What is it and how is it used?

Invirase is an antiviral agent. It is a member of a class of medicines called protease inhibitors. It is for the treatment of infection with the human immunodeficiency virus (HIV).

Invirase is used by HIV-infected individuals over 16 years of age. Invirase is prescribed for use in combination with ritonavir and other antiretroviral medicines.

Table of Contents
What do you have to consider before using it?
How is it used?
What are possible side effects?
How should it be stored?
Further information

What do you have to consider before using it?

Do not take Invirase

- if you are allergic (hypersensitive) to saquinavir, ritonavir or any of the other ingredients (see section ?Important information about an ingredient of Invirase? and section ?What Invirase contains?).
- if you were born with or have

  • any condition with certain abnormal electrocardiogram (ECG, electrical recording of the heart) changes,
  • a salt imbalance in the blood, especially low concentrations of potassium in the blood (hypokalaemia) which are currently not corrected by treatment,
  • a very slow heart rate (bradycardia),
  • a weak heart (heart failure), or
  • a history of abnormal heart rhythms (arrhythmias) - if you are taking other medicines that result in certain abnormal ECG changes:
  • certain HIV antiviral agents (e.g. atazanavir, lopinavir),
  • certain heart medicines (amiodarone, bepridil, dofetilide, flecainide, hydroquinidine, ibutilide, lidocaine, propafenone, quinidine, sotalol),
  • medicines to treat depression (amitryptiline, imipramine, trazodone),
  • medicines used to treat severe mental disorders (e.g. clozapine, haloperidol, mesoridazine, phenothiazines, sertindole, sultopride, thioridazine, ziprasidone),
  • certain anti-infectives (e.g. clarithromycin, erythromycin, halofantrine, pentamidine, sparfloxacin)
  • certain narcotic analgesics (e.g. methadone),
  • medicines used to treat erectile dysfunction (sildenafil, vardenafil, tadalafil),
  • some other medicines (alfentanyl, cisapride, dapsone, diphemanil, disopyramide, fentanyl, mizolastine, quinine, vincamine) - if you have liver disease with severe disease symptoms (e.g. jaundice or hepatitis with liquid accumulation in the belly, mental confusion and/or bleeding from veins of the oesophagus). - if you are currently taking any of the following medicines:
  • terfenadine and astemizole (commonly used to treat allergy symptoms),
  • pimozide (for psychiatric problems),
  • ergot alkaloids (used to treat migraine attacks),
  • triazolam and oral (taken by mouth) midazolam (used to help you sleep and/or relieve anxiety),
  • rifampicin (used to prevent or treat tuberculosis),
  • simvastatin and lovastatin (used to lower blood cholesterol).

Take special care with Invirase

You should know that Invirase/ritonavir is not a cure for HIV infection and that you may continue to develop infections or other illnesses associated with HIV disease. You should, therefore, remain under the care of your doctor while taking Invirase/ritonavir.

Treatment with Invirase/ritonavir has not been shown to reduce the risk of transmission of HIV to others through sexual contacts or contamination with blood. Therefore, you must continue to take appropriate precautions to avoid giving the virus to others.

At present, there is only limited information on the use of Invirase/ritonavir in children under the age of 16 years and in adults over 60 years.

Abnormal heart rhythms (arrhythmias):

Invirase can change your heart?s ECG, especially if you are female or elderly. If you are taking any medicine that decreases your blood potassium levels talk to your doctor before taking Invirase. Contact your doctor immediately, if you experience palpitations or an irregular heartbeat during treatment. He/she may wish to perform an ECG to measure your heart rhythm.

Consult your doctor if you have a history of kidney disease.

Please speak with your doctor if you have a history of liver disease. Patients with chronic hepatitis B or C and treated with antiretroviral agents are at increased risk for severe and potentially fatal liver adverse events and may require blood tests for control of liver function.

There are certain conditions, which you may have, or have had, which require special care before or while taking Invirase/ritonavir. Therefore, before using this medicine, you should have told your doctor if you suffer from diabetes mellitus, diarrhoea, or if you have allergies (see section 4) or if you have an intolerance to some sugars (see section ?Important information about an ingredient of Invirase?).

In some patients with advanced HIV infection (AIDS) and a history of opportunistic infection, signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started. It is believed that these symptoms are due to an improvement in the body?s immune response, enabling the body to fight infections that may have been present with no obvious symptoms. If you notice any symptoms of infection, please inform your doctor immediately (see section 4).

Redistribution, accumulation or loss of body fat may occur in patients receiving combination antiretroviral therapy. Contact your doctor if you notice changes in body fat (see section 4).

Bone problems: Some patients taking combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue caused by loss of blood supply to the bone). The length of combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index, among others, may be some of the many risk factors for developing this disease. Signs of osteonecrosis are joint stiffness, aches and pains (especially of the hip, knee and shoulder) and difficulty in movement. If you notice any of these symptoms please inform your doctor.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Invirase/ritonavir may be taken with a number of other medications that are commonly used in HIV infection.

There are some medications that must not be taken with Invirase/ritonavir (see section "Do not take

Invirase") or that require dosage reduction of that medicine or Invirase or ritonavir. Ask your doctor or pharmacist for more information about taking Invirase/ritonavir with other medicines.

Medicines that can interact with saquinavir andor ritonavir include other HIV antiviral agents e.g. nelfinavir, indinavir, nevirapine, delavirdine, efavirenz, some medicines affecting the immune system e.g. ciclosporin, sirolimus rapamycin, tacrolimus, various steroids e.g. dexamethasone, ethinyl estradiol, fluticasone, certain heart medicines e.g. calcium channel blockers, quinidine, digoxin, medicines used to lower blood cholesterol e.g. statins, antifungals ketoconazole, itraconazole, anticonvulsants e.g. phenobarbital, phenytoin, carbamazepine, sedative agents e.g. midazolam administered by injection, certain antibiotics e.g. quinupristindalfopristin, rifabutin, medicines to treat depression e.g. nefazodone, tricyclic antidepressants, medicines for anticoagulation warfarin, herbal preparations containing St. Johns wort or garlic capsules, some medicines that treat diseases related to the acid in the stomach e.g. omeprazole or other proton pump inhibitors

Therefore you should not take Invirase/ritonavir with other medicines without your doctor?s consent.

If you are taking an oral contraceptive to prevent pregnancy, you should use an additional or different type of contraception since ritonavir may reduce the effectiveness of oral contraceptives.

Taking Invirase with food and drinkInvirase must be taken together with ritonavir and with or after food.

Pregnancy and breast-feeding

Ask your doctor or pharmacist for advice before taking any medicine. Inform your doctor if you are pregnant or planning to become pregnant. This medicine should be taken during pregnancy only after consultation with your doctor.

You should not breast-feed your baby if you are taking Invirase/ritonavir.

Driving and using machines

Invirase has not been tested for its effect on your ability to drive a car or operate machinery. However, dizziness and fatigue have been reported during treatment with Invirase. Do not drive or operate machines if you experience these symptoms.

Important information about an ingredient of Invirase
Each capsule contains lactose (anhydrous) 63.3 mg. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

How is it used?

Always take Invirase/ritonavir exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure. Invirase is provided as 200 mg capsules. Your doctor will prescribe Invirase in combination with Norvir (ritonavir) and other HIV medicines. The dosage of Invirase is five 200 mg capsules with one 100 mg capsule of Norvir (ritonavir) two times daily. If you have not received other HIV medicines before and you are taking Invirase for the first time, you should take a reduced dosage of Invirase of one 500 mg film coated tablet with one 100 mg capsule of Norvir (ritonavir) two times daily for the first week (see Package Leaflet for INVIRASE 500 mg film-coated tablets). After the first week you should continue with the standard Invirase dosage of five 200 mg capsules with one 100 mg capsule of Norvir (ritonavir) two times daily. Patients who switch immediately without pause between the treatment regimens from another protease inhibitor in combination with Norvir (ritonavir) or from a non-nucleoside reverse transcriptase inhibitor based regimen should initiate and continue with the standard recommended dosage of Invirase of five 200 mg capsules two times daily with ritonavir 100 mg two times daily. Invirase should be taken at the same time as Norvir (ritonavir) and with or after food.

The capsules should be swallowed whole together with water.

If you take more Invirase than you shouldIf you have taken more than the prescribed dose of Invirase/ritonavir you must contact your doctor or pharmacist.

If you forget to take Invirase

Do not take a double dose to make up for a forgotten individual dose. If you forget to take one dose, take this dose as soon as you remember together with some food. Then go on with the regular schedule as prescribed. Do not change the prescribed dose yourself.

If you stop taking Invirase
Continue to take this medicine until your doctor tells you otherwise.

What are possible side effects?

Like all medicines, Invirase/ritonavir can cause side effects, although not everybody gets them.

When treating HIV infection it is not always possible to differentiate between unwanted effects caused by Invirase or by any other medicines you take at the same time or by the complications of the infection. For these reasons it is very important to inform your doctor of any change in your condition.

The most frequently (in more than ten in a hundred) reported side effects of saquinavir taken with ritonavir concern the gastrointestinal tract, with feeling sick, diarrhoea, tiredness, vomiting, wind and abdominal pain being the most common. Also,changes in laboratory markers (e.g., blood or urine tests) have been reported very commonly.

Other, less frequently reported side effects ( in more than one in a hundred but less than one in ten persons), which may occur are: rash, itching, eczema and dry skin, hair loss, dry mouth, headache, peripheral neuropathy (a disturbance of the nerves in the feet and hands that may take the form of numbness, pins and needles, shooting or burning pain), co-ordination problems, fainting, confusion, weakness, dizziness, depression, anxiety, mood swings, night sweats and hot flushes, inability to sleep, libido problems, taste alteration, warts, mouth ulcers, dehydration, abdominal discomfort, indigestion, fever, pain, constipation, decreased as well as increased appetite, inflammation of gastrointestinal tract, piles, discoloured faeces, visual disturbance, eye pain, raised blood pressure, infections of the respiratory tract, muscle spasms, joint pain, blood collection in the joint, painful urination and infections of the urinary tract, fever and shivering, shortness of breath and chest pain.

Furthermore, inflammation of the liver, fits, allergic reactions, sleepiness and abnormal renal function have been reported.

Your doctor will test your blood regularly to detect possible abnormalities.

Cases of diabetes mellitus or increased blood sugar levels have been reported in patients receiving this treatment or another protease inhibitor.

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.

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 other 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 at this time. Combination antiretroviral therapy may also cause raised lactic acid and sugar in the blood, hyperlipaemia (increased fats in the blood) and resistance to insulin.

There have been reports of muscle pain, tenderness or weakness, particularly with combination antiretroviral therapy including protease inhibitors and nucleoside analogues. On rare occasions these muscle disorders have been serious (rhabdomyolysis).

If you experience any side effects that are not in this leaflet, please tell your doctor or pharmacist. Also, tell your doctor if you have any severe or unusual symptoms or if any side effect that you think you may have gets worse or persists.

How should it be stored?

Keep out of the reach and sight of children.

Store in the original container.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Further information

What Invirase contains

The active substance is saquinavir. One capsule of Invirase contains 228.7 mg of saquinavir mesilate corresponding to 200 mg saquinavir. The other ingredients are lactose anhydrous 63.3 mg, microcrystalline cellulose, povidone, sodium starch glycollate, talc and magnesium stearate. The capsule shell consists of gelatine, iron oxide black, red and yellow E172, indigocarmine E132, titanium dioxide E171, and the printing ink contains titanium dioxide E 171, shellac, soya lecithin, polydimethylsiloxane.

What Invirase looks like and contents of the pack

Invirase 200 mg hard capsules are light brown and green. Each half of the capsule shell is marked with the printing ?ROCHE? and the code ?0245?. Invirase is available in an amber glass bottle containing 270 capsules.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Roche Registration Limited,
6 Falcon Way,
Shire Park,
Welwyn Garden City,
AL7 1TW,
United Kingdom.

Manufacturer

Roche Pharma AG,
Emil-Barell-Strasse 1,
79639 Grenzach-Wyhlen,
Germany.

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

LuxembourgLuxemburg Voirsiehe BelgiqueBelgien BelgiëBelgiqueBelgien N.V. Roche S.A. TélTel 32 0 2 525 82 11

359 2 818 44 44 Magyarország Roche Magyarország Kft. Tel 36 - 23 446 800

Malta See United Kingdom eská republika Roche s. r. o. Tel 420 - 2 20382111 Danmark Roche as Tlf 45 - 36 39 99 99 Nederland Roche Nederland B.V. Tel 31 0 348 438050

Deutschland Roche Pharma AG Tel 49 0 7624 140 Norge Roche Norge AS Tlf 47 - 22 78 90 00

Eesti Roche Eesti OÜ Tel 372 - 6 177 380 Österreich Roche Austria GmbH Tel 43 0 1 27739

Roche Hellas A.E. 30 210 61 66 100 Polska Roche Polska Sp.z o.o. Tel 48 - 22 345 18 88

España Roche Farma S.A. Tel 34 - 91 324 81 00 Portugal Roche Farmacêutica Química, Lda Tel 351 - 21 425 70 00

France Roche Tél 33 0 1 46 40 50 00 România Roche România S.R.L. Tel 40 21 206 47 01

Ireland Roche Products Ireland Ltd. Tel 353 0 1 469 0700 Slovenija Roche farmacevtska druba d.o.o. Tel 386 - 1 360 26 00

Slovenská republika Roche Slovensko, s.r.o. Tel 421 - 2 52638201 Ísland Roche as co Icepharma hf Sími 354 540 8000

Italia Roche S.p.A. Tel 39 - 039 2471 SuomiFinland Roche Oy PuhTel 358 0 10 554 500

K .. . 357 - 22 76 62 76 Sverige Roche AB Tel 46 0 8 726 1200

Latvija Roche Latvija SIA Tel 371 6 7039831 United Kingdom Roche Products Ltd. Tel 44 0 1707 366000

Lietuva

UAB ?Roche Lietuva?
Tel: +370 5 2546799

This leaflet was last approved in

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