How does it work?

Prezista tablets contain the active ingredient darunavir, whichis a type of medicine called a protease inhibitor. It is used in the treatmentof HIV (human immunodeficiency virus) infection.

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

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

There is no cure for HIV, but darunavir is one of a number ofmedicines that lowers the amount of virus in the body (viral load) and slowsthe progression of the disease from HIV to AIDS.

Darunavir MUST BE used together with another anti-HIV medicinecalledritonavir(Norvir). A low-dose of ritonavir increases the amount of darunavir inthe blood and is used to boost the effect of the darunavir, rather than to haveany effect on the virus itself. This combination is used in conjunction withother anti-HIV drugs that attack the HIV virus in different ways. This helpsprevent the virus becoming resistant to the medicine.

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

What is it used for?

• HIV infection.

Warning!

• Your Prezista tablets 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 make sure 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.
• If you forget to take a dose of this medicine and it is less than six hours late, you should take that dose with food as soon as possible and then take your next dose at the normal time. If you are more than six hours late taking a dose, you should not take the missed dose and continue taking your tablets at the normal time.
• 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 advanced HIV and a history of opportunistic infections such as pneumocystis carinii pneumonia (PCP), severe fungal infections 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.
• 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 get a skin rash while taking this medicine you should consult your doctor.

Use with caution in

• People over 65 years of age.
• Mild to moderately decreased liver function.
• Hepatitis, particularly chronic hepatitis B or C.
• People with an allergy to any sulphonamide medicines.
• People with the blood clotting disorder haemophilia (this medicine may increase the risk of bleeding in haemophilia).
• Diabetes.

Not to be used in

• Severely decreased liver function.
• This medicine is not recommended for children aged under six years or weighing less than 20kg.

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 an allergy.

If you feel you have experienced an allergic reaction, stopusing this medicine and inform your doctor 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 for use during pregnancy has not been established. It is not recommended for use in pregnancy unless the potential benefit outweighs any risks to the developing foetus. Seek medical advice from your doctor.
• It is recommended that women infected with the HIV virus should not breastfeed their infants under any circumstances, and regardless of their treatment, in order to avoid passing the virus to the baby via their breast milk. Seek further medical advice from your doctor.

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 thator any side effect.

• Disturbances of the gut, such as diarrhoea, indigestion, nausea and vomiting, abdominal pain, flatulence.
• Headache.
• Increase in the level of cholesterol and triglycerides in the blood.
• Dizziness.
• Fatigue, weakness or loss of strength (asthenia).
• Difficulty sleeping (insomnia).
• Skin reactions such as rash, itching, hair loss, acne, dry skin, sweating.
• Pins and needles or numb sensations.
• Balance problems involving the inner ear (vertigo).
• Increased blood pressure.
• Fever.
• Shortness of breath (dyspnoea).
• Dry mouth.
• Anxiety, irritability, confusion and memory problems.
• Swelling of the legs and ankles due to excess fluid retention (peripheral oedema).
• Increased blood glucose level (hyperglycaemia).
• Pain in the muscles or joints.
• Erectile dysfunction (impotence).
• Redistribution of body fat, eg decreased fat under the skin, increased fat on the abdomen, 'buffalo humps' and breast enlargement.
• Alteration in results of liver function tests.

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

For more information about any other possible risks associatedwith this medicine, please read the information provided with the medicine orconsult your doctor or 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 make sure that thecombination is safe.

As darunavir is used in combination with ritonavir, your doctoror pharmacist will also check whether any of your medicines interact withritonavir (Norvir).

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

• amiodarone
• astemizole
• bepridil
• cisapride
• ergot derivatives such as dihydroergotamine, ergotamine, ergonovine, and methylergonovine
• lidocaine given by injection
• lovastatin
• midazolam given by mouth
• pimozide
• quinidine
• sertindole
• simvastatin
• terfenadine
• triazolam.

The following medicines should not be taken in combination withdarunavir and ritonavir, as they may decrease the blood level of darunavir and thusmake it less effective against HIV:

• lopinavir/ritonavir (Kaletra)
• phenobarbital
• phenytoin
• rifampicin
• the herbal remedy St John's wort (Hypericum perforatum).

Dexamethasone may also decrease the blood level ofdarunavir from Prezista tablets. If you are taking this steroid your doctormay need to prescribe you a larger than normal dose of Prezista.

Darunavir with low-dose ritonavir is not generally recommendedfor use in combination with other protease inhibitors.

Darunavir and ritonavir increase the blood levels of thenucleoside reverse transcriptase inhibitors (NRTIs) efavirenz andtenofovir.

If you are taking Videx or Videx EC (didanosine) as part of youranti-HIV medication you should not take it within two hours of taking yourdarunavir plus ritonavir.This is because didanosine must be taken on an emptystomach, whereas darunavir plus ritonavir must be taken with food.

Darunavir and ritonavir may increase the blood level ofcholesterol-lowering medicines known as statins. Simvastatin and lovastatinmust not be used in combination with Prezista tablets, as the increased bloodlevels may lead to side effects on the muscles. If atorvastatin or pravastatinare used with Prezista tablets they should be given at the lowest possibledose.

Darunavir and ritonavir may increase the blood level of thecorticosteroids fluticasone or budesonide taken by inhaler or nasal spray. Thiscould increase the risk of systemic side effects of these steroids, such asCushing's syndrome, or decreased production of natural steroids by the adrenalglands. For this reason, the use of these corticosteroids in combination withdarunavir and ritonavir is not recommended, unless the benefits are thought tooutweigh the potential risks.

Darunavir with ritonavir may increase the blood levels of thefollowing medicines for erectile dysfunction (impotence) and so may increasethe risk of side effects such as fainting, visual disturbances and prolongederection from these medicines:

• sildenafil (if you are taking Prezista you should not take more than 25mg sildenafil in any 24 hour period)
• tadalafil (if you are taking Prezista you should not take more than 10mg tadalafil in any 72 hour period)
• vardenafil (if you are taking Prezista you should not take more than 2.5mg vardenafil in any 72 hour period).

Darunavir and ritonavir may also increase the blood levels ofthe following medicines. Since this may increase the risk of their sideeffects, people taking any of these in combination with darunavir and ritonavirmay need extra monitoring by their doctor:

• calcium channel blockers such as felodipine, nifedipine and nicardipine
• carbamazepine
• ciclosporin
• clarithromycin
• digoxin
• midazolam given by injection
• itraconazole (high doses of more than 200mg per day are not recommended in combination with Prezista)
• ketoconazole (high doses of more than 200mg per day are not recommended in combination with Prezista)
• rifabutin (rifabutin may also decrease the blood level of darunavir)
• sirolimus
• tacrolimus.

Oestrogen-containing oral contraceptives (eg the pill) may beless effective in women who are taking darunavir and ritonavir. For thisreason, women using oestrogen-containing oral contraceptives should use anextra method of contraception to prevent pregnancy, or use a different methodof contraception altogether, for example condoms. Condoms should also be usedas a regular safe sex practice, to prevent transmitting HIV to your sexualpartner. Ask your doctor for advice. Oestrogen-based hormone replacementtherapy (HRT) may also be less effective in women taking darunavir andritonavir.

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

Darunavir and ritonavir may lower the blood level of methadone.The manufacturer recommends that people taking methadone for long periods oftime in combination with this medicine should be monitored to make sure thattheir methadone dose is adequate.

Darunavir may decrease the blood levels of SSRI antidepressantssuch as paroxetine and sertraline. If you are taking an SSRI antidepressantwhen you start treatment with darunavir you should let your doctor know if youthink your antidepressant is becoming less effective.

Darunavir with ritonavir may affect the blood level of theanti-blood-clotting (anticoagulant) medicine, warfarin. If you are takingwarfarin with this medicine, your blood-clotting time (INR) should bemonitored.

Other medicines containing the same active ingredient

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