Norvir 100 mg film-coated tablets

Norvir is a protease inhibitor used to control HIV infection. Norvir is used in combination with other anti-HIV medicines (antiretrovirals) to control your HIV infection. Your doctor will discuss with you the best combination of medicines for you.

Norvir can be used at full dose on its own, or at lower doses (called booster doses) with other medicines.

Do not take Norvir

• if you are allergic (hypersensitive) to ritonavir or any of the other ingredients of Norvir (see section 6).
• if you have severe liver disease.
• if you are currently taking any of the following medicines:
• astemizole or terfenadine (commonly used to treat allergy symptoms ? these medicines may be available without prescription);
• amiodarone, bepridil, encainide, flecainide, propafenone, quinidine (used to correct irregular heartbeats);
• dihydroergotamine, ergotamine (used to treat migraine headache);
• ergonovine, methylergonovine (used to stop excessive bleeding that may occur following childbirth or an abortion);
• clorazepate, diazepam, estazolam, flurazepam, triazolam or oral (taken by mouth) midazolam (used to help you sleep and/or relieve anxiety);
• clozapine, pimozide, (used to treat abnormal thoughts or feelings);
• pethidine, piroxicam, propoxyphene (used to relieve pain);
• cisapride (used to relieve certain stomach problems);
• rifabutin (used to prevent/treat certain infections)*;
• voriconazole (used to treat fungal infections)*;
• simvastatin, lovastatin (used to lower blood cholesterol);
• alfuzosin (used to treat enlarged prostate gland);
• fusidic acid (used to treat bacterial infections);
• sildenafil if you suffer from a lung disease called pulmonary arterial hypertension that makes breathing difficult. Patients without this disease may use sildenafil for impotence (erectile dysfunction) under their doctor?s supervision (see the section on Taking other medicines);
• products containing St John?s wort ( Hypericum perforatum) as this may stop Norvir from working properly. St John?s wort is often used in herbal medicines that you can buy yourself.

* Your doctor may decide that you can take rifabutin and/or voriconazole with a booster (lower dose) of Norvir but a full dose of Norvir must not be taken together with these two medicines.

If you are currently taking any of these medicines, ask your doctor about switching to a different medicine while you are taking Norvir. Often, there are other medicines you can take instead.

Also read the list of medicines other ?Taking other medicines? for use with certain other medicines which require special care.

Take special care with Norvir

Important information

• If Norvir is taken in combination with other antiretroviral medicines, it is important that you also carefully read the leaflets that are provided with these other medicines. There may be additional information in those leaflets about situations when Norvir should be avoided. If you have any further questions about Norvir (ritonavir) or the other medicines prescribed, please ask your doctor or pharmacist.
• Norvir is not a cure for HIV infection or AIDS.
• People taking Norvir may still develop infections or other illnesses associated with HIV infection or AIDS. It is therefore important that you remain under the supervision of your doctor while taking Norvir.
• Norvir does not lower the risk of passing HIV to others. Appropriate precautions should be taken to prevent passing the disease through sexual contact (e.g. use of a condom) or blood contamination (you should not give blood or share needles).

Tell your doctor if you have/had:

• A history of liver disease.
• Hepatitis B or C and are being treated with a combination of antiretroviral agents, as you are at a greater risk of a severe and potentially life threatening reaction because of the effect on the liver. Regular blood tests may be required to check your liver is working properly.
• Haemophilia, as there have been reports of increased bleeding in patients with haemophilia who are taking this type of medicine (protease inhibitors). The reason for this is not known. You may need additional medicine to help your blood clot (factor VIII), in order to control any bleeding.
• Erectile Dysfunction, as the medicines used to treat erectile dysfunction can cause hypotension and prolonged erection.
• Diabetes, as there have been reports of worsening of or the development of diabetes (diabetes mellitus) in some patients taking protease inhibitors.
• Kidney (renal) disease, since your doctor may need to check the dose of your other medicines (such as protease inhibitors).

Tell your doctor if you experience:

• Changes in the distribution of the fat on your body, or a build up or loss of body fat (see section 4. Possible side effects).
• Diarrhoeaorvomiting that is not improving (persistent), as this may reduce how well the medicines you are taking work.
• Feeling sick (nausea), vomiting or have stomach pain, because these may be signs of inflammation of the pancreas (pancreatitis). Some patients taking Norvir can develop serious problems with their pancreas. Tell your doctor as soon as possible if this applies to you.
• Symptoms of infection ? inform your doctor immediately. Some patients with advanced HIV infection (AIDS) who then start anti-HIV treatment may develop the symptoms of infections they have had in the past even if they didn?t know they had had them. It is believed that this happens because the body's immune response improves and helps the body to fight these infections.
• Joint stiffness, aches and pains (especially of the hip, knee and shoulder) and difficulty moving, tell your doctor, as this may be a sign of a problem that can destroy bone (osteonecrosis). Some patients taking a number of antiretroviral medicines may develop this disease.
• Muscle pain, tenderness or weakness, particularly in combination with antiretroviral therapy including protease inhibitors and nucleoside analogues. On rare occasions these muscle disorders have been serious. (See section 4 Possible side effects)
• Dizziness, lightheadedness, fainting spells or abnormal heartbeat. Some patients taking Norvir may experiences changes in the electrocardiogram (ECG) Tell your doctor if you have a heart defect or conduction defect.
• if you have any other health concerns, discuss these with your doctor as soon as you can.

Norvir is not recommended in children below 2 years of age.

Taking other medicines

There are some medicines you cannot take at all with Norvir. These are listed earlier in Section 2, under ?Do not take Norvir?. There are some other medicines that can only be used under certain circumstances as described below. Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

The following warnings apply when Norvir is taken as a full dose. However, these warnings may also apply when Norvir is used in lower doses (a booster) with other medicines.

Tell your doctor if you are taking any of the medicines listed below, as special care should be taken.

• Sildenafil, tadalafil, vardenafil for impotence (erectile dysfunction). The dose and/or frequency of use of these medicines may need to be reduced to avoid hypotension and prolonged erection. You must not take Norvir with sildenafil if you suffer from pulmonary arterial hypertension (see also section 2. Before you take Norvir).
• Digoxin (heart medicine). Your doctor may need to adjust the dose of digoxin and monitor you while you are taking digoxin and Norvir in order to avoid heart problems.
• Hormonal contraceptives containing ethinyl oestradiol as Norvir may reduce the effectiveness of these medicines. It is recommended that a condom or other non-hormonal method of contraception is used instead. You may also notice irregular uterine bleeding if you are taking this type of hormonal contraceptive with Norvir.
• Atorvastatin or rosuvastatin (for high cholesterol) as Norvir may raise the blood levels of these medicines. Talk to your doctor before you take any cholesterol-reducing medicines with Norvir (see also ? Do not take Norvir? above).
• Steriods (eg dexamethasone, fluticasone propionate, prednisolone) as Norvir may raise the blood levels of these medicines which may lead to Cushing?s syndrome (development of a rounded face) and reduce production of the hormone cortisol. Your doctor may wish to reduce the steroid dose or monitor your side effects more closely.
• Trazodone (a medicine for depression) as, unwanted effects like nausea, dizziness, low blood pressure and fainting can occur when taken with Norvir.
• Rifampicin and saquinavir (used for tuberculosis and HIV, respectively) as serious liver damage can occur when taken with Norvir.

There are medicines that may not mix with Norvir because their effects could increase or decrease when taken together. In some cases your doctor may need to perform certain tests, change the dose or monitor you regularly. This is why you should tell your doctor if you are taking any medicines, including those you have bought yourself or herbal products, but it is especially important to mention these:

• amphetamine or amphetamine derivatives;
• antibiotics (eg erythromycin, clarithromycin);
• anticancer treatments (eg vincristine, vinblastine);
• antidepressants (eg amitriptyline, desipramine, fluoxetine, imipramine, nortriptyline, paroxetine, sertraline, trazodone);
• antifungals (eg ketoconazole, itraconazole);
• antihistamines (eg loratidine, fexofenadine);
• antiretroviral medicines including HIV-protease inhibitors and Non-nucleoside reverse transcriptase inhibitors( NNRTI);
• anxiety medicine, buspirone;
• asthma medicine, theophylline, salmeterol
• atovaquone, a medicine used to treat a certain type of pneumonia and malaria;
• buprenorphine, a medicine used for the treatment of chronic pain;
• bupropion, a medicine used to help you stop smoking;
• epilepsy medicines (eg carbamazepine, divalproex, lamotrigine, phenytoin);
• heart medicines (eg digoxin, disopyramide, mexiletine and calcium channel antagonists such as amlodipine, diltiazem and nifedipine);
• immune system (eg cyclosporine, tacrolimus, everolimus);
• morphine and morphine-like medicines used to treat severe pain (eg methadone, fentanyl);
• sleeping pills (eg alprazolam, zolpidem) and also midazolam administered by injection;
• tranquillisers (eg haloperidol, risperidone, thioridazine);
• warfarin, that thins the blood.

There are some medicines you cannot take at all with Norvir. These are listed earlier in section 2, under ?Do not take Norvir?.

Taking Norvir with food and drink

Norvir tablets should be taken with food.

Pregnancy and breast-feeding

If you think you are pregnant or you are planning to become pregnant, it is very important that you discuss this with your doctor.

There is very little information on the use of ritonavir (the active ingredient in Norvir) during pregnancy. In general, the pregnant mothers received ritonavir after the first three months of pregnancy at a lower dose (booster) along with other protease inhibitors. Norvir did not appear to increase the chance of developing birth defects compared to the general population.

It is not known if Norvir passes into breast milk. To avoid transmitting the infection, mothers with HIV should not breast feed their babies.

Driving and using machines

Norvir can cause sleepiness and dizziness. If you are affected do not drive or use machinery.

Always take Norvir exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure. It is taken by mouth usually two times every day. Norvir tablets should be taken with food as this can affect the way in which Norvir is absorbed into your body.

It is important that Norvir tablets are swallowed whole and not chewed, broken or crushed.

Recommended doses of Norvir are:

• if Norvir is used to boost the effects of certain other anti-HIV medicines the typical dose for adults is 1 to 2 tablets once or twice daily. For more detailed dose recommendations, including those for children, see the Package Leaflet of the anti-HIV medicines Norvir is given in combination with.
• if your doctor prescribes a full dose, adults may be started on a dose of 3 tablets in the morning and 3 tablets 12 hours later, gradually increasing over a period of up to 14 days to the full dose of 6 tablets twice daily (totaling 1,200mg per day). Children (2 ? 12 years of age) will start with a dose smaller than this and continue up to the maximum allowed for their size.

Your doctor will advise you on the dosage to be taken.

Like all anti-HIV medicines, Norvir should be taken every day to help control your HIV, no matter how much better you feel. If a side effect is preventing you from taking Norvir as directed, tell your doctor straight away. During episodes of diarrhoea your doctor may decide that extra monitoring is needed.

Always keep enough Norvir on hand so you don't run out. When you travel or need to stay in the hospital, make sure you have enough Norvir to last until you can get a new supply.

If you take more Norvir than you should

Numbness, tingling, or a ?pins and needles? sensation may occur if you take too much Norvir. If you realise you have taken more Norvir than you were supposed to, contact your doctor or the Accident and Emergency Department of your nearest hospital straight away.

If you forget to take Norvir

If you miss a dose, take the missed dose as soon as possible. If it is nearly time for the next dose, just take that one. Do not take a double dose to make up for a forgotten dose.

If you stop taking Norvir

Even if you feel better, do not stop taking Norvir without talking to your doctor. Taking Norvir as recommended should give you the best chance of delaying resistance to the medicines.

Like all medicines, Norvir can cause side effects, although not everybody gets them. Also, the side effects of Norvir when used with other antiretroviral medicines are dependent on the other medicines. So it is important that you carefully read the side effects section of the leaflets that are provided with these other medicines.

The frequency of possible side effects listed below is defined using the following convention:

very common common uncommon rare very rare not known affects more than 1 user in 10 affects 1 to 10 users in 100 affects 1 to 10 users in 1,000 affects 1 to 10 users in 10,000 affects less than 1 user in 10,000 frequency cannot be estimated from the available data.

Very common side effects:

• stomach ache ? a tingling sensation or numbness in
• vomiting the hands, feet or around the lips and ? diarrhoea mouth ? feeling sick (nausea) ? feeling weak/tired ? headache ? bad taste in the mouth

Common side effects:

• allergic reactions including skin ? sore throat rashes (may be red, raised, itchy), ? increased cough severe swelling of the skin and ? wind (flatulence) other tissues ? loss of appetite ? difficulty in breathing ? dry mouth ? flushing of the skin (vasodilation) ? belching ? changes in fat distribution (see ? mouth ulcer Side effects associated with ? sweating combination antiretroviral ? muscle aches therapy below) ? fever ? dizziness ? pain ? inability to sleep (insomnia) ? weight loss ? anxiety ? laboratory test results: ? sleepiness changes in blood test results ? numbness (such as blood chemistry and ? unusual sensitivity of the skin blood count)
• heartburn

Uncommon side effects:

• dehydration (thirst) ? hepatitis (inflammation of the liver)
• diabetes ? laboratory test results:
• jaundice (yellowing of the skin changes in blood test results (such or whites of eyes as blood chemistry and blood count)
• muscle pain, tenderness or weakness

Rare side effects:

• severe or life threatening skin ? serious allergic reaction (anaphylaxis) reaction including blisters ? high levels of sugar in the blood (Stevens Johnson syndrome)

Other side effects that have been reported with Norvir: low levels of blood platelets, kidney failure, seizures (fits), fainting and feeling faint when getting up, abnormally heavy periods. It is not known how frequently these effects may occur.

Tell your doctor if you fee sick (nauseous), are vomiting, or have stomach pain, because these may be signs of an inflamed pancreas. Also tell your doctor if you experience joint stiffness, aches and pains (especially of the hip, knee and shoulder) and difficulty moving, as this may be a sign of osteonecrosis. See also section 2 Before you take Norvir.

Side effects associated with combination antiretroviral therapy may cause changes in body shape due to changes in fat distribution. These may include loss of fat from legs, arms and face, increased fat in the abdomen (belly) and internal organs, breast enlargement and fatty lumps on the back of the neck ("buffalo hump"). The cause and long-term health effects of these conditions are not known. Combination antiretroviral therapy may also cause raised lactic acid and sugar in the blood, increased fats in the blood and resistance to insulin (insulin will not work as effectively).

In patients with haemophilia type A and B, there have been reports of increased bleeding while taking this treatment or another protease inhibitor. Should this happen to you, seek immediate advice from your doctor.

Cases of diabetes mellitus or increased blood sugars have been reported in patients receiving Norvir or other protease inhibitors.

Abnormal liver function tests, hepatitis (inflammation of the liver), and rarely jaundice, have been reported in patients taking Norvir. Some people had other illnesses or were taking other medicines. People with liver disease or hepatitis may have worsening of liver disease.

There have been reports of muscle pain, tenderness or weakness, particularly when taking medicines to lower cholesterol in combination with antiretroviral therapy, including protease inhibitors and nucleoside analogues. On rare occasions these muscle disorders have been serious (rhabdomyolysis). In the event of unexplained or continual muscle pain, tenderness, weakness or cramps, stop taking the medicine, contact your doctor as soon as possible or go to the Accident and Emergency Department of your nearest hospital.

Inform your doctor as soon as possible if you experience any symptoms that suggest an allergic reaction after taking Norvir such as rash, hives or breathing difficulties.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, contact your doctor, pharmacist, Accident and Emergency department or if it is urgent get immediate medical help.

Keep out of the reach and sight of children.

Do not use Norvir after the expiry date on the label. The expiry date refers to the last day of that month.

This medicinal product does not require any special temperature storage conditions. Store in the original bottle in order to protect from moisture.

What Norvir contains

• The active substance is ritonavir. Each film-coated tablet contains 100 mg ritonavir.
• The other tablet ingredients are: copovidone, sorbitan laurate, anhydrous calcium hydrogen phosphate, colloidal anhydrous silica, sodium stearyl fumarate.
• The tablet coating is composed of: hypromellose, titanium dioxide, macrogols, hydroxypropyl cellulose, talc, colloidal anhydrous silica, polysorbate 80.

What Norvir looks like and contents of the pack

Norvir film-coated tablets are white debossed with [Abbott logo] and the code ?NK?.

Three pack sizes are available for Norvir tablets:

• 1 bottle of 30 tablets
• 1 bottle of 60 tablets
• 3 bottles of 30 tablets (90 tablets)

Not all pack sizes may be marketed.

Norvir is also supplied as an oral solution containing 80 mg/ml of ritonavir and a soft gel capsule containing 100 mg ritonavir.

Marketing Authorisation Holder

Abbott Laboratories Limited
Abbott House,
Vanwall Business Park,
Vanwall Road,
Maidenhead,
Berkshire,
SL6 4XE
United Kingdom

Manufacturers

Abbott GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

BelgiëBelgiqueBelgien Abbott SA TélTel 32 10 475311 LuxembourgLuxemburg Abbott SA TélTel 32 10 475311

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eská republika Abbott Laboratories s. r. o. Tel 420 267 292 111 Malta V.J.Salomone Pharma Limited Tel 356 22983201

Danmark Abbott Laboratories AS Tlf 45 39 77-00-00 Nederland Abbott B.V. Tel 31 0 88 8222 688

Deutschland Abbott GmbH Co. KG Tel 49 0 6122 58-0 Norge Abbott Norge AS Tlf 47 81 55 99 20

Eesti Abbott Laboratories Baltics Tel 371 67605580 Österreich Abbott Ges.m.b.H. Tel 43 1 891-22

Abbott Laboratories .... 30 21 0 9985-222 Polska Abbott Laboratories Poland Sp. z o.o. tel 48 22 319 12 00

España Abbott Laboratories, S.A. Tel 34 9 1 337-5200 Portugal Abbott Laboratórios, Lda. Tel 351 0 21 472 7100

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Lifepharma ZAM Ltd 357 22 347440 Sverige Abbott Scandinavia AB Tel 46 0 8 5465 67 00

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Lietuva

Abbott Laboratories Baltics
Tel: + 371 67605580

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