ISENTRESS 400 mg film-coated tablets

What ISENTRESS is

ISENTRESS works against the Human Immunodeficiency Virus (HIV). This is the virus that causes Acquired Immune Deficiency Syndrome (AIDS).

How ISENTRESS works

The virus produces an enzyme called HIV integrase. This helps the virus to multiply in the cells in your body. ISENTRESS stops this enzyme working. When used with other medicines, ISENTRESS may reduce the amount of HIV in your blood (this is called your "viral load") and increase your CD4-cell count (a type of white blood cells that plays an important role in maintaining a healthy immune system to help fight infection). Reducing the amount of HIV in the blood may improve the functioning of your immune system. This means your body may fight infection better.
ISENTRESS may not have these effects in all patients.
ISENTRESS is not a cure for HIV infection.

When ISENTRESS should be used

ISENTRESS is used to treat adults who are infected by HIV. Your doctor has prescribed ISENTRESS to help control your HIV infection.

Do not take ISENTRESS

• If you are allergic (hypersensitive) to raltegravir or to any of the other ingredients in the tablets (listed in 6. Further information).

Take special care with ISENTRESS

Remember that ISENTRESS is not a cure for HIV infection. This means that you may keep getting infections or other illnesses associated with HIV. You should keep seeing your doctor regularly while taking ISENTRESS.

ISENTRESS is not for use in children and adolescents.

Some patients taking combination anti-retroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue caused by loss of blood supply to the bone). The length of combination anti-retroviral therapy, corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index, among others, may be some of the many risk factors for developing this disease. Signs of osteonecrosis are joint stiffness, aches and pains (especially of the hip, knee and shoulder) and difficulty in movement. If you notice any of these symptoms please inform your doctor.

Tell your doctor if you have had problems with your liver before, including hepatitis B or C. Your doctor may evaluate how severe your liver disease is before deciding if you can take ISENTRESS.

HIV infection is spread by contact with blood or sexual contact with a person with HIV. Taking ISENTRESS has not been shown to reduce the risk of giving HIV to others through sexual contact or contact with blood.

Tell your doctor immediately if you notice any symptoms of infection. In some patients with advanced HIV infection and a history of opportunistic infection, signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started. It is believed that these symptoms are due to an improvement in the body?s immune response, enabling the body to fight infections that may have been present with no obvious symptoms.

Contact your doctor promptly if you experience unexplained muscle pain, tenderness, or weakness while taking ISENTRESS.

In patients taking ISENTRESS and darunavir, rashes (generally mild or moderate) may occur more frequently than in patients taking either drug separately.

Taking other medicines

ISENTRESS might interact with other medicines. Raltegravir is not known to have an important effect on blood levels of other agents used to treat HIV. Also, blood levels of raltegravir are not known to be affected to an important extent by other agents used to treat HIV. However, further information is expected to become available as experience with the use of raltegravir increases.

Please tell your doctor or pharmacist if you are now or have recently taken:

• rifampicin (a medicine used to treat some infections such as tuberculosis)
• medicines used to treat stomach ulcer or heartburn (e.g., omeprazole, cimetidine, ranitidine)
• any other medicines with or without a prescription.

Taking ISENTRESS with food and drink

You can take ISENTRESS with or without food or drink.

Pregnancy and breast-feeding

Talk to your doctor before taking ISENTRESS if you are pregnant, might become pregnant or are breastfeeding. If you become pregnant, tell your doctor straight away.

• ISENTRESS is not recommended in pregnancy because it has not been studied in pregnant women.
• Women with HIV should not breast-feed their infants because babies can be infected with HIV through their breast milk. Talk with your doctor about the best way to feed your baby.

Ask your doctor or pharmacist for advice before taking any medicine if you are pregnant or breast-feeding.

Driving and using machines

Do not operate machines or drive if you feel dizzy after taking ISENTRESS.

Important information about some of the ingredients of ISENTRESS

ISENTRESS contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, talk to your doctor before taking this medicine.

Always take ISENTRESS exactly as your doctor has told you. You should check with your doctor if you are not sure. ISENTRESS must be used in combination with other medicines for HIV.

How much to take

• The usual dose of ISENTRESS is 1 tablet (400 mg) by mouth twice a day.
• It is recommended not to chew, crush or split the tablets.
• You can take ISENTRESS with or without food or drink.
• Do not change your dose or stop taking ISENTRESS without first talking with your doctor.

If you take more ISENTRESS than you should

Do not take more tablets than the doctor recommends. If you do take too many tablets, contact your doctor.

If you forget to take ISENTRESS

• If you forget to take a dose, take it as soon as you remember it.
• However, if it is time for your next dose, skip the missed dose and go back to your regular schedule.
• Do not take a double dose of ISENTRESS to make up for a forgotten dose.

If you stop taking ISENTRESS

It is important that you take ISENTRESS exactly as your doctor has instructed. Do not stop taking it because:

• It is very important to take all your HIV medicines as prescribed and at the right times of day. This can help your medicines work better. It also lowers the chance that your medicines will stop being able to fight HIV (also called "drug resistance").
• When your supply of ISENTRESS starts to run low, get more from your doctor or pharmacy. This is because it is very important not to be without the medicine, even for a short time. During a short break in taking the medicine the amount of virus in your blood may increase. This may mean that the HIV virus will develop resistance to ISENTRESS and become harder to treat.

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

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

Common side effects (affects 1 to 10 users in 100):

• trouble sleeping; abnormal dreams
• feeling dizzy; headache
• spinning sensation
• bloating; abdominal pain; diarrhoea; excessive gas in the stomach or bowel; feeling sick; vomiting
• certain kinds of rash (more often when used in combination with darunavir)
• tiredness, unusual tiredness or weakness; fever
• increased liver blood tests; abnormal white blood cells; increased fat levels in blood; increased level of enzyme from salivary glands or pancreas

Uncommon side effects (affects 1 to 10 users in 1,000):

• herpes infections including shingles; infection of the hair roots; influenza; skin infection due to virus; vomiting or diarrhoea due to an infectious agent; upper respiratory tract infection
• wart
• anaemia including due to low iron; lymph node pain; low count of white blood cells that fight infection; swollen glands in the neck, armpit and groin
• allergic reaction; signs and symptoms of inflammation from previous infections
• decreased or increased appetite; diabetes; increased blood cholesterol and lipids; high sugar levels in the blood; excessive thirst; severe weight loss; high levels of fat (such as cholesterol and triglycerides) in the blood
• mental disorder; feeling anxious; feeling of confusion; depressed mood; feelings of deep sadness and unworthiness; mood changes; nightmare; suicide attempt; panic attack
• loss of memory; pain in the hand due to nerve compression; disturbance in attention; dizziness with rapid changes in posture; abnormal taste; increased sleepiness; lack of energy; forgetfulness; migraine headache; loss of feeling, numbness or weakness of the arms and/or legs; tingling; sleepiness; tension headache; tremors
• visual disturbance
• buzzing, hissing, whistling, ringing or other persistent noise in the ears
• palpitations; slow heart rates; fast or irregular heart beats
• hot flush; high blood pressure
• harsh, raspy, or strained voice; nosebleed; nasal congestion
• stomach inflammation; abdominal pain upper; rectal discomfort; constipation; dry mouth; indigestion; belching; heartburn; pain when swallowing; inflammation of the pancreas; ulcer or sore in stomach or upper intestine; bleeding at anus; stomach discomfort; inflammation of the gums; swollen, red sore tongue
• inflammation of liver; accumulation of fat in the liver
• acne; unusual hair loss or thinning; redness of skin; unusual distribution of fat on the body, these may include loss of fat from legs, arms, and face, and increase in abdomen fat; excessive sweating; night sweats; thickening and itching of the skin due to repeated scratching; skin lesion; dry skin
• joint pain; painful joint disease; back pain; pain in bone/muscle; muscle tenderness or weakness; neck pain; pain in arms or legs; inflammation of the tendons; decrease in the amount of minerals in the bone
• certain kinds of kidney problems; kidney stones; urination at night; kidney cyst
• erectile dysfunction; breast enlargement in men; menopausal symptoms
• chest discomfort; chills; swelling of face; feeling jittery; generally feeling unwell; swelling of hands, ankles or feet; pain
• decreased white blood cell count; decreased count of platelets in blood (a kind of cell that helps blood clot); blood test showing reduced kidney function; high blood sugar level; increased muscle enzyme in blood; sugar present in urine; red blood cells present in urine; weight gain; increase in waist size; decreased blood protein (albumin)
• drug ingestion in quantities greater than recommended

During post-marketing experience the following side effects have been reported (frequency = uncommon):

• Severe skin reactions
• Suicidal thoughts and actions
• Localised loss of bone material

There have been reports of muscle pain, tenderness, or weakness during treatment with ISENTRESS.

In clinical studies, cancers were observed in patients receiving ISENTRESS at a rate similar to that observed in the patients receiving other HIV medicines.

If any of the side effects gets serious, or if you notice 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 take ISENTRESS after the expiry date which is stated on the bottle after EXP. The expiry date refers to the last day of that month.
• This product does not require any special storage conditions.

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.

What ISENTRESS contains

The active substance is raltegravir. Each film-coated tablet contains 400 mg of raltegravir (as potassium).

The other ingredients are: lactose monohydrate, microcrystalline cellulose, calcium phosphate dibasic anhydrous, hypromellose 2208, poloxamer 407, sodium stearyl fumarate, and magnesium stearate. In addition, the film coating contains the following inactive ingredients: polyvinyl alcohol, titanium dioxide (E 171), polyethylene glycol 3350, talc, red iron oxide (E 172) and black iron oxide (E 172).

What ISENTRESS looks like and contents of the pack

The film-coated tablet is oval-shaped, pink, marked with "227" on one side. Two pack sizes are available: 1 bottle with 60 tablets, and a multi-pack containing 3 bottles of 60 tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

The Marketing Authorisation Holder is The Product Manufacturer is

Merck Sharp Dohme Ltd. Hertford Road, Hoddesdon Hertfordshire EN11 9BU United Kingdom Merck Sharp Dohme B. V. Waarderweg 39, Postbus 581 NL-2003 PC Haarlem The Netherlands

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

Danmark Merck Sharp Dohme Tlf 45 43 28 77 66 dkmailmerck.com Nederland Merck Sharp Dohme B.V. Tel 31 0 23 5153153 msdbvnlmerck.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 ISENTRESSmsd.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 Icepharma hf. Sími 354 540 8000 ISmailmerck.com Slovenská republika Merck Sharp Dohme IDEA, Inc. Tel. 421 2 58282010 msdskmerck.com

talia Merck Sharp Dohme Italia S.p.A. 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 medinfoukmerck.com

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

This leaflet was last approved in