Kaletra (Lopinavir, ritonavir)

How does it work?

Kaletra tablets and oral solution contain two active ingredients, ritonavir and lopinavir. These are both anti-HIV medicines known as protease inhibitors. However, lopinavir is the active ingredient that provides the anti-HIV activity. There is a small amount of ritonavir included in this medicine because it slows the breakdown of lopinavir by the liver. This produces higher blood levels of lopinavir to fight the virus.

AIDS (acquired immune deficiency syndrome) is caused by infection with HIV (human immunodeficiency virus). This virus invades cells of the immune system, particularly the white blood cells known as CD4 T-helper lymphocytes. These cells normally activate other cells in the immune system to fight infection. Since HIV kills CD4 T-helper cells, the body cannot fight the virus or subsequent infections.

Once the virus is inside the CD4 T-cell it multiplies, producing numerous copies of itself. An enzyme produced by the HIV virus, called protease, plays an important role in this process. Protease breaks up new protein produced by the virus, so that new copies of the virus can be assembled from the pieces. If this enzyme is stopped from working, any new virus that is produced is faulty and unable to infect more CD4 cells. Protease inhibitors, such as lopinavir, work by stopping the protease enzyme from working.

There is no cure for HIV, but Kaletra is one of a number of medicines that slows the progression of the disease from HIV to AIDS. Kaletra is used in conjunction with other anti-HIV medicines that attack the virus in different ways. This minimises the chance of the virus becoming resistant to any one medicine.

What is it used for?

  • HIV infection.

Warning!

  • Kaletra oral solution should be taken with food. Kaletra tablets can be taken with or without food.
  • Kaletra tablets should be swallowed whole and not broken, chewed or crushed.
  • Kaletra oral solution should be stored at 2-8ºc in a refrigerator. When in use it may be kept outside of the fridge, but do not store it above 25ºc, and dispose of any unused medicine after 6 weeks. (Write the date of removal from the fridge on the package.) Kaletra tablets do not need to be kept in a fridge.
  • 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.
  • 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 triglycerides) and sugar (glucose) in your blood, and may prescribe additional medicines for any lipid disorders that occur during treatment with this medicine. Your cholesterol and triglyceride levels will need to be checked before you start 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.
  • If you 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.
  • Consult your doctor if you experience sudden stomach or abdominal pain, nausea or vomiting while taking this medicine, as this may be due to inflammation of the pancreas (pancreatitis), which must be treated.

Use with caution in

  • Severely decreased kidney function.
  • Liver disorders.
  • Hepatitis, especially chronic hepatitis B or C.
  • The blood clotting disorder haemophilia (this medicine may increase the risk of bleeding in haemophilia).
  • High levels of cholesterol in the blood (hypercholesterolaemia).
  • High levels of fats called triglycerides in the blood (hypertriglyceridaemia).
  • History of disorders involving the amount of fats (lipids) in the blood.
  • History of inflammation of the pancreas (pancreatitis).
  • Diabetes.
  • Heart disease or abnormal heart rhythms.

Kaletra oral solution contains propylene glycol, alcohol, fructose and potassium and as a result should be used with caution in:

  • People of Asian origin.
  • Children.
  • Alcoholism.
  • Epilepsy.
  • Brain damage or disease.
  • Hereditary fructose intolerance.
  • People on a low potassium diet.

Not to be used in

  • Children under two years of age.
  • Severely decreased liver function.

Kaletra oral solution contains propylene glycol and as a result should not be used in:

  • Pregnant women.
  • Liver failure.
  • Kidney failure.

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. It is not recommended for use in pregnancy unless considered essential by your doctor. Seek medical advice from your doctor.
  • It is recommended that women infected with the HIV virus must not breastfeed their infants under any circumstances, in order to avoid transmission of the virus to the baby. Seek medical advice from your doctor.

Label warnings

  • Kaletra oral solution should be taken with food. Kaletra tablets can be taken with or without food.

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.

  • Disturbances of the gut such as diarrhoea, nausea, vomiting, indigestion, abdominal pain, flatulence or constipation.
  • Headache.
  • Difficulty in sleeping (insomnia).
  • Weakness or loss of strength (asthenia).
  • Increase in the level of cholesterol and triglycerides in the blood.
  • High blood glucose level (hyperglycaemia).
  • Redistribution of body fat, eg decreased fat under the skin, increased fat on the abdomen, 'buffalo humps' and breast enlargement.
  • Skin reactions such as rash, itching, hair loss, acne, dry skin, sweating.
  • Changes in appetite or weight.
  • Abnormal dreams.
  • Mood swings.
  • Anxiety.
  • Confusion.
  • Dizziness.
  • Memory loss.
  • Muscle or nerve problems.
  • Pain in the muscle or joints.
  • Visual disturbances.
  • Sensation of ringing, or other noise in the ears (tinnitus).
  • Impotence and abnormal ejaculation.
  • Shortness of breath (dyspnoea).
  • Increased blood pressure.
  • Palpitations.
  • Inflammation of veins.
  • Inflammation of the pancreas (pancreatitis).
  • Liver disorders.
  • Kidney stones.

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 taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Likewise, always check with your doctor or pharmacist before taking any other medicines during treatment with this one so that they can ensure that the combination is safe.

Kaletra must not be taken in combination with any of the following medicines, because it could increase the blood levels of these medicines and result in serious side effects:

  • amiodarone
  • astemizole
  • cisapride
  • dihydroergotamine
  • ergotamine
  • midazolam
  • pimozide
  • terfenadine
  • triazolam
  • vardenafil.

Kaletra must also not be taken in combination with the following medicines, because these could decrease the blood level of lopinavir and so make Kaletra less effective at treating HIV infection:

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

As Kaletra oral solution contains alcohol, it should not be taken with the following medicines, as the alcohol content may cause reactions such as facial flushing, throbbing headache, palpitations, increased heart rate and nausea and vomiting:

  • disulfiram
  • metronidazole.

Your doctor may need to adjust the doses of other anti-HIV medicines you are already taking when Kaletra is added to your treatment.

If you are taking didanosine as part of your anti-HIV therapy, it is recommended that you take your didanosine at least one hour before or two hours after taking Kaletra with food. This is because didanosine must be taken on an empty stomach. If you are taking Kaletra tablets (which can be taken on an empty stomach) you can take them at the same time as didanosine.

Kaletra may increase the blood level of cholesterol-lowering medicines known as statins. Simvastatin and lovastatin are not recommended for use in combination with Kaletra, as the increased blood levels may lead to side effects on the muscles. If atorvastatin is used with Kaletra it should be at the lowest possible dose. If cholesterol-lowering treatment is needed, the recommended statins are fluvastatin or pravastatin, as the blood levels of these are not affected by Kaletra.

Kaletra increases the blood levels of sildenafil (Viagra) and tadalafil (Cialis) used for treating erectile dysfunction. This increases the risk of side effects such as dizziness, fainting, visual disturbances and prolonged erection caused by these medicines. These medicines should be used with extreme caution in people taking Kaletra.

Kaletra also increases the blood level of the corticosteroids fluticasone and 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 Kaletra is not recommended, unless the benefits are thought to outweigh the potential risks.

Kaletra may also increase the blood levels of the following medicines. Since this may increase the risk of their side effects, people taking any of these in combination with Kaletra may need extra monitoring by their doctor:

  • bepridil
  • calcium channel blockers such as felodipine, nifedipine and nicardipine
  • ciclosporin
  • clarithromycin
  • digoxin
  • itraconazole (high doses of more than 200mg per day are not recommended in combination with Kaletra)
  • ketoconazole (high doses of more than 200mg per day are not recommended in combination with Kaletra)
  • lidocaine
  • quinidine
  • rifabutin
  • sirolimus
  • tacrolimus
  • trazodone
  • vinblastine
  • vincristine.

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

Kaletra may lower the blood level of methadone. The manufacturer recommends that people taking methadone with this medicine should have their methadone blood levels monitored.

The ritonavir in Kaletra may lower the blood level of the antifungal medicine voriconazole, making it less effective at treating infection. As a result, voriconazole should be avoided where possible in people taking Kaletra.

The following medicines may decrease the blood level of lopinavir from Kaletra. If you are taking any of these, your doctor may need to prescribe you a larger dose of Kaletra:

  • carbamazepine
  • dexamethasone
  • phenobarbital
  • phenytoin (Kaletra may also decrease the blood level of phenytoin).

There may be an increased risk of abnormal heart rhythms (seen as a 'prolonged QT interval' on an ECG) if Kaletra is taken in combination with the following medicines:

  • clarithromycin
  • chlorphenamine
  • erythromycin
  • medicines to treat abnormal heartbeats (antiarrhythmics), eg quinidine, procainamide, sotalol.

Kaletra may reduce the effectiveness of hormonal contraceptives containing ethinylestradiol. For this reason, an additional or alternative method of contraception should be used to prevent pregnancy. A barrier method of contraception, such as condoms, will prevent pregnancy, as well as preventing transmission of the HIV virus. Discuss this with your doctor.

Other medicines containing the same active ingredients

There are currently no other medicines available in the UK that contain lopinavir and ritonavir as the active ingredients.