NORVIR 100 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Norvir 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 or your child.

• 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.

Contents of the pack and other information:

1. What is Norvir and what is it used for
2. What you need to know before you or your child takes Norvir
3. How to take Norvir
4. Possible side effects
   1. Storing Norvir

1. Contents of the pack and further information

1. What is Norvir and what is it used for

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

Norvir is used in children from 2 years of age and in adolescents and adults infected with HIV, the virus that causes AIDS.

2. What you need to know before you or your child takes Norvir

Do not take Norvir

• if you are allergic 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 (usually used to treat allergy symptoms – these medicines can be bought without a prescription);
• amiodarone, bepridil, dronedarone, encainide, flecainide, propafenone, quinidine (used to correct irregular heartbeats);
• dihydroergotamine, ergotamine (used to treat migraine headaches);

• ergonovine, methylergonovine (used to stop bleeding that may occur after childbirth or abortion);
• chlorazepate, diazepam, estazolam, flurazepam, triazolam, or oral midazolam (used to help you sleep and/or relieve anxiety);
• clozapine, pimozide, (used to treat abnormal thoughts or feelings):
• quetiapine (used to treat schizophrenia, bipolar disorder, and major depressive disorder);
• lurasidone (used to treat depression);
• ranolazine (used to treat chronic chest pain [angina]);

• pethidine, piroxicam, propoxyphene (used to relieve pain);
• cisapride (used to relieve certain stomach pains);
• rifabutin (used to prevent/treat certain infections)*;
• voriconazole (used to treat fungal infections)*;

• simvastatin, lovastatin (used to lower blood cholesterol);
• neratinib (used to treat breast cancer);
• lomitapide (used to lower blood cholesterol);
• alfuzosin (used to treat enlarged prostate);
• fusidic acid (used to treat bacterial infections).
• sildenafil if you have a lung disease called pulmonary arterial hypertension that makes it difficult to breathe. Patients without this disease may use sildenafil for impotence (erectile dysfunction) under the supervision of their doctor (see section Using Norvir with other medicines);
• avanafil or vardenafil (used to treat impotence);
• colchicine (used to treat gout) if you have liver and/or kidney problems (see section Using Norvir with other medicines);
• products containing St. John's Wort (Hypericum perforatum) as they may cause Norvir to stop 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 dose (lower dose) of Norvir but a full dose of Norvir should not be taken with these two medicines.

If you are currently taking any of these medicines, ask your doctor if you could change the medicine while taking Norvir.

For the use of other medicines that require special care, see the list included in the section “Using Norvir with other medicines”

Warnings and precautions

Consult your doctor before starting to take Norvir.

Important information

• If you take Norvir with other antiretroviral medicines, it is important that you read the leaflets for these other medicines carefully. In these leaflets, you may find additional important information about situations where you should avoid taking Norvir. If you have any further questions about Norvir (ritonavir) or any other medicines that you have been prescribed, ask your doctor or pharmacist.
• Norvir does not cure HIV infection or AIDS.
• People taking Norvir may still develop infections or other illnesses related to HIV infection or AIDS. It is therefore important that you remain under the supervision of your doctor while taking Norvir.
• Although effective antiretroviral treatment reduces the risk of transmission, while taking this medicine you can still transmit HIV to others. Consult your doctor about what precautions are necessary to avoid infecting others.

Tell your doctor if you have or have had:

• Liver diseasehistory.
• Hepatitis B or Cand are being treated with a combination of antiretroviral medicines, as you have a greater risk of serious and potentially life-threatening side effects due to the effect on the liver. You may need to have blood tests to check your liver function.
• Haemophilia, as there have been reports of patients with haemophilia being treated with this type of medicine (protease inhibitors) with increased bleeding. The reason for this is not known. You may need to be given additional medication to help your blood clot (Factor VIII) to control any bleeding.
• Erectile dysfunction, as medicines used to treat erectile dysfunction can cause low blood pressure and prolonged erection.
• Diabetes, as there have been reports of worsening or development of diabetes (diabetes mellitus) in some patients taking protease inhibitors.
• Kidney disease (renal), as your doctor may need to check the dose of other medicines you are taking (such as protease inhibitors).

Tell your doctor if you experience:

• Diarrhoea or vomitingthat does not improve (persistent), as this may reduce the effectiveness of the medicines you are taking.
• Nausea, vomitingor stomach pain, as these can be signs of pancreatitis (inflammation of the pancreas). Some patients taking Norvir may develop pancreas problems. Tell your doctor as soon as possible if this is the case.
• Infection symptoms– tell your doctor immediately. Some patients with advanced HIV infection (AIDS) who start anti-HIV treatment may develop symptoms of infections they have had in the past, even if they were not aware of them. This is believed to occur because the body's immune response improves and helps the body fight off these infections.

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

• Joint stiffness, discomfort, and pain(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 antiretroviral medicines may develop this disease.
• Muscle pain, discomfort, or weakness, particularly in combination with antiretroviral therapy including protease inhibitors and nucleoside analogues. In rare cases, these muscle disorders have been serious (see section 4 Possible side effects).
• Dizziness, drowsiness, fainting, or irregular heartbeat, some patients taking Norvir may experience changes in their electrocardiogram (ECG). Tell your doctor if you have any heart problems or problems with the electrical conduction of the heart.
• If you have any other health problems, consult your doctor as soon as possible.

Children and adolescents

Norvir is not recommended for use in children under 2 years of age.

Using Norvir with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those bought without a prescription. There are some medicines that you cannot take with Norvir. These medicines are listed in section 2, under the heading “Do not take Norvir”. There are some medicines that can only be taken under certain circumstances, as described below.

When Norvir is used at full dose, the following precautions will be taken. However, these precautions may also be necessary when low doses (boosting) of Norvir are taken with other medicines.

Tell your doctor if you are taking any of the following medicines, special precautions are needed.

• Sildenafil or tadalafilfor impotence (erectile dysfunction). You should reduce the dose and/or frequency of use of these medicines to avoid low blood pressure and prolonged erection. You should not take Norvir with sildenafil if you have pulmonary arterial hypertension (see section 2 What you need to know before you or your child takes Norvir). Tell your doctor if you are taking tadalafil for the treatment of pulmonary arterial hypertension.
• Colchicine(for gout) as Norvir can increase the levels of this medicine in the blood. You should not take Norvir with colchicine if you have liver and/or kidney problems (see also “Do not take Norvir” above).
• Digoxin(heart medicine). To prevent heart problems, your doctor may need to adjust the dose of digoxin and monitor you while you are taking digoxin and Norvir.
• Hormonal contraceptivesthat contain ethinyl estradiol, as Norvir can reduce the effectiveness of these medicines. It is recommended to use a condom or other non-hormonal contraceptive method instead. You may also experience irregular uterine bleeding if you take this type of hormonal contraceptive with Norvir.
• Atorvastatin or rosuvastatin(for high cholesterol) as Norvir can increase the levels of these medicines in the blood. Tell your doctor before taking cholesterol-lowering medicines with Norvir (see “Do not take Norvir” above).
• Corticosteroids(e.g. dexamethasone, fluticasone propionate, prednisolone, triamcinolone), as Norvir can increase the levels of these medicines in the blood, which can lead to Cushing's syndrome (development of a rounded face) and reduced production of the cortisol hormone. Your doctor may want to reduce the dose of corticosteroids or monitor their side effects more closely.
• Trazodone(depression medicine) as unwanted effects such as nausea, dizziness, low blood pressure, and fainting can occur when taken with Norvir.
• Rifampicin and saquinavir(used for tuberculosis and HIV respectively) as they can cause serious liver damage when taken with Norvir.
• Bosentan, riociguat(used for pulmonary arterial hypertension), as the amount of this medicine in the blood may increase when taken with Norvir.

There are medicines that should not be mixed with Norvir because their effects may increase or decrease when taken together. In some cases, your doctor may need to perform certain tests, change the dose, or monitor you regularly. For this reason, you should tell your doctor if you are taking any medicine, including those you have bought yourself or herbal products, especially the following:

• amphetamines or amphetamine derivatives;
• antibiotics (e.g. erythromycin, clarithromycin);
• cancer treatments (e.g. abemaciclib, afatinib, apalutamide, ceritinib, encorafenib, dasatinib, ibrutinib, nilotinib, venetoclax, vincristine, vinblastine);
• anticoagulants (e.g. rivaroxaban, vorapaxar, warfarin);
• antidepressants (e.g. amitriptyline, desipramine, fluoxetine, imipramine, nefazodone, nortriptyline, paroxetine, sertraline, trazodone);
• antifungals (e.g. ketoconazole, itraconazole);
• antihistamines (e.g. loratadine, fexofenadine);
• antiretroviral medicines including HIV protease inhibitors (amprenavir, atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, saquinavir, tipranavir) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) (delavirdine, efavirenz, nevirapine) and others (didanosine, maraviroc, raltegravir, zidovudine);
• medicines for tuberculosis (bedaquiline and delamanid);
• antiviral medicines for the treatment of chronic hepatitis C virus (HCV) infection in adults (e.g. glecaprevir/pibrentasvir and simeprevir);
• medicines for anxiety, buspirone;
• medicines for asthma, theophylline, salmeterol;
• atovaquone, a medicine used to treat certain types of pneumonia and malaria;
• buprenorphine, a medicine used for chronic pain;
• bupropion, a medicine used to help stop smoking;
• medicines for epilepsy (e.g. carbamazepine, divalproex, lamotrigine, phenytoin);
• medicines for the heart (e.g. disopyramide, mexiletine and calcium channel blockers such as amlodipine, diltiazem, and nifedipine);
• medicines that affect the immune system (e.g. cyclosporin, tacrolimus, everolimus);
• levothyroxine (used to treat thyroid problems);
• morphine and morphine derivatives used to treat severe pain (methadone, fentanyl);
• sleeping pills (e.g. alprazolam, zolpidem) and also midazolam given by injection;
• tranquillisers (e.g. haloperidol, risperidone, thioridazine);
• colchicine, a treatment for gout.

There are some medicines that you cannot take with Norvir. These are listed earlier in section 2 “Do not take Norvir”.

Taking Norvir with food and drink

Norvir tablets should be taken with food.

Pregnancy and breast-feeding

It is very important that you consult your doctor if you think you are pregnant or are planning to become pregnant.

There is a lot of information on the use of ritonavir (the active ingredient of Norvir) during pregnancy. In general, pregnant women received low doses (booster doses) of ritonavir together with other protease inhibitors after the first three months of pregnancy. Norvir does not appear to increase the risk of developing birth defects compared to the general population.

Norvir can pass into breast milk. To prevent transmission, mothers with HIV should not breast-feed their babies.

Driving and using machines

Norvir can cause dizziness. If you experience these effects, do not drive or use machines.

3. How to take Norvir

Follow the administration instructions for this medication exactly as indicated by your doctor or pharmacist. Consult your doctor or pharmacist if you have any doubts. Take this medication once or twice a day, every day with food.

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

The recommended doses of Norvir are:

Your doctor will indicate the appropriate dose you should take.

You must take Norvir every day to control HIV, regardless of whether you feel better. If there is any side effect that prevents you from taking Norvir as indicated, inform your doctor immediately. During episodes of diarrhea, your doctor may decide that you need additional monitoring.

Always have a sufficient amount of Norvir on hand so that you do not run out. When traveling or needing to stay in the hospital, check that you have enough Norvir until you can get more.

If you take more Norvir than you should

If you take too much Norvir, you may experience numbness, tingling, or a tingling sensation. If you realize you have taken more Norvir than you should, contact your doctor or the Emergency Service of the nearest hospital immediately.

If you forget to take Norvir

If you have forgotten to take a dose, take it as soon as possible. If the time of the next dose is near, take only one dose. Do not take a double dose to make up for forgotten doses.

If you stop taking Norvir

Even if you feel better, do not stop taking Norvir without consulting your doctor. If you take Norvir as indicated, you will have more chances of delaying the development of resistance to this medication.

4. Possible side effects

During HIV treatment, there may be an increase in weight and glucose and lipid levels in the blood. This may be partly related to the recovery of health and lifestyle, and in the case of blood lipids, sometimes to HIV medications themselves. Your doctor will monitor these changes.

Like all medications, Norvir can cause side effects, although not all people experience them. When Norvir is used with other antiretroviral medications, the side effects also depend on those other medications. Therefore, it is very important that you carefully read the section on adverse reactions in the package insert of these medications.

Very common:may affect more than 1 in 10 people

Common:may affect up to 1 in 10 people

Uncommon:may affect up to 1 in 100 people

Rare:may affect up to 1 in 1,000 people

Tell your doctor if you feel dizzy (nausea), are vomiting, or have stomach pain, as these can be symptoms of pancreatitis. Also, inform your doctor if you experience joint stiffness, discomfort, and pain (especially in the hip, knee, and shoulder) and difficulty moving, as this may be a sign of osteonecrosis. See section 2. What you need to know before you or your child takes Norvir.

There have been cases of increased bleeding in patients with hemophilia A and B during treatment with this or another protease inhibitor. If this happens to you, consult your doctor immediately.

It has been reported that patients taking Norvir have presented with alterations in liver function tests, hepatitis (liver inflammation), and rarely jaundice. Some people had other diseases or were taking other medications. Some people with liver disease or hepatitis may have worsened.

Cases of muscle pain, discomfort, or weakness have been described, particularly when taking cholesterol-lowering medications in combination with combined antiretroviral therapy, including protease inhibitors and nucleoside analogs. In rare cases, these muscle disorders were severe (rhabdomyolysis). In case of muscle pain, discomfort, weakness, or cramps of unknown cause or continuous, stop taking the medication, contact your doctor as soon as possible, or go to the Emergency Service of the nearest hospital.

Tell your doctor immediately if after taking Norvir you experience any symptoms that may suggest an allergic reaction, such as skin rash, hives, or difficulty breathing.

If you consider that any of the side effects you are experiencing is serious or if you notice any side effect not mentioned in this package insert, inform your doctor or pharmacist, go to the emergency department, or seek immediate medical attention if it is urgent.

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this package insert. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Norvir

Keep this medication out of sight and reach of children.

Do not use Norvir after the expiration date indicated on the label of the bottle. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions. Store in the original package to protect it from moisture.

Medications should not be disposed of through wastewater. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Package contents and additional information

Norvir composition

• The active ingredient is ritonavir. Each film-coated tablet contains 100 mg of ritonavir.

• The other ingredients are: copovidone, sorbitan laurate, calcium hydrogen phosphate anhydrous, colloidal anhydrous silica, and sodium stearyl fumarate.

• The ingredients of the film coating are: hypromellose, titanium dioxide, macrogol, hydroxypropyl cellulose, talc, colloidal anhydrous silica, and polysorbate 80.

Appearance of the product and package contents

Norvir film-coated tablets are white and have a relief imprint (Abbott logo) and the code “NK”.

Three sizes of Norvir tablet packaging are available:

• 1 bottle of 30 tablets
• 1 bottle of 60 tablets
• Multi-pack containing 3 bottles, each containing 30 film-coated tablets (90 tablets)

Not all pack sizes may be marketed.

Norvir is also supplied as a powder for oral suspension containing 100 mg of ritonavir.

Marketing authorization holder

AbbVie Deutschland GmbH & Co. KG, Knollstrasse, 67061 Ludwigshafen, Germany

Manufacturers:

AbbVie Deutschland GmbH & Co. KG

Knollstrasse

67061 Ludwigshafen

Germany

You can request more information about this medication by contacting the local representative of the marketing authorization holder.

This package insert has been revised in

Detailed information about this medication is available on the European Medicines Agency website http://www.ema.europa.eu