Package leaflet: Information for the patient

Ritonavir 100 mg film-coated tablets

ritonavir

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 of the side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

In this leaflet:

1.    What Ritonavir is and what it is used for

2.    What you need to know before you take Ritonavir

3.    How to take Ritonavir

4.    Possible side effects

5.    How to store Ritonavir

6.    Contents of the pack and other information

1. What Ritonavir is and what it is used for

Ritonavir is a protease inhibitor used to control HIV infection. Ritonavir 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.

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

2. What you need to know before you take Ritonavir Do not take Ritonavir

if you are allergic to ritonavir or any of the other ingredients of this medicine (listed in 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 Other medicines and Ritonavir);

-    products containing St John’s wort (Hypericumperforatum) as this may stop Ritonavir 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 Ritonavir but a full dose of Ritonavir 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 Ritonavir. Often, there are other medicines you can take instead.

Also read the list of medicines in ‘Other medicines and Ritonavir’ for use with certain other medicines which require special care.

Warnings and precautions

Important information

-    If Ritonavir 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 Ritonavir should be avoided. If you have any further questions about Ritonavir (ritonavir) or the other medicines prescribed, please ask your doctor or pharmacist.

-    Ritonavir is not a cure for HIV infection or AIDS.

-    People taking Ritonavir 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 Ritonavir.

-    Ritonavir 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).

Talk to your doctor or pharmacist before taking Ritonavir 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).

-    Diarrhoea or vomiting 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 Ritonavir 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, light-headedness, fainting spells or abnormal heartbeat. Some patients taking Ritonavir may experience 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.

Children

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

Other medicines and Ritonavir

There are some medicines you cannot take at all with Ritonavir. These are listed earlier in section 2, under ‘Do not take Ritonavir’. 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 Ritonavir is taken as a full dose. However, these warnings may also apply when Ritonavir is used in lower doses (a booster) with other medicines.

Tell your doctor or pharmacist if you are taking, have recently taken or might take 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 Ritonavir with sildenafil if you suffer from pulmonary arterial hypertension (see also ‘Do not take Ritonavir’ ). Tell your doctor if you are taking tadalafil for pulmonary arterial hypertension.

-    Digoxin (heart medicine). Your doctor may need to adjust the dose of digoxin and monitor you while you are taking digoxin and Ritonavir in order to avoid heart problems.

-    Hormonal contraceptives containing ethinyl oestradiol as Ritonavir 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 Ritonavir.

-    Atorvastatin or rosuvastatin (for high cholesterol) as Ritonavir may raise the blood levels of these medicines. Talk to your doctor before you take any cholesterol-reducing medicines with Ritonavir (see also ‘Do not take Ritonavir’).

-    Steroids (e.g. dexamethasone, fluticasone propionate, prednisolone) as Ritonavir 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 an increase of unwanted effects like nausea, dizziness, low blood pressure and fainting can occur when taken with Ritonavir.

-    Rifampicin and saquinavir (used for tuberculosis and HIV, respectively) as serious liver damage can occur when taken with Ritonavir.

-    Bosentan (used for pulmonary arterial hypertension) as ritonavir may increase the blood levels of this medicine.

There are medicines that may not mix with Ritonavir 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 (e.g. erythromycin, clarithromycin);

anticancer treatments (e.g. dasatinib, nilotinib, vincristine, vinblastine); anticoagulants (e.g. rivaroxaban, warfarin);

antidepressants (e.g. amitriptyline, desipramine, fluoxetine, imipramine, nortriptyline, paroxetine, sertraline, trazodone); antifungals (e.g. ketoconazole, itraconazole); antihistamines (e.g. loratadine, 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 (e.g. carbamazepine, divalproex, lamotrigine, phenytoin);

heart medicines (e.g. digoxin, disopyramide, mexiletine and calcium channel antagonists such as

amlodipine, diltiazem and nifedipine);

immune system (e.g. cyclosporine, tacrolimus, everolimus);

morphine and morphine-like medicines used to treat severe pain (e.g. methadone, fentanyl); sleeping pills (e.g. alprazolam, zolpidem) and also midazolam administered by injection; tranquillisers (e.g. haloperidol, risperidone, thioridazine); colchicine, a treatment for gout

There are some medicines you cannot take at all with Ritonavir. These are listed earlier in section 2 under ‘Do not take Ritonavir’.

Ritonavir with food and drink

Ritonavir film-coated 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 Ritonavir) 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. Ritonavir did not appear to increase the chance of developing birth defects compared to the general population.

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

Driving and using machines

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

This medicine contains 87.75 mg sodium per tablet. To be taken into consideration by patients on a controlled sodium diet.

3. How to take Ritonavir

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

It is taken by mouth usually two times every day. Ritonavir film-coated tablets should be taken with food as this can affect the way in which Ritonavir is absorbed into your body.

It is important that Ritonavir film-coated tablets are swallowed whole and not chewed, broken or crushed.

Recommended doses of Ritonavir are:

•    if Ritonavir 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. The appropriate dose for children may be less than 100 mg ritonavir and can thus not be achieved with this product. Other ritonavir formulations may have to be used instead. For more detailed dose recommendations see the Package Leaflet of the other anti-HIV medicines to be given with Ritonavir.

•    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 (totalling 1,200 mg 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, Ritonavir 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 Ritonavir as directed, tell your doctor straight away. During episodes of diarrhoea your doctor may decide that extra monitoring is needed. Always keep enough Ritonavir on hand so you don't run out. When you travel or need to stay in the hospital, make sure you have enough Ritonavir to last until you can get a new supply.

If you take more Ritonavir than you should

Numbness, tingling, or a ‘pins and needles’ sensation may occur if you take too much Ritonavir. If you realise you have taken more Ritonavir 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 Ritonavir

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 Ritonavir

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

4. Possible side effects

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

Also, the side effects of ritonavir 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.

Talk to your doctor immediately or get immediate medical help if you experience:

Common (may affect up to 1 in 10 people)

•    inflammation of the liver and yellowing of the skin or whites of the eyes

•    stomach pain, vomiting blood (or liquid with what looks like coffee grounds), blood in the faeces (stools/motions) as they may be signs of stomach bleeding

•    feel sick (nauseous), are vomiting, or have stomach pain, because these may be signs of an inflamed pancreas (see also section 2)

Uncommon (may affect up to 1 in 100 people)

•    heart attack

Rare (may affect up to 1 in 1,000 people)

•    serious allergic reaction (anaphylaxis) such as rash, hives or breathing difficulties

•    severe or life threatening skin reaction including blisters (Stevens Johnson syndrome, toxic epidermal necrolysis)

Not known (frequency cannot be estimated from the available data)

•    symptoms of infection such as fever, severe chills, sore throat or mouth ulcers (see also section 2)

Tell your doctor if you notice any of the following side effects:

Very common (may affect more than 1 in 10 people)

•    upper and lower stomach ache

•    vomiting

•    diarrhoea (may be severe)

•    feeling sick (nausea)

•    flushing, feeling hot

•    headache

•    dizziness

•    pain in the throat

•    cough

•    upset stomach or indigestion

•    a tingling sensation or numbness in the hands, feet or around the lips and mouth

•    feeling weak/tired

•    bad taste in the mouth

•    damage to the nerves that can cause weakness and pain

•    itching

•    rash

•    joint pain and back pain Common (may affect up to 1 in 10 people)

•    allergic reactions including skin rashes (may be red, raised, itchy), severe swelling of the skin and other tissues

•    changes in fat distribution (see Side effects associated with combination antiretroviral therapy below)

•    increase in cholesterol

•    inability to sleep (insomnia)

•    increase in triglycerides

•    anxiety

•    gout

•    increase in urination

•    reduced kidney function

•    seizures (fits)

•    low levels of blood platelets

•    thirst (dehydration)

•    abnormally heavy periods

•    wind (flatulence)

•    loss of appetite

•    mouth ulcer

•    muscle aches (pain), tenderness or weakness

•    fever

•    weight loss

•    laboratory test results: changes in blood test results (such as blood chemistry and blood count)

•    confusion

•    difficulty paying attention

•    fainting

•    blurred vision

•    swelling of the hands and feet

•    high blood pressure

•    low blood pressure and feeling faint when getting up

•    coldness in the hands and feet

•    acne

Uncommon (may affect up to 1 in 100 people)

•    diabetes

•    kidney failure

Rare (may affect up to 1 in 1,000 people)

• high levels of sugar in the blood

Not known (frequency cannot be estimated from the available data)

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 Warnings and precautions).

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 ritonavir or other protease inhibitors.

Abnormal liver function tests, hepatitis (inflammation of the liver), and rarely jaundice, have been reported in patients taking ritonavir. 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.

Reporting of side effects

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

Also you can help to make sure that medicines remain as safe as possible by reporting any unwanted side effects via the internet at www.mhra.gov.uk/yellowcard. Alternatively you can call Freephone 0808 100 3352 (available from 10 a.m. to 2 p.m. Mondays to Fridays) or fill in a paper form available from your local pharmacy.

5. How to store Ritonavir

Keep out of the sight and reach of children.

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

Do not store above 30°C. Store in the original bottle in order to protect from moisture.

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 protect the environment.

6. Contents of the pack and other information What Ritonavir contains

-    The active substance is ritonavir. Each film-coated tablet contains 100 mg ritonavir.

-    The other tablet ingredients are: copovidone, sorbitan laurate, silica colloidal anhydrous, methylene chloride, sodium chloride, sodium stearyl fumarate.

-    The tablet coating is composed of: hypromellose, titanium dioxide (E171), macrogols, hydroxypropyl cellulose, talc, iron oxide yellow (E172), silica colloidal anhydrous, polysorbate 80.

What Ritonavir looks like and contents of the pack

Ritonavir film-coated tablets are yellow, capsule shaped and debossed with ‘M163’ on one side and plain on the other.

Ritonavir film-coated tablets are available in HDPE bottles with screw caps with inbuilt desiccant of 30, 60, 84, 90, 100 and 120 film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Mylan, Potters Bar, Hertfordshire, EN6 1TL, United Kingdom Manufacturers

Generics [UK] Limited, Station Close, Potters Bar, Hertfordshire, EN6 1TL, United Kingdom Gerard Laboratories, 35/36 Baldoyle Industrial Estate, Grange Road, Dublin 13, Ireland Mylan Hungary Kft, H-2900 Komarom, Mylan utca 1, Hungary

This leaflet was last revised in May 2013.

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