrition 
disorders

decreased appetite common
polydipsia rare

Psychiatric disorders anxiety uncommon
disorientation, euphoric mood rare

Nervous system disorders headache common
dizziness, somnolence uncommon
cognitive disorder, lethargy, dysgeusia rare

Eye disorders conjunctivitis rare
Ear and labyrinth disorders tinnitus rare
Cardiac disorders palpitations uncommon

bradycardia, cardiovascular disorder rare
Vascular disorders hot flush uncommon
Respiratory, thoracic and 
mediastinal disorders

hiccups common
oropharyngeal pain, sneezing, cough, 
postnasal drip, throat irritation

rare

Gastrointestinal disorders constipation, dyspepsia common
eructation, nausea*, vomiting*, 
gastroesophageal reflux disease, abdominal 
pain, dry mouth, flatulence

uncommon

duodenal ulcer perforation, stomatitis, 
abdominal distension, faeces hard, neutropenic 
colitis

rare

Skin and subcutaneous tissue rash, acne uncommon

 



18

System organ class Adverse reaction Frequency
disorders photosensitivity reaction, hyperhidrosis, 

seborrhoea, skin lesion, rash pruritic, 
Stevens-Johnson syndrome/toxic epidermal 
necrolysis

rare

pruritus, urticaria not known
Musculoskeletal and connective 
tissue disorders

muscular weakness, muscle spasms rare

Renal and urinary disorders dysuria uncommon
pollakiuria rare

General disorders and 
administration site conditions

fatigue common
asthenia, malaise uncommon
oedema, chest discomfort, gait disturbance rare

Investigations ALT increased common
AST increased, blood alkaline phosphatase 
increased

uncommon

red blood cells urine positive, blood sodium 
decreased, weight decreased, neutrophil count 
decreased, glucose urine present, urine output 
increased

rare

*Nausea and vomiting were efficacy parameters in the first 5 days of post-chemotherapy treatment and were 
reported as adverse reactions only thereafter.

Description of selected adverse reactions
The adverse reactions profiles in adults in the Multiple-Cycle extension of HEC and MEC studies for 
up to 6 additional cycles of chemotherapy were generally similar to those observed in Cycle 1.

In an additional active-controlled clinical study in 1,169 adult patients receiving the 3-day oral 
aprepitant regimen and HEC, the adverse reactions profile was generally similar to that seen in the 
other HEC studies with the 3-day oral aprepitant regimen.

Additional adverse reactions were observed in patients treated with aprepitant for postoperative nausea 
and vomiting (PONV) and a greater incidence than with ondansetron: abdominal pain upper, bowel 
sounds abnormal, constipation*, dysarthria, dyspnoea, hypoaesthesia, insomnia, miosis, nausea, 
sensory disturbance, stomach discomfort, sub-ileus*, visual acuity reduced, wheezing.
*Reported in patients taking a higher dose of aprepitant.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

In the event of overdose, EMEND should be discontinued and general supportive treatment and 
monitoring should be provided. Because of the antiemetic activity of aprepitant, emesis induced by a 
medicinal product may not be effective.

Aprepitant cannot be removed by haemodialysis.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antiemetics and antinauseants, ATC code: A04AD12

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


19

Aprepitant is a selective high-affinity antagonist at human substance P neurokinin 1 (NK1) receptors. 
Fosaprepitant, a prodrug of aprepitant, when administered intravenously is rapidly converted to 
aprepitant.

Based on a comparable pharmacokinetic/pharmacodynamic profile, the 1-day oral regimen of 
EMEND 165 mg is anticipated to have a similar efficacy profile to that of the 1-day regimen of 
fosaprepitant 150 mg and 3-day regimen of oral aprepitant (see section 5.2) 

3-day regimen of aprepitant in adults
In 2 randomised, double-blind studies encompassing a total of 1,094 adult patients receiving
chemotherapy that included cisplatin  70 mg/m2, aprepitant in combination with an 
ondansetron/dexamethasone regimen (see section 4.2) was compared with a standard regimen (placebo 
plus ondansetron 32 mg intravenously administered on Day 1 plus dexamethasone 20 mg orally on 
Day 1 and 8 mg orally twice daily on Days 2 to 4). Although a 32 mg intravenous dose of ondansetron 
was used in clinical trials, this is no longer the recommended dose. See the product information for the 
selected 5-HT3 antagonist for appropriate dosing information.

Efficacy was based on evaluation of the following composite measure: complete response (defined as 
no emetic episodes and no use of rescue therapy) primarily during Cycle 1. The results were evaluated 
for each individual study and for the 2 studies combined.

A summary of the key study results from the combined analysis is shown in Table 1.

Table 1
Percent of adult patients receiving Highly Emetogenic Chemotherapy responding 

by treatment group and phase — Cycle 1

COMPOSITE MEASURES

Aprepitant 
regimen

(N= 521) †

%

Standard 
therapy

(N= 524) †

%

Differences*

         %             (95 % CI)

Complete response (no emesis and no rescue therapy)
Overall (0-120 hours)
0-24 hours
25-120 hours

67.7
86.0
71.5

47.8
73.2
51.2

19.9
12.7
20.3

(14.0, 25.8)
(7.9, 17.6)
(14.5, 26.1)

INDIVIDUAL MEASURES
No emesis (no emetic episodes regardless of use of rescue therapy)

Overall (0-120 hours)
0-24 hours
25-120 hours

71.9
86.8
76.2

49.7
74.0
53.5

22.2
12.7
22.6

(16.4, 28.0)
(8.0, 17.5)
(17.0, 28.2)

No significant nausea (maximum VAS < 25 mm on a scale of 0-100 mm)
Overall (0-120 hours)
25-120 hours 

72.1
74.0

64.9
66.9

7.2
7.1

(1.6, 12.8)
(1.5, 12.6)

* The confidence intervals were calculated with no adjustment for gender and concomitant chemotherapy, which 
were included in the primary analysis of odds ratios and logistic models.
†  One patient in the Aprepitant regimen only had data in the acute phase and was excluded from the overall and 
delayed phase analyses; one patient in the Standard regimen only had data in the delayed phase and was 
excluded from the overall and acute phase analyses.

 



20

The estimated time to first emesis in the combined analysis is depicted by the Kaplan-Meier plot in 
Figure 1.

Figure 1
Percent of adult patients receiving Highly Emetogenic Chemotherapy 

who remain emesis free over time – Cycle 1

0 12 24 36 48 60 72 84 96 108 120
0

40%

50%

60%

70%

80%

90%

100%

P
e

rc
e

n
t 

o
f 

P
a

ti
e
n

ts

Aprepitant Regimen (N=520)
Standard Therapy (N=523)

Time (hours)

Statistically significant differences in efficacy were also observed in each of the 2 individual studies.

In the same 2 clinical studies, 851 adult patients continued into the Multiple-Cycle extension for up to 
5 additional cycles of chemotherapy. The efficacy of the aprepitant regimen was apparently 
maintained during all cycles.

In a randomised, double-blind study in a total of 866 adult patients (864 females, 2 males) receiving 
chemotherapy that included cyclophosphamide 750-1,500 mg/m2; or cyclophosphamide 
500-1,500 mg/m2 and doxorubicin (< 60 mg/m2) or epirubicin (< 100 mg/m2), aprepitant in 
combination with an ondansetron/dexamethasone regimen (see section 4.2) was compared with 
standard therapy (placebo plus ondansetron 8 mg orally (twice on Day 1, and every 12 hours on 
Days 2 and 3) plus dexamethasone 20 mg orally on Day 1).

Efficacy was based on evaluation of the composite measure: complete response (defined as no emetic 
episodes and no use of rescue therapy) primarily during Cycle 1.

 



21

A summary of the key study results is shown in Table 2.

Table 2
Percent of adult patients responding by treatment group and phase — Cycle 1

Moderately Emetogenic Chemotherapy

COMPOSITE MEASURES

Aprepitant 
regimen

(N= 433) †

%

Standard 
therapy

(N= 424)
%

Differences*

        %             (95 % CI)

Complete response (no emesis and no rescue therapy)
Overall (0-120 hours)
0-24 hours
25-120 hours

50.8
75.7
55.4

42.5
69.0
49.1

8.3
6.7
6.3

(1.6, 15.0)
(0.7, 12.7)
(-0.4, 13.0)

INDIVIDUAL MEASURES
No emesis (no emetic episodes regardless of use of rescue therapy)

Overall (0-120 hours)
0-24 hours
25-120 hours

75.7
87.5
80.8

58.7
77.3
69.1

17.0
10.2
11.7

(10.8, 23.2)
(5.1, 15.3)
(5.9, 17.5)

No significant nausea (maximum VAS < 25 mm on a scale of 0-100 mm)
Overall (0-120 hours)
0-24 hours
25-120 hours

60.9
79.5
65.3

55.7
78.3
61.5

5.3
1.3
3.9

(-1.3, 11.9)
(-4.2, 6.8)
(-2.6, 10.3)

* The confidence intervals were calculated with no adjustment for age category (< 55 years, ≥ 55 years) and 
investigator group, which were included in the primary analysis of odds ratios and logistic models.
† One patient in the Aprepitant regimen only had data in the acute phase and was excluded from the overall and 
delayed phase analyses.

In the same clinical study, 744 adult patients continued into the Multiple-Cycle extension for up to 
3 additional cycles of chemotherapy. The efficacy of the aprepitant regimen was apparently 
maintained during all cycles.

In a second multicentre, randomised, double-blind, parallel-group, clinical study, the aprepitant 
regimen was compared with standard therapy in 848 adult patients (652 females, 196 males) receiving 
a chemotherapy regimen that included any intravenous dose of oxaliplatin, carboplatin, epirubicin, 
idarubicin, ifosfamide, irinotecan, daunorubicin, doxorubicin; cyclophosphamide intravenously 
(< 1,500 mg/m2); or cytarabine intravenously (> 1 g/m2). Patients receiving the aprepitant regimen 
were receiving chemotherapy for a variety of tumour types including 52 % with breast cancer, 21 % 
with gastrointestinal cancers including colorectal cancer, 13 % with lung cancer and 6 % with 
gynaecological cancers. The aprepitant regimen in combination with an ondansetron/dexamethasone 
regimen (see section 4.2) was compared with standard therapy (placebo in combination with 
ondansetron 8 mg orally (twice on Day 1, and every 12 hours on Days 2 and 3) plus dexamethasone 
20 mg orally on Day 1).

Efficacy was based on the evaluation of the following primary and key secondary endpoints: No 
vomiting in the overall period (0 to 120 hours post-chemotherapy), evaluation of safety and 
tolerability of the aprepitant regimen for chemotherapy induced nausea and vomiting (CINV), and 
complete response (defined as no vomiting and no use of rescue therapy) in the overall period (0 to 
120 hours post-chemotherapy). Additionally, no significant nausea in the overall period (0 to 
120 hours post-chemotherapy) was evaluated as an exploratory endpoint, and in the acute and delayed 
phases as a post-hoc analysis.

A summary of the key study results is shown in Table 3.

 



22

Table 3
Percent of adult patients responding by treatment group and phase for Study 2 – Cycle 1

Moderately Emetogenic Chemotherapy

Aprepitant 
regimen
(N= 425)

%

Standard 
therapy

(N= 406)
%

Differences*

        %             (95 % CI)

Complete response (no emesis and no rescue therapy)
Overall (0-120 hours)
0-24 hours
25-120 hours

68.7

89.2
70.8

56.3

80.3
60.9

12.4
8.9
9.9

(5.9, 18.9)
(4.0, 13.8)
(3.5, 16.3)

No emesis (no emetic episodes regardless of use of rescue therapy)
Overall (0-120 hours)
0-24 hours
25-120 hours

76.2
92.0
77.9

62.1
83.7
66.8

14.1
8.3
11.1

(7.9, 20.3)
(3.9, 12.7)
(5.1, 17.1)

No significant nausea (maximum VAS < 25 mm on a scale of 0-100 mm)
Overall (0-120 hours)
0-24 hours
25-120 hours

73.6

90.9
74.9

66.4

86.3
69.5

7.2
4.6
5.4

(1.0, 13.4)
(0.2, 9.0)
(-0.7, 11.5)

*The confidence intervals were calculated with no adjustment for gender and region, which were included in the 
primary analysis using logistic models.

The benefit of aprepitant combination therapy in the full study population was mainly driven by the 
results observed in patients with poor control with the standard regimen such as in women, even 
though the results were numerically better regardless of age, tumour type or gender. Complete 
response to the aprepitant regimen and standard therapy, respectively, was reached in 209/324 (65 %) 
and 161/320 (50 %) in women and 83/101 (82 %) and 68/87 (78 %) of men.

1-day regimen of fosaprepitant 150 mg in adults

In a randomised, parallel, double-blind, active-controlled study, fosaprepitant 150 mg (N=1,147) was 
compared with a 3-day aprepitant regimen (N=1,175) in adult patients receiving a HEC regimen that 
included cisplatin (≥ 70 mg/m2). The fosaprepitant regimen consisted of fosaprepitant 150 mg on 
Day 1 in combination with intravenous ondansetron 32 mg on Day 1 and dexamethasone 12 mg on 
Day 1, 8 mg on Day 2, and 8 mg twice daily on Days 3 and 4. The aprepitant regimen consisted of 
aprepitant 125 mg on Day 1 and 80 mg/day on Days 2 and 3 in combination with intravenous 
ondansetron 32 mg on Day 1 and dexamethasone 12 mg on Day 1 and 8 mg daily on Days 2 
through 4. Fosaprepitant placebo, aprepitant placebo, and dexamethasone placebo (in the evenings on 
Days 3 and 4) were used to maintain blinding (see section 4.2). Although a 32 mg intravenous dose of 
ondansetron was used in clinical trials, this is no longer the recommended dose. See the product 
information for the selected 5-HT3 antagonist for appropriate dosing information.

Efficacy was based on evaluation of the following composite measures: complete response in both the 
overall and delayed phases and no vomiting in the overall phase. Fosaprepitant 150 mg was shown to 
be non-inferior to that of the 3-day regimen of aprepitant. A summary of the primary and secondary 
endpoints is shown in Table 4.

 



23

Table 4 
Percent of adult patients receiving Highly Emetogenic Chemotherapy 

responding by treatment group and phase — Cycle 1

ENDPOINTS* Fosaprepitant 
regimen

(N =1,106) **
%

Aprepitant regimen
(N =1,134) **

%

Difference†

(95 % CI)

Complete response‡

Overall§ 71.9 72.3 -0.4 (-4.1, 3.3)
Delayed phase§§ 74.3 74.2 0.1 (-3.5, 3.7)

No vomiting
Overall§ 72.9 74.6 -1.7 (-5.3, 2.0)     

*Primary endpoint is bolded.
**N: Number of patients included in the primary analysis of complete response.
†Difference and confidence interval (CI) were calculated using the method proposed by 
Miettinen and Nurminen and adjusted for Gender.
‡Complete response = no vomiting and no use of rescue therapy.
§Overall = 0 to 120 hours post-initiation of cisplatin chemotherapy.
§§Delayed phase = 25 to 120 hours post-initiation of cisplatin chemotherapy.

Paediatric population
Studies evaluating the use of aprepitant in paediatric patients are on-going (see section 4.2 for 
information on paediatric use).

5.2 Pharmacokinetic properties

Aprepitant displays non-linear pharmacokinetics. Both clearance and absolute bioavailability decrease 
with increasing dose.

Absorption
The AUC0-∞ of aprepitant following oral administration of 165 mg was equivalent to the AUC0-∞ of 
150 mg fosaprepitant administered intravenously, while the Cmax was 2.4-fold lower.

Following a single oral dose of aprepitant 165 mg to healthy volunteers, the mean AUC0-∞ of 
aprepitant was 32.5 µghr/mL and the mean maximal aprepitant concentration was 1.67 µg/mL.

The mean peak plasma concentration (Cmax) of aprepitant occurred at approximately 4 hours (Tmax). 
Oral administration of the capsule with a standard light breakfast and a high-fat breakfast resulted in 
an up to an 8 % and a 47 % increase in AUC0-∞ of aprepitant, respectively. This increase is not 
considered clinically relevant.

Distribution
Aprepitant is highly protein bound, with a mean of 97 %. The geometric mean apparent volume of 
distribution at steady state (Vdss) is approximately 66 L in humans.

Biotransformation
Aprepitant undergoes extensive metabolism. In healthy young adults, aprepitant accounts for 
approximately 19 % of the radioactivity in plasma over 72 hours following a single intravenous 
administration 100 mg dose of [14C]-fosaprepitant, a prodrug for aprepitant, indicating a substantial 
presence of metabolites in the plasma. Twelve metabolites of aprepitant have been identified in human 
plasma. The metabolism of aprepitant occurs largely via oxidation at the morpholine ring and its side 
chains and the resultant metabolites were only weakly active. In vitro studies using human liver 
microsomes indicate that aprepitant is metabolised primarily by CYP3A4 and potentially with minor 
contribution by CYP1A2 and CYP2C19.

 



24

Elimination
Aprepitant is not excreted unchanged in urine. Metabolites are excreted in urine and via biliary 
excretion in faeces. Following a single intravenously administered 100 mg dose of [14C]-fosaprepitant, 
a prodrug for aprepitant, to healthy subjects, 57 % of the radioactivity was recovered in urine and 
45 % in faeces.

The plasma clearance of aprepitant is dose-dependent, decreasing with increased dose and ranged from 
approximately 60 to 72 mL/min in the therapeutic dose range. The terminal half-life ranged from 
approximately 9 to 13 hours.

Pharmacokinetics in special populations
Elderly: Following oral administration of a single 125 mg dose of aprepitant on Day 1 and 80 mg once 
daily on Days 2 through 5, the AUC0-24hr of aprepitant was 21 % higher on Day 1 and 36 % higher on 
Day 5 in elderly ( 65 years) relative to younger adults. The Cmax was 10 % higher on Day 1 and 24 % 
higher on Day 5 in elderly relative to younger adults. These differences are not considered clinically 
meaningful. No dose adjustment for EMEND is necessary in elderly patients.

Gender: Following oral administration of a single 125 mg dose of aprepitant, the Cmax for aprepitant is 
16 % higher in females as compared with males. The half-life of aprepitant is 25 % lower in females 
as compared with males and its tmax occurs at approximately the same time. These differences are not 
considered clinically meaningful. No dose adjustment for EMEND is necessary based on gender.

Hepatic impairment: Mild hepatic impairment (Child-Pugh class A) does not affect the 
pharmacokinetics of aprepitant to a clinically relevant extent. No dose adjustment is necessary for 
patients with mild hepatic impairment. Conclusions regarding the influence of moderate hepatic 
impairment (Child-Pugh class B) on aprepitant pharmacokinetics cannot be drawn from available data. 
There are no clinical or pharmacokinetic data in patients with severe hepatic impairment (Child-Pugh 
class C).

Renal impairment: A single 240 mg dose of aprepitant was administered to patients with severe renal 
impairment (CrCl < 30 mL/min) and to patients with end stage renal disease (ESRD) requiring 
haemodialysis.

In patients with severe renal impairment, the AUC0- of total aprepitant (unbound and protein bound) 
decreased by 21 % and Cmax decreased by 32 %, relative to healthy subjects. In patients with ESRD 
undergoing haemodialysis, the AUC0- of total aprepitant decreased by 42 % and Cmax decreased by 
32 %. Due to modest decreases in protein binding of aprepitant in patients with renal disease, the AUC 
of pharmacologically active unbound aprepitant was not significantly affected in patients with renal 
impairment compared with healthy subjects. Haemodialysis conducted 4 or 48 hours after dosing had 
no significant effect on the pharmacokinetics of aprepitant; less than 0.2 % of the dose was recovered 
in the dialysate.

No dose adjustment for EMEND is necessary for patients with renal impairment or for patients with 
ESRD undergoing haemodialysis.

Relationship between concentration and effect
Using a highly specific NK1-receptor tracer, positron emission tomography (PET) studies in healthy 
young men have shown that aprepitant penetrates into the brain and occupies NK1 receptors in a dose-
and plasma-concentration-dependent manner. Aprepitant plasma concentrations achieved with the 
3-day regimen of EMEND are predicted to provide greater than 95 % occupancy of brain NK1
receptors.

A PET study in healthy young men administered a single oral dose of 165 mg aprepitant or a single 
intravenous dose of 150 mg fosaprepitant demonstrated similar brain NK1 receptor occupancy at Tmax,
(≥ 99 %), 24 hours (≥ 99 %), 48 hours (≥ 97 %), and 120 hours (37 to 76 %) following dosing. 
Occupancy of brain NK1 receptors by aprepitant correlate well with aprepitant plasma concentrations.

 



25

5.3 Preclinical safety data

Pre-clinical data reveal no special hazard for humans based on conventional studies of single and 
repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and development. 
However, it should be noted that systemic exposure in rodents was similar or even lower than 
therapeutic exposure in humans at the 125 mg/80 mg and 165 mg doses. In particular, although no 
adverse effects were noted in reproduction studies at human exposure levels, the animal exposures are 
not sufficient to make an adequate risk assessment in man.

In a juvenile toxicity study in rats treated from post natal day 10 to day 63 aprepitant led to an earlier 
vaginal opening in females from 250 mg/kg b.i.d. and to a delayed preputial separation in males, from 
10 mg/kg b.i.d. There were no margins to clinically relevant exposure. There were no 
treatment-related effects on mating, fertility or embryonic/foetal survival, and no pathological changes 
in the reproductive organs. In a juvenile toxicity study in dogs treated from post natal day 14 to 
day 42, a decreased testicular weight and Leydig cell size were seen in the males at 6 mg/kg/day and 
increased uterine weight, hypertrophy of the uterus and cervix, and oedema of vaginal tissues were 
seen in females from 4 mg/kg/day. There were no margins to clinically relevant exposure of 
aprepitant. For short term treatment according to recommended dose regimen these findings are 
considered unlikely to be clinically relevant.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Capsule content
Sucrose
Microcrystalline cellulose (E 460)
Hydroxypropylcellulose (E 463)
Sodium laurilsulfate

Capsule shell
Gelatin
Titanium dioxide (E 171)
Indigo carmine (E 132)

Printing ink
Shellac
Potassium hydroxide
Black iron oxide (E 172)

6.2 Incompatibilities

Not applicable.

6.3 Shelf-life

4 years

6.4 Special precautions for storage

Store in the original package in order to protect from moisture.

 



26

6.5 Nature and contents of container

Aluminium blister containing one 165 mg capsule.
6 Aluminium blisters each containing one 165 mg capsule.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements for disposal.

7. MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

8. MARKETING AUTHORISATION NUMBER

EU/1/03/262/009
EU/1/03/262/010

9. DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION

Date of first authorisation: 11 November 2003
Date of latest renewal: 22 September 2008

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.

 



27

1. NAME OF THE MEDICINAL PRODUCT

EMEND 125 mg hard capsules
EMEND 80 mg hard capsules

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 125 mg capsule contains 125 mg of aprepitant. Each 80 mg capsule contains 80 mg of aprepitant.

Excipient with known effect
Each capsule contains 125 mg of sucrose (in the 125 mg capsule).
Excipient with known effect
Each capsule contains 80 mg of sucrose (in the 80 mg capsule).

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Hard capsule.

The 125 mg capsule is opaque with a white body and pink cap with “462” and “125 mg” printed 
radially in black ink on the body. The 80 mg capsules are opaque with a white body and cap with 
“461” and “80 mg” printed radially in black ink on the body.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Prevention nausea and vomiting associated with highly and moderately emetogenic cancer
chemotherapy in adults and adolescents from the age of 12.

EMEND 125 mg/80 mg is given as part of combination therapy (see section 4.2).

4.2 Posology and method of administration

Posology
Adults
EMEND is given for 3 days as part of a regimen that includes a corticosteroid and a 5-HT3 antagonist. 
The recommended dose is 125 mg orally once daily one hour before start of chemotherapy on Day 1 
and 80 mg orally once daily on Days 2 and 3 in the morning.

 



28

The following regimens are recommended in adults for the prevention of nausea and vomiting 
associated with emetogenic cancer chemotherapy:

Highly Emetogenic Chemotherapy Regimen
Day 1 Day 2 Day 3 Day 4

EMEND 125 mg orally 80 mg orally 80 mg orally none
Dexamethasone 12 mg orally 8 mg orally 8 mg orally 8 mg orally

5-HT3 antagonists Standard dose of 
5-HT3 antagonists.

See the product 
information for the 

selected 5-HT3
antagonist for 

appropriate dosing 
information

none none none

Dexamethasone should be administered 30 minutes prior to chemotherapy treatment on Day 1 and in 
the morning on Days 2 to 4. The dose of dexamethasone accounts for active substance interactions.

Moderately Emetogenic Chemotherapy Regimen
Day 1 Day 2 Day 3

EMEND 125 mg orally 80 mg orally 80 mg orally
Dexamethasone 12 mg orally none none

5-HT3 antagonists Standard dose of 5-HT3
antagonists. See the 

product information for 
the selected 5-HT3

antagonist for 
appropriate dosing 

information

none none

Dexamethasone should be administered 30 minutes prior to chemotherapy treatment on Day 1. The 
dose of dexamethasone accounts for active substance interactions.

Paediatric population
Adolescents (aged 12 through 17 years)
EMEND is given for 3 days as part of a regimen that includes a 5-HT3 antagonist. The recommended 
dose of capsules of EMEND is 125 mg orally on Day 1 and 80 mg orally on Days 2 and 3. EMEND is 
administered orally 1 hour prior to chemotherapy on Days 1, 2 and 3. If no chemotherapy is given on 
Days 2 and 3, EMEND should be administered in the morning. See the Summary of Product 
Characteristics (SmPC) for the selected 5-HT3 antagonist for appropriate dosing information. If a 
corticosteroid, such as dexamethasone, is co-administered with EMEND, the dose of the corticosteroid 
should be administered at 50 % of the usual dose (see sections 4.5 and 5.1).

The safety and efficacy of the 80 mg and 125 mg capsules have not been demonstrated in children less 
than 12 years of age. No data are available. Refer to the powder for oral suspension SmPC for 
appropriate dosing in infants, toddlers and children aged 6 months to less than 12 years.

General
Efficacy data in combination with other corticosteroids and 5-HT3 antagonists are limited. For 
additional information on the co-administration with corticosteroids, see section 4.5. Please refer to the 
SmPC of co-administered 5-HT3 antagonist medicinal products.

Special populations
Elderly (≥ 65 years)
No dose adjustment is necessary for the elderly (see section 5.2).

Gender
No dose adjustment is necessary based on gender (see section 5.2).

 



29

Renal impairment
No dose adjustment is necessary for patients with renal impairment or for patients with end stage renal 
disease undergoing haemodialysis (see section 5.2).

Hepatic impairment
No dose adjustment is necessary for patients with mild hepatic impairment. There are limited data in 
patients with moderate hepatic impairment and no data in patients with severe hepatic impairment. 
Aprepitant should be used with caution in these patients (see sections 4.4 and 5.2).

Method of administration
The hard capsule should be swallowed whole.
EMEND may be taken with or without food.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Co-administration with pimozide, terfenadine, astemizole or cisapride (see section 4.5).

4.4 Special warnings and precautions for use

Patients with moderate to severe hepatic impairment
There are limited data in patients with moderate hepatic impairment and no data in patients with 
severe hepatic impairment. EMEND should be used with caution in these patients (see section 5.2).

CYP3A4 interactions
EMEND should be used with caution in patients receiving concomitant orally administered active 
substances that are metabolised primarily through CYP3A4 and with a narrow therapeutic range, such 
as cyclosporine, tacrolimus, sirolimus, everolimus, alfentanil, ergot alkaloid derivatives, fentanyl, and 
quinidine (see section 4.5). Additionally, concomitant administration with irinotecan should be 
approached with particular caution as the combination might result in increased toxicity.

Co-administration with warfarin (a CYP2C9 substrate)
In patients on chronic warfarin therapy, the International Normalised Ratio (INR) should be monitored 
closely during treatment with EMEND and for 14 days following each 3-day course of EMEND (see 
section 4.5).

Co-administration with hormonal contraceptives
The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration 
of EMEND. Alternative non-hormonal back-up methods of contraception should be used during 
treatment with EMEND and for 2 months following the last dose of EMEND (see section 4.5).

Excipients
EMEND capsules contain sucrose. Patients with rare hereditary problems of fructose intolerance, 
glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Aprepitant (125 mg/80 mg) is a substrate, a moderate inhibitor, and an inducer of CYP3A4. Aprepitant 
is also an inducer of CYP2C9. During treatment with EMEND, CYP3A4 is inhibited. After the end of 
treatment, EMEND causes a transient mild induction of CYP2C9, CYP3A4 and glucuronidation. 
Aprepitant does not seem to interact with the P-glycoprotein transporter, as suggested by the lack of 
interaction of aprepitant with digoxin.

 



30

Effect aprepitant on the pharmacokinetics of other active substances
CYP3A4 inhibition
As a moderate inhibitor of CYP3A4, aprepitant (125 mg/80 mg) can increase plasma concentrations of 
co-administered active substances that are metabolised through CYP3A4. The total exposure of orally 
administered CYP3A4 substrates may increase up to approximately 3-fold during the 3-day treatment 
with EMEND; the effect of aprepitant on the plasma concentrations of intravenously administered 
CYP3A4 substrates is expected to be smaller. EMEND must not be used concurrently with pimozide, 
terfenadine, astemizole, or cisapride (see section 4.3). Inhibition of CYP3A4 by aprepitant could result 
in elevated plasma concentrations of these active substances, potentially causing serious or 
life-threatening reactions. Caution is advised during concomitant administration of EMEND and orally 
administered active substances that are metabolised primarily through CYP3A4 and with a narrow 
therapeutic range, such as cyclosporine, tacrolimus, sirolimus, everolimus, alfentanil, diergotamine, 
ergotamine, fentanyl, and quinidine (see section 4.4).

Corticosteroids
Dexamethasone: The usual oral dexamethasone dose should be reduced by approximately 50 % when 
co-administered with EMEND 125 mg/80 mg regimen. The dose of dexamethasone in chemotherapy 
induced nausea and vomiting clinical trials was chosen to account for active substance interactions 
(see section 4.2). EMEND, when given as a regimen of 125 mg with dexamethasone co-administered 
orally as 20 mg on Day 1, and EMEND when given as 80 mg/day with dexamethasone 
co-administered orally as 8 mg on Days 2 through 5, increased the AUC of dexamethasone, a 
CYP3A4 substrate, 2.2-fold on Days 1 and 5.

Methylprednisolone: The usual intravenously administered methylprednisolone dose should be 
reduced approximately 25 %, and the usual oral methylprednisolone dose should be reduced 
approximately 50 % when co-administered with EMEND 125 mg/80 mg regimen. EMEND, when 
given as a regimen of 125 mg on Day 1 and 80 mg/day on Days 2 and 3, increased the AUC of 
methylprednisolone, a CYP3A4 substrate, by 1.3-fold on Day 1 and by 2.5-fold on Day 3, when 
methylprednisolone was co-administered intravenously as 125 mg on Day 1 and orally as 40 mg on 
Days 2 and 3.

During continuous treatment with methylprednisolone, the AUC of methylprednisolone may decrease 
at later time points within 2 weeks following initiation of the EMEND dose, due to the inducing effect 
of aprepitant on CYP3A4. This effect may be expected to be more pronounced for orally administered 
methylprednisolone.

Chemotherapeutic medicinal products
In pharmacokinetic studies, EMEND, when given as a regimen of 125 mg on Day 1 and 80 mg/day on 
Days 2 and 3, did not influence the pharmacokinetics of docetaxel administered intravenously on 
Day 1 or vinorelbine administered intravenously on Day 1 or Day 8. Because the effect of EMEND on 
the pharmacokinetics of orally administered CYP3A4 substrates is greater than the effect of EMEND 
on the pharmacokinetics of intravenously administered CYP3A4 substrates, an interaction with orally 
administered chemotherapeutic medicinal products metabolised primarily or partly by CYP3A4 (e.g.,
etoposide, vinorelbine) cannot be excluded. Caution is advised and additional monitoring may be 
appropriate in patients receiving medicinal products metabolized primarily or partly by CYP3A4 (see 
section 4.4). Post-marketing events of neurotoxicity, a potential adverse reaction of ifosfamide, have 
been reported after aprepitant and ifosfamide co-administration.

Immunosuppressants
During the 3-day CINV regimen, a transient moderate increase followed by a mild decrease in 
exposure of immunosuppressants metabolised by CYP3A4 (e.g., cyclosporine, tacrolimus, everolimus 
and sirolimus) is expected. Given the short duration of the 3-day regimen and the time-dependent 
limited changes in exposure, dose reduction of the immunosuppressant is not recommended during the 
3 days of co-administration with EMEND.

 



31

Midazolam
The potential effects of increased plasma concentrations of midazolam or other benzodiazepines 
metabolised via CYP3A4 (alprazolam, triazolam) should be considered when co-administering these 
medicinal products with EMEND (125 mg/80 mg).

EMEND increased the AUC of midazolam, a sensitive CYP3A4 substrate, 2.3-fold on Day 1 and 
3.3-fold on Day 5, when a single oral dose of 2 mg midazolam was co-administered on Days 1 and 5 
of a regimen of EMEND 125 mg on Day 1 and 80 mg/day on Days 2 to 5.

In another study with intravenous administration of midazolam, EMEND was given as 125 mg on 
Day 1 and 80 mg/day on Days 2 and 3, and 2 mg midazolam was given intravenously prior to the 
administration of the 3-day regimen of EMEND and on Days 4, 8, and 15. EMEND increased the 
AUC of midazolam 25 % on Day 4 and decreased the AUC of midazolam 19 % on Day 8 and 4 % on 
Day 15. These effects were not considered clinically important. 

In a third study with intravenous and oral administration of midazolam, EMEND was given as 125 mg 
on Day 1 and 80 mg/day on Days 2 and 3, together with ondansetron 32 mg Day 1, dexamethasone 
12 mg Day 1 and 8 mg Days 2-4. This combination (i.e. EMEND, ondansetron and dexamethasone)
decreased the AUC of oral midazolam 16 % on Day 6, 9 % on Day 8, 7 % on Day 15 and 17 % on 
Day 22. These effects were not considered clinically important.

An additional study was completed with intravenous administration of midazolam and EMEND. 
Intravenous 2 mg midazolam was given 1 hour after oral administration of a single dose of EMEND 
125 mg. The plasma AUC of midazolam was increased by 1.5-fold. This effect was not considered 
clinically important.

Induction
As a mild inducer of CYP2C9, CYP3A4 and glucuronidation, aprepitant can decrease plasma 
concentrations of substrates eliminated by these routes within two weeks following initiation and 
treatment. This effect may become apparent only after the end of a 3-day treatment with EMEND. For 
CYP2C9 and CYP3A4 substrates, the induction is transient with a maximum effect reached 3-5 days 
after end of the EMEND 3-day treatment. The effect is maintained for a few days, thereafter slowly 
declines and is clinically insignificant by two weeks after end of EMEND treatment. Mild induction of 
glucuronidation is also seen with 80 mg oral aprepitant given for 7 days. Data are lacking regarding 
effects on CYP2C8 and CYP2C19. Caution is advised when warfarin, acenocoumarol, tolbutamide, 
phenytoin or other active substances that are known to be metabolised by CYP2C9 are administered 
during this time period.

Warfarin
In patients on chronic warfarin therapy, the prothrombin time (INR) should be monitored closely 
during treatment with EMEND and for 2 weeks following each 3-day course of EMEND for 
chemotherapy induced nausea and vomiting (see section 4.4). When a single 125 mg dose of EMEND 
was administered on Day 1 and 80 mg/day on Days 2 and 3 to healthy subjects who were stabilised on 
chronic warfarin therapy, there was no effect of EMEND on the plasma AUC of R(+) or S(-) warfarin 
determined on Day 3; however, there was a 34 % decrease in S(-) warfarin (a CYP2C9 substrate) 
trough concentration accompanied by a 14 % decrease in INR 5 days after completion of treatment 
with EMEND. 

Tolbutamide
EMEND, when given as 125 mg on Day 1 and 80 mg/day on Days 2 and 3, decreased the AUC of 
tolbutamide (a CYP2C9 substrate) by 23 % on Day 4, 28 % on Day 8, and 15 % on Day 15, when a 
single dose of tolbutamide 500 mg was administered orally prior to the administration of the 3-day 
regimen of EMEND and on Days 4, 8, and 15.

 



32

Hormonal contraceptives
The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration 
of EMEND. Alternative non-hormonal back-up methods of contraception should be used during 
treatment with EMEND and for 2 months following the last dose of EMEND.

In a clinical study, single doses of an oral contraceptive containing ethinyl estradiol and norethindrone 
were administered on Days 1 through 21 with EMEND, given as a regimen of 125 mg on Day 8 and 
80 mg/day on Days 9 and 10 with ondansetron 32 mg intravenously on Day 8 and oral dexamethasone 
given as 12 mg on Day 8 and 8 mg/day on Days 9, 10, and 11. During days 9 through 21 in this study, 
there was as much as a 64 % decrease in ethinyl estradiol trough concentrations and as much as a 60 % 
decrease in norethindrone trough concentrations. 

5-HT3 antagonists
In clinical interaction studies, aprepitant did not have clinically important effects on the 
pharmacokinetics of ondansetron, granisetron, or hydrodolasetron (the active metabolite of 
dolasetron).

Effect of other medicinal products on the pharmacokinetics of aprepitant
Concomitant administration of EMEND with active substances that inhibit CYP3A4 activity (e.g., 
ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone,
and protease inhibitors) should be approached cautiously, as the combination is expected to result 
several-fold in increased plasma concentrations of aprepitant (see section 4.4). 

Concomitant administration of EMEND with active substances that strongly induce CYP3A4 activity 
(e.g., rifampicin, phenytoin, carbamazepine, phenobarbital) should be avoided as the combination 
results in reductions of the plasma concentrations of aprepitant that may result in decreased efficacy of 
EMEND. Concomitant administration of EMEND with herbal preparations containing St. John’s Wort 
(Hypericum perforatum) is not recommended.

Ketoconazole
When a single 125 mg dose of aprepitant was administered on Day 5 of a 10-day regimen of 
400 mg/day of ketoconazole, a strong CYP3A4 inhibitor, the AUC of aprepitant increased 
approximately 5-fold and the mean terminal half-life of aprepitant increased approximately 3-fold.

Rifampicin
When a single 375 mg dose of aprepitant was administered on Day 9 of a 14-day regimen of 
600 mg/day of rifampicin, a strong CYP3A4 inducer, the AUC of aprepitant decreased 91 % and the 
mean terminal half-life decreased 68 %.

Paediatric population
Interaction studies have only been performed in adults.

4.6 Fertility, pregnancy and lactation

Contraception in males and females
The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration 
of EMEND. Alternative non-hormonal back-up methods of contraception should be used during 
treatment with EMEND and for 2 months following the last dose of EMEND (see sections 4.4 and 
4.5).

Pregnancy
For aprepitant no clinical data on exposed pregnancies are available. The potential for reproductive 
toxicity of aprepitant has not been fully characterised, since exposure levels above the therapeutic 
exposure in humans at the 125 mg/80 mg dose could not be attained in animal studies. These studies 
did not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal 
development, parturition or postnatal development (see section 5.3). The potential effects on 

 



33

reproduction of alterations in neurokinin regulation are unknown. EMEND should not be used during 
pregnancy unless clearly necessary.

Breast-feeding
Aprepitant is excreted in the milk of lactating rats. It is not known whether aprepitant is excreted in 
human milk; therefore, breast-feeding is not recommended during treatment with EMEND.

Fertility
The potential for effects of aprepitant on fertility has not been fully characterised because exposure 
levels above the therapeutic exposure in humans could not be attained in animal studies. These fertility 
studies did not indicate direct or indirect harmful effects with respect to mating performance, fertility, 
embryonic/foetal development, or sperm count and motility (see section 5.3).

4.7 Effects on ability to drive and use machines

EMEND may have minor influence on the ability to drive, cycle and use machines. Dizziness and 
fatigue may occur following administration of EMEND (see section 4.8).

4.8 Undesirable effects

Summary of the safety profile
The safety profile of aprepitant was evaluated in approximately 6,500 adults in more than 50 studies 
and 184 children and adolescents in 2 pivotal paediatric clinical trials.

The most common adverse reactions reported at a greater incidence in adults treated with the 
aprepitant regimen than with standard therapy in patients receiving Highly Emetogenic Chemotherapy 
(HEC) were: hiccups (4.6 % versus 2.9 %), alanine aminotransferase (ALT) increased (2.8 % versus 
1.1 %), dyspepsia (2.6 % versus 2.0 %), constipation (2.4 % versus 2.0 %), headache (2.0 % versus 
1.8 %), and decreased appetite (2.0 % versus 0.5 %). The most common adverse reaction reported at a 
greater incidence in patients treated with the aprepitant regimen than with standard therapy in patients 
receiving Moderately Emetogenic Chemotherapy (MEC) was fatigue (1.4 % versus 0.9 %).

The most common adverse reactions reported at a greater incidence in paediatric patients treated with 
the aprepitant regimen than with the control regimen while receiving emetogenic cancer chemotherapy 
were hiccups (3.3 % versus 0.0 %) and flushing (1.1 % versus 0.0 %).

Tabulated list of adverse reactions
The following adverse reactions were observed in a pooled analysis of the HEC and MEC studies at a 
greater incidence with aprepitant than with standard therapy in adults or paediatric patients or in 
postmarketing use. The frequency categories given in the table are based on the studies in adults; the 
observed frequencies in the paediatric studies were similar or lower, unless shown in the table. Some 
less common ADRs in the adult population were not observed in the paediatric studies.

Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon 
(≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000) and very rare (< 1/10,000), not known (cannot 
be estimated from the available data).

System organ class Adverse reaction Frequency
Infection and infestations candidiasis, staphylococcal infection rare
Blood and lymphatic system 
disorders

febrile neutropenia, anaemia uncommon

Immune system disorders hypersensitivity reactions including 
anaphylactic reactions

not known

Metabolism and nutrition 
disorders

decreased appetite common

polydipsia rare

 



34

System organ class Adverse reaction Frequency
Psychiatric disorders anxiety uncommon

disorientation, euphoric mood rare

Nervous system disorders headache common

dizziness, somnolence uncommon

cognitive disorder, lethargy, dysgeusia rare

Eye disorders conjunctivitis rare
Ear and labyrinth disorders tinnitus rare
Cardiac disorders palpitations uncommon

bradycardia, cardiovascular disorder rare

Vascular disorders hot flush/flushing uncommon
Respiratory, thoracic and 
mediastinal disorders

hiccups common

oropharyngeal pain, sneezing, cough, 
postnasal drip, throat irritation

rare

Gastrointestinal disorders constipation, dyspepsia common

eructation, nausea†, vomiting†, 
gastroesophageal reflux disease, abdominal 
pain, dry mouth, flatulence

uncommon

duodenal ulcer perforation, stomatitis, 
abdominal distension, faeces hard, neutropenic 
colitis

rare

Skin and subcutaneous tissue 
disorders

rash, acne uncommon

photosensitivity reaction, hyperhidrosis, 
seborrhoea, skin lesion, rash pruritic, 
Stevens-Johnson syndrome/toxic epidermal 
necrolysis

rare

pruritus, urticaria not known

Musculoskeletal and connective 
tissue disorders

muscular weakness, muscle spasms rare

Renal and urinary disorders dysuria uncommon

pollakiuria rare

 



35

System organ class Adverse reaction Frequency
General disorders and 
administration site conditions

fatigue common

asthenia, malaise uncommon

oedema, chest discomfort, gait disturbance rare

Investigations ALT increased common

AST increased, blood alkaline phosphatase 
increased

uncommon

red blood cells urine positive, blood sodium 
decreased, weight decreased, neutrophil count 
decreased, glucose urine present, urine output 
increased

rare

†Nausea and vomiting were efficacy parameters in the first 5 days of post-chemotherapy treatment and were 
reported as adverse reactions only thereafter.

Description of selected adverse reactions
The adverse reactions profiles in adults in the Multiple-Cycle extension of HEC and MEC studies for 
up to 6 additional cycles of chemotherapy were generally similar to those observed in Cycle 1.

In an additional active-controlled clinical study in 1,169 adult patients receiving aprepitant and HEC,
the adverse reactions profile was generally similar to that seen in the other HEC studies with 
aprepitant.

Additional adverse reactions were observed in adult patients treated with aprepitant for postoperative 
nausea and vomiting (PONV) and a greater incidence than with ondansetron: abdominal pain upper, 
bowel sounds abnormal, constipation*, dysarthria, dyspnoea, hypoaesthesia, insomnia, miosis, nausea, 
sensory disturbance, stomach discomfort, sub-ileus*, visual acuity reduced, wheezing.
*Reported in patients taking a higher dose of aprepitant.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

In the event of overdose, EMEND should be discontinued and general supportive treatment and 
monitoring should be provided. Because of the antiemetic activity of aprepitant, emesis induced by a 
medicinal product may not be effective.

Aprepitant cannot be removed by haemodialysis.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antiemetics and antinauseants, ATC code: A04AD12

Aprepitant is a selective high-affinity antagonist at human substance P neurokinin 1 (NK1) receptors.

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


36

3-day regimen of aprepitant in adults
In 2 randomised, double-blind studies encompassing a total of 1,094 adult patients receiving 
chemotherapy that included cisplatin  70 mg/m2, aprepitant in combination with an 
ondansetron/dexamethasone regimen (see section 4.2) was compared with a standard regimen (placebo 
plus ondansetron 32 mg intravenously administered on Day 1 plus dexamethasone 20 mg orally on 
Day 1 and 8 mg orally twice daily on Days 2 to 4). Although a 32 mg intravenous dose of ondansetron 
was used in clinical trials, this is no longer the recommended dose. See the product information for the 
selected 5-HT3 antagonist for appropriate dosing information.

Efficacy was based on evaluation of the following composite measure: complete response (defined as 
no emetic episodes and no use of rescue therapy) primarily during Cycle 1. The results were evaluated 
for each individual study and for the 2 studies combined.

A summary of the key study results from the combined analysis is shown in Table 1.

Table 1
Percent of adult patients receiving Highly Emetogenic Chemotherapy responding 

by treatment group and phase — Cycle 1

COMPOSITE MEASURES

Aprepitant regimen
(N= 521) †

%

Standard therapy
(N= 524) †

%

Differences*

         %             (95 % CI)

Complete response (no emesis and no rescue therapy)
Overall (0-120 hours)
0-24 hours
25-120 hours

67.7
86.0
71.5

47.8
73.2
51.2

19.9
12.7
20.3

(14.0, 25.8)
(7.9, 17.6)
(14.5, 26.1)

INDIVIDUAL MEASURES
No emesis (no emetic episodes regardless of use of rescue therapy)

Overall (0-120 hours)
0-24 hours
25-120 hours

71.9
86.8
76.2

49.7
74.0
53.5

22.2
12.7
22.6

(16.4, 28.0)
(8.0, 17.5)
(17.0, 28.2)

No significant nausea (maximum VAS < 25 mm on a scale of 0-100 mm)
Overall (0-120 hours)
25-120 hours 

72.1
74.0

64.9
66.9

7.2
7.1

(1.6, 12.8)
(1.5, 12.6)

* The confidence intervals were calculated with no adjustment for gender and concomitant chemotherapy, which 
were included in the primary analysis of odds ratios and logistic models.
†  One patient in the Aprepitant regimen only had data in the acute phase and was excluded from the overall and 
delayed phase analyses; one patient in the Standard regimen only had data in the delayed phase and was 
excluded from the overall and acute phase analyses.

 



37

The estimated time to first emesis in the combined analysis is depicted by the Kaplan-Meier plot in 
Figure 1.

Figure 1
Percent of adult patients receiving Highly Emetogenic Chemotherapy 

who remain emesis free over time – Cycle 1

0 12 24 36 48 60 72 84 96 108 120
0

40%

50%

60%

70%

80%

90%

100%

P
e

rc
e

n
t 

o
f 

P
a

ti
e
n

ts

Aprepitant Regimen (N=520)
Standard Therapy (N=523)

Time (hours)

Statistically significant differences in efficacy were also observed in each of the 2 individual studies.

In the same 2 clinical studies, 851 adult patients continued into the Multiple-Cycle extension for up to 
5 additional cycles of chemotherapy. The efficacy of the aprepitant regimen was apparently 
maintained during all cycles.

In a randomised, double-blind study in a total of 866 adult patients (864 females, 2 males) receiving 
chemotherapy that included cyclophosphamide 750-1,500 mg/m2; or cyclophosphamide 
500-1,500 mg/m2 and doxorubicin (< 60 mg/m2) or epirubicin (< 100 mg/m2), aprepitant in 
combination with an ondansetron/dexamethasone regimen (see section 4.2) was compared with 
standard therapy (placebo plus ondansetron 8 mg orally (twice on Day 1, and every 12 hours on 
Days 2 and 3) plus dexamethasone 20 mg orally on Day 1).

Efficacy was based on evaluation of the composite measure: complete response (defined as no emetic 
episodes and no use of rescue therapy) primarily during Cycle 1.

 



38

A summary of the key study results is shown in Table 2.

Table 2
Percent of adult patients responding by treatment group and phase — Cycle 1

Moderately Emetogenic Chemotherapy

COMPOSITE MEASURES

Aprepitant 
regimen

(N= 433) †

%

Standard 
therapy

(N= 424)
%

Differences*

        %             (95 % CI)

Complete response (no emesis and no rescue therapy)
Overall (0-120 hours)
0-24 hours
25-120 hours

50.8
75.7
55.4

42.5
69.0
49.1

8.3
6.7
6.3

(1.6, 15.0)
(0.7, 12.7)
(-0.4, 13.0)

INDIVIDUAL MEASURES
No emesis (no emetic episodes regardless of use of rescue therapy)

Overall (0-120 hours)
0-24 hours
25-120 hours

75.7
87.5
80.8

58.7
77.3
69.1

17.0
10.2
11.7

(10.8, 23.2)
(5.1, 15.3)
(5.9, 17.5)

No significant nausea (maximum VAS < 25 mm on a scale of 0-100 mm)
Overall (0-120 hours)
0-24 hours
25-120 hours

60.9
79.5
65.3

55.7
78.3
61.5

5.3
1.3
3.9

(-1.3, 11.9)
(-4.2, 6.8)
(-2.6, 10.3)

* The confidence intervals were calculated with no adjustment for age category (< 55 years, ≥ 55 years) and 
investigator group, which were included in the primary analysis of odds ratios and logistic models.
†   One patient in the Aprepitant regimen only had data in the acute phase and was excluded from the overall and 
delayed phase analyses.

In the same clinical study, 744 adult patients continued into the Multiple-Cycle extension for up to 
3 additional cycles of chemotherapy. The efficacy of the aprepitant regimen was apparently 
maintained during all cycles.

In a second multicentre, randomised, double-blind, parallel-group, clinical study, the aprepitant 
regimen was compared with standard therapy in 848 adult patients (652 females, 196 males) receiving 
a chemotherapy regimen that included any intravenous dose of oxaliplatin, carboplatin, epirubicin, 
idarubicin, ifosfamide, irinotecan, daunorubicin, doxorubicin; cyclophosphamide intravenously 
(< 1,500 mg/m2); or cytarabine intravenously (> 1 g/m2). Patients receiving the aprepitant regimen 
were receiving chemotherapy for a variety of tumour types including 52 % with breast cancer, 21 % 
with gastrointestinal cancers including colorectal cancer, 13 % with lung cancer and 6 % with 
gynaecological cancers. The aprepitant regimen in combination with an ondansetron/dexamethasone 
regimen (see section 4.2) was compared with standard therapy (placebo in combination with 
ondansetron 8 mg orally (twice on Day 1, and every 12 hours on Days 2 and 3) plus dexamethasone 
20 mg orally on Day 1).

Efficacy was based on the evaluation of the following primary and key secondary endpoints: No 
vomiting in the overall period (0 to 120 hours post-chemotherapy), evaluation of safety and 
tolerability of the aprepitant regimen for chemotherapy induced nausea and vomiting (CINV), and 
complete response (defined as no vomiting and no use of rescue therapy) in the overall period (0 to 
120 hours post-chemotherapy). Additionally, no significant nausea in the overall period (0 to 
120 hours post-chemotherapy) was evaluated as an exploratory endpoint, and in the acute and delayed 
phases as a post-hoc analysis.

A summary of the key study results is shown in Table 3.

 



39

Table 3
Percent of adult patients responding by treatment group and phase for Study 2 – Cycle 1

Moderately Emetogenic Chemotherapy

Aprepitant 
regimen
(N= 425)

%

Standard 
therapy

(N= 406)
%

Differences*

        %             (95 % CI)

Complete response (no emesis and no rescue therapy)
Overall (0-120 hours)
0-24 hours
25-120 hours

68.7

89.2
70.8

56.3

80.3
60.9

12.4
8.9
9.9

(5.9, 18.9)
(4.0, 13.8)
(3.5, 16.3)

No emesis (no emetic episodes regardless of use of rescue therapy)
Overall (0-120 hours)
0-24 hours
25-120 hours

76.2
92.0
77.9

62.1
83.7
66.8

14.1
8.3
11.1

(7.9, 20.3)
(3.9, 12.7)
(5.1, 17.1)

No significant nausea (maximum VAS < 25 mm on a scale of 0-100 mm)
Overall (0-120 hours)
0-24 hours
25-120 hours

73.6

90.9
74.9

66.4

86.3
69.5

7.2
4.6
5.4

(1.0, 13.4)
(0.2, 9.0)
(-0.7, 11.5)

*The confidence intervals were calculated with no adjustment for gender and region, which were included in the 
primary analysis using logistic models.

The benefit of aprepitant combination therapy in the full study population was mainly driven by the 
results observed in patients with poor control with the standard regimen such as in women, even 
though the results were numerically better regardless of age, tumour type or gender. Complete 
response to the aprepitant regimen and standard therapy, respectively, was reached in 209/324 (65 %) 
and 161/320 (50 %) in women and 83/101 (82 %) and 68/87 (78 %) of men.

Paediatric population
In a randomised, double-blind, active comparator-controlled clinical study that included 302 children 
and adolescents (aged 6 months to 17 years) receiving moderately or highly emetogenic 
chemotherapy, the aprepitant regimen was compared to a control regimen for the prevention of CINV. 
The efficacy of the aprepitant regimen was evaluated in a single cycle (Cycle 1). Patients had the 
opportunity to receive open-label aprepitant in subsequent cycles (Optional Cycles 2-6); however 
efficacy was not assessed in these optional cycles. The aprepitant regimen for adolescents aged 
12 through 17 years (n=47) consisted of EMEND capsules 125 mg orally on Day 1 and 80 mg/day on 
Days 2 and 3 in combination with ondansetron on Day 1. The aprepitant regimen for children aged 
6 months to less than 12 years (n=105) consisted of EMEND powder for oral suspension 3.0 mg/kg 
(up to 125 mg) orally on Day 1 and 2.0 mg/kg (up to 80 mg) orally on Days 2 and 3 in combination 
with ondansetron on Day 1. The control regimen in adolescents aged 12 through 17 years (n=48) and 
children aged 6 months to less than 12 years (n=102) consisted of placebo for aprepitant on Days 1, 2 
and 3 in combination with ondansetron on Day 1. EMEND or placebo and ondansetron were 
administered 1 hour and 30 minutes prior to initiation of chemotherapy, respectively. Intravenous 
dexamethasone was permitted as part of the antiemetic regimen for paediatric patients in both age 
groups, at the discretion of the physician. A dose reduction (50 %) of dexamethasone was required for 
paediatric patients receiving aprepitant. No dose reduction was required for paediatric patients 
receiving the control regimen. Of the paediatric patients, 29 % in the aprepitant regimen and 28 % in 
the control regimen used dexamethasone as part of the regimen in Cycle 1.

The antiemetic activity of EMEND was evaluated over a 5-day (120 hour) period following the 
initiation of chemotherapy on Day 1. The primary endpoint was complete response in the delayed 
phase (25 to 120 hours following initiation of chemotherapy) in Cycle 1. A summary of the key study 
results are shown in Table 4.

 



40

Table 4
Number (%) of paediatric patients with complete response and no vomiting by treatment group and 

phase – Cycle 1 (Intent to treat population)

Aprepitant regimen
n/m (%)

Control regimen
n/m (%)

PRIMARY ENDPOINT
Complete response* – Delayed phase 77/152 (50.7)† 39/150 (26.0)
OTHER PRESPECIFIED ENDPOINTS
Complete response* – Acute phase 101/152 (66.4)‡ 78/150 (52.0)
Complete response* – Overall phase 61/152 (40.1)† 30/150 (20.0)
No vomiting§ – Overall phase 71/152 (46.7)† 32/150 (21.3)
*Complete response = No vomiting or retching or dry heaves and no use of rescue medication.
†p < 0.01 when compared to control regimen
‡p < 0.05 when compared to control regimen
§No vomiting = No vomiting or retching or dry heaves
n/m = Number of patients with desired response/number of patients included in time point.
Acute phase: 0 to 24 hours following initiation of chemotherapy.
Delayed phase: 25 to 120 hours following initiation of chemotherapy.
Overall phase: 0 to 120 hours following initiation of chemotherapy.

The estimated time to first vomiting after initiation of chemotherapy treatment was longer with the 
aprepitant regimen (estimated median time to first vomiting was 94.5 hours) compared with the 
control regimen group (estimated median time to first vomiting was 26.0 hours) as depicted in the 
Kaplan-Meier curves in Figure 2.

Figure 2
Time to first vomiting episode from start of chemotherapy administration - paediatric patients in the 

overall phase-Cycle 1 (Intent to treat population)

An analysis of efficacy in subpopulations in Cycle 1 demonstrated that, regardless of age category, 
gender, use of dexamethasone for antiemetic prophylaxis, and emetogenicity of chemotherapy, the 
aprepitant regimen provided better control than the control regimen with respect to the complete 
response endpoints.

5.2 Pharmacokinetic properties

Aprepitant displays non-linear pharmacokinetics. Both clearance and absolute bioavailability decrease 
with increasing dose.

 



41

Absorption
The mean absolute oral bioavailability of aprepitant is 67 % for the 80 mg capsule and 59 % for the 
125 mg capsule. The mean peak plasma concentration (Cmax) of aprepitant occurred at approximately 
4 hours (tmax). Oral administration of the capsule with an approximately 800 Kcal standard breakfast 
resulted in an up to 40 % increase in AUC of aprepitant. This increase is not considered clinically 
relevant.

The pharmacokinetics of aprepitant is non-linear across the clinical dose range. In healthy young 
adults, the increase in AUC0- was 26 % greater than dose proportional between 80 mg and 125 mg 
single doses administered in the fed state.

Following oral administration of a single 125 mg dose of EMEND on Day 1 and 80 mg once daily on 
Days 2 and 3, the AUC0-24hr (mean±SD) was 19.6 ± 2.5 µgh/mL and 21.2 ± 6.3 µg h/mL on 
Days 1 and 3, respectively. Cmax was 1.6 ± 0.36 µg/mL and 1.4 ± 0.22 µg/mL on Days 1 and 3, 
respectively.

Distribution
Aprepitant is highly protein bound, with a mean of 97 %. The geometric mean apparent volume of 
distribution at steady state (Vdss) is approximately 66 L in humans.

Biotransformation
Aprepitant undergoes extensive metabolism. In healthy young adults, aprepitant accounts for 
approximately 19 % of the radioactivity in plasma over 72 hours following a single intravenous 
administration 100-mg dose of [14C]-fosaprepitant, a prodrug for aprepitant, indicating a substantial 
presence of metabolites in the plasma. Twelve metabolites of aprepitant have been identified in human 
plasma. The metabolism of aprepitant occurs largely via oxidation at the morpholine ring and its side 
chains and the resultant metabolites were only weakly active. In vitro studies using human liver 
microsomes indicate that aprepitant is metabolised primarily by CYP3A4 and potentially with minor 
contribution by CYP1A2 and CYP2C19.

Elimination
Aprepitant is not excreted unchanged in urine. Metabolites are excreted in urine and via biliary 
excretion in faeces. Following a single intravenously administered 100 mg dose of [14C]-fosaprepitant, 
a prodrug for aprepitant, to healthy subjects, 57 % of the radioactivity was recovered in urine and 
45 % in faeces.

The plasma clearance of aprepitant is dose-dependent, decreasing with increased dose and ranged from 
approximately 60 to 72 mL/min in the therapeutic dose range. The terminal half-life ranged from 
approximately 9 to 13 hours.

Pharmacokinetics in special populations
Elderly: Following oral administration of a single 125 mg dose of aprepitant on Day 1 and 80 mg once 
daily on Days 2 through 5, the AUC0-24hr of aprepitant was 21 % higher on Day 1 and 36 % higher on 
Day 5 in elderly ( 65 years) relative to younger adults. The Cmax was 10 % higher on Day 1 and 24 % 
higher on Day 5 in elderly relative to younger adults. These differences are not considered clinically 
meaningful. No dose adjustment for EMEND is necessary in elderly patients.

Gender: Following oral administration of a single 125 mg dose of aprepitant, the Cmax for aprepitant is 
16 % higher in females as compared with males. The half-life of aprepitant is 25 % lower in females 
as compared with males and its tmax occurs at approximately the same time. These differences are not 
considered clinically meaningful. No dose adjustment for EMEND is necessary based on gender.

Hepatic impairment: Mild hepatic impairment (Child-Pugh class A) does not affect the 
pharmacokinetics of aprepitant to a clinically relevant extent. No dose adjustment is necessary for 
patients with mild hepatic impairment. Conclusions regarding the influence of moderate hepatic 
impairment (Child-Pugh class B) on aprepitant pharmacokinetics cannot be drawn from available data. 

 



42

There are no clinical or pharmacokinetic data in patients with severe hepatic impairment (Child-Pugh 
class C).

Renal impairment: A single 240 mg dose of aprepitant was administered to patients with severe renal 
impairment (CrCl < 30 mL/min) and to patients with end stage renal disease (ESRD) requiring 
haemodialysis.

In patients with severe renal impairment, the AUC0- of total aprepitant (unbound and protein bound) 
decreased by 21 % and Cmax decreased by 32 %, relative to healthy subjects. In patients with ESRD 
undergoing haemodialysis, the AUC0- of total aprepitant decreased by 42 % and Cmax decreased by 
32 %. Due to modest decreases in protein binding of aprepitant in patients with renal disease, the AUC 
of pharmacologically active unbound aprepitant was not significantly affected in patients with renal 
impairment compared with healthy subjects. Haemodialysis conducted 4 or 48 hours after dosing had 
no significant effect on the pharmacokinetics of aprepitant; less than 0.2 % of the dose was recovered 
in the dialysate.

No dose adjustment for EMEND is necessary for patients with renal impairment or for patients with 
ESRD undergoing haemodialysis.

Paediatric population: As part of a 3-day regimen, dosing of aprepitant capsules (125/80/80-mg) in 
adolescent patients (aged 12 through 17 years) achieved an AUC0-24hr above 17 µg•hr/mL on Day 1 
with concentrations (Cmin) at the end of Days 2 and 3 above 0.4 µg/mL in a majority of patients. The 
median peak plasma concentration (Cmax) was approximately 1.3 µg/mL on Day 1, occurring at 
approximately 4 hours. As part of a 3-day regimen, dosing of aprepitant powder for oral suspension 
(3/2/2-mg/kg) in patients aged 6 months to less than12 years achieved an AUC0-24hr above 
17 µg•hr/mL on Day 1 with concentrations (Cmin) at the end of Days 2 and 3 above 0.1 µg/mL in a 
majority of patients. The median peak plasma concentration (Cmax) was approximately 1.2 µg/mL on 
Day 1, occurring between 5 and 7 hours.

A population pharmacokinetic analysis of aprepitant in paediatric patients (aged 6 months through 
17 years) suggests that gender and race have no clinically meaningful effect on the pharmacokinetics 
of aprepitant.

Relationship between concentration and effect
Using a highly specific NK1-receptor tracer, positron emission tomography (PET) studies in healthy 
young men have shown that aprepitant penetrates into the brain and occupies NK1 receptors in a dose-
and plasma-concentration-dependent manner. Aprepitant plasma concentrations achieved with the 
3-day regimen of EMEND in adults are predicted to provide greater than 95 % occupancy of brain 
NK1 receptors.

5.3 Preclinical safety data

Pre-clinical data reveal no special hazard for humans based on conventional studies of single and 
repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and development. 
However, it should be noted that systemic exposure in rodents was similar or even lower than 
therapeutic exposure in humans at the 125 mg/80 mg dose. In particular, although no adverse effects 
were noted in reproduction studies at human exposure levels, the animal exposures are not sufficient to 
make an adequate risk assessment in man.

In a juvenile toxicity study in rats treated from post natal day 10 to day 63 aprepitant led to an earlier 
vaginal opening in females from 250 mg/kg b.i.d. and to a delayed preputial separation in males, from 
10 mg/kg b.i.d. There were no margins to clinically relevant exposure. There were no 
treatment-related effects on mating, fertility or embryonic/foetal survival, and no pathological changes 
in the reproductive organs. In a juvenile toxicity study in dogs treated from post natal day 14 to 
day 42, a decreased testicular weight and Leydig cell size were seen in the males at 6 mg/kg/day and 
increased uterine weight, hypertrophy of the uterus and cervix, and oedema of vaginal tissues were 
seen in females from 4 mg/kg/day. There were no margins to clinically relevant exposure of 

 



43

aprepitant. For short term treatment according to recommended dose regimen these findings are 
considered unlikely to be clinically relevant.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Capsule content
Sucrose
Microcrystalline cellulose (E 460)
Hydroxypropylcellulose (E 463)
Sodium laurilsulfate

Capsule shell (125 mg)
Gelatin
Titanium dioxide (E 171)
Red iron oxide (E 172)
Yellow iron oxide (E 172)

Capsule shell (80 mg)
Gelatin
Titanium dioxide (E 171)

Printing ink
Shellac
Potassium hydroxide
Black iron oxide (E 172)

6.2 Incompatibilities

Not applicable.

6.3 Shelf-life

4 years

6.4 Special precautions for storage

Store in the original package in order to protect from moisture.

6.5 Nature and contents of container

Different pack sizes including different strengths are available.

Aluminium blister containing one 80 mg capsule.
Aluminium blister containing two 80 mg capsules.
5 Aluminium blisters each containing one 80 mg capsule.

Aluminium blister containing one 125 mg capsule.
5 Aluminium blisters each containing one 125 mg capsule.

Aluminium blister containing one 125 mg capsule and two 80 mg capsules.

Not all pack sizes may be marketed.

 



44

6.6 Special precautions for disposal

No special requirements for disposal.

7. MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

8. MARKETING AUTHORISATION NUMBER

EU/1/03/262/001
EU/1/03/262/002
EU/1/03/262/003
EU/1/03/262/004
EU/1/03/262/005
EU/1/03/262/006

9. DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION

Date of first authorisation: 11 November 2003
Date of latest renewal: 22 September 2008

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu/.

 



45

1. NAME OF THE MEDICINAL PRODUCT

EMEND 125 mg powder for oral suspension

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each sachet contains 125 mg of aprepitant. After reconstitution, 1 mL oral suspension contains 25 mg 
of aprepitant.

Excipients with known effect
Each sachet contains approximately 125 mg of sucrose and 468.7 mg lactose (as anhydrous).

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Powder for oral suspension.

Pink to light pink powder.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Prevention of nausea and vomiting associated with highly and moderately emetogenic cancer 
chemotherapy in children, toddlers and infants from the age of 6 months to less than 12 years.

EMEND powder for oral suspension is given as part of combination therapy (see section 4.2).

4.2 Posology and method of administration

The oral suspension should be prepared and the dose measured by healthcare professionals only.

Posology
Paediatric population
Infants, toddlers and children (aged 6 months to less than 12 years, and not less than 6 kg)
EMEND is given for 3 days as part of a regimen that includes a 5-HT3 antagonist. The recommended 
dose of EMEND powder for oral suspension is based on weight, as specified in the table below.
EMEND is administered orally 1 hour prior to chemotherapy on Days 1, 2 and 3. If no chemotherapy 
is given on Days 2 and 3, EMEND should be administered in the morning. See the Summary of 
Product Characteristics (SmPC) for the selected 5-HT3 antagonist for appropriate dosing information. 
If a corticosteroid, such as dexamethasone, is co-administered with EMEND, the dose of the 
corticosteroid should be administered at 50 % of the usual dose (see sections 4.5 and 5.1).

Recommended dose of EMEND oral suspension in paediatric patients aged 6 months to less than 
12 years

Day 1 Day 2 Day 3

EMEND oral 
suspension

25 mg/mL

3 mg/kg orally
Maximum dose 125 mg

2 mg/kg orally
Maximum dose 80 mg

2 mg/kg orally
Maximum dose 80 mg

 



46

The efficacy of the 125 mg powder for oral suspension has not been established in children 12 years of 
age and older. For adolescents aged 12-17 years, EMEND is available as capsules containing 80 mg,
or 125 mg of aprepitant.

The safety and efficacy of EMEND powder for oral suspension in infants below 6 months of age or 
weighing less than 6 kg has not been established. No data are available.

General
Efficacy data in combination with other corticosteroids and 5-HT3 antagonists are limited. For 
additional information on the co-administration with corticosteroids, see section 4.5. Please refer to the 
SmPC of co-administered 5-HT3 antagonist medicinal products.

Special populations
Gender
No dose adjustment is necessary based on gender (see section 5.2).

Renal impairment
No dose adjustment is necessary for patients with renal impairment or for patients with end stage renal 
disease undergoing haemodialysis (see section 5.2).

Hepatic impairment
No dose adjustment is necessary for patients with mild hepatic impairment. There are limited data in 
patients with moderate hepatic impairment and no data in patients with severe hepatic impairment. 
Aprepitant should be used with caution in these patients (see sections 4.4 and 5.2).

Method of administration
The oral suspension may be taken with or without food.
For details on preparation and administration of the suspension, see section 6.6.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Co-administration with pimozide, terfenadine, astemizole or cisapride (see section 4.5).

4.4 Special warnings and precautions for use

Patients with moderate to severe hepatic impairment
There are limited data in patients with moderate hepatic impairment and no data in patients with 
severe hepatic impairment. EMEND should be used with caution in these patients (see section 5.2).

CYP3A4 interactions
EMEND should be used with caution in patients receiving concomitant orally administered active 
substances that are metabolised primarily through CYP3A4 and with a narrow therapeutic range, such 
as cyclosporine, tacrolimus, sirolimus, everolimus, alfentanil, ergot alkaloid derivatives, fentanyl, and 
quinidine (see section 4.5). Additionally, concomitant administration with irinotecan should be 
approached with particular caution as the combination might result in increased toxicity.

Co-administration with warfarin (a CYP2C9 substrate)
In patients on chronic warfarin therapy, the International Normalised Ratio (INR) should be monitored 
closely during treatment with EMEND and for 14 days following each 3-day course of EMEND (see 
section 4.5).

Co-administration with hormonal contraceptives
The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration 
of EMEND. Alternative non-hormonal back-up methods of contraception should be used during 
treatment with EMEND and for 2 months following the last dose of EMEND (see section 4.5).

 



47

Excipients
EMEND powder for oral suspension contains sucrose and lactose. Patients with rare hereditary 
problems of fructose or galactose intolerance, glucose-galactose malabsorption, Lapp lactase 
deficiency, or sucrase-isomaltase insufficiency should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Aprepitant (125 mg/80 mg) is a substrate, a moderate inhibitor, and an inducer of CYP3A4. Aprepitant 
is also an inducer of CYP2C9. During treatment with EMEND, CYP3A4 is inhibited. After the end of 
treatment, EMEND causes a transient mild induction of CYP2C9, CYP3A4 and glucuronidation. 
Aprepitant does not seem to interact with the P-glycoprotein transporter, as suggested by the lack of 
interaction of aprepitant with digoxin.

Effect of aprepitant on the pharmacokinetics of other active substances
CYP3A4 inhibition
As a moderate inhibitor of CYP3A4, aprepitant (125 mg/80 mg) can increase plasma concentrations of 
co-administered active substances that are metabolised through CYP3A4. The total exposure of orally 
administered CYP3A4 substrates may increase up to approximately 3-fold during the 3-day treatment 
with EMEND; the effect of aprepitant on the plasma concentrations of intravenously administered 
CYP3A4 substrates is expected to be smaller. EMEND must not be used concurrently with pimozide, 
terfenadine, astemizole, or cisapride (see section 4.3). Inhibition of CYP3A4 by aprepitant could result 
in elevated plasma concentrations of these active substances, potentially causing serious or 
life-threatening reactions. Caution is advised during concomitant administration of EMEND and orally 
administered active substances that are metabolised primarily through CYP3A4 and with a narrow 
therapeutic range, such as cyclosporine, tacrolimus, sirolimus, everolimus, alfentanil, diergotamine, 
ergotamine, fentanyl, and quinidine (see section 4.4).

Corticosteroids
Dexamethasone: The usual oral dexamethasone dose should be reduced by approximately 50 % when 
co-administered with EMEND 125 mg/80 mg regimen. The dose of dexamethasone in chemotherapy 
induced nausea and vomiting clinical trials was chosen to account for active substance interactions 
(see section 4.2). EMEND, when given as a regimen of 125 mg with dexamethasone co-administered 
orally as 20 mg on Day 1, and EMEND when given as 80 mg/day with dexamethasone 
co-administered orally as 8 mg on Days 2 through 5, increased the AUC of dexamethasone, a 
CYP3A4 substrate, 2.2-fold on Days 1 and 5.

Methylprednisolone: The usual intravenously administered methylprednisolone dose should be 
reduced approximately 25 %, and the usual oral methylprednisolone dose should be reduced 
approximately 50 % when co-administered with EMEND 125 mg/80 mg regimen. EMEND, when 
given as a regimen of 125 mg on Day 1 and 80 mg/day on Days 2 and 3, increased the AUC of 
methylprednisolone, a CYP3A4 substrate, by 1.3-fold on Day 1 and by 2.5-fold on Day 3, when 
methylprednisolone was co-administered intravenously as 125 mg on Day 1 and orally as 40 mg on 
Days 2 and 3.

During continuous treatment with methylprednisolone, the AUC of methylprednisolone may decrease 
at later time points within 2 weeks following initiation of the EMEND dose, due to the inducing effect 
of aprepitant on CYP3A4. This effect may be expected to be more pronounced for orally administered 
methylprednisolone.

Chemotherapeutic medicinal products
In pharmacokinetic studies, EMEND, when given as a regimen of 125 mg on Day 1 and 80 mg/day on 
Days 2 and 3, did not influence the pharmacokinetics of docetaxel administered intravenously on 
Day 1 or vinorelbine administered intravenously on Day 1 or Day 8. Because the effect of EMEND on 
the pharmacokinetics of orally administered CYP3A4 substrates is greater than the effect of EMEND
on the pharmacokinetics of intravenously administered CYP3A4 substrates, an interaction with orally 
administered chemotherapeutic medicinal products metabolised primarily or partly by CYP3A4 (e.g.,

 



48

etoposide, vinorelbine) cannot be excluded. Caution is advised and additional monitoring may be 
appropriate in patients receiving medicinal products metabolized primarily or partly by CYP3A4 (see 
section 4.4). Post-marketing events of neurotoxicity, a potential adverse reaction of ifosfamide, have 
been reported after aprepitant and ifosfamide co-administration.

Immunosuppressants
During the 3-day CINV regimen, a transient moderate increase followed by a mild decrease in 
exposure of immunosuppressants metabolised by CYP3A4 (e.g., cyclosporine, tacrolimus, everolimus 
and sirolimus) is expected. Given the short duration of the 3-day regimen and the time-dependent 
limited changes in exposure, dose reduction of the immunosuppressant is not recommended during the 
3 days of co-administration with EMEND.

Midazolam
The potential effects of increased plasma concentrations of midazolam or other benzodiazepines 
metabolised via CYP3A4 (alprazolam, triazolam) should be considered when co-administering these 
medicinal products with EMEND (125 mg/80 mg).

EMEND increased the AUC of midazolam, a sensitive CYP3A4 substrate, 2.3-fold on Day 1 and 
3.3-fold on Day 5, when a single oral dose of 2 mg midazolam was co-administered on Days 1 and 5 
of a regimen of EMEND 125 mg on Day 1 and 80 mg/day on Days 2 to 5.

In another study with intravenous administration of midazolam, EMEND was given as 125 mg on 
Day 1 and 80 mg/day on Days 2 and 3, and 2 mg midazolam was given intravenously prior to the 
administration of the 3-day regimen of EMEND and on Days 4, 8, and 15. EMEND increased the 
AUC of midazolam 25 % on Day 4 and decreased the AUC of midazolam 19 % on Day 8 and 4 % on 
Day 15. These effects were not considered clinically important. 

In a third study with intravenous and oral administration of midazolam, EMEND was given as 125 mg 
on Day 1 and 80 mg/day on Days 2 and 3, together with ondansetron 32 mg Day 1, dexamethasone 
12 mg Day 1 and 8 mg Days 2-4. This combination (i.e. EMEND, ondansetron and dexamethasone)
decreased the AUC of oral midazolam 16 % on Day 6, 9 % on Day 8, 7 % on Day 15 and 17 % on 
Day 22. These effects were not considered clinically important.

An additional study was completed with intravenous administration of midazolam and EMEND. 
Intravenous 2 mg midazolam was given 1 hour after oral administration of a single dose of EMEND 
125 mg. The plasma AUC of midazolam was increased by 1.5-fold. This effect was not considered 
clinically important.

Induction
As a mild inducer of CYP2C9, CYP3A4 and glucuronidation, aprepitant can decrease plasma 
concentrations of substrates eliminated by these routes within two weeks following initiation and 
treatment. This effect may become apparent only after the end of a 3-day treatment with EMEND. For 
CYP2C9 and CYP3A4 substrates, the induction is transient with a maximum effect reached 3-5 days 
after end of the EMEND 3-day treatment. The effect is maintained for a few days, thereafter slowly 
declines and is clinically insignificant by two weeks after end of EMEND treatment. Mild induction of 
glucuronidation is also seen with 80 mg oral aprepitant given for 7 days. Data are lacking regarding 
effects on CYP2C8 and CYP2C19. Caution is advised when warfarin, acenocoumarol, tolbutamide, 
phenytoin or other active substances that are known to be metabolised by CYP2C9 are administered 
during this time period.

Warfarin
In patients on chronic warfarin therapy, the prothrombin time (INR) should be monitored closely 
during treatment with EMEND and for 2 weeks following each 3-day course of EMEND for 
chemotherapy induced nausea and vomiting (see section 4.4). When a single 125 mg dose of EMEND 
was administered on Day 1 and 80 mg/day on Days 2 and 3 to healthy subjects who were stabilised on 
chronic warfarin therapy, there was no effect of EMEND on the plasma AUC of R(+) or S(-) warfarin 
determined on Day 3; however, there was a 34 % decrease in S(-) warfarin (a CYP2C9 substrate) 

 



49

trough concentration accompanied by a 14 % decrease in INR 5 days after completion of treatment 
with EMEND. 

Tolbutamide
EMEND, when given as 125 mg on Day 1 and 80 mg/day on Days 2 and 3, decreased the AUC of 
tolbutamide (a CYP2C9 substrate) by 23 % on Day 4, 28 % on Day 8, and 15 % on Day 15, when a 
single dose of tolbutamide 500 mg was administered orally prior to the administration of the 3-day 
regimen of EMEND and on Days 4, 8, and 15.

Hormonal contraceptives
The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration 
of EMEND. Alternative non-hormonal back-up methods of contraception should be used during 
treatment with EMEND and for 2 months following the last dose of EMEND. 

In a clinical study, single doses of an oral contraceptive containing ethinyl estradiol and norethindrone 
were administered on Days 1 through 21 with EMEND, given as a regimen of 125 mg on Day 8 and 
80 mg/day on Days 9 and 10 with ondansetron 32 mg intravenously on Day 8 and oral dexamethasone 
given as 12 mg on Day 8 and 8 mg/day on Days 9, 10, and 11. During days 9 through 21 in this study, 
there was as much as a 64 % decrease in ethinyl estradiol trough concentrations and as much as a 60 % 
decrease in norethindrone trough concentrations. 

5-HT3 antagonists
In clinical interaction studies, aprepitant did not have clinically important effects on the 
pharmacokinetics of ondansetron, granisetron, or hydrodolasetron (the active metabolite of 
dolasetron).

Effect of other medicinal products on the pharmacokinetics of aprepitant
Concomitant administration of EMEND with active substances that inhibit CYP3A4 activity (e.g., 
ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone, 
and protease inhibitors) should be approached cautiously, as the combination is expected to result 
several-fold in increased plasma concentrations of aprepitant (see section 4.4). 

Concomitant administration of EMEND with active substances that strongly induce CYP3A4 activity 
(e.g., rifampicin, phenytoin, carbamazepine, phenobarbital) should be avoided as the combination 
results in reductions of the plasma concentrations of aprepitant that may result in decreased efficacy of 
EMEND. Concomitant administration of EMEND with herbal preparations containing St. John’s Wort 
(Hypericum perforatum) is not recommended.

Ketoconazole
When a single 125 mg dose of aprepitant was administered on Day 5 of a 10-day regimen of 
400 mg/day of ketoconazole, a strong CYP3A4 inhibitor, the AUC of aprepitant increased 
approximately 5-fold and the mean terminal half-life of aprepitant increased approximately 3-fold.

Rifampicin
When a single 375 mg dose of aprepitant was administered on Day 9 of a 14-day regimen of 
600 mg/day of rifampicin, a strong CYP3A4 inducer, the AUC of aprepitant decreased 91 % and the 
mean terminal half-life decreased 68 %. 

Paediatric population
Interaction studies have only been performed in adults.

4.6 Fertility, pregnancy and lactation

Contraception in males and females
The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration 
of EMEND. Alternative non-hormonal back-up methods of contraception should be used during 

 



50

treatment with EMEND and for 2 months following the last dose of EMEND (see sections 4.4 and 
4.5).

Pregnancy
For aprepitant no clinical data on exposed pregnancies are available. The potential for reproductive 
toxicity of aprepitant has not been fully characterised, since exposure levels above the therapeutic 
exposure in humans at the 125 mg/80 mg dose could not be attained in animal studies. These studies 
did not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal 
development, parturition or postnatal development (see section 5.3). The potential effects on 
reproduction of alterations in neurokinin regulation are unknown. EMEND should not be used during 
pregnancy unless clearly necessary.

Breast-feeding
Aprepitant is excreted in the milk of lactating rats. It is not known whether aprepitant is excreted in 
human milk; therefore, breast-feeding is not recommended during treatment with EMEND.

Fertility
The potential for effects of aprepitant on fertility has not been fully characterised because exposure 
levels above the therapeutic exposure in humans could not be attained in animal studies. These fertility 
studies did not indicate direct or indirect harmful effects with respect to mating performance, fertility, 
embryonic/foetal development, or sperm count and motility (see section 5.3).

4.7 Effects on ability to drive and use machines

EMEND may have minor influence on the ability to ride a bicycle and use machines. Dizziness and 
fatigue may occur following administration of EMEND (see section 4.8).

4.8 Undesirable effects

Summary of the safety profile
The safety profile of aprepitant was evaluated in approximately 6,500 adults in more than 50 studies
and 184 children and adolescents in 2 pivotal paediatric clinical trials.

The most common adverse reactions reported at a greater incidence in adults treated with the aprepitant 
regimen than with standard therapy in patients receiving Highly Emetogenic Chemotherapy (HEC) 
were: hiccups (4.6 % versus 2.9 %), alanine aminotransferase (ALT) increased (2.8 % versus 1.1 %), 
dyspepsia (2.6 % versus 2.0 %), constipation (2.4 % versus 2.0 %), headache (2.0 % versus 1.8 %), and 
decreased appetite (2.0 % versus 0.5 %). The most common adverse reaction reported at a greater 
incidence in patients treated with the aprepitant regimen than with standard therapy in adults receiving 
Moderately Emetogenic Chemotherapy (MEC) was fatigue (1.4 % versus 0.9 %).

The most common adverse reactions reported at a greater incidence in paediatric patients treated with 
the aprepitant regimen than with the control regimen while receiving emetogenic cancer chemotherapy 
were hiccups (3.3 % versus 0.0 %) and flushing (1.1 % versus 0.0 %).

Tabulated list of adverse reactions
The following adverse reactions were observed in a pooled analysis of the HEC and MEC studies at a 
greater incidence with aprepitant than with standard therapy or in postmarketing use. The frequency 
categories given in the table are based on the studies in adults; the observed frequencies in the 
paediatric studies were similar or lower, unless shown in the table. Some less common ADRs in the 
adult population were not observed in the paediatric studies.

Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon 
(≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000) and very rare (< 1/10,000), not known (cannot 
be estimated from the available data).

 



51

System organ class Adverse reaction Frequency
Infection and infestations candidiasis, staphylococcal infection rare

Blood and lymphatic system 
disorders

febrile neutropenia, anaemia uncommon

Immune system disorders hypersensitivity reactions including 
anaphylactic reactions

not known

Metabolism and nutrition 
disorders

decreased appetite common

polydipsia rare

Psychiatric disorders anxiety uncommon

disorientation, euphoric mood rare

Nervous system disorders headache common

dizziness, somnolence uncommon

cognitive disorder, lethargy, dysgeusia rare

Eye disorders conjunctivitis rare
Ear and labyrinth disorders tinnitus rare
Cardiac disorders palpitations uncommon

bradycardia, cardiovascular disorder rare

Vascular disorders hot flush/flushing uncommon

Respiratory, thoracic and 
mediastinal disorders

hiccups common

oropharyngeal pain, sneezing, cough, 
postnasal drip, throat irritation

rare

Gastrointestinal disorders constipation, dyspepsia common

eructation, nausea†, vomiting†, 
gastroesophageal reflux disease, abdominal 
pain, dry mouth, flatulence

uncommon

duodenal ulcer perforation, stomatitis, 
abdominal distension, faeces hard, neutropenic 
colitis

rare

Skin and subcutaneous tissue 
disorders

rash, acne uncommon

photosensitivity reaction, hyperhidrosis, 
seborrhoea, skin lesion, rash pruritic, 
Stevens-Johnson syndrome/toxic epidermal 
necrolysis

rare

pruritus, urticaria not known

Musculoskeletal and connective 
tissue disorders

muscular weakness, muscle spasms rare

Renal and urinary disorders dysuria uncommon

pollakiuria rare

 



52

System organ class Adverse reaction Frequency
General disorders and 
administration site conditions

fatigue common

asthenia, malaise uncommon

oedema, chest discomfort, gait disturbance rare

Investigations ALT increased common

AST increased, blood alkaline phosphatase 
increased

uncommon

red blood cells urine positive, blood sodium 
decreased, weight decreased, neutrophil count 
decreased, glucose urine present, urine output 
increased

rare

†Nausea and vomiting were efficacy parameters in the first 5 days of post-chemotherapy treatment and were 
reported as adverse reactions only thereafter.

Description of selected adverse reactions
The adverse reactions profiles in adults in the Multiple-Cycle extension of HEC and MEC studies for 
up to 6 additional cycles of chemotherapy were generally similar to those observed in Cycle 1.

In an additional active-controlled clinical study in 1,169 patients receiving aprepitant and HEC, the 
adverse reactions profile was generally similar to that seen in the other HEC studies with aprepitant.

Additional adverse reactions were observed in adult patients treated with aprepitant for postoperative 
nausea and vomiting (PONV) and a greater incidence than with ondansetron: abdominal pain upper, 
bowel sounds abnormal, constipation*, dysarthria, dyspnoea, hypoaesthesia, insomnia, miosis, nausea, 
sensory disturbance, stomach discomfort, sub-ileus*, visual acuity reduced, wheezing.
*Reported in patients taking a higher dose of aprepitant.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

In the event of overdose, EMEND should be discontinued and general supportive treatment and 
monitoring should be provided. Because of the antiemetic activity of aprepitant, emesis induced by a 
medicinal product may not be effective.

Aprepitant cannot be removed by haemodialysis.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antiemetics and antinauseants, ATC code: A04AD12

Aprepitant is a selective high-affinity antagonist at human substance P neurokinin 1 (NK1) receptors.

 

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53

3-day regimen of aprepitant in adults
In 2 randomised, double-blind studies encompassing a total of 1,094 adult patients receiving 
chemotherapy that included cisplatin  70 mg/m2, aprepitant in combination with an 
ondansetron/dexamethasone regimen (see section 4.2) was compared with a standard regimen (placebo 
plus ondansetron 32 mg intravenously administered on Day 1 plus dexamethasone 20 mg orally on 
Day 1 and 8 mg orally twice daily on Days 2 to 4). Although a 32 mg intravenous dose of ondansetron 
was used in clinical trials, this is no longer the recommended dose. See the product information for the 
selected 5-HT3 antagonist for appropriate dosing information.

Efficacy was based on evaluation of the following composite measure: complete response (defined as 
no emetic episodes and no use of rescue therapy) primarily during Cycle 1. The results were evaluated 
for each individual study and for the 2 studies combined.

A summary of the key study results from the combined analysis is shown in Table 1.

Table 1
Percent of adult patients receiving Highly Emetogenic Chemotherapy responding 

by treatment group and phase — Cycle 1

COMPOSITE MEASURES

Aprepitant 
regimen

(N= 521) †

%

Standard 
therapy

(N= 524) †

%

Differences*

         %             (95 % CI)

Complete response (no emesis and no rescue therapy)
Overall (0-120 hours)
0-24 hours
25-120 hours

67.7
86.0
71.5

47.8
73.2
51.2

19.9
12.7
20.3

(14.0, 25.8)
(7.9, 17.6)
(14.5, 26.1)

INDIVIDUAL MEASURES
No emesis (no emetic episodes regardless of use of rescue therapy)

Overall (0-120 hours)
0-24 hours
25-120 hours

71.9
86.8
76.2

49.7
74.0
53.5

22.2
12.7
22.6

(16.4, 28.0)
(8.0, 17.5)
(17.0, 28.2)

No significant nausea (maximum VAS < 25 mm on a scale of 0-100 mm)
Overall (0-120 hours)
25-120 hours 

72.1
74.0

64.9
66.9

7.2
7.1

(1.6, 12.8)
(1.5, 12.6)

* The confidence intervals were calculated with no adjustment for gender and concomitant chemotherapy, which 
were included in the primary analysis of odds ratios and logistic models.
†  One patient in the Aprepitant regimen only had data in the acute phase and was excluded from the overall and 
delayed phase analyses; one patient in the Standard regimen only had data in the delayed phase and was 
excluded from the overall and acute phase analyses.

 



54

The estimated time to first emesis in the combined analysis is depicted by the Kaplan-Meier plot in 
Figure 1.

Figure 1
Percent of adult patients receiving Highly Emetogenic Chemotherapy 

who remain emesis free over time – Cycle 1

0 12 24 36 48 60 72 84 96 108 120
0

40%

50%

60%

70%

80%

90%

100%

P
e

rc
e

n
t 

o
f 

P
a

ti
e
n

ts

Aprepitant Regimen (N=520)
Standard Therapy (N=523)

Time (hours)

Statistically significant differences in efficacy were also observed in each of the 2 individual studies.

In the same 2 clinical studies, 851 adult patients continued into the Multiple-Cycle extension for up to 
5 additional cycles of chemotherapy. The efficacy of the aprepitant regimen was apparently 
maintained during all cycles.

In a randomised, double-blind study in a total of 866 adult patients (864 females, 2 males) receiving 
chemotherapy that included cyclophosphamide 750-1,500 mg/m2; or cyclophosphamide 
500-1,500 mg/m2 and doxorubicin (< 60 mg/m2) or epirubicin (< 100 mg/m2), aprepitant in 
combination with an ondansetron/dexamethasone regimen (see section 4.2) was compared with 
standard therapy (placebo plus ondansetron 8 mg orally (twice on Day 1, and every 12 hours on 
Days 2 and 3) plus dexamethasone 20 mg orally on Day 1).

Efficacy was based on evaluation of the composite measure: complete response (defined as no emetic 
episodes and no use of rescue therapy) primarily during Cycle 1.

 



55

A summary of the key study results is shown in Table 2.

Table 2
Percent of adult patients responding by treatment group and phase — Cycle 1

Moderately Emetogenic Chemotherapy

COMPOSITE MEASURES

Aprepitant 
regimen

(N= 433) †

%

Standard 
therapy

(N= 424)
%

Differences*

        %             (95 % CI)

Complete response (no emesis and no rescue therapy)
Overall (0-120 hours)
0-24 hours
25-120 hours

50.8
75.7
55.4

42.5
69.0
49.1

8.3
6.7
6.3

(1.6, 15.0)
(0.7, 12.7)
(-0.4, 13.0)

INDIVIDUAL MEASURES
No emesis (no emetic episodes regardless of use of rescue therapy)

Overall (0-120 hours)
0-24 hours
25-120 hours

75.7
87.5
80.8

58.7
77.3
69.1

17.0
10.2
11.7

(10.8, 23.2)
(5.1, 15.3)
(5.9, 17.5)

No significant nausea (maximum VAS < 25 mm on a scale of 0-100 mm)
Overall (0-120 hours)
0-24 hours
25-120 hours

60.9
79.5
65.3

55.7
78.3
61.5

5.3
1.3
3.9

(-1.3, 11.9)
(-4.2, 6.8)
(-2.6, 10.3)

*  The confidence intervals were calculated with no adjustment for age category (< 55 years, ≥ 55 years) and 
investigator group, which were included in the primary analysis of odds ratios and logistic models.
†  One patient in the Aprepitant regimen only had data in the acute phase and was excluded from the overall and 
delayed phase analyses.

In the same clinical study, 744 adult patients continued into the Multiple-Cycle extension for up to 
3 additional cycles of chemotherapy. The efficacy of the aprepitant regimen was apparently 
maintained during all cycles.

In a second multicentre, randomised, double-blind, parallel-group, clinical study, the aprepitant 
regimen was compared with standard therapy in 848 adult patients (652 females, 196 males) receiving 
a chemotherapy regimen that included any intravenous dose of oxaliplatin, carboplatin, epirubicin, 
idarubicin, ifosfamide, irinotecan, daunorubicin, doxorubicin; cyclophosphamide intravenously 
(< 1,500 mg/m2); or cytarabine intravenously (> 1 g/m2). Patients receiving the aprepitant regimen 
were receiving chemotherapy for a variety of tumour types including 52 % with breast cancer, 21 % 
with gastrointestinal cancers including colorectal cancer, 13 % with lung cancer and 6 % with 
gynaecological cancers. The aprepitant regimen in combination with an ondansetron/dexamethasone 
regimen (see section 4.2) was compared with standard therapy (placebo in combination with 
ondansetron 8 mg orally (twice on Day 1, and every 12 hours on Days 2 and 3) plus dexamethasone 
20 mg orally on Day 1).

Efficacy was based on the evaluation of the following primary and key secondary endpoints: No 
vomiting in the overall period (0 to 120 hours post-chemotherapy), evaluation of safety and 
tolerability of the aprepitant regimen for chemotherapy induced nausea and vomiting (CINV), and 
complete response (defined as no vomiting and no use of rescue therapy) in the overall period (0 to 
120 hours post-chemotherapy). Additionally, no significant nausea in the overall period (0 to 
120 hours post-chemotherapy) was evaluated as an exploratory endpoint, and in the acute and delayed 
phases as a post-hoc analysis.

A summary of the key study results is shown in Table 3.

 



56

Table 3
Percent of adult patients responding by treatment group and phase for Study 2 – Cycle 1

Moderately Emetogenic Chemotherapy

Aprepitant 
regimen
(N= 425)

%

Standard 
therapy

(N= 406)
%

Differences*

        %             (95 % CI)

Complete response (no emesis and no rescue therapy)
Overall (0-120 hours)
0-24 hours
25-120 hours

68.7

89.2
70.8

56.3

80.3
60.9

12.4
8.9
9.9

(5.9, 18.9)
(4.0, 13.8)
(3.5, 16.3)

No emesis (no emetic episodes regardless of use of rescue therapy)
Overall (0-120 hours)
0-24 hours
25-120 hours

76.2
92.0
77.9

62.1
83.7
66.8

14.1
8.3
11.1

(7.9, 20.3)
(3.9, 12.7)
(5.1, 17.1)

No significant nausea (maximum VAS < 25 mm on a scale of 0-100 mm)
Overall (0-120 hours)
0-24 hours
25-120 hours

73.6

90.9
74.9

66.4

86.3
69.5

7.2
4.6
5.4

(1.0, 13.4)
(0.2, 9.0)
(-0.7, 11.5)

*The confidence intervals were calculated with no adjustment for gender and region, which were included in the 
primary analysis using logistic models.

The benefit of aprepitant combination therapy in the full study population was mainly driven by the 
results observed in patients with poor control with the standard regimen such as in women, even 
though the results were numerically better regardless of age, tumour type or gender. Complete 
response to the aprepitant regimen and standard therapy, respectively, was reached in 209/324 (65 %) 
and 161/320 (50 %) in women and 83/101 (82 %) and 68/87 (78 %) of men.

Paediatric population
In a randomised, double-blind, active comparator-controlled clinical study that included 302 children 
and adolescents (aged 6 months to 17 years) receiving moderately or highly emetogenic 
chemotherapy, the aprepitant regimen was compared to a control regimen for the prevention of CINV. 
The efficacy of the aprepitant regimen was evaluated in a single cycle (Cycle 1). Patients had the 
opportunity to receive open-label aprepitant in subsequent cycles (Optional Cycles 2-6); however 
efficacy was not assessed in these optional cycles. The aprepitant regimen for adolescents aged 12 
through 17 years (n=47) consisted of EMEND capsules 125 mg orally on Day 1 and 80 mg/day on 
Days 2 and 3 in combination with ondansetron on Day 1. The aprepitant regimen for children aged 
6 months to less than 12 years (n=105) consisted of EMEND powder for oral suspension 3.0 mg/kg 
(up to 125 mg) orally on Day 1 and 2.0 mg/kg (up to 80 mg) orally on Days 2 and 3 in combination 
with ondansetron on Day 1. The control regimen in adolescents aged 12 through 17 years (n=48) and 
children aged 6 months to less than 12 years (n=102) consisted of placebo for aprepitant on Days 1, 2 
and 3 in combination with ondansetron on Day 1. EMEND or placebo and ondansetron were 
administered 1 hour and 30 minutes prior to initiation of chemotherapy, respectively. Intravenous 
dexamethasone was permitted as part of the antiemetic regimen for paediatric patients in both age 
groups, at the discretion of the physician. A dose reduction (50 %) of dexamethasone was required for 
paediatric patients receiving aprepitant. No dose reduction was required for paediatric patients 
receiving the control regimen. Of the paediatric patients, 29 % in the aprepitant regimen and 28 % in 
the control regimen used dexamethasone as part of the regimen in Cycle 1.

The antiemetic activity of EMEND was evaluated over a 5-day (120 hour) period following the 
initiation of chemotherapy on Day 1. The primary endpoint was complete response in the delayed 
phase (25 to 120 hours following initiation of chemotherapy) in Cycle 1. A summary of the key study 
results are shown in Table 4.

 



57

Table 4
Number (%) of paediatric patients with complete response and no vomiting by treatment group and 

phase – Cycle 1 (Intent to treat population)

Aprepitant regimen
n/m (%)

Control regimen
n/m (%)

PRIMARY ENDPOINT
Complete response* – Delayed phase 77/152 (50.7)† 39/150 (26.0)
OTHER PRESPECIFIED ENDPOINTS
Complete response* – Acute phase 101/152 (66.4)‡ 78/150 (52.0)
Complete response* – Overall phase 61/152 (40.1)† 30/150 (20.0)
No vomiting§ – Overall phase 71/152 (46.7)† 32/150 (21.3)
*Complete response = No vomiting or retching or dry heaves and no use of rescue medication.
†p < 0.01 when compared to control regimen
‡p < 0.05 when compared to control regimen
§No vomiting = No vomiting or retching or dry heaves
n/m = Number of patients with desired response/number of patients included in time point.
Acute phase: 0 to 24 hours following initiation of chemotherapy.
Delayed phase: 25 to 120 hours following initiation of chemotherapy.
Overall phase: 0 to 120 hours following initiation of chemotherapy.

The estimated time to first vomiting after initiation of chemotherapy treatment was longer with the 
aprepitant regimen (estimated median time to first vomiting was 94.5 hours) compared with the 
control regimen group (estimated median time to first vomiting was 26.0 hours) as depicted in the 
Kaplan-Meier curves in Figure 2.

Figure 2
Time to first vomiting episode from start of chemotherapy administration - paediatric patients in the 

overall phase-Cycle 1 (Intent to treat population)

An analysis of efficacy in subpopulations in Cycle 1 demonstrated that, regardless of age category, 
gender, use of dexamethasone for antiemetic prophylaxis, and emetogenicity of chemotherapy, the 
aprepitant regimen provided better control than the control regimen with respect to the complete 
response endpoints.

5.2 Pharmacokinetic properties

Aprepitant displays non-linear pharmacokinetics. Both clearance and absolute bioavailability decrease 
with increasing dose.

 



58

Absorption
The mean absolute oral bioavailability of aprepitant is 67 % for the 80 mg capsule and 59 % for the 
125 mg capsule. The mean peak plasma concentration (Cmax) of aprepitant occurred at approximately 
4 hours (tmax). Oral administration of the capsule with an approximately 800 Kcal standard breakfast 
resulted in an up to 40 % increase in AUC of aprepitant. This increase is not considered clinically 
relevant.

The pharmacokinetics of aprepitant is non-linear across the clinical dose range. In healthy young 
adults, the increase in AUC0- was 26 % greater than dose proportional between 80 mg and 125 mg 
single doses administered in the fed state.

Following oral administration of a single 125 mg dose of EMEND on Day 1 and 80 mg once daily on 
Days 2 and 3, the AUC0-24hr (mean±SD) was 19.6 ± 2.5 µgh/mL and 21.2 ± 6.3 µg h/mL on 
Days 1 and 3, respectively. Cmax was 1.6 ± 0.36 µg/mL and 1.4 ± 0.22 µg/mL on Days 1 and 3, 
respectively.

Distribution
Aprepitant is highly protein bound, with a mean of 97 %. The geometric mean apparent volume of 
distribution at steady state (Vdss) is approximately 66 L in humans.

Biotransformation
Aprepitant undergoes extensive metabolism. In healthy young adults, aprepitant accounts for
approximately 19 % of the radioactivity in plasma over 72 hours following a single intravenous 
administration 100 mg dose of [14C]-fosaprepitant, a prodrug for aprepitant, indicating a substantial 
presence of metabolites in the plasma. Twelve metabolites of aprepitant have been identified in human 
plasma. The metabolism of aprepitant occurs largely via oxidation at the morpholine ring and its side 
chains and the resultant metabolites were only weakly active. In vitro studies using human liver 
microsomes indicate that aprepitant is metabolised primarily by CYP3A4 and potentially with minor 
contribution by CYP1A2 and CYP2C19.

Elimination
Aprepitant is not excreted unchanged in urine. Metabolites are excreted in urine and via biliary 
excretion in faeces. Following a single intravenously administered 100 mg dose of [14C]-fosaprepitant, 
a prodrug for aprepitant, to healthy subjects, 57 % of the radioactivity was recovered in urine and 
45 % in faeces.

The plasma clearance of aprepitant is dose-dependent, decreasing with increased dose and ranged from 
approximately 60 to 72 mL/min in the therapeutic dose range. The terminal half-life ranged from 
approximately 9 to 13 hours.

Pharmacokinetics in special populations
Gender: Following oral administration of a single 125 mg dose of aprepitant, the Cmax for aprepitant is 
16 % higher in females as compared with males. The half-life of aprepitant is 25 % lower in females 
as compared with males and its tmax occurs at approximately the same time. These differences are not 
considered clinically meaningful. No dose adjustment for EMEND is necessary based on gender.

Hepatic impairment: Mild hepatic impairment (Child-Pugh class A) does not affect the 
pharmacokinetics of aprepitant to a clinically relevant extent. No dose adjustment is necessary for 
patients with mild hepatic impairment. Conclusions regarding the influence of moderate hepatic 
impairment (Child-Pugh class B) on aprepitant pharmacokinetics cannot be drawn from available data. 
There are no clinical or pharmacokinetic data in patients with severe hepatic impairment (Child-Pugh 
class C).

Renal impairment: A single 240 mg dose of aprepitant was administered to patients with severe renal 
impairment (CrCl < 30 mL/min) and to patients with end stage renal disease (ESRD) requiring 
haemodialysis.

 



59

In patients with severe renal impairment, the AUC0- of total aprepitant (unbound and protein bound) 
decreased by 21 % and Cmax decreased by 32 %, relative to healthy subjects. In patients with ESRD 
undergoing haemodialysis, the AUC0- of total aprepitant decreased by 42 % and Cmax decreased by 
32 %. Due to modest decreases in protein binding of aprepitant in patients with renal disease, the AUC 
of pharmacologically active unbound aprepitant was not significantly affected in patients with renal 
impairment compared with healthy subjects. Haemodialysis conducted 4 or 48 hours after dosing had 
no significant effect on the pharmacokinetics of aprepitant; less than 0.2 % of the dose was recovered 
in the dialysate.

No dose adjustment for EMEND is necessary for patients with renal impairment or for patients with 
ESRD undergoing haemodialysis.

Paediatric population: As part of a 3-day regimen, dosing of aprepitant capsules (125/80/80-mg) in 
adolescent patients (aged 12 through 17 years) achieved an AUC0-24hr above 17 µg•hr/mL on Day 1 
with concentrations (Cmin) at the end of Days 2 and 3 above 0.4 µg/mL in a majority of patients. The 
median peak plasma concentration (Cmax) was approximately 1.3 µg/mL on Day 1, occurring at 
approximately 4 hours. As part of a 3-day regimen, dosing of aprepitant powder for oral suspension 
(3/2/2-mg/kg) in patients aged 6 months to less than12 years achieved an AUC0-24hr above 
17 µg•hr/mL on Day 1 with concentrations (Cmin) at the end of Days 2 and 3 above 0.1 µg/mL in a 
majority of patients. The median peak plasma concentration (Cmax) was approximately 1.2 µg/mL on 
Day 1, occurring between 5 and 7 hours.

A population pharmacokinetic analysis of aprepitant in paediatric patients (aged 6 months through 
17 years) suggests that gender and race have no clinically meaningful effect on the pharmacokinetics 
of aprepitant.
Relationship between concentration and effect
Using a highly specific NK1-receptor tracer, positron emission tomography (PET) studies in healthy 
young men have shown that aprepitant penetrates into the brain and occupies NK1 receptors in a dose-
and plasma-concentration-dependent manner. Aprepitant plasma concentrations achieved with the 
3-day regimen of EMEND in adults are predicted to provide greater than 95 % occupancy of brain 
NK1 receptors.

5.3 Preclinical safety data

Pre-clinical data reveal no special hazard for humans based on conventional studies of single and 
repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and development. 
However, it should be noted that systemic exposure in rodents was similar or even lower than 
therapeutic exposure in humans at the 125 mg/80 mg dose. In particular, although no adverse effects 
were noted in reproduction studies at human exposure levels, the animal exposures are not sufficient to 
make an adequate risk assessment in man.

In a juvenile toxicity study in rats treated from post natal day 10 to day 63 aprepitant led to an earlier 
vaginal opening in females from 250 mg/kg b.i.d. and to a delayed preputial separation in males, from 
10 mg/kg b.i.d. There were no margins to clinically relevant exposure. There were no 
treatment-related effects on mating, fertility or embryonic/foetal survival, and no pathological changes 
in the reproductive organs. In a juvenile toxicity study in dogs treated from post natal day 14 to 
day 42, a decreased testicular weight and Leydig cell size were seen in the males at 6 mg/kg/day and 
increased uterine weight, hypertrophy of the uterus and cervix, and oedema of vaginal tissues were 
seen in females from 4 mg/kg/day. There were no margins to clinically relevant exposure of 
aprepitant. For short term treatment according to recommended dose regimen these findings are 
considered unlikely to be clinically relevant.

 



60

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Hydroxypropylcellulose (E 463)
Sodium laurilsulfate (E 487)
Sucrose
Lactose (anhydrous)
Red iron oxide (E 172)
Sodium stearyl fumarate (E 485)

6.2 Incompatibilities

Not applicable.

6.3 Shelf-life

Unopened sachet: 2 years
After reconstitution: The oral suspension can be kept at room temperature (not above 30°C) for up to 
3 hours. It can also be stored refrigerated (between 2°C and 8°C) for up to 72 hours.

6.4 Special precautions for storage

This medicinal product does not require any special temperature storage conditions. Store in the 
original package in order to protect from moisture.
For storage conditions after reconstitution of the medicinal product, see section 6.3.

6.5 Nature and contents of container

PET/aluminium/LLDPE sachets
Single-use carton
Each carton contains one sachet with the powder for oral suspension, one 1 ml and one 5 mL oral 
dispenser (polypropylene with silicone o-ring), one cap, and one mixing cup (polypropylene).

6.6 Special precautions for disposal and other handling

The content of each single-use sachet is to be suspended in 4.6 mL of water giving a final 
concentration of 25 mg per mL.
• For more details on preparation and administration of the suspension, see the package leaflet

and the instructions for preparation of the oral suspension for healthcare professionals.
• Use the 5 mL oral dispenser to measure 4.6 mL of water, which is added into the mixing cup.
• Pour entire contents of the sachet into the 4.6 mL of water and mix.
• Once mixed, measure the recommended volume (dose) of suspension with the oral dispenser. 

Choose the oral dispenser based on the dose. Use the 1 mL oral dispenser if the dose is 1 mL or 
less and use the 5 mL oral dispenser if the dose is more than 1 mL. Administer the dose orally.
If the dose is not administered immediately after measuring, the filled oral dispenser can be 
refrigerated (between 2°C and 8°C) for up to 72 hours prior to use.

• The oral suspension can be kept at room temperature (not above 30°C) for up to 3 hours, prior 
to administration.

• Discard any remaining suspension and waste material.

Any unused medicinal product or waste material should be disposed of in accordance with local 
regulations.

 



61

7. MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

8. MARKETING AUTHORISATION NUMBER

EU/1/03/262/011

9. DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION

Date of first authorisation: 11 November 2003
Date of latest renewal: 22 September 2008

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.

 



62

ANNEX II

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 
RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 
SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT

 



63

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer(s) responsible for batch release

Merck Sharp & Dohme B. V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to medical prescription.

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

 Periodic Safety Update Reports

The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT

 Risk Management Plan (RMP)

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP.

An updated RMP should be submitted:
 At the request of the European Medicines Agency;
 Whenever the risk management system is modified, especially as the result of  new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached.

 



64

ANNEX III

LABELLING AND PACKAGE LEAFLET

 



65

A. LABELLING

 



66

PARTICULARS TO APPEAR ON OUTER PACKAGING

OUTER PACKAGING – STANDARD PACK (CARTON)

1. NAME OF THE MEDICINAL PRODUCT

EMEND 40 mg hard capsules
Aprepitant

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each hard capsule contains 40 mg of aprepitant.

3. LIST OF EXCIPIENTS

Contains sucrose. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

1 hard capsule
5 x 1 hard capsule

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from moisture.

 



67

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/03/262/007 1 hard capsule
EU/1/03/262/008 5 x 1 hard capsule

13. BATCH NUMBER

Batch

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

EMEND 40 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC:
SN:
NN:

 



68

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER TEXT

1. NAME OF THE MEDICINAL PRODUCT

EMEND 40 mg hard capsules
Aprepitant

2. NAME OF THE MARKETING AUTHORISATION HOLDER

MSD

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Batch

5. OTHER

 



69

PARTICULARS TO APPEAR ON OUTER PACKAGING

OUTER PACKAGING – STANDARD PACK (CARTON)

1. NAME OF THE MEDICINAL PRODUCT

EMEND 80 mg hard capsules
Aprepitant

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each hard capsule contains 80 mg of aprepitant.

3. LIST OF EXCIPIENTS

Contains sucrose. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

1 hard capsule
2-day treatment pack containing: 2 x 80 mg hard capsule
5 x 1 hard capsule

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from moisture.

 



70

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/03/262/001 1 hard capsule
EU/1/03/262/002 2 x 1 hard capsule
EU/1/03/262/003 5 x 1 hard capsule

13. BATCH NUMBER

Batch

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

EMEND 80 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC:
SN:
NN:

 



71

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING
(INCLUDING 2 HARD CAPSULES 80 MG)

IMMEDIATE PACKAGING – TRIFOLD – 2-day treatment pack

1. NAME OF THE MEDICINAL PRODUCT

EMEND 80 mg hard capsules
Aprepitant

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each hard capsule contains 80 mg of aprepitant.

3. LIST OF EXCIPIENTS

Contains sucrose. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

2-day treatment pack containing:
2 x 80 mg hard capsule

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use.

Please read enclosed leaflet before use.

See enclosed leaflet for additional information about how to take EMEND.

WHEN and HOW to take EMEND

Your doctor has prescribed EMEND, an anti-emetic, to help prevent nausea and vomiting associated 
with chemotherapy.

HOW:
EMEND 80 mg hard capsules are taken just once a day for 2 consecutive days.
EMEND capsules can be taken with or without food.

Do not remove all capsules at one time.

To remove, push capsules through from this side.

Start of Therapy
WHEN:
Take one EMEND 80 mg capsule each morning. Start on the day after your chemotherapy.

Day 1

 



72

Day 2

EMEND 80 mg capsule

As nausea and vomiting may occur in the days following your chemotherapy, it is important that you 
take EMEND for 2 consecutive days as prescribed by your doctor.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from moisture.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/03/262/002 

13. BATCH NUMBER

Batch

14. GENERAL CLASSIFICATION FOR SUPPLY

 



73

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

17. UNIQUE IDENTIFIER – 2D BARCODE

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

 



74

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER TEXT

1. NAME OF THE MEDICINAL PRODUCT

EMEND 80 mg hard capsules
Aprepitant

2. NAME OF THE MARKETING AUTHORISATION HOLDER

MSD

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Batch

5. OTHER

 



75

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER PACKAGING – STANDARD PACK (CARTON)

1. NAME OF THE MEDICINAL PRODUCT

EMEND 125 mg hard capsules
Aprepitant

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each hard capsule contains 125 mg of aprepitant.

3. LIST OF EXCIPIENTS

Contains sucrose. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

1 hard capsule
5 x 1 hard capsule

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from moisture.

 



76

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/03/262/004 1 hard capsule
EU/1/03/262/005 5 x 1 hard capsule

13. BATCH NUMBER

Batch

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

EMEND 125 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC:
SN:
NN:

 



77

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER TEXT

1. NAME OF THE MEDICINAL PRODUCT

EMEND 125 mg hard capsules
Aprepitant

2. NAME OF THE MARKETING AUTHORISATION HOLDER

MSD

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Batch

5. OTHER

 



78

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER PACKAGING – STANDARD PACK (CARTON) 

1. NAME OF THE MEDICINAL PRODUCT

EMEND 165 mg hard capsules
Aprepitant

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each hard capsule contains 165 mg of aprepitant.

3. LIST OF EXCIPIENTS

Contains sucrose. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

1 hard capsule
6 x 1 hard capsule

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from moisture.

 



79

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/03/262/009 1 hard capsule
EU/1/03/262/010 6 x 1 hard capsule

13. BATCH NUMBER

Batch

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

EMEND 165 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC:
SN:
NN:

 



80

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER TEXT

1. NAME OF THE MEDICINAL PRODUCT

EMEND 165 mg hard capsules
Aprepitant

2. NAME OF THE MARKETING AUTHORISATION HOLDER

MSD

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Batch

5. OTHER

 



81

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER PACKAGING – TRIFOLD PACK (CARTON) – 3-day treatment pack

1. NAME OF THE MEDICINAL PRODUCT

EMEND 125 mg hard capsule
EMEND 80 mg hard capsules
Aprepitant

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each 125 mg hard capsule contains 125 mg of aprepitant.
Each 80 mg hard capsule contains 80 mg of aprepitant.

3. LIST OF EXCIPIENTS

Contains sucrose. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

3-day treatment pack containing:
1 x 125 mg hard capsule and 
2 x 80 mg hard capsule

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from moisture.

 



82

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/03/262/006 

13. BATCH NUMBER

Batch

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

EMEND 125 mg/80 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC:
SN:
NN:

 



83

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING
(INCLUDING 1 HARD CAPSULE 125 MG AND 2 HARD CAPUSULES 80 MG)

IMMEDIATE PACKAGING – TRIFOLD – 3-day treatment pack

1. NAME OF THE MEDICINAL PRODUCT

EMEND 125 mg hard capsule
EMEND 80 mg hard capsules
Aprepitant

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each 125 mg hard capsule contains 125 mg of aprepitant.
Each 80 mg hard capsule contains 80 mg of aprepitant.

3. LIST OF EXCIPIENTS

Contains sucrose. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

3-day treatment pack containing:
1 x 125 mg hard capsule and 
2 x 80 mg hard capsule

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use.

Please read enclosed leaflet before use.

See enclosed leaflet for additional information about how to take EMEND.

WHEN and HOW to take EMEND

Your doctor has prescribed EMEND, an anti-emetic, to help prevent nausea and vomiting associated 
with chemotherapy.

HOW:
EMEND is taken just once a day for 3 consecutive days.
EMEND capsules can be taken with or without food.

Do not remove all capsules at one time.

To remove, push capsules through from this side.

Start of Therapy
WHEN:
Take one EMEND 125 mg capsule by mouth 1-hour BEFORE you start your chemotherapy treatment.

 



84

Day 1

EMEND 125 mg capsule

WHEN:
Take one EMEND 80 mg capsule each morning on the next two days.

Day 2

Day 3

EMEND 80 mg capsule

As nausea and vomiting may occur in the days following your chemotherapy, it is important that you 
take EMEND for 3 consecutive days as prescribed by your doctor.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from moisture.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/03/262/006

 



85

13. BATCH NUMBER

Batch

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

17. UNIQUE IDENTIFIER – 2D BARCODE

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

 



86

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON EMEND 125 mg powder for oral suspension

1. NAME OF THE MEDICINAL PRODUCT

EMEND 125 mg powder for oral suspension
Aprepitant
For children aged 6 months to less than 12 years

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each sachet contains125 mg of aprepitant. After reconstitution, 1 mL of oral suspension contains 
25 mg of aprepitant.

3. LIST OF EXCIPIENTS

Contains sucrose and lactose. See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Powder for oral suspension.
One sachet, two oral dispensers, one cap and one mixing cup.

5. METHOD AND ROUTES OF ADMINISTRATION

Read the package leaflet before use.
Oral use. 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from moisture.

 



87

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/03/262/011

13. BATCH NUMBER

Batch

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

EMEND 125 mg powder for oral suspension

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC:
SN:
NN:

 



88

PARTICULARS TO APPEAR ON THE SMALL IMMEDIATE PACKAGING

Sachet for EMEND 125 mg powder for oral suspension

1. NAME OF THE MEDICINAL PRODUCT

EMEND 125 mg powder for oral suspension
Aprepitant
Oral use

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

6. OTHER

 



89

B. PACKAGE LEAFLET

 



90

Package leaflet: Information for the user

EMEND 40 mg hard capsules
aprepitant

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor, pharmacist, or nurse.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
- If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What EMEND is and what it is used for
2. What you need to know before you take EMEND
3. How to take EMEND
4. Possible side effects
5. How to store EMEND
6. Contents of the pack and other information

1. What EMEND is and what it is used for

EMEND contains the active substance aprepitant and belongs to a group of medicines called 
"neurokinin 1 (NK1) receptor antagonists" (antiemetics and antinauseants). The brain has a specific 
area that controls nausea and vomiting. EMEND works by blocking signals to that area and is used to 
prevent nausea and vomiting after surgery in adults.

2. What you need to know before you take EMEND

Do not take EMEND:
- if you are allergic to aprepitant or any of the other ingredients of this medicine (listed in 

section 6).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking EMEND.

Before treatment with this medicine, tell your doctor if you have liver disease because your liver is 
important in breaking down the medicine in your body. Your doctor may therefore have to monitor the 
condition of your liver.

Children and adolescents
Do not give EMEND 40 mg to children and adolescents under 18 years of age, because the 40 mg 
capsules have not been studied in this population.

Other medicines and EMEND
This medicine can affect other medicines. 
The effects of EMEND or other medicines might be influenced if you take EMEND together with 
other medicines including those listed below. Please talk to your doctor or pharmacist if you are taking 
any of the following medicines:

- birth control medicines which can include birth control pills, skin patches, implants, and certain 
Intrauterine devices (IUDs) that release hormones may not work adequately when taken 

 



91

together with EMEND. Another or additional non-hormonal form of birth control should be 
used during treatment with EMEND and for up to 2 months after using EMEND,

- pimozide (used to treat psychiatric illnesses),
- terfenadine; astemizole (used for hay fever and other allergic conditions),
- cisapride (used for treating digestive problems),
- medicines containing ergot alkaloid derivatives (used for treating migraines),
- rifampicin, clarithromycin, telithromycin (antibiotics used to treat infections),
- phenytoin (a medicine used to treat seizures),
- carbamazepine (used to treat depression and epilepsy),
- midazolam, phenobarbital (medicines used to produce calmness or help you sleep),
- St. John’s Wort (an herbal preparation used to treat depression),
- protease inhibitors (used to treat HIV infections),
- nefazodone (used to treat depression),
- ketoconazole except shampoo (used to treat Cushing’s syndrome - when the body produces an 

excess of cortisol),
- itraconazole, voriconazole, posaconazole (antifungals),
- corticosteroids (such as dexamethasone)

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other 
medicines.

Pregnancy and breast-feeding
You should not use this medicine during pregnancy unless clearly necessary. If you are pregnant or 
breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice 
before taking this medicine.

For information regarding birth control, see ‘Other medicines and EMEND’.

It is not known whether EMEND is excreted in human milk; therefore, breast-feeding is not 
recommended during treatment with this medicine. It is important that you tell your doctor if you are 
breast-feeding or are planning to breast-feed before taking this medicine.

Driving and using machines
It should be taken into account that some people feel dizzy and sleepy after taking EMEND. If you 
feel dizzy or sleepy, you should avoid driving or using machines after taking this medicine (see 
‘Possible side effects’).

EMEND contains sucrose
EMEND capsules contain sucrose. If you have been told by your doctor that you have an intolerance 
to some sugars, contact your doctor before taking this medicine.

3. How to take EMEND

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.

The recommended oral dose of EMEND is one 40 mg capsule within 3 hours prior to the start of 
anaesthesia.

Swallow the capsule whole with some liquid.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 



92

Stop taking EMEND and see a doctor immediately if you notice any of the following side effects, 
which may be serious, and for which you may need urgent medical treatment:
- Hives, rash, itching, difficulty breathing or swallowing (frequency not known, cannot be 

estimated from the available data); these are signs of an allergic reaction.

Other side effects that have been reported are listed below.

Common side effects (may affect up to 1 in 10 people) are:
- increased amount of liver enzymes in your blood.

Uncommon side effects (may affect up to 1 in 100 people) are:
- upper stomach pain, bowel sounds abnormal, dry mouth, nausea, stomach discomfort, serious 

constipation, small bowel not working properly (sub-ileus),
- decreased feeling or sensitivity (especially in skin), sensory disturbance, difficulty in speaking,
- decrease in pupil size, decrease in sharpness of vision (vision loss), 
- inability to sleep,
- slow heartbeat,
- whistling sound while breathing, shortness of breath.

Side effects for which the frequency is not known:
- Stevens-Johnson syndrome/toxic epidermal necrolysis (rare severe skin reaction).

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store EMEND

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date 
refers to the last day of that month.

Store in the original package in order to protect from moisture.

Do not remove the capsule from its blister until you are ready to take it.

Do not throw away any medicines via wastewater or house hold waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What EMEND contains
- The active substance is aprepitant. Each capsule contains 40 mg of aprepitant.
- The other ingredients are: sucrose, microcrystalline cellulose (E 460), hydroxypropylcellulose 

(E 463), sodium laurilsulfate, gelatin, titanium dioxide (E 171), shellac, potassium hydroxide, 
black iron oxide (E 172), and yellow iron oxide (E 172). 

What EMEND looks like and contents of the pack
The 40 mg hard capsule is opaque with a white body and mustard yellow cap with “464” and “40 mg” 
printed radially in black ink on the body.

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


93

EMEND 40 mg hard capsules are supplied in the following pack sizes:
- Aluminium blister containing one 40 mg capsule
- 5 Aluminium blisters each containing one 40 mg capsule

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder.

Belgique/België/Belgien 
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Lietuva
UAB Merck Sharp & Dohme
Tel. + 370 5278 02 47
msd_lietuva@merck.com

България
Мерк Шарп и Доум България ЕООД
Тел.: +359 2 819 3737
info-msdbg@merck.com

Luxembourg/Luxemburg
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Česká republika
Merck Sharp & Dohme s.r.o.
Tel: +420 233 010 111
dpoc_czechslovak@merck.com

Magyarország
MSD Pharma Hungary Kft.
Tel.: +36 1 888 5300
hungary_msd@merck.com

Danmark
MSD Danmark ApS
Tlf: + 45 4482 4000
dkmail@merck.com

Malta
Merck Sharp & Dohme Cyprus Limited
Tel: 8007 4433 (+356 99917558)
malta_info@merck.com 

Deutschland
MSD SHARP & DOHME GMBH
Tel: 0800 673 673 673 (+49 (0) 89 4561 2612)
e-mail@msd.de

Nederland
Merck Sharp & Dohme B.V.
Tel: 0800 9999000 

(+31 23 5153153)
medicalinfo.nl@merck.com

Eesti
Merck Sharp & Dohme OÜ
Tel.: +372 6144 200
msdeesti@merck.com

Norge
MSD (Norge) AS
Tlf: +47 32 20 73 00
msdnorge@msd.no

Eλλάδα
MSD Α.Φ.Β.Ε.Ε.
Τηλ: +30 210 98 97 300
dpoc_greece@merck.com

Österreich
Merck Sharp & Dohme Ges.m.b.H.
Tel: +43 (0) 1 26 044
msd-medizin@merck.com

España
Merck Sharp & Dohme de España, S.A.
Tel: +34 91 321 06 00
msd_info@merck.com

Polska
MSD Polska Sp. z o.o. 
Tel: +48 22 549 51 00
msdpolska@merck.com

 



94

France
MSD France
Tél: +33 (0) 1 80 46 40 40

Portugal
Merck Sharp & Dohme, Lda
Tel: +351 21 4465700
inform_pt@merck.com

Hrvatska
Merck Sharp & Dohme d.o.o.
Tel: + 385 1 6611 333
croatia_info@merck.com

România
Merck Sharp & Dohme Romania S.R.L.
Tel: +40 21 529 29 00
msdromania@merck.com

Ireland
Merck Sharp & Dohme Ireland (Human Health) 
Limited
Tel: +353 (0)1 2998700
medinfo_ireland@merck.com

Slovenija
Merck Sharp & Dohme, inovativna zdravila 
d.o.o.
Tel: +386 1 5204 201
msd_slovenia@merck.com

Ísland
Vistor hf.
Simi: +354 535 7000

Slovenská republika
Merck Sharp & Dohme, s. r. o.
Tel: +421 2 58282010
dpoc_czechslovak@merck.com

Ιtalia
MSD Italia S.r.l.
Tel: +39 06 361911
medicalinformation.it@merck.com

Suomi/Finland
MSD Finland Oy
Puh/Tel: +358 (0)9 804 650
info@msd.fi

Κύπρος
Merck Sharp & Dohme Cyprus Limited
Τηλ.: 800 00 673 (+357 22866700)
cyprus_info@merck.com

Sverige
Merck Sharp & Dohme (Sweden) AB
Tel: +46 77 5700488
medicinskinfo@merck.com

Latvija
SIA Merck Sharp & Dohme Latvija
Tel: +371 67364224
msd_lv@merck.com

United Kingdom
Merck Sharp & Dohme Limited
Tel: +44 (0) 1992 467272
medicalinformationuk@merck.com

This leaflet was last revised in

Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.

 

http://www.ema.europa.eu/


95

Package leaflet: Information for the user

EMEND 165 mg hard capsules
aprepitant

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor, pharmacist, or nurse.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
- If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What EMEND is and what it is used for
2. What you need to know before you take EMEND
3. How to take EMEND
4. Possible side effects
5. How to store EMEND
6. Contents of the pack and other information

1. What EMEND is and what it is used for

EMEND contains the active substance aprepitant and belongs to a group of medicines called 
"neurokinin 1 (NK1) receptor antagonists". The brain has a specific area that controls nausea and 
vomiting. EMEND works by blocking signals to that area, thereby reducing nausea and vomiting. 
EMEND is used in adults in combination with other medicines to prevent nausea and vomiting 
caused by chemotherapy (cancer treatment) containing cisplatin (a strong trigger of nausea and 
vomiting) and with chemotherapy that is a moderate trigger of nausea and vomiting (such as 
cyclophosphamide, doxorubicin or epirubicin). 

2. What you need to know before you take EMEND

Do not take EMEND:
- if you are allergic to aprepitant or any of the other ingredients of this medicine (listed in 

section 6).

- with medicines containing pimozide (used to treat psychiatric illnesses), terfenadine and 
astemizole (used for hay fever and other allergic conditions), cisapride (used for treating 
digestive problems). Tell your doctor if you are taking these medicines since your treatment 
must be modified before you start taking EMEND.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking this medicine.

Before treatment with EMEND, tell your doctor if you have liver disease because your liver is 
important in breaking down the medicine in your body. Your doctor may therefore have to monitor the 
condition of your liver.

Children and adolescents
Do not give EMEND 165 mg to children and adolescents under 18 years of age, because the 165 mg 
capsules have not been studied in this population.

 



96

Other medicines and EMEND
EMEND can affect other medicines both during and after treatment with EMEND. There are some 
medicines that should not be taken with EMEND (such as pimozide, terfenadine, astemizole, and 
cisapride) or that require a dose adjustment (see also Do not take EMEND). 

The effects of EMEND or other medicines might be influenced if you take EMEND together with 
other medicines including those listed below. Please talk to your doctor or pharmacist if you are taking 
any of the following medicines:

- birth control medicines which can include birth control pills, skin patches, implants, and certain 
Intrauterine devices (IUDs) that release hormones may not work adequately when taken 
together with EMEND. Another or additional non-hormonal form of birth control should be 
used during treatment with EMEND and for up to 2 months after using EMEND,

- cyclosporine, tacrolimus, sirolimus, everolimus (immunosuppressants), 
- alfentanil, fentanyl (used to treat pain), 
- quinidine (used to treat an irregular heart beat),
- irinotecan, etoposide, vinorelbine, ifosfamide (medicines used to treat cancer),
- medicines containing ergot alkaloid derivatives such as ergotamine and diergotamine (used for 

treating migraines),
- warfarin, acenocoumarol (blood thinners; blood tests may be required),
- rifampicin, clarithromycin, telithromycin (antibiotics used to treat infections),
- phenytoin (a medicine used to treat seizures), 
- carbamazepine (used to treat depression and epilepsy),
- midazolam, triazolam, phenobarbital (medicines used to produce calmness or help you sleep),
- St. John’s Wort (an herbal preparation used to treat depression), 
- protease inhibitors (used to treat HIV infections),
- ketoconazole except shampoo (used to treat Cushing’s syndrome - when the body produces an 

excess of cortisol),
- itraconazole, voriconazole, posaconazole (antifungals),
- nefazodone (used to treat depression),
- corticosteroids (such as dexamethasone and methylprednisolone),
- anti-anxiety medicines (such as alprazolam),
- tolbutamide (a medicine used to treat diabetes)

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other 
medicines.

Pregnancy and breast-feeding
You should not use this medicine during pregnancy unless clearly necessary. If you are pregnant or 
breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice
before taking this medicine.

For information regarding birth control, see 'Other medicines and EMEND'.

It is not known whether EMEND is excreted in human milk; therefore, breast-feeding is not 
recommended during treatment with this medicine. It is important that you tell your doctor if you are 
breast-feeding or are planning to breast-feed before taking this medicine.

Driving and using machines
It should be taken into account that some people feel dizzy and sleepy after taking EMEND. If you 
feel dizzy or sleepy, you should avoid driving or using machines after taking this medicine (see 
‘Possible side effects’).

EMEND contains sucrose
EMEND capsules contain sucrose. If you have been told by your doctor that you have an intolerance 
to some sugars, contact your doctor before taking this medicine.

 



97

3. How to take EMEND

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. Take the EMEND capsule on the first day of your chemotherapy 
cycle, together with other medicines, to prevent nausea and vomiting. Your doctor will ask you to 
continue taking other medicines including a corticosteroid (such as dexamethasone) and a ‘5HT3
antagonist’ (such as ondansetron) for preventing nausea and vomiting the following three days.

The recommended oral dose of EMEND is one 165 mg capsule on the first day of your chemotherapy 
treatment cycle. Take the capsule 1 hour before you start your chemotherapy session. 

EMEND can be taken with or without food.

Swallow the capsule whole with some liquid.

If you take more EMEND than you should
Do not take more capsules than the doctor recommends. If you have taken too many capsules, contact 
your doctor immediately. 

If you forget to take EMEND
If you have missed a dose, contact your doctor for advice.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

Stop taking EMEND and see a doctor immediately if you notice any of the following side effects, 
which may be serious, and for which you may need urgent medical treatment:
- Hives, rash, itching, difficulty breathing or swallowing (frequency not known, cannot be 

estimated from the available data); these are signs of an allergic reaction.

Other side effects that have been reported are listed below.

Common side effects (may affect up to 1 in 10 people) are:
- constipation, indigestion,
- headache,
- tiredness,
- loss of appetite,
- hiccups,
- increased amount of liver enzymes in your blood.

Uncommon side effects (may affect up to 1 in 100 people) are:
- dizziness, sleepiness,
- acne, rash,
- anxiousness,
- burping, nausea, vomiting, heartburn, stomach pain, dry mouth, passing wind, 
- increased painful or burning urination,
- weakness, generally feeling unwell,
- hot flush,
- fast or irregular heartbeats,
- fever with increased risk of infection, lowering of red blood cells.

 



98

Rare side effects (may affect up to 1 in 1,000 people) are:
- difficulty thinking, lack of energy, taste disturbance,
- sensitivity of the skin to sun, excessive sweating, oily skin, sores on skin, itching rash, 

Stevens-Johnson syndrome/toxic epidermal necrolysis (rare severe skin reaction),
- euphoria (feeling of extreme happiness), disorientation,
- bacterial infection, fungal infection,
- severe constipation, stomach ulcer, inflammation of the small intestine and colon, sores in 

mouth, bloating,
- frequent urination, passing more urine than normal, presence of sugar or blood in urine,
- chest discomfort, swelling, change in the manner of walking,
- cough, mucus in back of throat, throat irritation, sneezing, sore throat,
- eye discharge and itching,
- ringing in the ear,
- muscle spasms, muscle weakness,
- excessive thirst,
- slow heartbeat, heart and blood vessel disease,
- lowering of white blood cells, low sodium levels in the blood, weight loss.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store EMEND

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the blister and carton after EXP. The 
expiry date refers to the last day of that month.

Store in the original package in order to protect from moisture.

Do not remove the capsule from its blister until you are ready to take it.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What EMEND contains
The active substance is aprepitant. Each capsule contains 165 mg of aprepitant.

The other ingredients are: sucrose, microcrystalline cellulose (E 460), hydroxypropylcellulose (E 463), 
sodium laurilsulfate, gelatin, titanium dioxide (E 171), Indigo carmine (E 132), shellac, potassium 
hydroxide, and black iron oxide (E 172). 

What EMEND looks like and contents of the pack
The 165 mg hard capsule is opaque with a light blue cap and a white body with “466” and “165 mg” 
printed radially in black ink on one side of the body and the Merck logo on the other side.

EMEND 165 mg hard capsules are supplied in cartons in the following pack sizes:
- Aluminium blister containing one 165 mg capsule
- 6 Aluminium blisters each containing one 165 mg capsule

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


99

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder.

Belgique/België/Belgien 
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Lietuva
UAB Merck Sharp & Dohme
Tel. + 370 5278 02 47
msd_lietuva@merck.com

България
Мерк Шарп и Доум България ЕООД
Тел.: +359 2 819 3737
info-msdbg@merck.com

Luxembourg/Luxemburg
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Česká republika
Merck Sharp & Dohme s.r.o.
Tel: +420 233 010 111
dpoc_czechslovak@merck.com

Magyarország
MSD Pharma Hungary Kft.
Tel.: +36 1 888 5300
hungary_msd@merck.com

Danmark
MSD Danmark ApS
Tlf: + 45 4482 4000
dkmail@merck.com

Malta
Merck Sharp & Dohme Cyprus Limited
Tel: 8007 4433 (+356 99917558)
malta_info@merck.com 

Deutschland
MSD SHARP & DOHME GMBH
Tel: 0800 673 673 673 (+49 (0) 89 4561 2612)
e-mail@msd.de

Nederland
Merck Sharp & Dohme B.V.
Tel: 0800 9999000 

(+31 23 5153153)
medicalinfo.nl@merck.com

Eesti
Merck Sharp & Dohme OÜ
Tel.: +372 6144 200
msdeesti@merck.com

Norge
MSD (Norge) AS
Tlf: +47 32 20 73 00
msdnorge@msd.no

Eλλάδα
MSD Α.Φ.Β.Ε.Ε.
Τηλ: +30 210 98 97 300
dpoc_greece@merck.com

Österreich
Merck Sharp & Dohme Ges.m.b.H.
Tel: +43 (0) 1 26 044
msd-medizin@merck.com

España
Merck Sharp & Dohme de España, S.A.
Tel: +34 91 321 06 00
msd_info@merck.com

Polska
MSD Polska Sp. z o.o. 
Tel: +48 22 549 51 00
msdpolska@merck.com

France
MSD France
Tél: +33 (0) 1 80 46 40 40

Portugal
Merck Sharp & Dohme, Lda
Tel: +351 21 4465700
inform_pt@merck.com

 



100

Hrvatska
Merck Sharp & Dohme d.o.o.
Tel: + 385 1 6611 333
croatia_info@merck.com

România
Merck Sharp & Dohme Romania S.R.L.
Tel: +40 21 529 29 00
msdromania@merck.com

Ireland
Merck Sharp & Dohme Ireland (Human Health) 
Limited
Tel: +353 (0)1 2998700
medinfo_ireland@merck.com

Slovenija
Merck Sharp & Dohme, inovativna zdravila 
d.o.o.
Tel: +386 1 5204 201
msd_slovenia@merck.com

Ísland
Vistor hf.
Simi: +354 535 7000

Slovenská republika
Merck Sharp & Dohme, s. r. o.
Tel: +421 2 58282010
dpoc_czechslovak@merck.com

Ιtalia
MSD Italia S.r.l.
Tel: +39 06 361911
medicalinformation.it@merck.com

Suomi/Finland
MSD Finland Oy
Puh/Tel: +358 (0)9 804 650
info@msd.fi

Κύπρος
Merck Sharp & Dohme Cyprus Limited
Τηλ.: 800 00 673 (+357 22866700)
cyprus_info@merck.com

Sverige
Merck Sharp & Dohme (Sweden) AB
Tel: +46 77 5700488
medicinskinfo@merck.com

Latvija
SIA Merck Sharp & Dohme Latvija
Tel: +371 67364224
msd_lv@merck.com

United Kingdom
Merck Sharp & Dohme Limited
Tel: +44 (0) 1992 467272
medicalinformationuk@merck.com

This leaflet was last revised in

Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu.

 

http://www.ema.europa.eu/


101

Package leaflet: Information for the user

EMEND 125 mg hard capsules
EMEND 80 mg hard capsules

aprepitant

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. If you are the parent of a child taking EMEND, please read this 
information carefully.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask the doctor, pharmacist, or nurse.
- This medicine has been prescribed for you or the child only. Do not pass it on to others. It may 

harm them, even if their signs of illness are the same.
- If you or the child gets any side effects, talk to your doctor, pharmacist, or nurse. This includes 

any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What EMEND is and what it is used for
2. What you need to know before you take or give EMEND
3. How to take EMEND
4. Possible side effects
5. How to store EMEND
6. Contents of the pack and other information

1. What EMEND is and what it is used for

EMEND contains the active substance aprepitant and belongs to a group of medicines called 
"neurokinin 1 (NK1) receptor antagonists". The brain has a specific area that controls nausea and 
vomiting. EMEND works by blocking signals to that area, thereby reducing nausea and vomiting. 
EMEND capsules are used in adults and adolescents from the age of 12 years in combination with 
other medicines to prevent nausea and vomiting caused by chemotherapy (cancer treatment) that are 
strong and moderate triggers of nausea and vomiting (such as cisplatin, cyclophosphamide, 
doxorubicin or epirubicin).

2. What you need to know before you take or give EMEND

Do not take EMEND:
- if you or the child is allergic to aprepitant or any of the other ingredients of this medicine (listed 

in section 6).

- with medicines containing pimozide (used to treat psychiatric illnesses), terfenadine and 
astemizole (used for hay fever and other allergic conditions), cisapride (used for treating 
digestive problems). Tell the doctor if you or the child is taking these medicines since the 
treatment must be modified before you or the child start taking EMEND.

Warnings and precautions
Talk to the doctor, pharmacist, or nurse before you take EMEND or give this medicine to the child.

Before treatment with EMEND, tell the doctor if you or the child have liver disease because the liver 
is important in breaking down the medicine in the body. The doctor may therefore have to monitor the 
condition of your or the child’s liver.

 



102

Children and adolescents
Do not give EMEND 80 mg and 125 mg capsules to children under 12 years of age, because the 
80 mg and 125 mg capsules have not been studied in this population.

Other medicines and EMEND
EMEND can affect other medicines both during and after treatment with EMEND. There are some 
medicines that should not be taken with EMEND (such as pimozide, terfenadine, astemizole, and 
cisapride) or that require a dose adjustment (see also ‘Do not take EMEND’). 

The effects of EMEND or other medicines might be influenced if you or the child take EMEND 
together with other medicines including those listed below. Please talk to the doctor or pharmacist if 
you or the child is taking any of the following medicines:

- birth control medicines which can include birth control pills, skin patches, implants, and certain 
Intrauterine devices (IUDs) that release hormones may not work adequately when taken 
together with EMEND. Another or additional non-hormonal form of birth control should be 
used during treatment with EMEND and for up to 2 months after using EMEND,

- cyclosporine, tacrolimus, sirolimus, everolimus (immunosuppressants),
- alfentanil, fentanyl (used to treat pain),
- quinidine (used to treat an irregular heart beat),
- irinotecan, etoposide, vinorelbine, ifosfamide (medicines used to treat cancer),
- medicines containing ergot alkaloid derivatives such as ergotamine and diergotamine (used for 

treating migraines),
- warfarin, acenocoumarol (blood thinners; blood tests may be required),
- rifampicin, clarithromycin, telithromycin (antibiotics used to treat infections),
- phenytoin (a medicine used to treat seizures),
- carbamazepine (used to treat depression and epilepsy),
- midazolam, triazolam, phenobarbital (medicines used to produce calmness or help you sleep),
- St. John’s Wort (an herbal preparation used to treat depression), 
- protease inhibitors (used to treat HIV infections)
- ketoconazole except shampoo (used to treat Cushing’s syndrome - when the body produces an 

excess of cortisol), 
- itraconazole, voriconazole, posaconazole (antifungals),
- nefazodone (used to treat depression),
- corticosteroids (such as dexamethasone and methylprednisolone),
- anti-anxiety medicines (such as alprazolam), 
- tolbutamide (a medicine used to treat diabetes)

Tell the doctor or pharmacist if you or the child are taking, have recently taken, or might take any 
other medicines.

Pregnancy and breast-feeding
This medicine should not be used during pregnancy unless clearly necessary. If you or the child are 
pregnant or breast-feeding, may be pregnant or are planning to have a baby, ask the doctor for advice 
before taking this medicine.

For information regarding birth control, see ‘Other medicines and EMEND’.

It is not known whether EMEND is excreted in human milk; therefore, breast-feeding is not 
recommended during treatment with this medicine. It is important to tell the doctor if you or the child 
are breast-feeding or are planning to breast-feed before taking this medicine.

Driving and using machines
It should be taken into account that some people feel dizzy and sleepy after taking EMEND. If you or 
the child feels dizzy or sleepy, avoid driving, riding a bicycle or using machines or tools after taking 
this medicine (see ‘Possible side effects’).

 



103

EMEND contains sucrose
EMEND capsules contain sucrose. If you or the child have been told by your doctor that you or the 
child have an intolerance to some sugars, contact the doctor before taking this medicine.

3. How to take EMEND

Always take this medicine or give this medicine to the child exactly as the doctor, pharmacist or nurse 
has told you. You should check with the doctor, pharmacist or nurse if you are not sure. Always take 
EMEND together with other medicines, to prevent nausea and vomiting. After treatment with 
EMEND, the doctor may ask you or the child to continue taking other medicines including a 
corticosteroid (such as dexamethasone) and a ‘5HT3 antagonist’ (such as ondansetron) for preventing 
nausea and vomiting. Check with the doctor, pharmacist or nurse if you are not sure.

The recommended oral dose of EMEND is 
Day 1:
- one 125 mg capsule 1 hour before you start your chemotherapy session 

and

Days 2 and 3:
- one 80 mg capsule each day
- If no chemotherapy is given, take EMEND in the morning.
- If chemotherapy is given, take EMEND 1 hour before you start your chemotherapy session. 

EMEND can be taken with or without food.

Swallow the capsule whole with some liquid.

If you take more EMEND than you should
Do not take more capsules than the doctor recommends. If you or the child has taken too many 
capsules, contact your doctor immediately. 

If you forget to take EMEND
If you or the child has missed a dose, contact your doctor for advice.

If you have any further questions on the use of this medicine, ask the doctor or pharmacist.

4. Possible side effects 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

Stop taking EMEND and see a doctor immediately if you or the child notice any of the following 
side effects, which may be serious, and for which you or the child may need urgent medical 
treatment:
- Hives, rash, itching, difficulty breathing or swallowing (frequency not known, cannot be 

estimated from the available data); these are signs of an allergic reaction.

Other side effects that have been reported are listed below.

Common side effects (may affect up to 1 in 10 people) are:
- constipation, indigestion,
- headache,
- tiredness,
- loss of appetite,
- hiccups,

 



104

- increased amount of liver enzymes in your blood.

Uncommon side effects (may affect up to 1 in 100 people) are:
- dizziness, sleepiness,
- acne, rash,
- anxiousness,
- burping, nausea, vomiting, heartburn, stomach pain, dry mouth, passing wind,
- increased painful or burning urination,
- weakness, generally feeling unwell,
- hot flush/reddening of the face or skin,
- fast or irregular heartbeats, 
- fever with increased risk of infection, lowering of red blood cells.

Rare side effects (may affect up to1 in 1,000 people) are:
- difficulty thinking, lack of energy, taste disturbance,
- sensitivity of the skin to sun, excessive sweating, oily skin, sores on skin, itching rash, 

Stevens-Johnson syndrome/toxic epidermal necrolysis (rare severe skin reaction),
- euphoria (feeling of extreme happiness), disorientation,
- bacterial infection, fungal infection,
- severe constipation, stomach ulcer, inflammation of the small intestine and colon, sores in 

mouth, bloating,
- frequent urination, passing more urine than normal, presence of sugar or blood in urine,
- chest discomfort, swelling, change in the manner of walking,
- cough, mucus in back of throat, throat irritation, sneezing, sore throat,
- eye discharge and itching,
- ringing in the ear,
- muscle spasms, muscle weakness,
- excessive thirst,
- slow heartbeat, heart and blood vessel disease,
- lowering of white blood cells, low sodium levels in the blood, weight loss.

Reporting of side effects
If you or the child gets any side effects, talk to your doctor, pharmacist, or nurse. This includes any 
possible side effects not listed in this leaflet. You can also report side effects directly via the national 
reporting system listed in Appendix V. By reporting side effects you can help provide more 
information on the safety of this medicine.

5. How to store EMEND

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date 
refers to the last day of that month.

Store in the original package in order to protect from moisture.

Do not remove the capsule from its blister until you are ready to take it.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


105

6. Contents of the pack and other information

What EMEND contains
- The active substance is aprepitant. Each 125 mg hard capsule contains 125 mg of aprepitant. 

Each 80 mg hard capsule contains 80 mg of aprepitant.
- The other ingredients are: sucrose, microcrystalline cellulose (E 460), hydroxypropylcellulose 

(E 463), sodium laurilsulfate, gelatin, titanium dioxide (E 171), shellac, potassium hydroxide, 
and black iron oxide (E 172); the 125 mg hard capsule also contains red iron oxide (E 172) and 
yellow iron oxide (E 172).

What EMEND looks like and contents of the pack
The 125 mg hard capsule is opaque with a white body and pink cap with “462” and “125 mg” printed 
radially in black ink on the body.
The 80 mg hard capsule is opaque with a white cap and body with “461” and “80 mg” printed radially 
in black ink on the body.

EMEND 125 mg and 80 mg hard capsules are supplied in the following pack sizes:
- Aluminium blister containing one 80 mg capsule
- 2-day treatment pack containing two 80 mg capsules
- 5 Aluminium blisters each containing one 80 mg capsule
- Aluminium blister containing one 125 mg capsule
- 5 Aluminium blisters each containing one 125 mg capsule
- 3-day treatment pack containing one 125 mg capsule and two 80 mg capsules

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder.

Belgique/België/Belgien 
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Lietuva
UAB Merck Sharp & Dohme
Tel. + 370 5278 02 47
msd_lietuva@merck.com

България
Мерк Шарп и Доум България ЕООД
Тел.: +359 2 819 3737
info-msdbg@merck.com

Luxembourg/Luxemburg
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Česká republika
Merck Sharp & Dohme s.r.o.
Tel: +420 233 010 111
dpoc_czechslovak@merck.com

Magyarország
MSD Pharma Hungary Kft.
Tel.: +36 1 888 5300
hungary_msd@merck.com

Danmark
MSD Danmark ApS
Tlf: + 45 4482 4000
dkmail@merck.com

Malta
Merck Sharp & Dohme Cyprus Limited
Tel: 8007 4433 (+356 99917558)
malta_info@merck.com 

 



106

Deutschland
MSD SHARP & DOHME GMBH
Tel: 0800 673 673 673 (+49 (0) 89 4561 2612)
e-mail@msd.de

Nederland
Merck Sharp & Dohme B.V.
Tel: 0800 9999000 

(+31 23 5153153)
medicalinfo.nl@merck.com

Eesti
Merck Sharp & Dohme OÜ
Tel.: +372 6144 200
msdeesti@merck.com

Norge
MSD (Norge) AS
Tlf: +47 32 20 73 00
msdnorge@msd.no

Eλλάδα
MSD Α.Φ.Β.Ε.Ε.
Τηλ: +30 210 98 97 300
dpoc_greece@merck.com

Österreich
Merck Sharp & Dohme Ges.m.b.H.
Tel: +43 (0) 1 26 044
msd-medizin@merck.com

España
Merck Sharp & Dohme de España, S.A.
Tel: +34 91 321 06 00
msd_info@merck.com

Polska
MSD Polska Sp. z o.o. 
Tel: +48 22 549 51 00
msdpolska@merck.com

France
MSD France
Tél: +33 (0) 1 80 46 40 40

Portugal
Merck Sharp & Dohme, Lda
Tel: +351 21 4465700
inform_pt@merck.com

Hrvatska
Merck Sharp & Dohme d.o.o.
Tel: + 385 1 6611 333
croatia_info@merck.com

România
Merck Sharp & Dohme Romania S.R.L.
Tel: +40 21 529 29 00
msdromania@merck.com

Ireland
Merck Sharp & Dohme Ireland (Human Health) 
Limited
Tel: +353 (0)1 2998700
medinfo_ireland@merck.com

Slovenija
Merck Sharp & Dohme, inovativna zdravila 
d.o.o.
Tel: +386 1 5204 201
msd_slovenia@merck.com

Ísland
Vistor hf.
Simi: +354 535 7000

Slovenská republika
Merck Sharp & Dohme, s. r. o.
Tel: +421 2 58282010
dpoc_czechslovak@merck.com

Ιtalia
MSD Italia S.r.l.
Tel: +39 06 361911
medicalinformation.it@merck.com

Suomi/Finland
MSD Finland Oy
Puh/Tel: +358 (0)9 804 650
info@msd.fi

Κύπρος
Merck Sharp & Dohme Cyprus Limited
Τηλ.: 800 00 673 (+357 22866700)
cyprus_info@merck.com

Sverige
Merck Sharp & Dohme (Sweden) AB
Tel: +46 77 5700488
medicinskinfo@merck.com

Latvija
SIA Merck Sharp & Dohme Latvija
Tel: +371 67364224
msd_lv@merck.com

United Kingdom
Merck Sharp & Dohme Limited
Tel: +44 (0) 1992 467272
medicalinformationuk@merck.com

 



107

This leaflet was last revised in

Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.

 

http://www.ema.europa.eu/


108

Package leaflet: Information for the user

EMEND 125 mg powder for oral suspension
aprepitant

Read all of this leaflet carefully before you start using this medicine because it contains 
important information. This leaflet has been written for the parent or carer who will give this 
medicine to the child- please read this information carefully.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask the doctor, pharmacist, or nurse.
- This medicine has been prescribed for the child only. Do not pass it on to others. It may harm 

them, even if their signs of illness are the same.
- If the child gets any side effects, talk to the doctor, pharmacist, or nurse. This includes any 

possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What EMEND is and what it is used for
2. What you need to know before you give EMEND
3. How to give EMEND
4. Possible side effects
5. How to store EMEND
6. Contents of the pack and other information

1. What EMEND is and what it is used for

EMEND contains the active substance ‘aprepitant.’ It belongs to a group of medicines called 
‘neurokinin 1 (NK1) receptor antagonists’.
The brain has a specific area that controls nausea and vomiting. EMEND works by blocking signals to 
that area, thereby reducing nausea and vomiting.
The powder for oral suspension is used in children aged 6 months to less than 12 years in 
combination with other medicines to prevent nausea and vomiting caused by chemotherapy (cancer 
treatment) that are strong and moderate triggers of nausea and vomiting (such as cisplatin, 
cyclophosphamide, doxorubicin or epirubicin).

2. What you need to know before you give EMEND

Do not give EMEND:
- if the child is allergic to aprepitant or any of the other ingredients of this medicine (listed in 

section 6).
- if the child is using medicines that contain ‘pimozide’ (for mental health problems).
- if the child is using ‘terfenadine’ or ‘astemizole’ (for hay fever and other allergies).
- if the child is using ‘cisapride’ - (for problems with digestion).
Do not give this medicine if any of the above applies to the child and tell the child’s doctor if they are 
using any of the medicines above. This is because their treatment will need to be changed before 
starting this medicine. If you are not sure, talk to the doctor, pharmacist or nurse before giving this 
medicine.

Warnings and precautions
Talk to the doctor, pharmacist, or nurse before giving this medicine to the child.

Liver problems
Tell the doctor before treatment with EMEND starts, if the child has liver problems. This is because 
the liver is important in breaking down the medicine in the body. The doctor may have to check the 
condition of the child’s liver during treatment.

 



109

Children and adolescents
Do not give EMEND powder for oral suspension to children under 6 months of age or who weigh less 
than 6 kg, or to adolescents between 12 and 18 years, because the powder for oral suspension has not 
been studied in this population.

Other medicines and EMEND
Tell the doctor, pharmacist or nurse if the child is using, has recently used or might use any other 
medicines. This is because EMEND can affect how other medicines work, during and after treatment 
with EMEND. Also, some other medicines can affect the way this medicine works.

Do not give EMEND and tell the doctor or pharmacist if the child is using any of the following 
medicines (see also under ‘Do not give EMEND’). This is because their treatment will need to be 
changed before starting EMEND:
- pimozide - for mental health problems
- terfenadine and astemizole - for hay fever and other allergies
- cisapride - for problems with digestion
Do not give this medicine and tell the doctor or pharmacist if any of the above apply to the child.

Talk to the doctor, pharmacist or nurse if the child is taking any of the following medicines:
- medicines that affect the immune system – such as cyclosporine, tacrolimus, sirolimus, 

everolimus
- alfentanil, fentanyl – for pain
- quinidine – for irregular heart beat
- medicines for cancer – such as irinotecan, etoposide, vinorelbine, ifosfamide
- medicines containing ‘ergot alkaloid derivatives’ - such as ergotamine and diergotamine - for 

migraines
- medicines that thin the blood – such as warfarin, acenocoumarol. Your child may need blood 

tests during treatment with EMEND
- antibiotics to treat infections – such as rifampicin, clarithromycin, telithromycin
- phenytoin - for fits (seizures)
- carbamazepine - for depression and epilepsy
- midazolam, triazolam, phenobarbital - to produce calmness or help you sleep
- St. John’s Wort - a herbal medicine for depression
- protease inhibitors - for HIV infections
- ketoconazole except shampoo (used to treat Cushing’s syndrome - when the body produces an 

excess of cortisol)
- antifungal medicines such as itraconazole, voriconazole, posaconazole
- nefazodone - for depression
- corticosteroids - such as dexamethasone and methylprednisolone
- medicines for anxiety such as alprazolam
- tolbutamide - for diabetes
- contraceptive medicines including pills, patches, implants, and some Intrauterine devices 

(IUDs) that release hormones. These may not work properly when taken with this medicine. 
You may need to use a different or an extra non-hormonal contraceptive during treatment with 
this medicine and for up to 2 months after treatment has finished.

If any of the above apply to the child (or you are not sure), talk to the doctor, pharmacist or nurse 
before giving this medicine.

Pregnancy and breast-feeding
This medicine should not be used during pregnancy and breastfeeding unless clearly necessary.

For information regarding pregnancy, breast-feeding and contraception, ask your doctor for advice.

Driving and using machines
It should be taken into account that some people may feel dizzy and sleepy after taking EMEND. If 
the child feels dizzy or sleepy, they should not ride a bicycle or use any tools or machines.

 



110

EMEND contains sucrose and lactose
The powder for oral suspension contains sucrose and lactose. If a doctor has told you that the child has 
an intolerance to some sugars, contact the doctor before giving this medicine to the child.

3. How to give EMEND

Healthcare professionals: See the instructions for preparation of the oral suspension for healthcare 
professionals at the end of this package leaflet. This tells you how to prepare a dose of EMEND as an
oral suspension.

Parents and caregivers: Always give this medicine to the child exactly as the doctor, pharmacist or 
nurse has told you. Check with the child’s doctor, pharmacist or nurse if you are not sure.
It is very important that this medicine is given exactly as directed below.

For each dose of EMEND, you will get a pre-filled oral dispenser that contains the child’s 
prescribed dose.
Keep the oral dispenser in the refrigerator (between 2

oC and 8oC) until you give the medicine to 
the child

Use this medicine within 2 days of getting the medicine from the healthcare provider.
The medicine can be kept at room temperature (not above 30oC) for up to 3 hours, prior to 
administration.

The color of the medicine in the oral dispenser may be different shades of pink (light pink to 
dark pink). This is normal and the medicine is okay to use.

- Take the cap off the oral dispenser.
- Place the tip of the oral dispenser in the child’s mouth along in the inner cheek on 

either the right or left side.
- Slowly push the plunger all the way down to give all the medicine in the oral 

dispenser.

If the child could not take the whole dose, call the child’s healthcare provider.

 



111

When you have finished do not throw away any medicines via wastewater or household waste. 
Ask your pharmacist how to throw away medicines you no longer use. These measures will help 
protect the environment.

How much to take
- The doctor will work out the right dose of powder for oral suspension based on the weight of 

the child.
- Do not change the dose or stop treatment without first talking to the doctor, pharmacist or nurse.

When to take
Day 1:
- Give this medicine one hour before the start of the chemotherapy session.
Day 2 and Day 3:
- If the child will not have chemotherapy - give this medicine in the morning. 
- If the child will have chemotherapy - give this medicine one hour before the start of the 

chemotherapy session.

EMEND can be taken with or without food.

Always give this medicine together with other medicines, to prevent nausea and vomiting. After 
treatment with EMEND, the doctor may ask the child to continue taking other medicines for 
preventing nausea and vomiting which may include:
- a corticosteroid - such as dexamethasone and
- a ‘5-HT3 antagonist’ - such as ondansetron 
Check with the doctor, pharmacist or nurse if you are not sure.

If you give more EMEND than you should
Do not give the child more of this medicine than the doctor recommends. If you give the child more 
than you should, contact the doctor straight away.

If you forget to give EMEND
If the child misses a dose of this medicine, talk to the doctor.
If you have any further questions on the use of this medicine, ask the doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

Serious side effects
Stop giving this medicine and see a doctor straight away if you or the child notice any of the following 
serious side effects – the child may need urgent medical treatment:
- allergic reaction – the signs may include hives, rash, itching, difficulty breathing or swallowing 

(it is not known how often this happens).
Stop giving this medicine and see a doctor straight away if you notice any of the serious side effects 
above.

Other side effects
Tell the doctor, pharmacist or nurse if you or the child notice any of the following side effects:

Common: may affect up to 1 in 10 people
- constipation or indigestion
- headache
- feeling tired
- loss of appetite
- hiccups
- increased amount of liver enzymes in the blood (shown in tests).

 



112

Uncommon: may affect up to 1 in 100 people
- feeling dizzy or sleepy
- acne, rash
- feeling anxious
- burping, nausea, vomiting, heartburn, stomach pain, dry mouth, passing wind
- pain or burning when urinating
- feeling weak, generally feeling unwell
- hot flushes/reddening of the face or skin
- fast or irregular heart beat
- fever with increased risk of infection, low number of red blood cells (shown in tests).

Rare: may affect up to1 in 1,000 people
- difficulty thinking, lack of energy, changes in taste
- sensitivity of the skin to sun, excessive sweating, oily skin, sores on the skin, itchy rash, 

Stevens-Johnson syndrome or toxic epidermal necrolysis (rare severe skin reactions)
- euphoria (feeling of extreme happiness), feeling confused
- bacterial infection, fungal infection
- severe constipation, stomach ulcer, inflamed small intestine and colon, sores in the mouth, 

bloating
- urinating more often or passing more urine than normal, sugar or blood in urine
- chest discomfort, swelling, change in the manner of walking
- cough, mucus in the back of the throat, throat irritation, sneezing, sore throat
- eye discharge and itching
- ringing in the ears
- muscle spasms, muscle weakness
- feeling very thirsty
- slow heartbeat, heart and blood vessel disease
- low number of white blood cells, low sodium levels in the blood, weight loss.

Reporting of side effects
If the child gets any side effects, talk to the doctor, pharmacist, or nurse. This includes any possible 
side effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store EMEND

Keep this medicine out of the sight and reach of children.

Before reconstitution:

Emend will generally be stored by healthcare professionals. The storage details, should you need 
them, are as follows:
Do not give this medicine to the child after the expiry date which is stated on the carton and sachet 
after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special temperature storage conditions.

Store in the original package in order to protect from moisture.

After reconstitution:

The oral suspension can be kept at room temperature (not above 30oC) for up to 3 hours, prior to 
administration. It can also be stored refrigerated (between 2oC and 8oC) for up to 72 hours.

 

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113

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What EMEND contains
- The active substance is aprepitant. Each sachet contains 125 mg of aprepitant. After 

reconstitution, 1 mL oral suspension contains 25 mg of aprepitant
- The other ingredients are: hydroxypropyl-cellulose (E 463), sodium laurilsulfate (E 487), 

sucrose and lactose (see section 2 under ‘EMEND contains sucrose and lactose’), red iron oxide 
(E 172) and sodium stearyl fumarate (E 485).

What EMEND looks like and contents of the pack
The powder for oral suspension is a pink to light pink powder in a single-use sachet.

Single-use carton
Pack size of one carton contains one sachet, one 1 mL and one 5 mL oral dispenser (polypropylene 
with silicone o-ring), one cap and one mixing cup (polypropylene).

Marketing Authorisation Holder and Manufacturer

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder.

Belgique/België/Belgien 
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Lietuva
UAB Merck Sharp & Dohme
Tel.: +370 5 278 02 47
msd_lietuva@merck.com

България
Мерк Шарп и Доум България ЕООД
Тел.: +359 2 819 3737
info-msdbg@merck.com

Luxembourg/Luxemburg
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Česká republika
Merck Sharp & Dohme s.r.o.
Tel.: +420 233 010 111
dpoc_czechslovak@merck.com

Magyarország
MSD Pharma Hungary Kft.
Tel.: +36 1 888 53 00
hungary_msd@merck.com

Danmark
MSD Danmark ApS
Tlf: +45 44824000
dkmail@merck.com

Malta
Merck Sharp & Dohme Cyprus Limited
Tel: 8007 4433 (+356 99917558)
malta_info@merck.com 

Deutschland
MSD SHARP & DOHME GMBH
Tel: 0800 673 673 673 (+49 (0) 89 4561 2612)
e-mail@msd.de

Nederland
Merck Sharp & Dohme B.V.
Tel: 0800 9999000 (+31 23 5153153)
medicalinfo.nl@merck.com

 



114

Eesti
Merck Sharp & Dohme OÜ
Tel.: +372 6144 200
msdeesti@merck.com

Norge
MSD (Norge) AS
Tlf: +47 32 20 73 00
msdnorge@msd.no

Eλλάδα
MSD Α.Φ.Β.Ε.Ε.
Τηλ: + 30 210 98 97 300
dpoc_greece@merck.com

Österreich
Merck Sharp & Dohme Ges.m.b.H.
Tel: +43 (0) 1 26 044
msd-medizin@merck.com

España
Merck Sharp & Dohme de España, S.A.
Tel: +34 91 321 06 00
msd_info@merck.com

Polska
MSD Polska Sp.z o.o. 
Tel: +48 22 549 51 00
msdpolska@merck.com

France
MSD France
Tél: +33 (0) 1 80 46 40 40

Portugal
Merck Sharp & Dohme, Lda
Tel: +351 21 4465700
inform_pt@merck.com

Hrvatska
Merck Sharp & Dohme d.o.o.
Tel: + 385 1 6611 333
croatia_info@merck.com

România
Merck Sharp & Dohme Romania S.R.L.
Tel: + 4021 529 29 00
msdromania@merck.com

Ireland
Merck Sharp & Dohme Ireland (Human Health) 
Limited
Tel: +353 (0)1 2998700
medinfo_ireland@merck.com

Slovenija
Merck Sharp & Dohme, inovativna zdravila 
d.o.o.
Tel: + 386 1 5204201
msd_slovenia@merck.com

Ísland
Vistor hf.
Simi: +354 535 7000

Slovenská republika
Merck Sharp & Dohme, s. r. o.
Tel.: +421 2 58282010
dpoc_czechslovak@merck.com

Ιtalia
MSD Italia S.r.l.
Tel: +39 06 361911
medicalinformation.it@merck.com

Suomi/Finland
MSD Finland Oy
Puh/Tel: +358 (0)9 804650
info@msd.fi

Κύπρος
Merck Sharp & Dohme Cyprus Limited
Τηλ: 80000 673 (+357 22866700)
cyprus_info@merck.com

Sverige
Merck Sharp & Dohme (Sweden) AB
Tel: +46 (0) 77 5700488
medicinskinfo@merck.com

Latvija
SIA Merck Sharp & Dohme Latvija
Tel: +371 67364 224
msd_lv@merck.com

United Kingdom
Merck Sharp & Dohme Limited
Tel: +44 (0) 1992 467272
medicalinformationuk@merck.com

This leaflet was last revised in

Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.

 

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115

------------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only:

Instructions for healthcare professionals on the preparation of the oral suspension

Each pack of EMEND contains a sachet with the 
powder for oral suspension, a 1 ml and a 5 ml oral 
dispenser, one cap and one mixing cup.

1. Fill the mixing cup with room temperature 
drinking water.

2. Fill the 5 mL oral dispenser with 4.6 mL of water 
from the mixing cup.
Make sure no air is in the oral 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 oral dispenser 
back into the mixing cup.

5. Each sachet 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 powder for oral suspension 
sachet upright and shake the contents to the bottom 
before opening the sachet.

6. Pour the entire contents of the sachet 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.

 



116

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 oral dispenser with the prescribed dose 
from the mixing cup according to the table below.
- Choose the oral dispenser based on dose:

- Use 1 mL oral dispenser if dose is 
1 mL or less. 

- Use 5 mL oral dispenser if dose is 
more than 1 mL.

- It is common to have medicine leftover in the 
cup.

Make sure no air is in the oral dispenser (if air is 
present, remove).

Make sure the oral dispenser contains the 
prescribed dose.

Day 1 Day 2 Day 3
EMEND oral suspension

25 mg/mL

3 mg/kg orally
Maximum dose 125 mg

2 mg/kg orally
Maximum dose 80 mg

2 mg/kg orally
Maximum dose 80 mg

10. Place the cap on the oral dispenser until it clicks.

11. If the dose is not administered immediately after 
measuring, store filled oral dispenser(s) in the 
refrigerator between 2°C-8°C for up to 72 hours 
prior to use. When dispensing dose(s) to the 
caregiver, instruct them to refrigerate the oral 
dispenser(s) until they are ready to administer the 
dose. 

12. The oral suspension can be kept at room 
temperature (not above 30oC) for up to 3 hours, 
prior to administration.

Discard any remaining suspension and waste material. 
Any unused medicinal product or waste material 
should be disposed of in accordance with local 
regulations.

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET