How does it work?

Isentress tablets contain the active ingredient raltegravir, which is medicine used to treat infection with HIV (human immunodeficiency virus). Raltegravir is a new type of anti-HIV medicine known as an integrase strand transfer inhibitor.

AIDS (acquired immune deficiency syndrome) is caused by infection with HIV. This virus cannot replicate and increase in numbers on its own, so it invades human cells to use their metabolism. The virus invades cells of the immune system, particularly the white blood cells known as CD4 T-helper lymphocytes. These cells normally work to activate other cells in the immune system to fight infection. The HIV virus kills the CD4 T-helper cells in the process of its replication, and because of this, over time the body becomes less able to fight the virus or subsequent infections.

Once the virus is inside the CD4 T-cell it multiplies. Part of the process of viral multiplication involves the integration of the viral genetic material, DNA, into the CD4 T-cell’s DNA. This is achieved by a compound essential to the virus, called HIV-1 integrase. HIV-1 integrase is known as an enzyme. Raltegravir works by blocking the action of this enzyme, thereby interfering with the integration of viral DNA into the CD4 T-cell DNA. This stops the virus from multiplying.

This mechanism of action is different from all the other currently available anti-HIV drugs, which means that raltegravir is active against strains of HIV that have become resistant to other anti-HIV medicines.

There is no cure for HIV, but raltegravir is one of a number of medications that lowers the amount of virus in the body (viral load) and slows the progression of the disease from HIV to AIDS. Raltegravir is used in conjunction with other anti-HIV drugs that attack the HIV virus in different ways. This helps prevent the virus becoming resistant to the medicine.

What is it used for?

• HIV infection.

Warning!

• Isentress tablets should be taken twice a day. If you forget to take a dose you can take it as soon as you remember. However, more than two doses should not be taken on the same day. The tablets should be swallowed whole with water and not broken, crushed or chewed.
• The HIV virus is very good at becoming resistant to anti-HIV medicines. For this reason it is very important that you carefully follow your doctor's instructions for taking your anti-HIV medicines, in order to maintain effective levels of the medicines in your blood. If the blood levels drop, the virus will be given more chance to replicate and develop resistance to the drugs. Skipping even a few doses increases the risk of treatment failure, so you should try to ensure that you take all your doses at the correct time, and that you visit your doctor for repeat prescriptions before you run out.
• Treatment of HIV infection with anti-HIV medicines such as this one does not reduce the risk of transmitting the virus to other people through sexual contact or blood contamination. You should continue to use condoms to prevent transmitting the virus to your sexual partner.
• If you have advanced HIV and a history of opportunistic infections such as pneumocystis carinii pneumonia (PCP) or cytomegalovirus (CMV), you may experience signs and symptoms of inflammation from previous infections soon after you start combination anti-HIV treatment. It is believed that these symptoms are due to an improvement in the body’s immune response, which enables the body to fight infections that may have been present with no obvious symptoms. You should tell your doctor immediately if you experience any signs or symptoms of infection, such as inflammation or high temperature, after starting treatment with this medicine.
• Combination antiretroviral therapy has been associated with a redistribution of body fat (lipodystrophy) in people with HIV. The long-term consequences of this are currently unknown, however your doctor may wish to monitor your body fat, and the levels of lipids (eg cholesterol) and sugar (glucose) in your blood, and may prescribe additional medicines for any lipid disorders that occur during treatment with this medicine. Contact your doctor if you notice any changes in your body fat during treatment with your HIV medicines.
• Some people being treated with combination antiretroviral therapy may develop a bone condition called osteonecrosis. This condition is caused by loss of blood supply to a bone, causing death of the bone tissue. The risk of the condition is thought to be increased by corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index, advanced HIV disease and long-term use of antiretroviral medicines. If you notice any joint stiffness, aches and pains (especially of the hip, knee and shoulder) or difficulty in movement while using this medicine, you should tell your doctor so this can be investigated.
• Tell your doctor immediately if you experience any muscular symptoms such as pain, tenderness, cramps, or weakness while taking this medicine, particularly if it is accompanied by a fever or feeling generally unwell. Your doctor may need to check for side effects on the muscles by taking a blood test to measure the level of a compound called creatinine phosphokinase in your blood. If this is the case, the test should not be done following strenuous exercise.
• If have any problems with your liver, in particular chronic hepatitis B or C, you should have regular blood tests to monitor your liver function while you are taking this medicine.
• This medicine has not been studied in children and adolescents under 16 years of age and adults over 65 years of age.

Use with caution in

• Elderly people.
• Severely decreased liver function.
• Hepatitis, particularly chronic hepatitis B or C.
• People with a history of muscle disorders (myopathy) or muscle breakdown (rhabdomyolysis).
• People taking medicines that can have side effects on the muscles, such as statins or fibrates.
• People with cancer or at risk of cancer.

Not to be used in

• Allergy to any ingredient.
• Isentress tablets contain lactose and so should not be taken by people with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.

If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

• The safety of this medicine for use during pregnancy has not been established. The manufacturer states that it should not be used during pregnancy. Seek medical advice from your doctor.
• It is recommended that women infected with the HIV virus must not breastfeed their infants under any circumstances and regardless of their treatment, in order to avoid transmitting the virus to the baby in the breast milk. Seek further medical advice from your doctor.

Label warnings

• This medicine should be swallowed whole, not chewed.

Side effects

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here does not mean that all people using this medicine will experience that or any side effect.

Common (affect between 1 in 10 and 1 in 100 people)

• Disturbances of the gut such as diarrhoea, constipation, nausea and vomiting, abdominal pain or bloating, or flatulence.
• Headache.
• Dizziness.
• Difficulty sleeping (insomnia).
• Excessive sweating, including night sweats.
• Rash or itchy skin.
• Joint pain (arthralgia).
• Feeling weak or fatigued.
• Raised level of fats called triglycerides in the blood.
• Changes in the levels of liver enzymes.

Uncommon (affect between 1 in 100 and 1 in 1000 people)

• Diabetes.
• Raised levels of cholesterol or sugar in the blood.
• Loss or gain of body fat and other changes in fat distribution (see warning section above).
• Anxiety or depression.
• Abnormal dreams.
• Disorder of the peripheral nerves causing numbness or tingling in the hands or feet (peripheral neuropathy).
• Visual disturbances.
• Spinning sensation (vertigo).
• Decrease in the number of white blood cells, red blood cells or platelets in the blood (neutropenia, anaemia or thrombocytopenia).
• Nasal congestion or nosebleeds.
• Change in your voice.
• Muscle pain or weakness.
• Inflammation of the liver (hepatitis).
• Inflammation of the pancreas (pancreatitis).
• Kidney problems such as kidney failure or kidney stones.
• Erectile dysfunction.
• Menopausal symptoms.
• Palpitations.
• Fever (pyrexia).

The side effects listed above may not include all of the side effects reported by the medicine's manufacturer.

For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

How can this medicine affect other medicines?

It is important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before taking any new medicines while taking this one, to ensure that the combination is safe.

There may be an increased risk of side effects on the muscles (myopathy) if raltegravir is taken with any of the following medicines:

• statins for lowering cholesterol, eg simvastatin, rosuvastatin
• fibrates for lowering cholesterol, eg bezafibrate, gemfibrozil
• ezetimibe
• nicotinic acid (niacin).

The antibiotic rifampicin may decrease the blood level of raltegravir. Your doctor may need to increase your dose of raltegravir if you need to take rifampicin while taking this medicine.

The following medicines may increase the absorption of raltegravir from the gut:

• H2 antagonists, eg ranitidine, famotidine
• proton pump inhibitors, eg omeprazole, lansoprazole.

Other medicines containing the same active ingredient

There are currently no other medicines available in the UK that contain raltegravir as the active ingredient.