IVEMEND 150 mg powder for solution for infusion

IVEMEND contains the active substance fosaprepitant which is converted to aprepitant in your body. IVEMEND is used in combination with other medicines to prevent nausea and vomiting caused by chemotherapy (cancer treatment) in adults.

Do not use IVEMEND

• if you are allergic (hypersensitive) to fosaprepitant, aprepitant, or to polysorbate 80 or any of the other ingredients.
• 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 using IVEMEND.

Take special care with IVEMEND:

• if you have liver disease.

Children

IVEMENDis not for use in children and adolescents under 18 years.

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

The effects of IVEMEND or other medicines might be influenced if you take IVEMEND together with other medicines including those listed below.

• 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 IVEMEND. Another or additional form of birth control should be used during treatment with IVEMEND and for up to 2 months after using IVEMEND,
• cyclosporine, tacrolimus, sirolimus, and everolimus (immunosupressants),
• alfentanil, and fentanyl (used to treat pain),
• quinidine (used to treat an irregular heart beat),
• irinotecan, etoposide, and vinorelbine (medicines used to treat cancer),
• medicines containing ergot alkaloid derivatives such as ergotamine and diergotamine (used for treating migraines),
• warfarin and acenocoumarol (blood thinners; blood tests may be required),
• rifampin, clarithromycin, telithromycin (antibiotics used to treat infections),
• phenytoin (a medicine used to treat seizures),
• carbamazepine (used to treat depression and epilepsy),
• midazolam, triazolam, and 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, itraconazole, voriconazole, and posaconazole (antifungals),
• nefazodone (used to treat depression),
• diltiazem (a medicine used to treat high blood pressure),
• corticosteroids (such as dexamethasone),
• anti-anxiety medicines (such as alprazolam), and
• tolbutamide (a medicine used to treat diabetes)

Before starting treatment, it is important that you tell your doctor about any other medicines or herbal medicines you are taking, have recently taken, or plan to take, even those obtained without a prescription.

Pregnancy and breast-feeding

You should not use IVEMEND during pregnancy unless clearly necessary. It is important that you tell your doctor if you are pregnant or are planning to become pregnant before receiving IVEMEND.

For information regarding birth control, see Using IVEMEND with other medicines.

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

Driving and using machines

It should be taken into account that some people get dizzy and get sleepy after using IVEMEND. If you get dizzy or get sleepy, you should avoid driving or operating machines after using IVEMEND. (See POSSIBLE SIDE EFFECTS).

Important information about some of the ingredients of IVEMEND

This medicine contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ?sodium- free?.

The recommended dose of IVEMEND is150 mg fosaprepitant (IVEMEND 150 mg) on Day 1 (day of chemotherapy) only.

The powder is reconstituted and diluted before use. The solution for infusion is given to you by a health care professional, such as a doctor or nurse, via an intravenous infusion (a drip) approximately 30 minutes before you start your chemotherapy treatment.

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

The frequency of possible side effects listed below is defined using the following convention:

very common (affects more than 1 user in every 10)
common (affects 1 to 10 users in 100)
uncommon (affects 1 to 10 users in 1,000)
rare (affects 1 to 10 users in 10,000)
very rare (affects less than 1 user in 10,000)
not known (frequency cannot be estimated from the available data).

Common side effects are:

• burping, constipation, diarrhoea, indigestion,
• dizziness, headache,
• weakness, tiredness,
• loss of appetite,
• hiccups,
• increased liver blood tests.

Uncommon side effects are:

• abnormal dreaming, difficulty thinking, lack of energy, sleepiness,
• acne, oily skin, rash, itching, sensitivity of the skin to sun, sores on skin, excessive sweating,
• anxiousness, euphoria (feeling of extreme happiness), disorientation,
• bacterial infection, fungal infection,
• stomach ulcer, nausea, vomiting, heartburn, taste disturbance, stomach pain, bloating, severe constipation, dry mouth, inflammation of the small intestine and colon, passing wind, sores in mouth,
• presence of blood in the urine, increased painful or burning urination, passing more urine than normal,
• chest discomfort, swelling, generally feeling unwell, chills, change in the manner of walking,
• reddening of the face/skin, hot flush,
• cough, mucus in back of throat, throat irritation, sneezing, sore throat,
• eye discharge and itching,
• ringing in the ear,
• muscle cramp, muscle pain, muscle weakness,
• excessive thirst, weight gain or loss, high sugar levels in the blood,
• slow heartbeat, fast or irregular heart beats, heart and blood vessel disease, blood pressure increased,
• fever with increased risk of infection, lowering of red blood cells, lowering of white blood cells, low sodium levels in the blood,
• infusion site pain, hardening of site of infusion, infusion-site redness, infusion-site itching, infusion site vein inflammation.

Side effects for which the frequency is not known:

• Allergic reactions, which may be sudden and/or serious, and may include hives, rash, itching, redness of the face/skin and cause difficulty in breathing or swallowing.

Single cases of the following have been reported:

• Stevens-Johnson syndrome (rare severe skin reaction),
• angioedema (swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing),
• serious constipation, small bowel not working properly (sub-ileus),
• urticaria (hives).

If any of the side effects gets serious, or if you experience any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use this medicine after the expiry date which is stated on the carton and vial after EXP. The first 2 numbers indicate the month; the next 4 numbers indicate the year.

Store in a refrigerator (2°C - 8°C).

The reconstituted and diluted solution is stable for 24 hours at 25°C.

Medicines should not be disposed of via wastewater or house hold waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What IVEMEND contains

• The active substance is fosaprepitant. Each vial contains fosaprepitant dimeglumine equivalent to 150 mg fosaprepitant. After reconstitution and dilution 1 ml of solution contains 1 mg fosaprepitant (1 mg/ml).
• The other ingredients are: disodium edetate (E386), polysorbate 80 (E433), lactose anhydrous, sodium hydroxide (E524) (for pH adjustment) and/or hydrochloric acid diluted (E507) (for pH adjustment).

What IVEMEND looks like and contents of the pack

IVEMEND is a white to off-white powder for solution for infusion.

The powder is contained in a clear glass vial with a rubber stopper and an aluminum seal with a grey plastic flip off cap.

Each vial contains 150 mg of fosaprepitant. Pack sizes: 1 or 10 vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder Merck Sharp Dohme Ltd. Hertford Road, Hoddesdon Hertfordshire EN11 9BU United Kingdom Manufacturer Merck Sharp Dohme B.V. Waarderweg 39, 2031 BN Haarlem Nederland

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

BelgiqueBelgiëBelgien Merck Sharp Dohme B.V. Succursale belgeBelgisch bijhuis TélTel 32 0 800 38693 MSDBelgiuminfomerck.com LuxembourgLuxemburg Merck Sharp Dohme B.V. Succursale belge Tél 32 0 800 38693 MSDBelgiuminfomerck.com

. 359 2 819 3740 info-msdbgmerck.com Magyarország MSD Magyarország Kft. Tel. 361 888 53 00 hungarymsdmerck.com

eská republika Merck Sharp Dohme IDEA, Inc., org. sl. Tel. 420 233 010 111 msdcrmerck.com Malta Merck Sharp Dohme Middle East LimitedTel 357 22866700 infocyprusmerck.com ipru

Danmark Merck Sharp Dohme Tlf 45 43 28 77 66 dkmailmerck.com Nederland Merck Sharp Dohme BV Tel 0800 99 99 000 medicalinfo.nlmerck.com

Deutschland MSD SHARP DOHME GMBH Tel 49 0 89 4561 2612 Infocentermsd.de Norge MSD Norge AS Tlf 47 32 20 73 00 msdnorgemsd.no

Eesti Merck Sharp Dohme OÜ Tel. 372 613 9750 msdeestimerck.com Österreich Merck Sharp Dohme G.m.b.H. Tel 43 0 1 26 044 msd-medizinmerck.com

E BIANE . 3 0210 80091 11 Mailboxvianex.gr Polska MSD Polska Sp.z o.o. Tel. 48 22 549 51 00 msdpolskamerck.com

España Merck Sharp Dohme de España, S.A. Tel 34 91 321 06 00 Ivemendmsd.es Portugal Merck Sharp Dohme, Lda Tel 351 21 4465700 informacaodoentemerck.com

France Laboratoires Merck Sharp Dohme Chibret Tél 33 0 1 47 54 87 00 contactmsd-france.com România Merck Sharp Dohme Romania S.R.L. Tel 4021 529 29 00 msdromaniamerck.com

Ireland Merck Sharp and Dohme Ireland Human Health Limited Tel 353 01 2998700 medinfoirelandmerck.com Slovenija Merck Sharp Dohme, inovativna zdravila d.o.o. Tel 386 1 5204201 msdsloveniamerck.com

Ísland Merck Sharp Dohme Ísland ehf. Icepharma hf Simi 354 540 8000 ISmailmerck.com Slovenská republika Merck Sharp Dohme IDEA, Inc. Tel. 421 2 58282010 msdskmerck.com

talia MSD Italia S.r.l. Tel 39 06 361911 doccenmerck.com SuomiFinland MSD Finland Oy PuhTel 358 0 9 804650 infomsd.fi

Merck Sharp Dohme Middle East Limited. 357 22866700 infocyprusmerck.com Sverige Merck Sharp Dohme Sweden AB Tel 46 0 8 626 1400 medicinskinfomerck.com

Latvija SIA Merck Sharp Dohme Latvija. Tel 371 67364 224 msdlvmerck.com United Kingdom Merck Sharp and Dohme Limited Tel 44 0 1992 467272 medicalinformationukmerck.com

Lietuva
UAB ?Merck Sharp & Dohme?.
Tel.: +370 5 278 02 47msd_lietuva@merck.com

This leaflet was last approved in

---------------------------------------------------------------------------------------------------------------------------

The following information is intended for medical or healthcare professionals only:

Note that the preparation (volume for dilution), infusion rate and doses of concomitant therapy for IVEMEND 150 mg are different from those for IVEMEND 115 mg.

Oral aprepitant on Days 2 and 3 is only administered in combination with IVEMEND 115 mg on Day 1. No aprepitant is administered orally in combination with IVEMEND 150 mg.

The recommended dose of dexamethasone with IVEMEND 150 mg differs from the recommended dose of dexamethasone with IVEMEND 115 mg on Days 3 and 4.

Instructions of how to reconstitute and dilute IVEMEND 150 mg

1. Inject 5 ml sodium chloride 9 mg/ml (0.9 %) solution for injection into the vial. Assure that sodium chloride 9 mg/ml (0.9 %) solution for injection is added to the vial along the vial wall in order to prevent foaming. Swirl the vial gently. Avoid shaking and jetting sodium chloride 9 mg/ml (0.9 %) solution for injection into the vial.

2. Prepare an infusion bag filled with 145 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection (for example, by removing 105 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection from a 250 ml sodium chloride 9 mg/ml (0.9 %) solution for injection infusion bag).

3. Withdraw the entire volume from the vial and transfer it into an infusion bag containing 145 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection to yield a total volume of 150 ml. Gently invert the bag 2-3 times (see HOW TO USE IVEMEND).

The reconstituted and diluted final solution is stable for 24 hours at 25°C.

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

The appearance of the reconstituted solution is the same as the appearance of the diluent.