Aptivus (Tipranavir)

How does it work?

Aptivus capsules and oral solution both contain the active ingredient tipranavir, which is a type of medicine called a protease inhibitor. It is used in the treatment of HIV (human immunodeficiency virus) infection.

AIDS (acquired immune deficiency syndrome) is caused by infection with HIV. This 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. Since HIV kills CD4 T-helper cells, over time the body becomes less able to fight the virus or subsequent infections.

Once the virus has invaded a CD4 T-cell it multiplies, and new copies of the virus are released to infect more CD4 cells. Certain chemicals produced by HIV, called enzymes, play an important role in this multiplication. One of these enzymes, protease, has an essential involvement in assembling the new copies of the virus. Tipranavir works by stopping the protease enzyme from working. This means that new copies of the virus that are produced are faulty and cannot infect more CD4 cells.

There is no cure for HIV, but tipranavir 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.

Tipranavir MUST BE used together with another anti-HIV medicine called ritonavir (Norvir). A low-dose of ritonavir increases the amount of tipranavir in the bood and is used to boost the effect of the tipranavir, rather than to have any effect on the virus itself. This combination 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.

This medicine will be reserved for people who have taken several anti-HIV medicines in the past and whose virus has become resistant to several other protease inhibitors.

Warning!

  • Your Aptivus capsules and low-dose ritonavir should be taken with food.
  • 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 of medicine.
  • 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.
  • You will need to have regular blood tests to monitor your liver function while you are taking this medicine. This is especially important if you already have any problems with your liver, in particular chronic hepatitis B or C. Symptoms that may suggest a liver problem include persistent nausea and vomiting, abdominal pain, or the development of jaundice (a yellow colouring to the skin and the whites of the eyes). Consult your doctor if you experience any of these symptoms.
  • 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, a higher body mass index (BMI), 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.
  • Aptivus capsules should be stored in a fridge at 2 to 8°C. However, bottles of capsules that are in use may be kept out of the fridge (below 25°C) for up to 60 days after you first open the bottle. You should write the date of opening on the label of the bottle.
  • Aptivus capsules contain small amounts of alcohol.

Use with caution in

  • Elderly people.
  • Mild decrease in liver function.
  • Liver enzyme abnormalities.
  • History of hepatitis.
  • Hepatitis B.
  • Hepatitis C.
  • People with the blood clotting disorder haemophilia (this medicine may increase the risk of bleeding).
  • People at increased risk of bleeding, eg due to accidents, surgery or other medical conditions.
  • People taking medicines that may increase the risk of bleeding, eg anticoagulant or antiplatelet medicines.
  • Diabetes.

Not to be used in

  • Moderate or severely decreased liver function.
  • Rare hereditary problems of fructose intolerance (Aptivus capsules contain sorbitol).
  • The safety and efficacy of this medicine in children has not yet been established and the manufacturer does not recommended it for children under 12 years of age.

This medicine should not be used if you are allergic to 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 in pregnancy has not been established. It should be used with caution during pregnancy, and only if the benefits to the mother outweigh any risks to the foetus. Seek further medical advice from your doctor.
  • Oestrogen-containing oral contraceptives (eg the Pill) may be less effective in women who are taking tipranavir in combination with ritonavir. For this reason, women using oestrogen-containing oral contraceptives should use an extra method of contraception to prevent pregnancy, or use a different method of contraception altogether, for example condoms. Condoms should also be used as a regular safe sex practice, to prevent transmitting HIV to your sexual partner.
  • It is recommended that women infected with the HIV virus do 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 medical advice from your doctor.

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.

Very common (affect more than 1 in 10 people)

  • Diarrhoea.
  • Feeling sick (nausea).

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

  • Vomiting.
  • Flatulence.
  • Abdominal pain or bloating.
  • Indigestion.
  • Rash or itching.
  • Fatigue.
  • Loss of appetite.
  • Headache.
  • Raised levels of fats called triglycerides in the blood.

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

  • Abnormalities in liver enzymes.
  • Weight loss.
  • Decreased numbers of red or white blood cells or platelets in the blood.
  • Dizziness.
  • Sleepiness.
  • Difficulty sleeping (insomnia).
  • Disorder of the peripheral nerves causing numbness or tingling in the hands or feet (peripheral neuropathy).
  • Shortness of breath.
  • Muscles cramps or pain.
  • General feeling of being unwell (malaise).
  • Flu-like symptoms.
  • Inflammation of the pancreas (pancreatitis).
  • Inflammation of the liver (hepatitis) or fatty liver.
  • Decreased kidney function.
  • Raised levels of cholesterol in the blood (hypercholesterolaemia).
  • Diabetes.
  • Loss or gain of body fat and other changes in fat distribution (see warning section above).

Rare (affect less than 1 in 10,000 people)

  • Dehydration.
  • Liver failure.

People taking Aptivus tend to have an increased risk of bleeding.

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 very 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, you must check with your doctor or pharmacist before taking any new medicines while taking this one, to ensure that the combination is safe.

As tipranavir is used in combination with ritonavir (Norvir), your doctor or pharmacist will also check whether any of your medicines interact with ritonavir.

The following medicines must not be used in combination with tipranavir, as tipranavir may increase their blood levels and subsequently increase the risk of their side effects:

  • amiodarone
  • astemizole
  • bepridil
  • cisapride
  • ergot derivatives such as dihydroergotamine, ergotamine, ergonovine, and methylergonovine
  • flecainide
  • lovastatin
  • pimozide
  • propafenone
  • quinidine
  • sertindole
  • simvastatin
  • terfenadine
  • triazolam.

You should not take the following medicines in combination with tipranavir and ritonavir, as they may decrease the blood level of tipranavir and thus make it less effective against the HIV virus:

  • the herbal remedy St John's wort (Hypericum perforatum)
  • rifampicin.

The antimalarials halofantrine and lumefantrine, and the anticholinergic tolterodine are not recommended for people taking tipranavir and ritonavir.

You should not take antacids (for heartburn or indigestion) in the two hours before and after taking this medicine, as they may decrease its absorption from the gut and therefore make it less effective. Other medicines that reduce the acidity in the stomach, for example H2antagonists such as ranitidine, should be used with caution in people taking tipranavir, because they may also decrease its absorption from the gut.

If you are taking Videx or Videx EC (didanosine) as part of your anti-HIV medication you should not take it within two hours of taking your tipranavir plus ritonavir.

Tipranavir and ritonavir decrease the blood level of the nucleoside reverse transcriptase inhibitors (NRTIs) abacavirand zidovudine. These are not recommended for use in combination with tipranavir and ritonavir unless there are no suitable alternatives.

Tipranavir with low-dose ritonavir is not recommended for use in combination with other protease inhibitors.

Oestrogen-containing oral contraceptives (eg the Pill) may be less effective in women who are taking tipranavir and ritonavir. For this reason, women using oestrogen-containing oral contraceptives should use an extra method of contraception to prevent pregnancy, or use a different method of contraception altogether, for example condoms. Condoms should also be used as a regular safe sex practice, to prevent transmitting HIV to your sexual partner. Ask your doctor for advice.

Oestrogen-based hormone replacement therapy (HRT) may also be less effective in women taking tipranavir and ritonavir.

Women using oestrogens may have an increased risk of experiencing a non-serious rash due to tipranavir.

Tipranavir with ritonavir may decrease the blood level of the following medicines. If you are taking these with this medicine your doctor may therefore need to increase their dose:

  • bupropion
  • esomeprazole
  • methadone
  • omeprazole
  • theophylline.

Tipranavir with ritonavir may affect the blood level of the immunosuppressants ciclosporin, tacrolimus and sirolimus. If you are taking one of these immunosuppressants with this medicine your doctor may need to monitor its blood level and adjust your dose.

Aptivus capsules contain alcohol and so could produce unpleasant reactions (such as facial flushing, throbbing headache, palpitations, increased heart rate and nausea and vomiting) if taken with disulfiram or the antibiotic metronidazole, as these medicines reduce the metabolism of alcohol.

Tipranavir and ritonavir may increase the blood level of the corticosteroids fluticasoneand budesonide taken by inhaler or nasal spray. This could increase the risk of systemic side effects of these steroids, such as Cushing's syndrome, or decreased production of natural steroids by the adrenal glands. For this reason, the use of these corticosteroids in combination with tipranavir and ritonavir is not recommended, unless the benefits are thought to outweigh the potential risks.

Tipranavir and ritonavir may increase the blood level of cholesterol-lowering medicines known as statins. Atorvastatin is not recommended for use in combination with tipranavir and ritonavir, as the increased blood levels may lead to side effects on the muscles. If cholesterol-lowering treatment is needed, fluvastatin, rosuvastatin or pravastatin are recommended.

Tipranavir and ritonavir may increase the blood level of the antidepressant medicine trazodone. As this may increase the risk of trazodone related side effects, your doctor may prescribe you a lower dose of trazodone if you take it with this medicine.

Tipranavir may increase the blood level of the antibiotic rifabutin. Lower than normal doses of rifabutin will be prescribed if you need this antibiotic while taking tipranavir and ritonavir.

Tipranavir may increase the blood level of the antifungals itraconazole and ketoconazole. Doses of more than 200mg per day of these antifungals are not recommended for people taking tipranavir.

The antifungal fluconazole may increase the blood level of tipranavir. Fluconazole doses of more than 200mg per day are not recommended for people taking tipranavir.

The antibiotic clarithromycin may increase the blood level of tipranavir and this may increase the risk of side effects. Your doctor may want to perform extra monitoring if you are prescribed more than 500mg twice a day of clarithromycin. If you have any problems with your kidneys you may be prescribed a lower than normal dose of clarithromycin.

Tipranavir with ritonavir may increase the risk of side effects such as fainting, visual disturbances and prolonged erection from the following medicines for erectile dysfunction (impotence):

  • sildenafil
  • tadalafil
  • vardenafil.

Tipranavir with ritonavir may affect the blood level of the anti-blood-clotting (anticoagulant) medicine, warfarin. If you are taking warfarin with ritonavir, your blood-clotting time (INR) should be monitored.

There may be an increased risk of bleeding if tipranavir is taken in combination with any of the following medicines, which also increase the risk of bleeding:

  • anti-blood-clotting (anticoagulant) medicines such as warfarin
  • anti-platelet medicines to reduce the risk of blood clots or 'thin the blood', eg low-dose aspirin, clopidogrel, dipyridamole
  • vitamin E supplements.

Other medicines containing the same active ingredient

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