Invirase - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

Package Leaflet: Information for the user

Invirase 500 mg film-coated tablets

Saquinavir

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

• 1. What Invirase is and what it is used for

• 2. What you need to know before you take Invirase

• 3. How to take Invirase

• 4. Possible side effects

• 5. How to store Invirase

• 6. Contents of the pack and other information

1. What Invirase is and what it is used for

Invirase contains the active substance saquinavir which 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-1-infected adults. Invirase is prescribed for use in combination with ritonavir (Norvir) and other antiretroviral medicines.

2. What you need to know before you take Invirase

Do not take Invirase if you have:

• an allergy to saquinavir, ritonavir or any of the other ingredients (see “Invirase contains lactose” later in this section and “What Invirase contains” in Section 6)
• any heart problems that show on an electrocardiogram (ECG, electrical recording of the heart) -you may have been born with that
• a very slow heart rate (bradycardia)
• a weak heart (heart failure)
• a history of an irregular heart beat (arrhythmias)
• a salt imbalance in your blood, especially low blood concentrations of potassium (hypokalaemia), which is not currently controlled by treatment
• severe liver problems such as jaundice, hepatitis or liver failure – where your belly fills with fluid, you get confused or your oesophagus (the tube that runs from your mouth to your stomach) bleeds
• recently taken the HIV medicine rilpivirine.

Do not take Invirase if any of the above applies to you. If you are not sure, talk to your doctor or pharmacist before taking Invirase.

Do not take Invirase if you are taking any of the following medicines:

Any medicine that can change your heart beat, such as:

• certain medicines for HIV – such as atazanavir, lopinavir, rilpivirine
• certain heart medicines – amiodarone, bepridil, disopyramide, dofetilide, flecainide, hydroquinidine, ibutilide, lidocaine, propafenone, quinidine, sotalol

certain medicines for depression – amitriptyline, imipramine, trazodone, maprotiline medicines for other severe mental health problems – such as clozapine, haloperidol, mesoridazine, phenothiazines, sertindole, sultopride, thioridazine, ziprasidone

certain medicines for infection – such as clarithromycin, dapsone, erythromycin, halofantrine, pentamidine, sparfloxacin

certain strong pain killers (narcotics) – such as alfentanyl, fentanyl, methadone

medicines for erectile dysfunction – sildenafil, vardenafil, tadalafil

certain medicines that may be used for a variety of things: cisapride, diphemanil, mizolastine, quinine, vincamine.

certain medicines used to prevent rejection of new organs after a transplant operation such as tacrolimus

certain medicines used to treat the symptoms of Benign Prostatic Hyperplasia (an increase in size of the prostate) such as alfuzosin

certain medicines commonly used for allergy symptoms such as terfenadine and astemizole

certain medicines for severe mental health problems such as pimozide

certain medicines (so called tyrosine kinase inhibitors) used to treat different types of cancer such as dasatinib and sunitinib.

Any of these other medicines:

• ergot alkaloids – for migraine attacks
• triazolam and midazolam (taken by mouth) – to help you sleep or for anxiety
• rifampicin – for preventing or treating tuberculosis
• simvastatin and lovastatin – for lowering blood cholesterol
• quetiapine – used to treat schizophrenia, bipolar disorder and major depressive disorder
• luras idone – us ed to treat s chizophrenia.

Do not take Invirase with any other drug unless you have talked to your doctor first. The drugs listed above might cause serious side effects if you take them together with Invirase.

Do not take Invirase if any of the above applies to you. If you are not sure, talk to your doctor or pharmacist before taking Invirase.

Warnings and precautions

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.

You can still pass on HIV when taking this medicine, although the risk is lowered by effective antiretroviral therapy. Discuss with your physician the precautions needed to avoid infecting other people.

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

Abnormal heart rhythms (arrhythmias):

Invirase can change how your heart beats – this can be serious. This can happen 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 get palpitations or an irregular heart beat during treatment. Your doctor may wish to do an ECG to check your heart beat.

Other conditions

There are certain conditions, which you may have, or have had, which require special care before or while taking Invirase/ritonavir. Therefore, before taking this medicine, you should have told your doctor if you suffer from diarrhoea, or if you have allergies (see Section 4) or if you have an intolerance to some sugars (see section “Invirase contains lactose”).

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

Liver 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 of severe and potentially fatal liver adverse events and may require blood tests for control of liver function.

Infection: 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 antiHIV 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).

In addition to the opportunistic infections, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may also occur after you start taking medicines for the treatment of your HIV infection. Autoimmune disorders may occur many months after the start of treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness beginning in the hands and feet and moving up towards the trunk of the body, palpitations, tremor or hyperactivity, please inform your doctor immediately to seek necessary treatment.

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.

Other medicines and Invirase

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

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 if you are taking any of the following medicines:“ above). There are also some medicines that require dosage reduction of that medicine or Invirase or ritonavir (see section “Medicines that can interact with saquinavir or ritonavir include:” below). Ask your doctor or pharmacist for more information about taking Invirase/ritonavir with other medicines.

Medicines that can interact with saquinavir or ritonavir include:

• other HIV medicines – such as nelfinavir, indinavir, nevirapine, delavirdine, efavirenz, maraviroc, cobicistat
• some medicines affecting the immune system – such as ciclosporin, sirolimus (rapamycin), tacrolimus
• various steroids – such as dexamethasone, ethinyl estradiol, fluticasone
• certain heart medicines – such as calcium channel blockers, quinidine, digoxin
• medicines used to lower blood cholesterol – such as statins
• antifungals – ketoconazole, itraconazole, fluconazole, miconazole
• anticonvulsants – such as phenobarbital, phenytoin, carbamazepine
• sedative agents – such as midazolam administered by injection
• certain antibiotics – such as quinupristin/dal­fopristin, rifabutin, fusidic acid
• medicines to treat depression – such as nefazodone, tricyclic antidepressants
• medicines for anticoagulation – warfarin
• herbal preparations containing St. John’s wort or garlic capsules
• some medicines that treat diseases related to the acid in the stomach – such as omeprazole or other proton pump inhibitors
• medicines used to treat asthma or other chest illness such as Chronic Obstructive Pulmonary Disease (COPD) such as salmeterol
• medicines for gout, such as colchicine
• medicines used to treat high blood pressure in the arteries of the lungs (a disease known as pulmonary arterial hypertension) such as bosentan.

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.

Invirase with food and drink

Invirase 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, fatigue and visual impairment have been reported during treatment with Invirase. Do not drive or operate machines if you experience these symptoms.

Invirase contains lactose

Each film-coated tablet contains lactose (monohydrate) 38.5 mg. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

3. How to take Invirase

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure. Invirase comes as a 500 mg film-coated tablet. Your doctor will prescribe Invirase in combination with ritonavir (Norvir) and other HIV medicines.

How to take

• Take Invirase at the same time as your ritonavir (Norvir) capsules.
• Take your Invirase film-coated tablets with or after food.
• Swallow them whole with water.

How much to take

Standard dose

• Take two 500 mg film-coated tablets of Invirase twice a day.
• Take one 100 mg capsule of ritonavir (Norvir) twice a day.

If this is your first medicine for HIV or the first time you are taking ritonavir (Norvir) You need to take a lower dose of Invirase for your first week.

Week 1:

• Take one 500 mg film-coated tablet of Invirase twice a day.
• Take one 100 mg capsule of ritonavir (Norvir) twice a day.

Week 2 onwards:

• Continue with the standard dose.

If you take more Invirase than you should

If 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.

If you have any further questions on the use of this medicine, ask your doctor or pharmascist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This is partly linked to restored health and lifestyle, and in the case of blood lipids sometimes to the HIV medicines themselves. Your doctor will test for these changes.

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 persons) 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 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), weakness, dizziness, libido problems, taste alteration, mouth ulcers, dry lips, abdominal discomfort, indigestion, weight loss, constipation, increased appetite, muscle spasms and shortness of breath.

Other less frequently reported side effects (in more than one in one thousand persons but less than one in a hundred persons) include: decreased appetite, visual disturbance, inflammation of the liver, fits, allergic reactions, blisters, sleepiness, abnormal renal function, inflammation of the pancreas, yellowing of the skin or whites of the eyes caused by liver problems and Steven’s Johnson syndrome (a serious illness with blistering of the skin, eyes, mouth and genitals).

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.

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).

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed inBy reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Invirase

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date (EXP) which is stated on the bottle and carton. The expiry date refers to the last day of that month.

Invirase does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

6. Contents of the pack and other information

What Invirase contains

• The active substance is saquinavir. One film-coated tablet of Invirase contains 500 mg of saquinavir as saquinavir mesilate.
• The other ingredients (excipients) are microcrystalline cellulose, croscarmellose sodium, povidone, lactose (monohydrate) 38.5 mg, magnesium stearate, hypromellose, titanium dioxide (E171), talc, glycerol triacetate, iron oxide yellow (E172) and iron oxide red (E172).

What Invirase looks like and contents of the pack

Invirase 500 mg film-coated tablets are light orange to greyish or brownish orange tablets of oval shape with the marking „SQV 500“ on one side and „ROCHE“ on the other side. One plastic (HDPE) bottle contains 120 tablets.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

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:

Belgie/Belgiqu­e/Belgien N.V. Roche S.A. Tél/Tel: +32 (0) 2 525 82 11	Lietuva UAB “Roche Lietuva” Tel: +370 5 2546799
Etnrapan Pom Etnrapua EOO^ Ten: +359 2 818 44 44	Luxembourg/Lu­xemburg (Voir/siehe Belgique/Belgien)
Česká republika Roche s. r. o. Tel: +420 – 2 20382111	Magyarország Roche (Magyarország) Kft. Tel: +36 – 1 279 4500
Danmark Roche a/s Tlf: +45 – 36 39 99 99	Malta (See Ireland)
Deutschland Roche Pharma AG Tel: +49 (0) 7624 140	Nederland Roche Nederland B.V. Tel: +31 (0) 348 438050
Eesti Roche Eesti OÜ Tel: + 372 – 6 177 380	Norge Roche Norge AS Tlf: +47 – 22 78 90 00
EZ/.áňa Roche (Hellas) A.E. TnX: +30 210 61 66 100	Österreich Roche Austria GmbH Tel: +43 (0) 1 27739
España Roche Farma S.A. Tel: +34 – 91 324 81 00	Polska Roche Polska Sp.z o.o. Tel: +48 – 22 345 18 88
France Roche Tél: +33 (0) 1 47 61 40 00	Portugal Roche Farmacéutica Química, Lda Tel: +351 – 21 425 70 00
Hrvatska Roche d.o.o. Tel: + 385 1 47 22 333	Romania Roche Romania S.R.L. Tel: +40 21 206 47 01
Ireland Roche Products (Ireland) Ltd. Tel: +353 (0) 1 469 0700	Slovenija Roche farmacevtska družba d.o.o. Tel: +386 – 1 360 26 00
Ísland Roche a/s c/o Icepharma hf Sími: +354 540 8000	Slovenská republika Roche Slovensko, s.r.o. Tel: +421 – 2 52638201
Italia Roche S.p.A. Tel: +39 – 039 2471	Suomi/Finland Roche Oy Puh/Tel: +358 (0) 10 554 500

United Kingdom (Northern Ireland)

Roche Products (Ireland) Ltd.

Tel: +44 (0) 1707 366000

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:

This leaflet is available in all EU/EEA languages on the European Medicines Agency website.

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