Crixivan - patient leaflet, side effects, dosage

1. What CRIXIVAN is and what it is used for

What CRIXIVAN is

CRIXIVAN contains a substance called indinavir. It belongs to a group of medicines called ‘protease inhibitors’.

What CRIXIVAN is used for

CRIXIVAN is used to treat Human Immunodeficiency Virus (HIV) in adults. CRIXIVAN is used at the same time as other HIV treatments (antiretroviral medicines). This is called combination antiretroviral therapy.

• An example of another medicine that might be given to you, at the same time as CRIXIVAN, is ritonavir.

How CRIXIVAN works

CRIXIVAN treats HIV and helps to lower the number of HIV particles in your blood.

CRIXIVAN helps to:

• lower the risk that you get illnesses related to HIV
• lower the amount of HIV in your body (your ‘viral load’)
• raise your CD4 (T) cell count. CD4 cells are an important part of your immune system. The main role of the immune system is to protect you from infections.

CRIXIVAN may not do these things in all patients. Your doctor will monitor how this medicine works for you.

2. What you need to know before you take CRIXIVAN

Do not take CRIXIVAN:

• if you are allergic to indinavir or any of the other ingredients of this medicine (listed in Section 6).
• if you are taking any of the following medicines:

• – rifampicin – an antibiotic used to treat infections

• – cisapride – used for gut problems

• – amiodarone – used for heart rhythm problems

• – pimozide – used for some mental health problems

• – lovastatin or simvastatin – used to lower cholesterol

• – St. John's wort (Hypericum perforatum ) – a herbal medicine used for depression

• – ergot tartramine (with or without caffeine) – used for migraines

• – astemizole or terfenadine – antihistamines used for hay fever and other allergies

• – quetiapine – used for some mental illnesses such as schizophrenia, bipolar disorder and major depressive disorder

• – alprazolam, triazolam and midazolam (by mouth) – used to make you calmer or help you sleep.

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

In addition, when CRIXIVAN is given at the same time as the medicine ritonavir:

Do not take either CRIXIVAN or ritonavir:

• if you have liver problems
• if you are taking any of the following medicines:

• – fusidic acid – an antibiotic used to treat infections

• – piroxicam – used for arthritis

• – alfuzosin – used for prostate problems

• – bepridil – used for chest pain (angina)

• – clozapine – used for some mental health problems

• – pethidine or propoxyphene – used for pain

• – estazolam or flurazepam – used to help you sleep

• – clorazepate or diazepam – used to make you calmer

• – encainide, flecanide, propafenone, or quinidine – used for uneven heartbeat problems.

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

Warnings and precautions

Talk to your doctor, pharmacist or nurse before taking CRIXIVAN if you have had or develop any of the following:

• allergies
• kidney problems (including inflammation of the kidneys, kidney stones, or back pain with or without blood in your urine)
• ‘haemophilia’ – CRIXIVAN may make you more likely to bleed. If you notice bleeding or if you feel weak, talk to your doctor straight away.
• liver problems – people with ‘chronic hepatitis B or C’ or ‘cirrhosis’ who are treated with ‘antiretroviral’ medicines are more likely to have serious and potentially fatal liver side effects with this medicine. You may need to have blood tests to check how your liver is working.
• severe pain, tenderness or weakness in your muscles – this is more likely to happen if you are taking cholesterol-lowering medicines called ‘statins’ (such as simvastatin). On rare occasions the muscle problems can be serious (rhabdomyolysis). Inform your doctor as soon as possible if you develop severe muscle pain or weakness.
• signs of infection – this may be a previous infection which comes back soon after anti-HIV treatment is started. This may be because the body is able to start fighting infections again. This happens in some people with advanced HIV infection (AIDS) and who have had HIV related infections before. If you notice any symptoms of infection, please inform your doctor immediately.
• 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 – signs include stiff joints, aches and pains, especially the hip and difficulty moving. If you notice any of these signs, talk to your doctor. Such problems might be due to a bone disease called ‘osteonecrosis’ (loss of blood supply to the bone causing bone death), which can occur months to years after starting HIV therapy. The risk of you having bone problems is higher if you:

• – drink alcohol

• – have a high body mass index

• – have an immune system that is very weak

• – have been taking corticosteroids at the same time as CRIXIVAN

• – take combination antiretroviral therapy for a long time.

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before taking CRIXIVAN.

Children and adolescents

CRIXIVAN is not recommended in children under the age of 18 years.

Other medicines and CRIXIVAN

Tell your doctor, pharmacist or nurse if you are taking, have recently taken, or might take any other medicines. This includes medicines obtained without a prescription, including herbal medicines.

CRIXIVAN can affect the way some other medicines work. Also some other medicines can affect the way CRIXIVAN works.

Ritonavir

Ritonavir is used for increasing the blood levels of CRIXIVAN or, less frequently and then at higher doses, for HIV treatment. Talk to your doctor if you are going to take both CRIXIVAN and ritonavir. Also look at the Package Leaflet for ritonavir.

Please see ‘Do not take CRIXIVAN’ and ‘Do not take either CRIXIVAN or ritonavir’ above under Section 2 for an important list of medicines that you must not combine with CRIXIVAN. Do not take CRIXIVAN if you are taking or have recently taken any of these medicines. If you are not sure, talk to your doctor, pharmacist or nurse before taking CRIXIVAN.

In addition, talk to your doctor, pharmacist or nurse before taking CRIXIVAN if you are taking any of the following medicines since your doctor may want to adjust the dose of your medicines:

• theophylline – used for asthma
• warfarin – used to thin the blood
• morphine, fentanyl – used for pain
• buspirone – used to make you calmer
• fluconazole – used for fungal infections
• venlafaxine, trazodone – used for depression
• tacrolimus, ciclosporin – used mainly after organ transplantation
• delavirdine, efavirenz, nevirapine – used for HIV
• amprenavir, saquinavir, atazanavir – used for HIV
• sildenafil, vardenafil, tadalafil – used for impotence
• dexamethasone – used to stop swelling (inflammation)
• itraconazole, ketoconazole – used to treat fungal infections
• atorvastatin, rosuvastatin, pravastatin, fluvastatin – used to lower cholesterol
• fexofenadine, loratidine – antihistamines used for hay fever and other allergic conditions
• oral contraceptive medicines (‘The Pill’) containing norethindrone or ethinyl estradiol
• phenobarbital, phenytoin, carbamazepine, divalproex, lamotrigine – medicines used to treat fits (epilepsy)
• midazolam (by injection) – used for acute fits (seizures) and to send patients to sleep before some medical procedures
• amlodipine, felodipine, nifedipine, nicardipine, digoxin, diltiazem – used for high blood pressure and some heart problems.
• quetiapine – used for some mental illnesses such as schizophrenia, bipolar disorder and major depressive disorder

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before taking CRIXIVAN.

CRIXIVAN with food and drink

See Section 3 below for information on how to take CRIXIVAN. It is however especially important that you:

• do not take CRIXIVAN with food that is high in calories, fat and protein. This is because these

foods stop your body being able to take in as much CRIXIVAN and it will not work as well.

Pregnancy and breast-feeding

• If you are pregnant, think you may be pregnant or are planning to have a baby, only take

CRIXIVAN if your doctor decides it is clearly necessary. It is not known whether CRIXIVAN is harmful to an unborn baby when taken by a pregnant woman.

• It is recommended that women with HIV do not breast-feed. This is to stop HIV being passed

on to their baby.

Driving and using machines

Dizziness and blurred vision have been reported during treatment with CRIXIVAN. If this happens, do not drive or operate machines.

Other things you should know

CRIXIVAN is not a cure for HIV. You may still get infections or other illnesses related to HIV. So you still need to keep seeing your doctor while you are taking CRIXIVAN.

HIV is spread by blood or sexual contact with a person with HIV. 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.

CRIXIVAN contains lactose

This medicine contains lactose (type of sugar). If you have been told by your doctor that you cannot tolerate or digest some sugars, talk to your doctor before taking this medicine.

3. How to take CRIXIVAN

Always take this medicine exactly as your doctor, pharmacist or nurse has told you. Check with your doctor, pharmacist or nurse if you are not sure.

How much to take

The recommended dose of CRIXIVAN is:

• Four 200 mg capsules (800 mg) – taken three times a day (every 8 hours).

This means you will take a total of twelve 200 mg capsules (2400 mg) each day.

You usually take less CRIXIVAN if you are also taking ritonavir. The recommended doses are:

• CRIXIVAN – two 200 mg capsules (400 mg) – taken twice a day.

This means you will take a total of four 200 mg capsules (800 mg) each day.

• ritonavir – 100 mg – taken twice a day.

Taking this medicine

• Take this medicine by mouth.
• Swallow the capsules whole with a drink of water, skimmed or low fat milk, juice, tea or

coffee.

• Do not crush or chew the capsules.
• It is important for adults to drink at least 1.5 litres of liquid each day while taking CRIXIVAN.

This will help lower the risk of you getting kidney stones.

• Do not take CRIXIVAN with food that is high in calories, fat and protein. This is because these

stop your body being able to take in as much CRIXIVAN and it will not work as well.

When to take

• Take 1 hour before or 2 hours after a meal.
• If you cannot take it without food then take CRIXIVAN with a low-fat light meal. This could

be dry toast with jam or cornflakes with skimmed or low-fat milk and sugar.

• If you are also taking ritonavir, then you can take CRIXIVAN at any time of the day with or

without food.

If you take more CRIXIVAN than you should

If you take more CRIXIVAN than you should, talk to your doctor as soon as possible. The following effects may happen:

• nausea
• vomiting
• diarrhoea
• back pain
• blood in your urine.

If you forget to take CRIXIVAN

Do not take a double dose to make up for a forgotten dose. If you have missed a dose, do not take it later in the day. Simply continue to follow your usual schedule.

If you stop taking CRIXIVAN

It is important that you take CRIXIVAN exactly as your doctor tells you to – he or she will tell you how long you should take your medicine.

• Do not stop taking CRIXIVAN without talking to your doctor.
• This is because reducing or missing doses will make it more likely that HIV will become

resistant to CRIXIVAN.

• If this happens, your treatment will stop working.

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

4. Possible side effects

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 life style, and in the case of blood lipids sometimes to the HIV medicines themselves. Your doctor will test for these changes.

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

The following side effects have been reported by patients taking CRIXIVAN:

See your doctor straight away if you notice any of the following serious side effects – you may need urgent medical treatment:

• allergic reactions – signs include itchy skin, redness of the skin, ‘wheals’ or ‘hives’, swelling of

the face, lips, tongue or throat and difficulty breathing. It is not known how often this may happen (cannot be estimated from the available data), but the reaction can sometimes be severe and include shock

There are also other side effects that you may get while taking this medicine such as increased bleeding in haemophiliacs, muscle problems, signs of infection, and bone problems. Please see ‘Warnings and precautions’ in Section 2 above.

Additional side effects include:

Very common (affects more than 1 in 10 people):

• headache
• rash or dry skin
• nausea
• vomiting
• altered taste sensations
• indigestion or diarrhoea
• stomach pain or swelling
• feeling dizzy, weak or tired.

Common (affects less than 1 in 10 people):

• passing gas
• itching
• dry mouth
• acid reflux
• muscle pain
• pain on urination
• difficulty getting to sleep
• feeling numb or unusual feeling of the skin.

The following side effects have also been reported since the medicine has been used. How often they happen is not known:

• hair loss
• inflamed pancreas
• severe skin reactions
• darkening skin colour
• having a numb mouth
• low red blood cell count
• ingrown toenails with or without infection
• liver problems such as inflammation or liver failure
• kidney problems such as kidney infection, worsening or loss of kidney function
• pain and difficulty moving shoulder.

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 CRIXIVAN

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

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

Store CRIXIVAN in the original bottle and keep the bottle tightly closed to protect it from moisture. The bottle contains desiccant canisters that should remain in the bottle.

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 CRIXIVAN contains

• The active substance is indinavir. Each hard capsule contains indinavir sulphate corresponding

to 200 mg of indinavir.

• The other ingredients are anhydrous lactose, magnesium stearate, gelatin and titanium dioxide

(E 171).

• The capsules are printed with printing ink containing indigo carmine (E 132).

What CRIXIVAN looks like and contents of the pack

CRIXIVAN 200 mg hard capsules are supplied in HDPE bottles with a polypropylene cap and a foil seal containing 180, 270 or 360 capsules. Not all pack sizes may be marketed.

The capsules are semi-translucent white and coded ‘CRIXIVAN 200 mg’ on them in blue.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder: Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, The Netherlands

Manufacturer: Merck Sharp & Dohme B.V., Waarderweg 39, Postbus 581, 2003 PC Haarlem

The Netherlands

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

Belgique/België/Bel­gien MSD Belgium BVBA/SPRL Tél/Tel: +32(0)27766211	Lietuva UAB Merck Sharp & Dohme Tel.: +370 5 278 0247
Efc^rapufl MepK fflapn u ^ovm Btnrapua EOOfl Ten.:+359 2 819 3737	Luxembourg/Lu­xemburg MSD Belgium BVBA/SPRL Tél/Tel: +32(0)27766211
Česká republika Merck Sharp & Dohme s.r.o. Tel.: +420 233 010 111	Magyarország MSD Pharma Hungary Kft. Tel.: +361 888 53 00
Danmark MSD Danmark ApS Tlf: +45 4482 4000	Malta Merck Sharp & Dohme Cyprus Limited Tel: 8007 4433 (+356 99917558)
Deutschland MSD SHARP & DOHME GMBH Tel: 0800 673 673 673 (+49 (0) 89 4561 2612)	Nederland Merck Sharp & Dohme BV Tel: 0800 9999000 (+31 23 5153153)
Eesti Merck Sharp & Dohme OÜ Tel.: +372 6144 200	Norge MSD (Norge) AS Tlf: +47 32 20 73 00 msdnorge@ msd.no
EXÁáóa MSD A.O.B.E.E. Tql: +30 210 98 97 300	Österreich Merck Sharp & Dohme Ges.m.b.H. Tel: +43 (0) 1 26 044
España Merck Sharp & Dohme de España, S.A. Tel: +34 91 321 06 00	Polska MSD Polska Sp. z o.o. Tel.: +48 22 549 51 00
France MSD France Tél: + 33 (0) 1 80 46 40 40	Portugal Merck Sharp & Dohme, Lda Tel: +351 21 4465700
Hrvatska Merck Sharp & Dohme d.o.o. Tel: + 385 1 6611 333	România Merck Sharp & Dohme Romania S.R.L. Tel: +40 21 529 29 00

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.