How does it work?

Norvir capsules and solution contain the active ingredientritonavir, which is a type of medicine called a protease inhibitor. It is usedin the treatment of HIV (human immunodeficiency virus) infection.

AIDS (acquired immune deficiency syndrome) is caused byinfection with HIV. This virus invades cells of the immune system, particularlythe white blood cells known as CD4 T-helper lymphocytes. These cells normallywork to activate other cells in the immune system to fight infection. Since HIVkills CD4 T-helper cells, over time the body becomes less able to fight thevirus or subsequent infections.

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

There is no cure for HIV, but ritonavir is one of a number ofmedications that lowers the amount of virus in the body (viral load) and slowsthe progression of the disease from HIV to AIDS. Ritonavir is used inconjunction with other anti-HIV drugs that attack the HIV virus in differentways. This helps prevent the virus becoming resistant to themedicine.

Ritonavir is also used in low doses to boost the effect of otherprotease inhibitors, such as amprenavir and saquinavir. This is becauseritonavir slows the breakdown of these protease inhibitors by the liver and soreduces the doses that are needed. The low doses of ritonavir that are used forthis purpose are too small to have any anti-HIV effect themselves.

What is it used for?

• HIV infection.
• Low doses used to boost the effect of other protease inhibitors, eg saquinavir, amprenavir, indinavir.

Warning!

• Norvir capsules contain 12% alcohol. The oral solution contains 43% alcohol.
• Norvir capsules and solution should be taken with or after food.
• The bitter aftertaste of the oral solution can be masked by mixing with chocolate milk. Do not mix with water - make sure the measuring cup provided is dry before taking a dose of the solution.
• This medicine may make you feel sleepy or dizzy. You should take care when performing potentially hazardous activites, such as driving or operating machinery, until you know how this medicine affects you and are sure you can perform such activities safely.
• 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 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.
• 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.
• If you have any problems with your kidneys, your kidney function should be regularly monitored while you are taking this medicine.

Use with caution in

• 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).
• Diabetes.
• Hereditary blood disorders known as porphyrias.

Not to be used in

• Decompensated liver disease.
• Norvir is not recommended for children under two years of age, as the manufacturer has not studied its safety and efficacy in this age group.

This medicine should not be used if you are allergic to one orany of its ingredients. Please inform your doctor or pharmacist if you havepreviously experienced such anallergy.If you feel you haveexperienced an allergic reaction, stop using this medicine and inform yourdoctor or pharmacist immediately.

Pregnancy and breastfeeding

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

• The safety of this medicine in pregnancy has not been established. It should therefore be used with caution during pregnancy, and only if the benefits to the mother outweigh any risks to the foetus. 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

• Take this medication with or after food.

Side effects

Medicines and their possible side effects can affect individualpeople in different ways. The following are some of the side effects that areknown to be associated with this medicine. Just because a side effect is statedhere does not mean that all people using this medicine will experience that orany side effect.

• Disturbances of the gut such as nausea, vomiting, diarrhoea or abdominal pain.
• Headache.
• Weakness or loss of strength (asthenia).
• Alteration in taste.
• A tingling sensation or numbness in the hands, feet or around the lips or mouth.
• Dizziness.
• Sleepiness (somnolence).
• Difficulty sleeping (insomnia).
• Anxiety.
• Throat irritation.
• Widening of blood vessels (vasodilatation).
• Loss of appetite.
• Mouth ulcers.
• Rash, itching or sweating.
• Pain in the muscles (myalgia).
• Low blood pressure and fainting.
• Blood disorders.
• Redistribution of body fat, eg decreased fat under the skin, increased fat on the abdomen, 'buffalo humps' and breast enlargement.
• High blood glucose level (hyperglycaemia).
• Increase in the level of fats eg cholesterol in the blood (hyperlipidaemia).
• Inflammation of the pancreas (pancreatitis).
• Muscle breakdown (rhabdomyolysis).
• Liver disorders.

The side effects listed above may not include all of the sideeffects reported by the drug'smanufacturer.For moreinformation about any other possible risks associated with this medicine,please read the information provided with the medicine or consult your doctoror pharmacist.

How can this medicine affect other medicines?

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

The following medicines must not be used in combination withritonavir, as ritonavir may increase their blood levels and subsequentlyincrease the risk of serious side effects:

• alfuzosin
• amiodarone
• astemizole
• bepridil
• bupropion
• cisapride
• clozapine
• dextropropoxyphene
• dihydroergotamine
• encainide
• ergotamine
• flecainide
• fusidic acid
• lovastatin
• pethidine
• pimozide
• piroxicam
• propafenone
• quinidine
• rifabutin
• simvastatin
• terfenadine
• the sedatives clorazepate, diazepam, estazolam, flurazepam, midazolam taken by mouth and triazolam.

You should not take the herbal remedy St John's wort (Hypericumperforatum) with this medicine, as it may decrease the blood level of ritonavirand make it less effective.

As Norvir capsules and oral solution contain alcohol, theyshould not be taken with the following, as the alcohol content may causereactions such as facial flushing, throbbing headache, palpitations, increasedheart rate and nausea and vomiting:

• disulfiram
• metronidazole.

Ritonavir may increase the blood level of cholesterol-loweringmedicines known as statins. Simvastatin and lovastatin should not be used incombination with ritonavir, as the increased blood levels may lead to sideeffects on the muscles. If cholesterol-lowering treatment is needed,fluvastatin or pravastatin are recommended.

Ritonavir may increase the blood levels of the followingmedicines used for erectile dysfunction, which may increase the risk of sideeffects such as fainting, visual disturbances and prolongederection:

• sildenafil (Viagra) (Not recommended in combination with ritonavir. If used, do not take more than 25mg sildenafil in 48 hours.)
• vardenafil (Levitra) (Do not take more than 2.5 mg in 72 hours while taking ritonavir.)
• tadalafil (Cialis) (Do not take more than 10 mg in 72 hours while taking ritonavir.)

Ritonavir also increases the blood level of the corticosteroidsfluticasone and budesonide taken by inhaler or nasal spray. This could increasethe risk of systemic side effects of these steroids, such as Cushing'ssyndrome, or decreased production of natural steroids by the adrenal glands.For this reason, the use of these corticosteroids in combination with ritonaviris not recommended, unless the benefits are thought to outweigh the potentialrisks.

Ritonavir may also increase the blood levels of the followingmedicines. Since this may increase the risk of their side effects, peopletaking any of these in combination with ritonavir may need extra monitoring bytheir doctor:

• alprazolam
• amphetamine and amphetamine derivatives
• antifungals, eg itraconazole, ketoconazole
• macrolide-type antibiotics, eg erythromycin, clarithromycin
• antipsychotics, eg haloperidol, risperidone, thioridazine
• tricyclic antidepressants, eg desipramine, amitriptyline, imipramine, nortriptyline
• other antidepressants, eg fluoxetine, paroxetine, sertraline, trazodone
• various corticosteroids, eg dexamethasone, prednisolone
• immunosuppressants, eg ciclosporin, tacrolimus
• other HIV protease inhibitors, eg saquinavir, indinavir, nelfinavir
• non-sedating antihistamines, eg loratidine
• buspirone
• digoxin
• calcium channel blockers, eg verapamil
• opioid analgesics, eg fentanyl
• carbamazepine
• tolbutamide
• midazolam given by injection
• zolpidem.

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.

If ritonavir is taken with efavirenz, blood levels of bothmedicines may be increased, with an increased risk of side effects.

Delavirdine may increase the blood level of ritonavir and peopletaking this combination may need a lower dose of ritonavir.

Ritonavir may reduce the effectiveness of hormonalcontraceptives containing ethinylestradiol. For this reason, a higher dose ofthese contraceptives may be needed to prevent pregnancy. Alternatively, othermethods of contraception could be used. A barrier method of contraception, suchas condoms, will prevent pregnancy, as well as preventing transmission of theHIV virus. Discuss this with your doctor.

Voriconazole should not be taken in combination with ritonavir(400 mg twice daily or more), because ritonavir decreases the blood level ofvoriconazole and makes it less effective at treating infection.

Ritonavir may also decrease the blood level of the followingmedicines. If you are taking these with ritonavir your doctor may thereforeneed to increase their dose:

• theophylline
• methadone.

There may be an increased risk of irregular heartbeats orneurological side effects if ritonavir is taken with the following:

• disopyramide
• fluoxetine
• mexiletine
• nefazadone.

The antibiotic rifampicin should not be given to people who aretaking ritonavir in combination with saquinavir, because the combination ofthese three medicines can cause severe liver problems.

Other medicines containing the same active ingredient

There are currently no other medicines available in the UK thatcontain ritonavir as the sole active ingredient.