EMEND 125 MG CAPSULES

Israel - English - Ministry of Health

Buy It Now

Active ingredient:
APREPITANT
Available from:
MERCK SHARP & DOHME ISRAEL LTD
ATC code:
A04AD12
Pharmaceutical form:
CAPSULES
Composition:
APREPITANT 125 MG
Administration route:
PER OS
Prescription type:
Required
Manufactured by:
MERCK SHARP & DOHME CORP., USA
Therapeutic group:
APREPITANT
Therapeutic area:
APREPITANT
Therapeutic indications:
Emend in combination with other antiemetic agents is indicated for the: - prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy including high-dose cisplatin. - prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.
Authorization number:
135 09 31207 13
Authorization date:
2013-04-30

Documents in other languages

Patient Information leaflet Patient Information leaflet - Hebrew

01-08-2019

This leaflet format has been determined by the Ministry of Health and the content has been checked and

approved by the Ministry of Health in June 2016 and updated according to the Ministry of Health guideline

in July 2019.

PATIENT PACKAGE INSERT IN ACCORDANCE WITH THE PHARMACISTS REGULATIONS

(PREPARATIONS) 1986

This medicine can be sold under doctor's prescription only

EMEND

®

80 mg

Capsules

EMEND

®

125 mg

Capsules

Each capsule contains:

Aprepitant 80 mg

Each capsule contains:

Aprepitant 125 mg

For a list of inactive ingredients see section 6 "FURTHER INFOMATION". See also section 2.8 “Important

information about some of the ingredients of EMEND”.

Read the entire leaflet carefully before you start taking this medicine.

This leaflet contains concise information about the medicine. If you have any further questions, ask the

doctor or the pharmacist.

This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their

medical condition seems similar to yours.

This medicine is not intended for children and adolescents under 18 years of age.

1. WHAT EMEND IS INTENDED FOR?

EMEND capsules are intended for use in adult patients, in combination with other anti-emetic

medicines:

To prevent acute and delayed nausea and vomiting caused by chemotherapy (cancer treatment) of

highly emetogenic potential (strong trigger of nausea and vomiting).

To prevent chemotherapy induced nausea and vomiting (CINV) that are caused by chemotherapy

(cancer treatment) of moderate emetogenic potential (moderate trigger of nausea and vomiting).

Therapeutic group: EMEND is a neurokinin 1 (NK

) receptor antagonist.

2. BEFORE YOU TAKE EMEND

2.1 Do not take EMEND:

if you are hypersensitive (allergic) to aprepitant or any of the other ingredients of EMEND (for a list

of inactive ingredients, see 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. Taking EMEND with these medications could result in serious or life-threatening

problems.

2.2 Special warnings concerning use of EMEND

Before starting 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.

2.3 Children and adolescents

EMEND is not approved for use in children.

2.4 Taking other medicines

If you are taking or have recently taken other medicines, including non-prescription medicines and

nutritional supplements, you should tell the attending doctor or pharmacist.

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 section 2.1 “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.

Especially inform your doctor or pharmacist if you are taking:

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 (Hypericum - a 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)

2.5 Taking EMEND with food

EMEND can be taken with or without food.

2.6 Pregnancy, breast-feeding and fertility

This medicine should not be used 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 section 2.4 “Taking other medicines”.

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.

2.7 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 or tools after taking this medicine (see section 4

SIDE EFFECTS”).

2.8 Important information about some of the ingredients of EMEND

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 (see also section 6 “What EMEND

contains?”).

3. HOW SHOULD YOU USE EMEND?

Always take this medicine as instructed by the doctor. You should check with the doctor or pharmacist if

you are not sure about the dosage and method of treatment.

The dosage and method of treatment will be determined by the doctor only.

Always take EMEND together with other medicines, to prevent nausea and vomiting. After your treatment

with EMEND, your doctor will ask you to continue taking other medicines including a corticosteroid (such as

dexamethasone) and a ”5HT

antagonist” (such as ondansetron) for preventing nausea and vomiting.

Check with the doctor or pharmacist if you are not sure.

The usually recommended dose 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, in the morning.

Do not exceed the recommended dose.

EMEND can be taken with or without food.

Swallow the capsule whole with some liquid.

No information is available regarding opening and dispersing content of capsules.

Examinations and monitoring

Before starting treatment with EMEND tell your doctor if you have liver disease. Your doctor may have to

monitor the condition of your liver.

If you have accidentally taken a higher dose than you should

Do not take more capsules than the doctor recommends.

If you have taken more capsules than the doctor recommends, or if a child has accidentally swallowed the

medicine, proceed immediately to a hospital emergency room and bring the package of the medicine with

you.

If you forget to take EMEND

If you have missed a dose, contact your doctor for advice.

Complete the course of treatment as recommended by the doctor.

Do not take medicines in the dark! Check the label and the dose each time you take your medicine.

Wear glasses if you need them.

While good nutrition is important for everyone, it is especially important for people on chemotherapy.

Small, frequent meals or eating a snack before your chemotherapy treatment may also help you tolerate it

better.

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

4. SIDE EFFECTS

Like all medicines, EMEND can cause side effects, in some of the users.

Do not be alarmed by reading the list of side effects, you may not suffer from any of 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.

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 adverse 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.

If a side effect appears, if any of the side effects worsens or if you notice a side effect not

mentioned in this leaflet, consult your doctor.

Side effects can be reported to the Ministry of Health by using the link "Adverse Drug Reactions Report" at

the home page of the Ministry of Health's web site (www.health.gov.il) which refers to the online side effects

reporting form, or by using the link:

https://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@moh.gov.il

5. HOW TO STORE EMEND?

Avoid Poisoning! This medicine, as all other medicines, must be stored in a safe place out of the reach

and sight of children and/or infants, in order to avoid poisoning. Do not induce vomiting unless explicitly

instructed to do so by a doctor.

Do not use the medicine after the expiry date (exp. date) which is stated on the pack. The expiry date

refers to the last day of the indicated month.

Storage conditions: Store below 30ºC. 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.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to

dispose of medicines no longer required. These measures will help to protect the environment.

6. FURTHER INFORMATION

What EMEND contains?

In addition to the active ingredient the medicine also contains inactive ingredients: Sucrose, Microcrystalline

Cellulose Beads, Hydroxypropyl Cellulose SL, Micronized Sodium Lauryl Sulfate, Sodium Lauryl sulfate,

gelatin, titanium dioxide (E 171), shellac, potassium hydroxide, black iron oxide (E 172); The 125 mg

capsule also contains red iron oxide (E 172), yellow iron oxide (E 172).

EMEND contains sucrose (see also section 2.8, “Important information about some of the ingredients

of EMEND”).

EMEND 125 mg capsule contains 125 mg sucrose.

EMEND 80 mg capsule contains 80 mg sucrose.

What EMEND looks like and contents of the pack

The 125 mg capsule is a gelatin capsule, opaque with a white body and pink cap with “462” and “125 mg”

printed radially in black ink on the body.

The 80 mg capsule is a gelatin capsule, opaque with a white cap and body with “461” and “80 mg” printed

radially in black ink on the body.

Pack sizes: 3-day treatment pack containing one 125 mg capsule and two 80 mg capsules.

Marketing authorization holder:

Merck Sharp & Dohme (Israel-1996) Company Ltd., P.O.Box 7121, Petah-Tikva 49170.

Manufacturer:

Merck Sharp & Dohme Corp., New-Jersey, USA.

This leaflet was checked and approved by the Ministry of Health in June 2016 and updated according to the

Ministry of Health guideline in July 2019.

Drug registration no. listed in the official registry of the Ministry of Health:

EMEND 80 mg capsules: 135.08.31206

EMEND 125 mg capsules: 135.09.31207

ב תואירבה דרשמ י"ע רשואו קדבנ ונכותו תואירבה דרשמ י"ע עבקנ הז ןולע טמרופ ינוי

2016

תוארוהל םאתהב ןכדועו , ב תואירבה דרשמ ילוי

2019

1.

NAME OF THE MEDICINAL PRODUCT

EMEND 125 mg capsules

EMEND 80 mg 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

Capsule.

The 125 mg gelatin capsule (no. 1) 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 gelatin capsules (no. 2) 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

EMEND, in combination with other antiemetic agents, is indicated for the:

prevention of acute and delayed nausea and vomiting associated with initial and repeat courses

of highly emetogenic cancer chemotherapy, including high-dose cisplatin (see section 4.2).

Prevention of nausea and vomiting associated with initial and repeat courses of moderately

emetogenic cancer chemotherapy (see section 4.2)

4.2

Posology and method of administration

Posology

EMEND is given for 3 days as part of a regimen that includes a corticosteroid and a 5-HT

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.

The following regimens are recommended 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-HT

antagonists

Standard dose of

5-HT

antagonists. See

the product

information for

the selected

5-HT

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-HT

antagonists

Standard dose of 5-HT

antagonists. See the

product information for

the selected 5-HT

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.

General

Efficacy data in combination with other corticosteroids and 5-HT

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-HT

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).

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).

Paediatric population

EMEND is not approved for use in paediatric patients.

Method of administration

The 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 on 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 contains sucrose. Patients with rare hereditary problems of fructose intolerance,

glucose-galactose malabsorption 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 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 coadministration.

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 giv

en 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.

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-HT

3

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 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 %.

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

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).

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.

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 %).

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:

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

System organ class

Adverse reaction

Frequency

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

General disorders and

administration site conditions

fatigue

common

asthaenia, 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.

Any suspected adverse events should be reported to the Ministry of Health according to the National

Regulation by using an online form

http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@moh.go

v.il

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 (NK

) receptors.

3-day regimen of aprepitant

In 2 randomised, double-blind studies encompassing a total of 1,094 adult patients receiving

chemotherapy that included cisplatin

70 mg/m

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-HT

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

(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.

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

100%

Percent of Patients

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/m

; or cyclophosphamide 500-

1,500 mg/m

and doxorubicin (<60 mg/m

) or epirubicin (<100 mg/m

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.

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

(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

(-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

(< 1500 mg/m

); or cytarabine intravenously (> 1 g/m

). 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.

Table 3

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

Moderately Emetogenic Chemotherapy

Aprepitant

regimen

Standard

therapy

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

(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

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

(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

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 (C

) of aprepitant occurred at approximately

4 hours (t

). 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 AUC

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 AUC

0-24hr

(mean±SD) was 19.6±2.5 µg

h/mL and 21.2±6.3 µg

h/mL on

Days 1 and 3, respectively. C

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 (Vd

) 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 [

C]-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 [

C]-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 AUC

0-24hr

of aprepitant was 21 % higher on Day 1 and 36 % higher on

Day 5 in elderly (

65 years) relative to younger adults. The C

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 C

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 t

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 AUC

of total aprepitant (unbound and protein bound)

decreased by 21 % and C

decreased by 32 %, relative to healthy subjects. In patients with ESRD

undergoing haemodialysis, the AUC

of total aprepitant decreased by 42 % and C

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 NK

-receptor tracer, positron emission tomography (PET) studies in healthy

young men have shown that aprepitant penetrates into the brain and occupies NK

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 NK

receptors.

5.3

Pre-clinical 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.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Capsule content

Sucrose

Microcrystalline cellulose beads

Hydroxypropyl cellulose SL

Micronized Sodium lauryl sulfate

Sodium lauryl sulfate

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

The expiry date of the product is indicated on the packaging materials.

6.4

Special precautions for storage

Store below 30ºC. 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 125 mg capsule and two 80 mg capsules.

Not all pack sizes may be marketed.

6.6

Special precautions for disposal

No special requirements.

7.

Manufacturer

Merck, Sharp & Dohme Corp., USA, a subsidiary of Merck & Co., Inc., NJ, USA

8.

Marketing Authorization Holder

Merck Sharp & Dohme Israel Ltd.,

PO Box 7121, Petah-Tiqva 49170.

The content of this leaflet was approved by the Ministry of Health in June 2016 and updated according to

the guideline of the Ministry of Health in July 2019.

וי יל

2019

ה/דבכנ ה/אפור

/חקור

ה/דבכנ

:ןודנה

mg CAPSULES

mg and 125

80

®

EMEND

א

י

דנמ

80

ו ג"מ

-

125

ג"מ

תולוספק

Composition:

EMEND

80 mg each capsule contains 80 mg aprepitant

EMEND

125 mg each capsule contains 125 mg aprepitant

לארשי םהודו פראש קרמ תרבח

MSD)

וכדע לע עדייל תשקבמ (

ן

ה

ןכרצלו אפורל םינולע

ש

ל

®

EMEND

.

:רישכתה ינונימ רובע תורשואמה תויוותהה ןושל ןלהל

EMEND

®

, in combination with other antiemetic agents, is indicated for the:

Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of

highly emetogenic cancer chemotherapy, including high-dose cisplatin.

Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic

cancer chemotherapy.

הזיראב קוושמ רישכתה לש תחא הלוספק הליכמה

לש תולוספק יתשו ג"מ

ג"מ תדעוימה ,

.לופיט ימי

.תואירבה דרשמ ידי לע רשואמה אפורל ןולעב ןייעל שי ,תוטרופמ ןתמ תוארוהלו אלמ עדימל

םינוכדע ןולעב םייתוהמ

אפורל

:

ףיעס

תליטנ יבגל ןכדוע ןולעב

דנמיא תלוספק

ג"מ :ןלהל טרופמכ ,רקובב

טסקט

ףסוותהש

שגדומ

םע

וק

ןותחת

4.2

Posology and method of administration

Posology

EMEND is given for 3 days as part of a regimen that includes a corticosteroid and a 5-HT

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.

םינוכדע ןכרצל ןולעב םייתוהמ

ףיעסה

"

"?דנמיא תדעוימ המל

אל .בתכוש לח

יוניש היוותהב

:ןכרצל ןולעב עיפומש יפכ ןכדועמה ףיעסה ןלהל

1

.

?דנמיא תדעוימ המל

תולוספק דנמיא

,םירגובמ םילוחב שומישל תודעוימ תודגונ תופורת םע בולישב

-

תורחא האקה

:

םרוג) הובג יטמא לאיצנטופ םע (ןטרסב לופיט) יפרתומיכ לופיטמ תומרגנה ,תורחואמו תויטוקא תואקהו תוליחב תעינמל קזח .(תואקהו תוליחבל

) היפרתומיכמ האצותכ תואקהו תוליחב תעינמל

CINV

יטמא לאיצנטופ םע (ןטרסב לופיט) יפרתומיכ לופיטמ תומרגנה ,( .(תואקהו תוליחבל ינוניב םרוג) ינוניב

ולעב םינ אפורל

ןכרצלו

ויה םינוכדע

םניאש םיפסונ םייתוהמ

םניאו

םיללכנ

העדוהב

וז

ןכרצלו אפורל םינולעה

םלבקל ןתינו ,תואירבה דרשמ רתאבש תופורתה רגאמב םימסרופמ

,םושירה לעבל הינפ ידי לע םיספדומ

תרבח

,לארשי ןופלטב

09-9533333

®

EMEND

פומ

.מ"עב גולובונ תרבח י"ע

כרבב

ןיליב תירוא

הנוממ תחקור

לארשי

References:

Israeli approved PC 06.2016, updated according to the guideline of the Ministry of Health in July 2019

Israeli approved PPI 06.2016, updated according to the guideline of the Ministry of Health in July 2019

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