Label: information for the user

Isentress 400mg film-coated tablets

raltegravir

Read this label carefully before starting to take this medicine, as it contains important information for you.

If you are the parent of a child taking Isentress, please read this information carefully with your child.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed only for you or your child, and should not be given to

other people even if they have the same symptoms as you, as it may harm them.

• If you experience any adverse effects, consult your doctor, pharmacist, or nurse,

even if they are not listed in this label. See section4.

What is Isentress

Isentress contains the active ingredient raltegravir. Isentress is an antiviral medication that acts against the human immunodeficiency virus (HIV). This is the virus that causes acquired immunodeficiency syndrome (AIDS).

How Isentress works

The virus produces an enzyme called HIV integrase, which helps the virus to enter the body's cells and multiply. Isentress prevents this enzyme from functioning. When used with other medications, Isentress can reduce the amount of HIV in the blood (this is known as its “viral load”) and increase the count of CD4 cells (a type of white blood cell that plays an important role in maintaining a healthy immune system to help fight infection). By reducing the amount of HIV in the blood, it can improve the functioning of the immune system. This means that the body can fight better against the infection.

When to use Isentress

Isentress is used to treat patients who are infected with HIV. Your doctor has prescribed Isentress to help you control the HIV infection you have.

Do not take Isentress:

• if you are allergic to raltegravir or any of the other components of this medication (listed in section6).

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to take Isentress.

Remember that Isentress does not cure HIV infection. This means that you may still experience infections or other HIV-related illnesses. You should continue to visit your doctor regularly while taking this medication.

Mental health problems

Inform your doctor if you have a history of depression or mental illness. Depression, including suicidal thoughts and behaviors, has been observed in some patients taking this medication, especially in patients with a previous history of depression or mental illness.

Bone problems

Some patients taking combination antiretroviral therapy may develop a bone disease called osteonecrosis (bone tissue death caused by loss of blood supply to the bone). Factors that may increase the risk of developing this disease include the duration of combination antiretroviral therapy, the use of corticosteroids, alcohol consumption, severe immunosuppression, significant weight gain, and others. Signs of osteonecrosis include joint stiffness, pain, and difficulty moving (especially in the hip, knee, and shoulder). If you experience any of these symptoms, visit your doctor.

Liver problems

Inform your doctor, pharmacist, or nurse if you have had liver problems in the past, including hepatitisB or C. Your doctor may evaluate the severity of your liver disease before deciding whether you can take this medication.

Infections

If you notice any symptoms of infection, such as fever and/or feeling unwell, inform your doctor, pharmacist, or nurse immediately. Some patients with advanced HIV infection and a history of opportunistic infections may experience signs and symptoms of inflammation due to previous infections shortly after starting HIV treatment. These symptoms are believed to be due to the improvement of the body's immune response, which allows the body to fight infections that may have been present but not producing obvious symptoms.

In addition to opportunistic infections, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may also occur after starting HIV treatment. These disorders can occur many months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and ascending to the trunk of the body, palpitations, tremors, or hyperactivity, inform your doctor immediately to receive necessary treatment.

Muscle problems

Contact your doctor, pharmacist, or nurse immediately if you experience unexplained muscle pain, sensitivity to pressure, or muscle weakness during treatment with this medication.

Skin problems

Contact your doctor immediately if you experience a rash. Severe and potentially life-threatening skin reactions and allergic reactions have been reported in some patients taking this medication.

Other medications and Isentress

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication with or without a prescription.

Isentress may interact with other medications.

Inform your doctor, pharmacist, or nurse if you are taking, have taken recently, or may need to take:

• antacids (a medication that counteracts or neutralizes stomach acid and relieves indigestion and heartburn). Do not take Isentress with some antacids (those containing aluminum and/or magnesium). Consult your doctor about other antacids you may take.
• iron supplements (to treat and prevent iron deficiency or anemia). You should wait at least twohours between taking iron supplements and taking Isentress, as these medications may reduce the effectiveness of Isentress.
• rifampicin (a medication used to treat some infections such as tuberculosis), as it may lower your Isentress levels. If you are taking rifampicin, your doctor may consider increasing your Isentress dose.

Taking Isentress with food and drinks

See section3.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

• It is not recommended that HIV-positive women breastfeed, as HIV infection can be transmitted to the baby through breast milk.
• If you are breastfeeding or plan to breastfeed, you should consult your doctor as soon as possible.

If you are pregnant or breastfeeding, consult your doctor, pharmacist, or nurse before using any medication.

Driving and operating machinery

Do not operate machinery, drive, or ride a bike if you feel dizzy after taking this medication.

Isentress contains lactose

This medication contains lactose. If your doctor has told you that you have a certain sugar intolerance, consult with them before taking this medication.

Isentress contains sodium

This medication contains less than 1mmol of sodium (23mg) per tablet; it is essentially "sodium-free".

Follow exactly the administration instructions of this medication indicated by your doctor, pharmacist or nurse. In case of doubt, consult your doctor, pharmacist or nurse again. Isentress should be used in combination with other medications for HIV infection.

How muchto take

Adults

The recommended dose is 1tablet (400mg) by mouth twice a day.

Use in children and adolescents

The recommended dose of Isentress is 400mg by mouth twice a day for adolescents and children who weigh at least 25kg,

Do not chew, crush or break the tablets because it may alter the amount of medication in your body. You can take this medication with or without food or drinks.

Isentress is also available in 600mg tablets, chewable tablets and granules for oral suspension.

Do not interchange between the 400mg tablets, 600mg tablets, chewable tablets or granules for oral suspension without consulting your doctor, pharmacist or nurse first.

If you take more Isentress than you should

Do not take more tablets than your doctor has recommended. If you take more tablets than recommended, consult your doctor.

If you forgot to take Isentress

• If you forget to take a dose, take it as soon as you remember that you have not taken it.
• However, if it is time to take the next dose, do not take the missed dose and follow your usual dosing schedule.
• Do not take a double dose to compensate for the missed doses.

If you interrupt the treatment with Isentress

It is very important that you take Isentress exactly as your doctor has told you.Do not change the dose or stop taking this medication without consulting your doctor, pharmacist or nurse first.Do not stop taking it, because:

• It is very important that you take all HIV medications as prescribed and at the correct times of the day. This makes the medications work better and also reduces the possibility that they will no longer be able to combat HIV (this is also called “drug resistance”).
• When you have few tablets of Isentress left, go to your doctor or pharmacy to get more. The reason is that it is very important not to run out of medication, not even for a few days. If you stop taking the medication for a few days, the amount of virus in the blood may increase and, as a consequence, HIV may develop resistance to Isentress and the disease may be more difficult to treat.

If you have any other doubts about the use of this medication, ask your doctor, pharmacist or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Severe side effects–these are rare (may affect up to 1 in 100people)

Seek medical attention immediately if you notice any of the following side effects:

• herpes infections, including shingles
• anemia, including iron deficiency anemia
• signs and symptoms of infection or inflammation
• mental disorder
• suicidal attempt or intention
• gastritis
• hepatitis
• liver failure
• allergic rash
• specific types of kidney problems
• ingestion of the medicine in quantities greater than recommended

Seek medical attention immediately if you notice any of the side effects mentioned above.

Frequent:the following side effects may affect up to 1 in 10people

• loss of appetite
• sleep problems; strange dreams; nightmares; abnormal behavior; deep sadness and low self-esteem
• dizziness; headache
• vertigo
• flatulence or gas; abdominal pain; diarrhea; excessive gas in the stomach or intestines; nausea; vomiting; indigestion; belching
• specific types of rash (more frequently when used in combination with darunavir)
• unusual fatigue, weakness, or tiredness; fever
• high levels of liver parameters; abnormal white blood cell counts; high levels of blood fat; high levels of salivary gland or pancreatic enzymes

Rare: the following side effects may affect up to 1 in 100people

• hair follicle infection; flu; skin infection due to virus; vomiting or diarrhea due to an infectious agent; upper respiratory tract infection; lymph node abscess
• warts
• lymph node pain; low white blood cell count; swelling of the neck, armpit, and groin glands
• allergic reaction
• increased appetite; diabetes; high cholesterol and blood lipids; high blood sugar levels; excessive thirst; severe weight loss; high levels of blood fat (such as cholesterol and triglycerides); body fat disorders
• anxiety; confusion; depressed mood; mood changes; panic attack
• memory loss; hand pain due to nerve compression; altered attention; dizziness upon rapid change of posture; abnormal taste; increased somnolence; lack of energy; forgetfulness; migraines; numbness, tingling, or weakness of the arms and/or legs; paresthesia; somnolence; tension headache; tremors; poor sleep
• vision changes
• tinnitus, high-pitched sounds, buzzing, or other persistent noises in the ears
• palpitations; slow heart rate; irregular heartbeats
• angina; high blood pressure
• hoarse, rough, or forced voice; nasal bleeding; nasal congestion
• upper abdominal pain; rectal discomfort; constipation; dry mouth; stomach burning; difficulty swallowing; pancreatitis; stomach or intestinal ulcer; rectal bleeding; stomach discomfort; gum inflammation; swollen tongue and ulcers
• liver fat accumulation
• acne; hair loss or thinning; skin redness; unusual body fat distribution, including loss of fat in legs, arms, and face, and increased fat in the abdomen; excessive sweating; night sweats; skin itching and scratching; skin lesions; dry skin
• joint pain; painful joints; back pain; bone or muscle pain; muscle weakness or pain; neck pain; arm or leg pain; tendon inflammation; decreased bone mineral content
• kidney stones; nocturia; renal cyst
• erectile dysfunction; gynecomastia in men; menopausal symptoms
• chest discomfort; chills; facial swelling; feeling of nervousness; general feeling of discomfort; neck lump; hand, foot, or ankle swelling; pain
• low white blood cell count; low platelet count in blood (a type of cell involved in blood clotting); decreased renal function in blood test; high blood sugar levels; elevated muscle enzymes in blood; sugar in urine; red blood cells in urine; weight gain; increased waist circumference; decreased blood protein (albumin); prolonged blood clotting time

Other side effects in children and adolescents

• hyperactivity

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect not listed in this leaflet.You can also report them directly through thenational notification system included in theAppendixV. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the bottle after CAD. The expiration date is the last day of the month indicated.
• No special storage conditions are required.
• Keep the bottle perfectly closed, with the desiccant (drying agent) to protect it from moisture. Do not ingest the desiccant.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Isentress

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

The other components are: lactose monohydrate, microcrystalline cellulose, anhydrous dibasic calcium phosphate, hypromellose 2208, poloxamer 407, sodium stearate, and magnesium stearate. Additionally, the coating contains the following inactive ingredients: polyvinyl alcohol, titanium dioxide, polyethylene glycol 3350, talc, red iron oxide, and black iron oxide.

Appearance of the product and contents of the package

The film-coated tablet of 400 mg is oval in shape, pink in color, and has the inscription "227" engraved on one side.

There are two package sizes available: a bottle of 60 tablets and a multiple-pack containing three bottles of 60 tablets each. The bottle contains a desiccant.

Only some package sizes may be marketed.

Marketing authorization holder and responsible manufacturer

Merck Sharp & Dohme B.V.

Waarderweg 39

2031 BN Haarlem

Netherlands

For more information about this medication, please contact the local representative of the marketing authorization holder:

Last review date of this leaflet: {MM/AAAA}

For detailed information about this medication, please visit the European Medicines Agency website: http://www.ema.europa.eu