ISENTRESS 100 MG CHEWABLE TABLETS

2. What you need to know before you take Isentress

Do not take Isentress:

• if you are allergic to raltegravir or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before you start taking Isentress.

Remember that Isentress does not cure HIV infection. This means you may still get illnesses or infections related to HIV. You must keep seeing your doctor regularly while taking this medicine.

Mental health problems

Tell your doctor if you have a history of depression or mental health problems. Depression, including thoughts and behaviors of suicide, has been seen in some patients taking this medicine, especially in patients with a history of depression or mental health problems.

Bone problems

Some patients taking combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue caused by loss of blood supply to the bone). The length of time taking combination antiretroviral therapy, the use of corticosteroids, alcohol consumption, severe immune system suppression, increased body mass index, among others, may be some of the many risk factors for developing this disease. Signs of osteonecrosis are joint stiffness, pain, and difficulty moving. If you experience any of these symptoms, see your doctor.

Liver problems

Tell your doctor, pharmacist, or nurse if you have had liver problems in the past, including hepatitis B or C. Your doctor may assess the severity of your liver disease before deciding if you can take this medicine.

Infections

If you notice any symptoms of infection, such as fever and/or feeling unwell, tell your doctor, pharmacist, or nurse immediately. Some patients with advanced HIV infection who have previously had opportunistic infections may show signs and symptoms of inflammation from previous infections soon after starting treatment for HIV. It is believed that these symptoms are due to the improvement in the body's immune response, which enables the body to fight off infections that may have been present without causing obvious symptoms.

In addition to opportunistic infections, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may occur after you have started taking medicines for the treatment of your HIV infection. Autoimmune disorders may 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 moving up towards the trunk of the body, palpitations, tremor, or hyperactivity, tell your doctor immediately to receive the necessary treatment.

Muscle problems

Contact your doctor, pharmacist, or nurse immediately if you notice unexplained muscle pain, tenderness, or muscle weakness while taking this medicine.

Skin problems

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

Other medicines and Isentress

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, with or without a prescription.

Isentress may interact with other medicines.

Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take:

• antacids (a medicine that counteracts or neutralizes stomach acid and relieves indigestion and heartburn). It is not recommended to take Isentress with some antacids (those containing aluminum and/or magnesium). Ask your doctor about other antacids you may take.
• iron salts (to treat and prevent iron deficiency or anemia). You should wait at least 2 hours between taking iron salts and taking Isentress, as these medicines may reduce the effectiveness of Isentress.
• rifampicin (a medicine used to treat some infections such as tuberculosis), as it may decrease Isentress levels. If you are taking rifampicin, your doctor may consider increasing your dose of Isentress.

Taking Isentress with food and drinks

See section 3.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

• Isentress chewable tablets are not recommended during pregnancy, as they have not been studied in pregnant women.
• It is not recommended that HIV-infected women breastfeed their babies because HIV infection can be passed to the baby through breast milk.
• If you are breastfeeding or thinking of breastfeeding, consult your doctor as soon as possible.

If you are pregnant or breastfeeding, ask your doctor, pharmacist, or nurse for advice before taking any medicine.

Driving and using machines

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

Isentress 25 mg chewable tablet

Isentress 25mg chewable tablet contains fructose

This medicine contains up to 0.54 mg of fructose in each tablet.

Fructose may damage teeth.

Isentress 25mg chewable tablet contains sorbitol

This medicine contains up to 1.5 mg of sorbitol (E 420) in each tablet.

Isentress 25mg chewable tablet contains sucrose

This medicine contains up to 3.5 mg of sucrose in each 25 mg chewable tablet.

Sucrose may damage teeth.

If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

Isentress 25mg chewable tablet contains aspartame

This medicine contains up to 0.47 mg of aspartame (E 951) in each 25 mg chewable tablet, which is equivalent to up to 0.05 mg of phenylalanine. Aspartame is a source of phenylalanine that may be harmful if you have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine accumulates because the body cannot eliminate it properly.

Isentress 25mg chewable tablet contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; this is essentially “sodium-free”.

Isentress 100 mg chewable tablet

Isentress 100mg chewable tablet contains fructose

This medicine contains up to 1.07 mg of fructose in each tablet.

Fructose may damage teeth.

Isentress 100mg chewable tablet contains sorbitol

This medicine contains up to 2.9 mg of sorbitol (E 420) in each tablet.

Isentress 100mg chewable tablet contains sucrose

This medicine contains up to 7 mg of sucrose in each 100 mg chewable tablet.

Sucrose may damage teeth.

If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

Isentress 100mg chewable tablet contains aspartame

This medicine contains up to 0.93 mg of aspartame (E 951) in each 100 mg chewable tablet, which is equivalent to up to 0.10 mg of phenylalanine. Aspartame is a source of phenylalanine that may be harmful if you have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine accumulates because the body cannot eliminate it properly.

Isentress 100mg chewable tablet contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; this is essentially “sodium-free”.

3. How to take Isentress

Always take this medicine exactly as your doctor, pharmacist, or nurse has told you. If you are not sure, check with your doctor, pharmacist, or nurse. Isentress must be used in combination with other medicines for HIV.

The 100 mg chewable tablet can be divided into two equal halves. However, it is recommended to avoid splitting the tablets whenever possible.

How much to take

Dose for children between 2 and 11years of age

Your doctor will recommend the appropriate dose of chewable tablets based on the child's age and weight. This dose should not exceed 300 mg twice a day. Your doctor will tell you how many chewable tablets the child should take.

Isentress is also available as a 400 mg tablet, a 600 mg tablet, and an oral suspension.

Do not switch between the chewable tablet, the oral suspension, the 600 mg tablet, or the 400 mg tablet without first consulting your doctor, pharmacist, or nurse.

Children should attend scheduled visits with their doctor as their dose of Isentress may need to be adjusted as they get older, grow, or gain weight. Your doctor may also want to prescribe the 400 mg tablet when they are able to swallow a tablet.

This medicine can be taken with or without food or drinks.

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, talk to your doctor.

If you forget to take Isentress

• If you forget to take a dose, take it as soon as you remember.
• However, if it is time for your next dose, do not take the missed dose and continue with your regular dosing schedule.
• Do not take a double dose to make up for a forgotten dose.

If you stop taking Isentress

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

• It is very important that you take all your HIV medicines exactly as they have been prescribed and at the right times of the day. This makes the medicines work better and also reduces the chance of the medicines becoming unable to combat HIV (this is also called “drug resistance”).
• When you have only a few Isentress tablets left, go to your doctor or pharmacy to get more. The reason is that it is very important not to run out of medicine, even for a few days. If you stop taking the medicine for a few days, the amount of virus in your blood may increase and, as a result, the HIV may develop resistance to Isentress and the disease may become harder to treat.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Severe Adverse Effects– these are rare (may affect up to 1 in 100 people)

See a doctor immediately if you notice any of the following adverse effects:

• herpes infections, including shingles
• anemia, including iron deficiency anemia
• signs and symptoms of infection or inflammation
• mental disorder
• suicidal thoughts or intentions
• stomach inflammation
• liver inflammation
• liver failure
• allergic rash
• certain types of kidney problems
• ingestion of the medicine in quantities higher than recommended

See a doctor immediately if you notice any of the above-mentioned adverse effects.

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

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

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

• infection of the hair roots; flu; skin infection due to a virus; vomiting or diarrhea due to an infectious agent; upper respiratory tract infection; accumulation of pus in a lymph node
• warts
• lymph node pain; low count of white blood cells that fight infections; swelling of the glands in the neck, armpits, and groin
• allergic reaction
• increased appetite; diabetes; elevated blood cholesterol and lipid levels; increased blood sugar levels; excessive thirst; severe weight loss; high levels of blood fat (such as cholesterol and triglycerides); body fat disorders
• feeling of anxiety; feeling of confusion; depressed mood; mood changes; panic attack
• memory loss; hand pain due to nerve compression; attention disorder; dizziness when changing position quickly; abnormal taste; increased drowsiness; lack of energy; forgetfulness; migraines; loss of sensation, numbness, or weakness in the arms and/or legs; tingling; drowsiness; tension headache; tremors; poor sleep
• vision changes
• ringing, high-pitched sounds, whistling, or other persistent noises in the ears
• palpitations; slow pulse; rapid or irregular heartbeats
• hot flashes; increased blood pressure
• hoarse, rough, or forced voice; nosebleeds; nasal congestion
• upper abdominal pain; rectal discomfort; constipation; dry mouth; heartburn; pain when swallowing; pancreatitis; ulcers or wounds in the stomach or upper intestine; anal bleeding; stomach discomfort; gum inflammation; swelling, redness, and ulcers on the tongue
• fat accumulation in the liver
• acne; hair loss or thinning; skin redness; unusual fat distribution in the body, which may include fat loss in the legs, arms, and face, and increased fat in the abdomen; excessive sweating; night sweats; thickening and itching of the skin due to repeated scratching; skin lesions; dry skin
• joint pain; painful joint disease; back pain; bone/muscle pain; muscle pain or weakness; neck pain; pain in the arms or legs; tendon inflammation; decreased bone mineral density
• kidney stones; nocturia; kidney cyst
• erectile dysfunction; breast enlargement in men; menopausal symptoms
• chest discomfort; chills; facial swelling; feeling of nervousness; feeling of general malaise; lump in the neck; swelling of the hands, ankles, or feet; pain
• low white blood cell count; low platelet count in the blood (a type of cell involved in blood clotting); decreased kidney function in blood tests; high blood sugar levels; elevated muscle enzymes in the blood; sugar in the urine; red blood cells in the urine; weight gain; increased waist circumference; decreased blood protein levels (albumin); increased blood coagulation time

Other adverse effects in children and adolescents

• hyperactivity

Reporting Adverse Effects

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

5. Storage of Isentress

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

• Do not use this medicine after the expiration date stated on the bottle after CAD. The expiration date is the last day of the month indicated.
• Keep the bottle tightly closed, with the desiccant (drying agent) to protect it from moisture. Do not swallow the desiccant.
• Before breaking the seal, no special storage conditions are required.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Isentress Composition

The active ingredient is raltegravir.

25 mg chewable tablets:

Each chewable tablet contains 25 mg of raltegravir (potassium salt).

The other ingredients are: hydroxypropylcellulose, sucralose, sodium saccharin, sodium citrate dihydrate, mannitol (E 421), yellow iron oxide, monoammonium glycyrrhizinate, sorbitol (E 420), fructose, natural and artificial flavors (orange, banana, and masking), aspartame (E 951), sucrose, crospovidone Type A, magnesium stearate, sodium stearyl fumarate, ethylcellulose 20 cP, ammonium hydroxide, medium-chain triglycerides, oleic acid, hypromellose 2910/6cP, and macrogol/PEG 400.

100 mg chewable tablets:

Each chewable tablet contains 100 mg of raltegravir (potassium salt).

The other ingredients are: hydroxypropylcellulose, sucralose, sodium saccharin, sodium citrate dihydrate, mannitol (E 421), red iron oxide, yellow iron oxide, monoammonium glycyrrhizinate, sorbitol (E 420), fructose, natural and artificial flavors (orange, banana, and masking), aspartame (E 951), sucrose, crospovidone Type A, magnesium stearate, sodium stearyl fumarate, ethylcellulose 20 cP, ammonium hydroxide, medium-chain triglycerides, oleic acid, hypromellose 2910/6cP, and macrogol/PEG 400.

Product Appearance and Package Contents

Isentress 25 mg chewable tablets:

Light yellow chewable tablet, orange and banana flavor, round, with the MSD corporate logo on one side and "473" on the other side.

One pack size is available: 1 bottle with 60 tablets. The bottle contains a desiccant.

Isentress 100 mg chewable tablets:

Light orange chewable tablet, orange and banana flavor, oval, scored on both sides, engraved on one side with the MSD corporate logo and the code "477" and without engraving on the other side.

One pack size is available: 1 bottle with 60 tablets. The bottle contains a desiccant.

Marketing Authorization Holder and Manufacturer

Merck Sharp & Dohme B.V.

Waarderweg 39

2031 BN Haarlem

Netherlands

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:<{MM/AAAA}><{month YYYY}>.

Detailed information about this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu.